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RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: [email protected]@INET@LNGTWY (
[email protected]@INET@LNGTWYJOA] ) (SYS)
CREATION DATE/TIME: 3-MAR-1997 14:42:24.00
SUBJECT: Auto reply from Cell Tissue Account
TO: Jennifer J. Kulynych@EOP ( Jennifer J. Kulynych@EOP [ OSTP 1)
READ:UNKNOWN
TEXT:
PROPOSED APPROACH TO REGULATION OF
CELLULAR AND TISSUE-BASED PRODUCTS
The Food and Drug Administration
February 28, 1997
PROPOSED APPROACH TO REGULATION OF
CELLULAR AND TISSUE-BASED PRODUCTS
[Docket Number 97N-0068]
For further information regarding this document, contact:
Sharon Carayiannis
Center for Biologics Evaluation and Research
(HFM-630)
Food and Drug Administration
1401 Rockville Pike, Suite 200N
Rockville, MD 20852-1448
301-594-3074
Submit written comments on this document to:
Dockets Management Branch (HFA-305)
Food and Drug Administration
12420 Parklawn Drive, Room 1-23
Rockville, MD 20857
Comments should be identified with the docket number found in the
heading of this page.
Submit written requests for additional copies of this document or
any other CBER guidance to:
Office of Communication, Training, and Manufacturers Assistance
(HFM-40)
Food and Drug Administration
1401 Rockville Pike, Suite 200N
Rockville, MD 20852-1448
Send one self-addressed adhesive label to assist that office in
processing your request.
These documents may also be obtained by mail by calling the
CBER Voice Information System at 1-800-835-4709 or
301-827-1800, or by fax by calling the FAX Information System at
1-888-CBER-FAX or 301-827-3844.
Persons with access to the INTERNET may obtain these documents
using, the World Wide Web (WWW), or bounce-back e-mail. For
WWW access, connect to CBER at
"http://www.fda.gov/cber/cberftp.html". To receive this document
by bounce-back e-mail send a message to
"[email protected]"
TABLE OF CONTENTS
Executive Summary
I. Introduction
II. Background
III. Public health and regulatory concerns associated with cellular
and tissue-based products
IV. Product factors (tissue characteristics and uses) affecting each
area of concern - an overview
A) Direct transmission of communicable disease
B) Processing concerns
C) Clinical safety and effectiveness concerns
D) Promotion and labeling
E) FDA's baseline knowledge of cell and tissue industry
V. The regulatory scheme: product concerns, product
characteristics, and uses; required industry actions; and required
regulatory submissions
A) Direct Transmission of Communicable Disease - Donor
Screening, Donor/Product Testing
1) Overview
2) Regulatory Requirements
a) Row A1
b) Row A2
B) Control of Processing
1) Overview
2) Factors Affecting Processing Concerns and Clinical Safety and
Effectiveness Concerns
a) Non-cell/non-tissue components
b) Manipulation
c) Non-homologous function
d) Metabolic function
e) Reproductive Function
f) Structural Function
3) Regulatory Requirements
a) Row B1
b) Row B2
c) Row B3
C) Clinical Safety and Effectiveness - Use-specific Concerns
1) Overview
2) Regulatory Requirements
a) Row C1
b) Row C2
c) Row C3
D) Promotion and Labeling
E) Monitoring and Education
VI. Implementation of Regulatory Procedures
A) Stem cells
1) Registration and Listing
2) Communicable-Disease Screening and Testing
3) Processing Standards
B) Demineralized bone
VII. Conclusion
Glossary of Terms as Used in this Document
Table I
Table 2
NOTE: This ASCII version does not contain all tables and
other formatted items. Printed copies are available
by mail or FAX by calling 1-800-835-4709.
PROPOSED APPROACH TO REGULATION OF
CELLULAR AND TISSUE-BASED PRODUCTS
February 28, 1997
EXECUTIVE SUMMARY
The Food and Drug Administration is proposing a new approach to
the regulation of human cellular and tissue-based products. Tissues
have long been transplanted in medicine for widespread uses-such
as skin replacement after severe burns, tendons and ligaments to
repair injuries, heart valves to replace defective ones, corneas to
restore eyesight, and the use of human semen and implantation of
eggs to help infertile couples start a family. In recent years,
scientists have developed new techniques, many derived from
biotechnology, that enhance and expand the use of human cells and
tissues as therapeutic products. These new techniques hold the
promise of some day providing therapies for cancer, AIDS,
Parkinson's Disease, hemophilia, anemia, diabetes, and other
serious conditions.
The existing FDA approach to the regulation of human cellular and
tissue-based products is highly fragmented. The agency has not
previously clearly defined criteria for product characterization,
sometimes resulting in confusion on the part of both industry and
FDA reviewers. The new regulatory framework, as articulated in
this document, would provide a unified approach to the regulation
of both traditional and new products. The framework clearly
specifies criteria for regulation, and would provide for harmonized
review of applications by different Centers within the agency.
Additionally, the framework would provide only the degree of
government oversight necessary to protect the public health. For
products with limited public health concerns, the new framework
would allow flexibility and innovation without an application
review process.
This new framework would provide a tiered approach to cell and
tissue regulation. Regulation would focus on three general areas: 1)
preventing unwitting use of contaminated tissues with the potential
for transmitting infectious diseases such as AIDS and hepatitis; 2)
preventing improper handling or processing that might contaminate
or damage tissues; 3) ensuring that clinical safety and effectiveness
is demonstrated for tissues that are highly processed, are used for
other than their normal function, are combined with non-tissue
components, or are used for metabolic purposes.
The agency would recommend, but not require, that screening and
testing procedures be followed when reproductive tissues are used
between sexually intimate partners, and when tissues are
transplanted back into the person from whom they were obtained.
The agency would require infectious disease screening and testing
for cells and tissues transplanted from one person to another (except
for reproductive tissues used between sexually intimate partners).
The agency would also require that cells and tissues be handled
according to procedures designed to prevent contamination and to
preserve tissue function and integrity. In general, there would be no
agency submissions required regarding infectious disease controls
and handling requirements. Thus, most conventional and
reproductive tissues would not be subject to premarket approval
requirements (The agency would impose no requirements on cells
and tissues transplanted within a patient's body in a single surgical
procedure.)
Cells and tissues that were manipulated extensively, combined
with non-tissue components, or were to be used for other than their
normal functions would be regulated as biologics or devices
requiring premarket approval by FDA.
Metabolic cells and tissues, unless minimally manipulated and
used for their normal function in the person from whom they were
obtained or in close blood relatives of that person, also would be
regulated as biologics requiring premarket approval by FDA.
The agency would require that all tissue processing facilities
register with the agency, and list their products, via a simple
electronic system.
And the agency would require that all labeling and promotion be
clear,
accurate, balanced, and non-misleading.
This new system would provide a rational, comprehensive and
comprehensible framework under which tissue processors could
develop and market their products. It would ensure that innovation
and product development in this rapidly growing medical field
could proceed unhindered by unnecessary regulation. At the same
time, it would provide physicians and patients with the assurance
of safety that the public has come to expect from drugs, biologics,
medical devices and other medical products overseen by the FDA.
I. INTRODUCTION
The FDA has formulated a comprehensive approach to the regulation
of human cellular and tissue-based products. This approach would
provide more appropriate oversight for the wide spectrum of cellular
and tissue-based products that are now marketed or envisioned for the
future. It would maintain or improve protection of the public and
increase public confidence in these new technologies, while permitting
significant innovation to go forward unfettered by unnecessary
regulatory requirements.
The approach does not encompass vascularized organs or
minimally-manipulated bone marrow (both of which are regulated by
the Health Resources and Services Administration), transfusable blood
products (e.g., whole blood, red blood cells, platelets, and plasma),
which the agency already comprehensively regulates, or tissues
derived from animals. It also does not encompass other tissue-related
products, such as products used in the propagation of cells or tissues,
or that are secreted by or extracted from cells or tissues (e.g. human
milk, collagen, urokinase, cytokines, and growth factors.) Such
products often raise different manufacturing, safety, and effectiveness
issues, and generally are covered by other rules, regulations, and/or
standards.
II. BACKGROUND
The term "tissues" covers a wide range of products used for many
medical purposes. In the past, most human tissue used in medicine
was comprised of such body components as skin, bone, corneas, and
heart valves that were transplanted for replacement purposes, and
semen and ova implanted for reproductive purposes. Except for a
small number of tissues previously regulated as devices since 1993,
FDA's regulation of the conventional tissues used for replacement
purposes has focused on preventing the transmission of communicable
disease, as authorized by the Public Health Service Act (PHS Act).
Three years ago, FDA promulgated interim requirements that such
conventional non-reproductive tissues be tested for HIV and hepatitis
and that their donors be screened for risk of infection. FDA has not
previously regulated reproductive tissues.
In recent years, scientists have developed innovative methods of
manipulating and using human cells and tissues for therapeutic uses.
For example, in what is known as somatic cell therapy, scientists are
studying the use of human cells that have been manipulated in the
laboratory to treat viral infections (including HIV infection),
Parkinson's Disease, diabetes, and other diseases and conditions.
Other tissue research includes the use of blood from the
placental/umbilical cord, to treat diseases or conditions. In general,
these forms of cellular and tissue therapy are regulated by FDA as
"biologics" under both the PHS Act and the Federal Food, Drug, and
Cosmetic Act (FDCA), with premarketing approval requirements.
III. PUBLIC HEALTH AND REGULATORY CONCERNS
ASSOCIATED WITH CELLULAR AND TISSUE-BASED PRODUCTS.
Cellular and tissue-based products and their potential uses are too
diverse for a single set of regulatory requirements to be appropriate
for all. In an effort to develop a comprehensive scheme that would
treat like products alike, but that would establish appropriate
regulatory distinctions among cellular and tissue-based products in
areas where there were differences, the agency identified the
principal public health concerns and attendant regulatory issues
associated with the use of these products. Stated as questions,
these five overarching public health and regulatory concerns are:
A) How can the transmission of communicable disease be prevented?
B) What processing controls are necessary, e.g., to prevent
contamination that could result in an unsafe or ineffective
product, and to preserve integrity and function so that products
will work as they are intended?
C) How can clinical safety and effectiveness be assured?
D) What labeling is necessary, and what kind of promotion is
permissible, for proper use of the product?
E) How can the FDA best monitor and communicate with the cell
and tissue industry?
With these concerns in mind, the FDA differentiated cells and
tissues and their uses by their risk relative to each concern, so as
to enable the agency to provide only that level of oversight relevant
to each of the individual areas of concern. Thus, under the plan,
tissues would be regulated with a tiered approach based on risk and
the necessity for FDA review.
IV. PRODUCT FACTORS (TISSUE CHARACTERISTICS AND USES)
AFFECTING EACH AREA OF CONCERN - AN OVERVIEW
The agency has identified the following key product factors relating to
the above concerns.
A) Direct transmission of communicable disease. The level of public
health concern about communicable disease varies depending in
substantial part on the following factors: whether the cells or tissues
are used in the same person from whom they were obtained (autologous
use); whether the cells or tissues are used in a person different from
whom they were obtained (allogeneic use); whether they are banked
(stored), shipped, or processed in a facility that handles cells and
tissues from multiple donors; whether the cells or tissues are minimally,
or more-than-minimally, manipulated;
whether the tissue is viable or nonviable; and for reproductive cells or
tissue, whether they are obtained from a sexually-intimate partner of the
transplant/insemination recipient.
B) Processing concerns. The level of concern relating to processing is
dependent on the following factors: whether or not the cells or tissues
are more-than-minimally manipulated; whether or not they are used for
their normal (homologous) function; whether or not they are combined
with non-cell/non-tissue components; and whether or not they are used
for metabolic function. As will be discussed below in VI B,
Control of Processing, products that are more-than-minimally manipulated,
or are used for purposes other than their normal function, or are
combined with non-cell/non-tissue components, or are used for metabolic
function, generally will be subject to more comprehensive regulation of
processing than products not characterized by any of these factors,
although some exceptions may apply. (For example, use for metabolic
function would not in and of itself lead to more comprehensive
processing regulation when the product was used in the person from whom
it was obtained, or in a close blood relative of that person; use of
minimally manipulated tissue for other than its normal function may lead
to only limited additional regulation of processing, as appropriate to
help ensure intended function). Products not characterized by any of
these factors would be regulated under section 361 of the PHS Act, and
would not be subject to premarketing requirements. Products
characterized by one or more of these factors would be regulated under
section 351 of the PHS Act and/or under the FDCA, and generally
would be subject to some level of premarketing requirements.
C) Clinical safety and effectiveness concerns. Clinical safety and
effectiveness concerns depend on the same factors as do processing
concerns (i.e., extent of manipulation; homologous or non-homologous
function (that is, whether or not tissue is used for its normal
function); combination with non-cell/non-tissue components; and
metabolic function). The kinds of information the agency will need to
address these concerns may differ depending on whether the cellular or
tissue-based product is to be used for a local structural purpose
(i.e., reconstruction or repair), a reproductive purpose, or a metabolic
purpose. As noted above for processing concerns, and as will be
discussed below in section VI C, Clinical Safety and Effectiveness,
products that are more-than-minimally manipulated, or are used for
non-homologous function, or are combined with non-cell/non-tissue
components, or are used for metabolic function, will generally be
subject to more comprehensive regulatory controls than products
without any of these factors. However, for some products subject
to regulation under section 351 and/or the FDCA (see section VI, A,
Stem Cells) the agency anticipates establishing product-class-specific
processing controls and product standards based on data demonstrating
that such controls or standards ensure safety and effectiveness. For
these products, applicants would be eligible to certify that these
controls and standards have been met in lieu of submitting the
underlying data to support such controls and standards.
D) and E) Promotion and labeling and the agency's baseline
knowledge of industry are cross-cutting issues that apply to all
cellular and tissue-based products, with the exception of cells and
tissues obtained from and transplanted back into the same person during
a single surgical procedure.
V. THE REGULATORY SCHEME: PRODUCT CONCERNS, PRODUCT CHARACTERISTICS
AND USES, REQUIRED INDUSTRY ACTIONS, AND REQUIRED REGULATORY
SUBMISSIONS.
The agency has developed a chart (Table 1) that outlines the five
principal areas of public health or regulatory concern (rows A
through E, as described below), the product factors that affect those
concerns (and that are the basis for the subdivisions within rows A,
B, and C), the industry actions that would be required to address each
set of concerns, and the types of required notifications or submissions
to the agency. Thus, to determine all the regulatory mechanisms that
would apply to any particular product or use, one must look at all the
items in the table. The table is provided only as a very short summary
of the regulatory approach. As such, it is not intended to stand alone,
but to be referred to in conjunction with this document. The following
text elaborates on the issues as presented by row in Table 1.
A) Direct transmission of communicable disease - donor screening,
donor/product testing.
1) Overview.
Transmission of communicable disease is a concern for all uses of
all cellular or tissue-based products. However, the degree of risk, and
the appropriate measures to control risk, vary with the source and use
of the product. FDA intends to adjust its regulatory approach
accordingly.
Row A of Table I broadly distinguishes between cellular and
tissue-based products for which the agency would not require
communicable-disease controls (A1), and products for which it would
require communicable-disease controls (A2). A2 is further subdivided
according to the kinds of requirements and tests the agency would
consider appropriate, based on the source, use, and characteristics
of the tissue. Proposals for specific screening, testing, and related
requirements for products in these categories are provided in Table
2.
2) Regulatory requirements.
a) Row A1. The agency would not assert any regulatory control
over cells or tissues that are removed from a patient and transplanted
back into that patient during a single surgical procedure. The
communicable disease risks, as well as safety and effectiveness
risks, would generally be no different from those typically associated
with surgery. Regulated products used in such procedures would continue
to be regulated.
b) Row A2. The use of allogeneic rather than autologous cellular or
tissue-based products increases the risk of transmission of communicable
disease, because the donor from whom the cells or tissue was obtained
could carry an infectious agent to which the recipient is susceptible.
Also, for both autologous and allogeneic settings, the use of cellular
or tissue-based products that are banked, transported, or processed in
facilities with other cellular or tissue-based products increases the
risk of transmission of communicable disease, because the products are
susceptible to contamination or mix-up at each step of such procedures.
For example, an infected product could cross-contaminate other cellular
or tissue-based products stored in the same liquid nitrogen freezer, or
could contaminate processing equipment, which, if not properly treated,
could contaminate other tissue processed with that equipment. If
contaminated tissue is not properly tested or labeled, health care
workers as well as patients may be put at risk.
Therefore, as shown in rows A2b and A2c of Table 1 and in Table 2,
the agency intends to require establishments and persons that bank,
ship, or process cells or tissues for allogeneic use (except reproductive
tissues from sexually intimate partners of the intended recipient of
the tissue) to follow specific donor screening and/or donor or product
testing and/or product quarantine procedures. Test requirements will
differ depending on whether the cells or tissues are nonviable (A2b) or
viable (A2c). Viable cells and tissues that are rich in leukocytes (such
as stem cells) can harbor human T-cell lymphotropic virus (HTLV) and
cytomegalovirus (CMV), and thus would be required to be tested for those
viruses. Viable tissues that are not rich in leukocytes (such as
corneas and skin), and nonviable tissues (which do not contain viable
leukocytes) would not be subject to HTLV and CMV testing requirements.
In general, the screening and testing would be required to be
completed prior to final release of the cells or tissue for
transplantation. The establishment or person responsible for
determining suitability of release of cells or tissues would be
responsible for ensuring that required screening and testing had
been performed prior to final release of the material. For cells or
tissue to be obtained from a living donor for allogeneic use, screening
and testing would be required prior to collection of the cells or tissue
(except in extenuating circumstances).
Additionally, as shown in row A2a of Table 1 and in Table 2, the
agency intends to recommend (but not require) that establishments
and persons that bank, ship or process cells or tissues from multiple
donors for autologous use, or reproductive cells or tissues for
reproductive use obtained from sexually intimate partners of the intended
recipients of the cells or tissues, also follow the screening and testing
procedures prior to collecting the cells or tissue. The agency intends
to require that such establishments and persons keep records and label
their products as to whether or not recommended donor screening and
testing was performed, and if performed, the results obtained. Untested
products would be labeled as "untested for BIOHAZARDS."
The screening and testing procedures would be recommended rather than
required for such autologous or reproductive uses because 1) autologous
use of cells and tissues raises lesser communicable-disease
concerns than does allogeneic use; and 2) use of reproductive tissues
from sexually intimate partners of intended recipients raises lesser
communicable-disease concerns than other allogeneic uses of tissues
because the recipient generally will have had prior exposure to the
potential risk of receiving communicable disease from that partner.
(In contrast, cells or tissue from family-related donors raise the same
communicable-disease risks as do cells or tissue from unrelated donors,
and consequently family-related donors would be subject to the same
testing and screening procedures as are unrelated donors. However,
the agency believes that it is appropriate to leave it up to the
family and their physician to decide whether to use such tissue, and
would not prohibit use even of contaminated material from closely-related
donors.)
Cells or tissue from donors who test positive for an infectious disease
agent or who have positive risk factors (that is, whose behavior or
experiences could have exposed them to infection) would be required
to be labeled "BIOHAZARD" or "UNTESTED FOR BIOHAZARD" as applicable,
and could only be used for transplantation with the documented
advance informed consent of the recipient. Autologous tissue from
such donors would be required to be labeled "FOR AUTOLOGOUS USE ONLY".
In those situations in which cells or tissues from such donors are not
destroyed, the material could be released from a bank or quarantine
only upon documented concurrence of the recipient's physician. Such
situations would include cells or tissue to be used in the person from
whom it was obtained or in a close blood relative (e.g., autologous
stem cells); and reproductive tissue for reproductive use (e.g., semen)
from a sexually intimate partner of the intended recipient or from a
directed donor; medically necessary and otherwise unavailable cells or
tissue (e.g., the tissue is a rare histocompatibility match in a setting
where matching is critical).
The agency would engage in rulemaking under section 361 of the PHS Act
to establish procedures and standards for cellular and tissue-based
products not subject to premarket requirements under the PHS Act or
the FDCA. While under the section 361 rule there would be no required
premarketing submissions to the agency concerning communicable-disease
testing, the agency would have authority to inspect facilities subject
to the requirements, and to take actions to prevent transmission of
communicable disease (e.g., orders of retention, recall, and
destruction of cellular and tissue-based products).
Cellular and tissue-based products subject to premarket requirements
because of processing or clinical attributes (see sections V B and VC
below) would still be subject, unless the requirements were unnecessary
in a particular situation, to the same core communicable-disease
standards and procedures as are cellular and tissue-based products
regulated under section 361, and would generally be subject to no
additional submission requirements regarding these communicable-disease
issues. To the extent that a product requiring premarketing approval were
to raise additional communicable-disease concerns as a result of its
source,
processing, or use, additional standards or procedures could be required
in the marketing application to address these concerns.
B) Control of Processing.
1) Overview.
Row B of Table 1 differentiates products based on whether their
characteristics and uses warrant handling and processing controls
aimed only at preventing transmission of communicable disease
(B2);
or warrant processing controls aimed at providing assurance of
clinical safety and effectiveness, including but not restricted to
preventing transmission of communicable disease (B3). Autologous use of
cells and tissues harvested and transplanted in a single surgical
procedure would be subject to no FDA oversight (B1). Regulated products
used with the cells or tissues or to process the cells or tissues would
continue to be regulated.
Improper handling can alter or destroy the integrity or function of
cells or tissues. Improper handling also can allow cells or tissues to
become contaminated (e.g, bacterial contamination during collection,
processing, storage, or transplantation, or cross contamination from
other contaminated tissues). Similarly, inadequately-controlled
processing can alter or destroy the integrity or function of cells or
tissues. Use of cells or tissues contaminated with an infectious
agent obviously increases the risk of transmission of communicable
disease. Use of cells or tissue with impaired integrity or function also
increases the risk of transmission of communicable disease: tissue with
impaired integrity or function can lead to transplantation failure, with
attendant communicable disease risks (e.g., by increasing the patient's
susceptibility to communicable disease, or requiring additional
transplantation procedures, with their attendant communicable-disease
risks.)
2) Factors Affecting Processing Concerns and Clinical Safety and
Effectiveness Concerns.
As previously discussed above, the factors affecting the level of
concern regarding processing controls and product safety and
effectiveness are: manipulation (i.e., whether the product is
minimally or more-than-minimally manipulated); homologous or
non-homologous function; whether or not the cells or tissue are
combined with non-cell/non-tissue components; and whether or not
the product is used for metabolic function as opposed to reproductive
or structural function. The agency describes these factors and their
regulatory implications below.
(a) Non-cell/non-tissue components. Cellular and tissue-based
products may be combinations of cells or tissues with mechanical
or synthetic components, with drugs, or with non-cell/non-tissue
biologics. The largest and fastest growing class of such
combination products are those containing synthetic or mechanical
components. These components raise concerns about function, compatibility,
and durability. Examples of such combination products would include
epithelial cells on a biomatrix to cover burns; allogeneic pancreas
cells in a capsule that allows exit of insulin but not entry of antibodies;
and bone when combined with collagen or growth factors.
The agency does not anticipate that its planned regulatory approach
for cellular and tissue-based products would alter existing agency
regulatory policies concerning cellular and tissue-based products
containing non-cell/non-tissue components. These combination products
are generally subject to premarketing requirements. The decision as to
which part of the agency has primary regulatory responsibility for such
combination products will depend on the primary mode of action of the
product.
Combination products whose primary mode of action is that of a
device are regulated by the Center for Devices and Radiological
Health (CDRH). Combination products whose primary mode of action is
that of a biologic are regulated by the Center for Biologics Evaluation
and Research (CBER). Combination products whose primary mode of action
is that of a drug are regulated by the Center for Drug Evaluation and
Research (CDER). The agency intends to assure that its reviews of these
products are consistently performed, regardless of which Center is
responsible for the review.
For combination products with synthetic or mechanical components
(which comprise the largest class of combination products), clinical
trials and marketing applications must address the clinical safety
and effectiveness of the overall product, as well as the function and
compatibility of the synthetic or mechanical components. The agency's
principal concerns with the use of these materials are that they function
correctly, that they last a predictable and adequate length of time, and
that they are compatible with surrounding tissue. Clinical trials would
thus be required under IND or IDE, as appropriate.
The agency is setting up a Tissue Reference Group to assist in making
jurisdictional decisions and applying consistent policy to these
products. The agency hopes thereby to resolve expeditiously any
scientific or regulatory questions that arise as to where and how
such products should be reviewed. The Tissue Reference Group will
consist of three CBER and three CDRH employees. It will provide a
single reference point for all tissue-related questions received by
the Centers or the Office of the Chief Mediator and Ombudsman.
b) Manipulation. The agency would consider processing of structural
tissue to be "minimal manipulation" when the processing does not
alter the original relevant characteristics of the tissue. The relevant
characteristics of structural tissue are those relating to the tissue's
ability to carry out the function of reconstruction and/or repair.
Thus, separation of structural tissue into components whose
characteristics relating to reconstruction and/or repair are not altered
would be minimal manipulation. Similarly, extraction or separation of
cells from structural tissue, in which the remaining structural tissue's
characteristics relating to carrying out reconstruction and/or repair
were unaltered, would be considered minimal manipulation. Other
examples of procedures that would be considered to constitute only
minimal manipulation include cutting, grinding, and shaping; soaking
in antibiotic solution; sterilization by ethylene oxide treatment or
gamma irradiation; cell separation; lyophilization; cryopreservation;
and freezing.
In contrast, extraction of endogenous substances such as minerals or
proteins from structural tissue would be considered more-than-minimal
manipulation, because such modifications would ordinarily alter the
tissue's relevant characteristics.
The agency would consider processing of cells (both structural and
non-structural) and non-structural tissues to be "minimal
manipulation" when the processing does not alter the biological
characteristics of the cells or tissue. The agency would consider
processing of cells and non-structural tissues to be
"more-than-minimal manipulation" when the processing alters the
biological characteristics (and thus potentially the function or
integrity) of the cells or tissue, or when adequate information does
not exist to determine whether the processing will alter the biological
characteristics of the cell or tissue. Examples of more-than-minimal
manipulation of cells and tissues include cell expansion, encapsulation,
activation, or genetic modification.
Cells or tissues that are more-than-minimally manipulated would be
subject to processing controls that generally would cover chemistry,
manufacturing, and controls (CMCs), and to premarket requirements
for determination of safety and effectiveness because manipulation
has the potential, or is intended, to change the cell or tissue's
biological characteristics or function. The agency has previously
used the concept of manipulation to identify those cellular therapies
for which premarket approval would be required. In the somatic cell and
gene therapy statement published in October, 1993 (58 FR 53248), the
agency stated:
Cells subject to licensure as final biological products when intended
for use as cell therapy include cells manipulated in a way that changes
the biological characteristics of the cell population.
As described for row B3 in section V B2c below, these products would
continue to be subject to CMCs, including process controls and
product specifications designed to ensure safety, purity, and potency,
and to IND or IDE and marketing application procedures. The agency
has prepared CMC guidances for some of these products.
As additional information is generated about procedures in the
"more-than-minimal-manipulation' category, the agency intends to
consider them to be in the "minimal-manipulation" category when
clinical data and experience show that the procedure does not alter the
biological characteristics of the cells or non-structural tissue, or the
relevant structure-related characteristics of structural tissue. This
flexibility will permit product processing that has been found not to
affect the pertinent characteristics of the product to be subjected to
a lower level of regulation.
In the somatic cell and gene therapy statement, the agency stated
that it considered cell selection to constitute more-than-minimal
manipulation. After additional experience and deliberation, the
agency now considers cell selection (e.g., selection of stem cells from
amongst lymphocytes and mature cells of other lineages) to be minimal
manipulation.
In cases where the agency has not made known whether it considers a
particular kind of processing to be "minimal" or "more-than-minimal
manipulation", individuals may request an opinion from the agency's
Tissue Reference Group. Individuals who believe that a particular
kind of processing is only minimal manipulation and choose to proceed
without seeking clarification assume the risk that they may
be out of compliance with premarketing and labeling requirements if
the agency determines that the processing is more-than-minimal
manipulation.
c) Homologous and non-homologous function. The distinction
between homologous and non-homologous function will differ
depending on whether or not the product is a structural tissue. The
agency considers structural tissue to be used for a homologous
function when used to replace an analogous structural tissue that
has been damaged or otherwise does not function adequately. Conversely,
the agency would consider structural tissue to be performing a
non-homologous function when used for a purpose different from that
which it fulfills in its native state, or in a location of the body
where such structural function does not normally occur.
Examples of homologous uses of structural tissues include bone
allograft obtained from a long bone but used in a vertebra; skin
allograft obtained from the arm but used as a skin graft on the face;
pericardium, a structural covering of the heart, used as a structural
covering for the brain; human heart valves; and human dura mater, a
fibrous covering of the brain, used as a covering. (Thus, the agency
would redesignate human heart valves and human dura mater from devices
to tissues subject to section 361 oversight.)
Examples of non-homologous use of structural tissue include amniotic
membrane used for wound healing on the cornea, and cartilage placed
under the sub-mucosal layer of the urinary bladder to change the angle
of the ureter and thereby prevent backflow of urine from the bladder
into the ureter. The amniotic membrane, which covers the amniotic
sac in utero, would be intended to heal a damaged corneal epithelium
by growing new corneal epithelial cells, a function it does not
normally perform in utero. The cartilage would be acting as a
structural support (its normal function), but in a location where
such structural support does not normally exist.
The agency considers cellular products to be used for a homologous
function when they are used to perform their native function, and
for a non-homologous function when they are used to perform other
functions. An example of homologous use would be hematopoietic
stem cells used for hematopoietic reconstitution of individuals with
marrow aplasia, chemotherapy-induced marrow ablation, Fanconi's
anemia, or severe combined immunodeficiency disease. An example
of non-homologous use of the same cellular product would be treatment
of some adrenal leukodystrophies (which are congenital metabolic
deficiencies), because the sponsor would be intending for the stem
cells to perform a metabolic function other than hematopoietic
reconstitution.
As for manipulation, the agency would have increased safety and
effectiveness concerns for cellular and tissue-based products that
are used for non-homologous function, because there is less basis on
which to predict the product's behavior. Thus, a tendon used to
replace a tendon, even one elsewhere in the body, is still being used
for a homologous function and can reasonably be expected to function
appropriately. However, without clinical trials, one cannot predict
with any certainty how a tendon would act when used for a
non-homologous function, such as to constrict a blood vessel to
prevent pulmonary embolism.
As described above for manipulation, in cases where the agency has
not made known whether it considers a particular use to be homologous
or non-homologous, investigators may request an opinion from the
agency's Tissue Reference Group. Individuals who believe that a use
is homologous and choose to proceed without seeking clarification
assume the risk that they may be out of compliance with premarketing
and labeling requirements if the agency determines that the use is
non-homologous.
d) Metabolic function. Products with a metabolic mode of action
usually rely on viable, functioning cells (e.g., pancreatic islet cells,
pituitary cells, stem cells) for function. They therefore are
sensitive to perturbations and may not retain normal function after the
transplantation process. Failure or improper functioning of such
products often can have a broad variety of systemic adverse effects,
and can be life-threatening (e.g., hematopoietic stem cell replacement
after marrow ablation by chemotherapy, pancreatic islet cell therapy
for diabetes). Relatively few such products have an established
history of safe use. (The agency believes that some autologous and
family-related-allogeneic uses of hematopoietic stem cells may have
such an established history.)
As noted above, minimally manipulated cellular and tissue-based
products with metabolic function raise greater clinical safety and
effectiveness concerns than do products with structural or
reproductive function. The agency intends to assert premarketing
requirements over these products (except when the cells or tissues
are used in the person from whom they were obtained or in a close
blood relative of the donor, in which case as a policy matter the
agency would not require premarket submissions). Thus, for example,
the agency would not call for clinical safety and effectiveness
information for autologous or family-related allogeneic use of
minimally manipulated hematopoietic stem cells (for which no
non-homologous use promotional claims were made), but would require
clinical safety and effectiveness information for non-family-related
allogeneic use of the same cells. As noted in B3 above and section
IV below, the agency believes that, for minimally manipulated stem
cells used allogeneically to reconstitute the cellular components of
blood, sufficient clinical safety and effectiveness data may exist in
the near future to enable the development of processing and product
standards for certain uses that would obviate the need for applicants
to submit CMC and clinical safety and effectiveness information prior
to marketing.
e) Reproductive function. In contrast to other metabolic tissues,
reproductive tissues raise less substantial issues of rejection, graft
versus host disease, or compatibility. Indeed, unlike other tissue,
they perform their normal biological functions in an allogeneic setting.
Failure of reproductive tissue generally does not have life-threatening
or systemic adverse effects except for fertility per se.
Reproductive tissues have a long history of use in the medical community.
(Assessments of pregnancy success rates for live births in clinics is
currently being addressed by the Centers for Disease Control and
Prevention, under the Fertility Clinics Success Rate and
Certification Act of 1992.)
f) Structural function. Cells and tissues used for structural
purposes generally raise different clinical safety and effectiveness
concerns than do metabolic cells and tissues. Many structural cellular
and tissue-based products raise limited safety concerns beyond adverse
local effects. Depending on location, failure of most structural
cellular and tissue-based products is unlikely to lead to life-threatening
consequences. In many cases, determination of effectiveness of
structural therapies is more straightforward than is determination
of effectiveness of metabolic therapies.
Additionally, many structural tissue-based products rely predominantly
on non-living tissues (e.g., tendons) for function. They therefore
usually are relatively insensitive to external factors and are more
likely to retain normal function after the transplantation process.
Also, many structural tissue-based products are conventional tissues
having a long and established history of safe use in the medical
community.
3) Regulatory requirements.
a) Row B1. Autologous cells and tissues collected and
transplanted in a single surgical procedure (e.g., skin or vein grafts)
would not be subjected to any regulatory requirements.
b) Row B2. Cells and tissues not collected from and transplanted
into the same person in a single surgical procedure, and not having any
of the factors that lead FDA to require section 351 and/or FDCA
regulation (i.e., they are minimally manipulated, for homologous
use, without non-cell/non-tissue components, and not for metabolic use
when from an unrelated donor), would be subject only to handling
and processing requirements under section 361 of the PHS Act. The
agency intends to promulgate, under section 361, good tissue
practice requirements (GTPs) that would be aimed at preventing
contamination and preserving product integrity and function through proper
handling and processing practices. Apart from registration, listing, and
reporting requirements, there would be no required FDA submissions;
for example, there would be no premarketing approvals. All establishments
or persons that recover, screen, test, procure, bank, process,
transport or distribute cells or tissues for allogeneic use or from
multiple donors would be subject to some or all of these requirements
as appropriate.
Examples of B2 products would include banked tissues, such as semen,
human heart valves, powdered lyophilized non-demineralized bone and
other conventional tissues, as well as banked autologous and banked
or unbanked family-related allogeneic peripheral and
placental/umbilical cord blood stem cells.
c) Row B3. Inadequately controlled or otherwise improper
processing can result in products that are ineffective, and in products
that are unsafe for reasons other than increasing the risk of
transmission of communicable disease. For example, products may be
unsafe because they are ineffective (e.g., nonviable stem cells used for
hematopoietic reconstitution after chemotherapy) or because they function
improperly (e.g., cells or tissue that inappropriately secrete a hormone
may cause unwanted metabolic effects). Thus, processing controls for
products that raise such clinical concerns often must be more comprehensive
than those needed to address risks of transmission of communicable disease.
As discussed in sections IV and V, cellular and tissue-based products
that are more-than-minimally manipulated, or are used for non-homologous
function, or in combination with non-tissue components, or for a
metabolic purpose raise a higher level of processing concerns pertinent
to assurance of clinical safety and effectiveness. The agency would
subject such products/uses to processing-controls under section 351 of
the PHS Act and/or under relevant sections of the FDCA.
Such processing controls generally would cover product chemistry,
manufacturing, and controls (CMCs) and be subject to premarket
submissions. However, if FDA determines that class-wide standards
can be developed such that products in a specified product class are
known to be clinically safe and effective when manufactured in
accordance with certain defined product specifications and process
controls, FDA could establish such standards through rulemaking
and require premarketing submission of certification by the applicant
that the products met the published standards, rather than a more
detailed submission of the clinical data.
For non-family-related allogeneic cord or peripheral blood stem
cells for hematopoietic reconstitution, which in some cases have been
studied without an investigational new drug exemption (IND), the
agency intends to call for a phase in of IND and licensure
submissions (see section VI, Implementation of Regulatory Procedures).
If, prior to the end of the phase-in period, the agency has received
adequate data and information to enable the agency to promulgate standards
designed to ensure safety and effectiveness for particular uses of these
products, FDA anticipates making a class-specific finding of safety and
effectiveness for products meeting those standards (see section V C,
Clinical Safety and Effectiveness, and section VI, Implementation
of Regulatory Procedures) Individuals pursuing licensure subsequent to
the adoption of such standards would not have to submit clinical safety
and effectiveness data to the agency in their premarketing applications,
but would merely have to certify that they meet the standards.
Examples of B3 products used for metabolic function would include
hematopoietic stem cells intended for use in recipients who are not
close blood relatives of the cell donor or for uses other than to
reconstitute the cellular components of the blood; cloned and/or
activated lymphocyte therapies for cancer or infectious diseases;
and hematopoietic stem cells that have been expanded or modified as
part of gene therapy.
Examples of B3 products used for structural function would include
demineralized bone (which the agency plans to propose to classify
as a class I device and to exempt from premarket submissions), and
bone combined with collagen or growth factors.
C) Clinical Safety and Effectiveness - Use-specific Concerns.
1) Overview.
Row C of Table I distinguishes products based on whether they
have none of the factors relating to clinical safety or effectiveness that
would lead FDA to require section 351 or FDCA premarketing
submissions requirements (C1); whether they have one or more of
such factors and are used to achieve a local structural function (i.e.,
reconstruction or repair) (C2); and whether they have one or more
of such factors and are used to achieve a reproductive or metabolic
function (C3).
Products described under CI would be subject to no section 351 or
FDCA requirements for clinical trials demonstrating safety and
effectiveness. Products under C2 and C3 would be subject to section
351 and/or FDCA requirements. Requirements for premarket clinical
data submissions for C2 and C3 cellular and tissue-based products
would generally be as for other regulated products, tailored as
appropriate to the characteristics of the product and the concerns
raised by the specific indication and product. For serious and
life-threatening illnesses, all other applicable policies (e.g.,
expedited review, treatment IND, accelerated approval) would be
available to help speed product availability.
C2 products are separated from C3 products to indicate that in
general they would be subject to different safety and effectiveness
endpoints to fulfill clinical trial requirements. Clinical trial
requirements for C2 products (whether regulated as biologics or devices)
would generally be consistent with those for devices for the same
indication, whether regulated under INDs or IDEs (investigational
device exemptions). Clinical trial requirements for C3 products would
generally be consistent with those for new drugs or biologics for the same
indication.
2) Regulatory Requirements.
a) Row C1. FDA would not require premarket review and approval
for cellular and tissue-based products that are minimally manipulated,
are used for homologous function, do not contain non-cell/non-tissue
components, and are for structural or reproductive use. Such products
raise relatively limited clinical safety and effectiveness concerns,
and thus would not be subject to premarket submission of clinical data.
Additionally, as a policy matter the agency would not require
premarket submission of clinical data for cellular or tissue-based
products that are minimally manipulated, are used for homologous
function, do not contain non-cell/non-tissue components, and are
for metabolic use, when they are to be used autologously or in a close
blood relative of the donor. Communicable-disease risks would be
addressed under section 361 as discussed above in sections VI, A,
2, and VI, B, 2.
Examples of such products would include heart valve and dura mater
transplants, vein grafts, tendons to repair or replace tendons,
autologous or family use of peripheral or cord blood stem cells for
hematopoietic reconstitution, and human gametes (sperm and eggs),
zygotes, and embryos intended for insemination, fertilization, or
transfer.
b) Row C2. The agency recognizes that cellular and tissue-based
products for structural use raise different safety and effectiveness
issues than do products for metabolic or reproductive use, and that
they can be evaluated in a manner generally consistent with that of
devices for the same indication, modified as appropriate for the
nature of the product. (They may also be classified as devices). The
agency outlined its approach for evaluating a major subset of such
products in the May, 1996 Guidance on Applications for Products Composed
of Living Autologous Cells Manipulated Ex Vivo and Intended for
Structural Repair or Reconstruction (MAS Cells) and the CMC
Guidance for Autologous Cell Therapy (1997).
The agency recognizes that many of the highly manipulated cellular
and tissue-based products intended for structural purposes often
will be used for the same indication as are some devices, or will be
classified as devices. It is the intent of CBER and CDRH to ensure
consistent review of such products, whether regulated as devices or
biologics, and to establish clinical effectiveness standards for
structural cells regulated as biologics that would be consistent with
those existing for comparable devices. However, different products may
raise different safety, effectiveness, or durability concerns, and may
be amenable to different methods for measuring outcomes.
Some examples of C2 cellular and tissue-based products include
manipulated cells for autologous structural use (MAS cells) such as
expanded chondrocytes to repair damaged knee cartilage, and devices
such as demineralized bone. (The agency does not intend for
demineralized bone used alone to be subject to premarket submission
requirements. The agency plans to propose to classify demineralized
bone as a class I device and to exempt it from premarket submissions,
as described in section VI.)
c) Row C3. Some examples of C3 cellular products include autologous
genetically-manipulated cellular therapies involving
correction of genetic defects, non-family-related allogeneic cord or
peripheral blood stem cells, stem cell therapies involving growth
factors such as interleukin-3 and stem cell factor or gene therapy,
activated lymphocytes for treatment of cancer, and cloned
lymphocytes for the treatment of HIV infection or other infection.
(See section VI A below regarding phase-in of licensure
requirements for non-family-related allogeneic cord and blood stem cells.)
D) Promotion and Labeling. Row D of table I addresses the issue of
potentially false or misleading claims. For cellular and tissue-based
products regulated under section 361, labeling would need to be clear,
accurate, balanced, and non-misleading. Such labeling could include
what the tissue is and how it has been processed; the homologous uses
of the tissue; and the communicable-disease screening, testing and
quarantine procedures that were followed and results obtained. FDA
intends to propose regulations to address labeling requirements under
section 361 of the PHS Act.
Products that are intended or promoted for use for a non-homologous
function would fall outside the scope of the section 361 regulation
the agency intends to promulgate, and would be subject to regulation
as biological drugs or devices under section 351 of the PHS Act and/or
the FDCA. For cellular and tissue-based products regulated under
FDCA and/or section 351 of the PHS Act, the agency intends to regulate
labeling under existing authorities therein.
E) Monitoring and Education. At present, FDA does not know the
full size and scope of the cell and tissue industry and its potential
products. The agency believes that, in order for it to understand
the issues raised by these new products and be able to educate the
industry and keep it up to date regarding FDA policies, guidances, and
requirements, as well as to enable the agency to inspect
establishments for compliance with applicable laws and regulations, all
establishments that recover, screen, test, procure, bank, process,
transport or distribute cells or tissues from multiple or allogeneic
donors, should register and list their products with FDA. Therefore,
the agency would require registration and listing for all such
establishments and products over which FDA is asserting its
jurisdiction under section 361 of the PHS Act, section 351 of the PHS
Act, or the FDCA. The agency is developing a simple electronic
filing system that it will use for establishment registration and
product listing. Registration and listing for products subject to
section 361 oversight would not be required until the electronic
system is in place.
FDA does not intend to require that it be sent reports of errors and
accidents that occur during processing and distribution of cellular
and tissue-based products subject to section 361 controls. However, as
part of the GTP requirements, establishments and persons will be
required to identify and investigate errors and accidents, take
appropriate corrective action, and maintain records of such failure
assessments. The agency does intend to propose post-market adverse
event reporting requirements relating to transmission of communicable
disease.
The agency intends to apply registration and listing requirements in
section 510 of the FDCA as well as existing post-market reporting
requirements to those cellular and tissue-based products subject to
regulation under section 351 of the PHS Act and/or the FDCA. The
agency intends to propose regulations for registration, listing,
GTPs, and post-market adverse event reporting of those cellular and
tissue-based products regulated under section 361 of the PHS Act.
VI. IMPLEMENTATION OF REGULATORY PROCEDURES
The agency intends to implement this regulatory plan in a step-by-step
fashion. The agency intends to promulgate through notice and comment
rule-making new regulatory requirements, and to allow for phase-in as
appropriate. Some examples of how FDA intends to implement this
regulatory plan for selected products are as follows.
A) Stem cells. The agency intends to phase in its regulatory
oversight of minimally manipulated hematopoietic stem cells derived from
cord or peripheral blood and used for hematopoietic reconstitution in
patients who are not close blood relatives of the donors from whom
the cells were obtained. (Minimally manipulated hematopoietic stem
cells to be used for their normal function in the person from whom they
were obtained or in a close blood relative would be regulated under
section 361, and would not be subject to premarket application
requirements.) The agency intends to phase in regulation of
allogeneic use of these products as follows.
1) Registration and Listing. FDA intends that all facilities that
recover, screen, test, procure, bank, process, transport or distribute
stem cells, derived from umbilical cord blood or peripheral blood,
to treat, cure, diagnosis, or mitigate diseases in humans, be required
to register with the FDA and list the products at their facility.
Registration and listing would be accomplished through an electronic
system that the agency is developing.
2) Communicable-Disease Screening and Testing. The agency intends to
require testing of blood samples from allogeneic donors of
hematopoietic stem cells in order to prevent the transmission of
communicable diseases. For peripheral blood stem cell donors, the
donor's blood, and for umbilical cord blood donors, the mother's
blood, would be required to be tested for HIV, cytomegalovirus, HTLV,
syphilis and hepatitis infection (i.e., HBsAg, anti-HIV-1,
anti-HIV-2, HIV-1-Ag, anti-HTLV-I/II, anti-HCV, a serologic test for
syphilis, and anti-CMV). The medical history and physical examination of
prospective donors would include screening for high risk for HIV and
hepatitis, Creutzfeldt Jacob Disease (CJD), and tuberculosis.
The agency intends to recommend, but not require, that testing be
performed when the stem cells will be used in the person from whom
they were obtained. In such case, the agency would recommend only
the following tests: HBsAg, anti-HCV, anti-HIV-1, anti-HIV-2, HIV-1-Ag,
and anti-HTLV-I/II. The agency also would recommend that the history
and physical examination of the donor include screening for high risk
for HIV and hepatitis. The agency would require that record-keeping
and labeling reveal which of the recommended tests were performed,
and the results obtained from those tests, as well as which of the
recommended tests were not performed. Appropriate labeling would be
as follows: "tested and negative", "tested and positive", or "not
tested for biohazards".
Ordinarily, cells or tissue would not be collected from a donor
testing positive for any of these viruses, and if collected would be
required to be destroyed. However, the agency recognizes that there may
be circumstances justifying storing or using such cells or tissues. For
example, in cases where a stem cell donor tests positive for a virus
or has been found to be at risk of infection (even if testing negative),
and the stem cells are intended for autologous use, for use in a close
blood relative, or for use in a transplant recipient with a rare
histocompatibility match, the agency intends to require that 1) the
cells be labeled "BIOHAZARD", 2) autologous products also be labeled
"FOR AUTOLOGOUS USE ONLY", 3) written advanced informed consent of the
recipient be documented, and 4) there be documented concurrence of the
recipient's physician before the cells could be released from a cell bank.
3) Processing Standards. The agency intends to promulgate
establishment controls, processing controls, and product standards
under section 351 of the PHS Act. For minimally manipulated stem
cells used for hematopoietic reconstitution, the agency believes
that it may be possible to develop product standards (including
manufacturing controls and product specifications aimed at
ensuring product safety and efficacy) from existent published clinical
trial data or data developed in the near future. FDA intends to invite
professional groups and individuals to submit to the agency data and
standards that they believe would ensure safety and effectiveness. If
sufficient data are not available to develop processing and product
standards after a specified period of time, the stem cell products
would be subject to IND and marketing application requirements.
FDA intends to list in the Federal Register relevant questions for
developing the data and standards, and the deadline for submission
of responses. Examples of the kind of information that the agency
believes will be necessary to have in standards include criteria for
acceptance of a unit (such as volume, storage temperature limits,
limits on microbial or other contamination, viable cell number, and
functionality), and procedures for handling, transporting, storing,
and thawing materials, and for when and how contamination and
viability testing should be carried out.
Upon development and promulgation of standards designed to ensure
safety, purity, and potency, FDA would issue licenses based on a
certification by the applicant that the standards are met. The
certification could be made in the same submission as the registration
and listing. FDA would issue a license based on the certification
submission.
During the interim period, FDA would not call for licensure of such
products for unrelated allogeneic use, but would require establishment
registration and product listing. The agency also could perform
inspections for applicable GMP compliance, and could take enforcement
action against facilities as needed (for example, because
of lack of appropriate communicable disease-testing).
B) Demineralized bone. FDA would consider demineralized bone
(decalcified freeze dried bone allograft) to be an unclassified
pre-Amendments device rather than a tissue under section 361
because the bone is more-than minimally manipulated. FDA would seek a
classification recommendation from the Orthopedic/Dental Advisory
Panels. The device to be classified would be defined as including
allograft bone that is processed ONLY to demineralize and preserve
the bone, and ONLY intended to be used as a bone filler in orthopedic
and/or dental procedures.
Based on current information, FDA expects to propose that
demineralized allograft bone be regulated as a Class I medical device
exempted from premarket notification. In addition, FDA expects that
it would also propose to exempt demineralized allograft bone from the
GMP requirements except for certain requirements consistent with
those proposed for human tissues regulated under section 361.
To ensure that the GMP requirements applicable to demineralized
bone are ultimately consistent with the requirements for human
cellular and tissue-based products regulated under section 361, the
Federal Register documents regarding the requirements for each would
be published as companion documents.
VII. CONCLUSION
The agency believes that the above-described proposed approach to
the comprehensive regulation of cellular and tissue-based products
would provide adequate protection of public health, both from the risks
of transmission of communicable disease and from the risks of therapies
that may be dangerous, while enabling investigators to develop new
therapies and products with as little regulatory burden as possible.
The agency intends for this regulatory scheme to encourage research
and innovation, while at the same time set boundaries between the
kinds of experimentation with human products that warrant only minimal
FDA oversight and the kinds of experimentation with human products
that warrant greater FDA oversight.
GLOSSARY OF TERMS AS USED IN THIS DOCUMENT
ablation
Removal or destruction
allogeneic use
Cells or tissue transplanted from
one person to another.
autologous use
Cells or tissue removed from and
transplanted back into the same person.
close blood relative A first degree blood relative (i.e.,
parent, child, or sibling).
cord blood
Blood in the placenta and
umbilical cord, e.g., blood taken at the
time of birth
family relative
A first degree blood
relative (i.e., parent, child, or sibling).
hematopoietic
Giving rise to the cellular
elements of the blood (e.g., white blood cells,
red blood cells, platelets).
hematopoietic
Cells capable of generating white
stem cells
blood cells, red blood cells, and platelets.
For the purposes of this document, these would
include progenitor cells that are committed
to develop into a particular cellular lineage.
Hematopoietic stem cells presently can be
collected (as a very small fraction of the cells)
from peripheral blood, placental/umbilical
cord blood, and bone marrow, often for
transplantation into patients whose own
hematopoietic stem cells have been destroyed by
anticancer treatment or disease.
homologous function Use for the normal function of
the cell or tissue, and, for structural tissue,
use for a structural purpose in a location of the
body where such functional purpose normally occurs
(see P. 15).
MAS cells
Manipulated Autologous cells for
Structural use.
metabolic use
For systemic effect.
minimal manipulation Processing that does not alter the biological
or relevant functional characteristics of cells
or tissue (see P. 13).
more-than-minimal
Processing that alters the
manipulation
biological or relevant functional characteristics
of cells or tissue (see P.13).
non-homologous
Use for other than the normal
function
function of the cell or tissue, or for structural
tissue, use for a structural purpose in a location
of the body where such functional purpose does not
normally occur (see P. 15).
peripheral blood
Circulating blood (in contrast to,
for example, blood in bone marrow).
reproductive tissue
Semen, ova, embryos.
reproductive use
To treat infertility.
stem cells
Cells capable of replicating themselves and of
generating more-differentiated daughter cells.
structural use
For anatomic reconstruction or
repair.
unrelated
Someone other than a close
blood relative.
Table I Relationaships among product concerns, product
characteristics, regulatory approaches
Table 2 Regulatory Framework for Cells and Tissue Related
Products
NOTE: This ASCII version does not contain Tables 1 and 2. A
printed copy is available by mail or FAX by calling
1-800-835-4709.
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CREATOR: [email protected] ([email protected] [ UNKNOWN
CREATION DATE/TIME:19-MAR-1997. 14:27:26.00
SUBJECT: Re: More thoughts on cloning:
TO: [email protected] [email protected] [ UNKNOWN )
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On Wed, 19 Mar 1997 [email protected] wrote:
>
1. I re-read the 1982 report Splicing Life, by the President's
>
Commission and found it most interesting. Evidently the impetus for this
> report was a letter from three religious leaders to President Carter
> expressing concern over genetic engineering. I would be most interested
in > any comments by those who participated in that earlier Commission.
Would > it be useful for us to invite organized religious groups to
present their > views? Having professors give their opinions on what
religions would say > isn't quite the same as asking the religious leaders
directly. Following > on my concerns about leaving voices unheard, should
we invite leaders of
> fundamentalist, born-again groups to present their views, which may be
> different from the Protestant views we heard last week. My own belief
is > that it is better to hear before we write our report how vocal
minorities
> will respond. Even if we think we know what they will say, it may be
> helpful (and politically sage) to listen to them directly.
Two comments:
A. Since the Commission's work was in some sense a response to the
concerns voiced by the three major umbrella organizations for Catholics,
Protestants, and Jews, it made sense to have formal statements from them,
esp. because we expected (as turned out to be the case) that such
statements would be much less alarmist than the views written by Jeremy
Rifkin that the groups' leaders were initially persuaded to send to
President Carter. As I recall, in fact, several of the organizations
basically said, in effect, "we don't have much doctrinally to contribute
on this subject."
B. In the present circumstance, I agree it is useful to know where the
potential players stand before issuing a report than afterwards.
Obviously, in inviting the religious groups to share their views with us,
we aren't "commissioning" papers from them nor promising them time on our
agenda (expect during public comment); we have to husband our resources
(including time) and I suspect that much of what we hear (if very many
groups actually follow through and submit statements) will be quite
similar (perhaps sorting in two or three different groups). As is going
to be true for a lot of the material we get (both that which we
commission and that which comes in "voluntarily"), we will need a staff
member to sort through any such statements and prepare summaries and
syntheses of them (some textual, and perhaps preliminarily in a chart in
which the contributors and their positions/conclusions are organized).
>
2. The Splicing Life report organized ethical concerns into two
> main categories: Concerns about playing God and Concerns about
consequencs.
> Would a consequentialist/nonconsequentialist distinction be helpful in
> organizing our report?
Yes, I think the objections on grounds of inherent rightness/wrongness and
on consequentialist grounds would probably be useful here as well. We can
probably borrow from SPLICING LIFE some of the material on the "playing
God" argument (esp. from the religious views that for "people of the
Book," man [& woman] are SUPPOSED to be co-creators, in the sense of
changing the world provided that we must do so responsibly; all of
medicine is in this sense "playing God").
>
3. Would it be helpful to analyze specific scenarios which are
>
offered as situations in which cloning a human being would be justified?
> The ones commonly discussed are the infertile couple who has a dying
child, > an infertile couple who are Holocaust survivors, or a couple with
a child
> with leukemia who needs a bone marrow transplant. I am stuck that many
> such cases involve cloning a child, who may not be capable of giving
> informed consent. Furthermore, I'm not clear what the benefits would be
of
> cloning a child with leukemia in order to get stem cells for
> transplantation.
>
Yes, I think it would be useful to discuss such scenarios. My personal
inclination would be to discuss them EARLY as a way of teasing out the
reasons for and against, and then go on to examine those reasons.
As for the specific objection: I share the sense that the stem cell
example is problematic (here, we can look at the same concern that has
been raised about banking stem cells from cord blood: in the case of
neoplastic disease, a question has been raised whether one would even
want to use autologous cells as treatment and whether it wouldn't be
better to use "well matched" cells from another donor).
One other example is comparable to what is being talked about with the
racehorse Cigar (and interesting that racing assn forbids even AID and
apparently also IVF and by implication cloning stronger rules for
horse than for humans, though for different reasons!). The situation is
one of the potential parent (male or female) who does not produce
gametes. The argument (comparable to the Holocaust survivor one) is that
the person has a strong interest in having a genetically related
offspring and that there is no other way for this to occur. The contra-
arguments have to do with whether this makes too much of genetics (and
that implications of that view for a lot of other subjects) as well as
the consequentialist and nonconsequentialist arguments about "using" a
child-clone in this fashion.
Alex
*
Alexander M. Capron
[email protected]
*
*
Henry W. Bruce Professor of Law (213) 740-2557 (voice)
*
*
University Professor of Law and Medicine (213) 740-5502 (fax)
*
*
University of Southern California
(213) 740-0149 (fax)
*
*
Los Angeles, CA 90089-0071
*
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: Rachel E. Levinson ( CN=Rachel E. Levinson/OU=OSTP/O=EOP [ OSTP 1)
CREATION DATE/TIME:20-MAY-1997 14:30:37.00
SUBJECT: Re: Ethics, part II
TO: nbac-members ( nbac-members @ lists.Princeton.EDU [ UNKNOWN ])
READ:UNKNOWN
TEXT:
See edits in brackets in very last paragraph
bernie @ itsa.ucsf.edu
05/15/97 02:29:39 PM
Please respond to [email protected]
Record Type: Record
To: nbac-members @ lists.Princeton.EDU
cc:
Subject: Ethics, part II
VIII. Cloning research involving human embryos.
Any research on cloning human beings through nuclear transfer from somatic
cells would involve human embryo research. The fusion of a human somatic
cell and a oocyte whose nucleus has been removed would produce a human
embryo, with the potential to be implanted in utero and develop to
delivery. Currently, federal funding for human embryo research is
severely restricted. Congress has inserted restrictions on embryo
research into the 1996 and 1997 Appropriations Bills. Congress forbids
human embryo research that leads to the destruction or discarding of human
embryos. Furthermore, research may not present more than minimal risk to
the embryo. In addition, a 1994 Executive Order [delete Executive Order
and insert "Presidential directive"] forbids federal funding for the
creation of human embryos expressly for the purpose of research. Kathi,
Rachel, is this an accurate description of current federal policy?
Although federal support for human embryo research is heavily restricted,
there are few restrictions of human embryo research carried out in the
private sector, using nonfederal funds.
From a scientific viewpoint, progress in understanding molecular genetics
and cellular differentiation currently can proceed through research using
[human and ] animal cells and animals. Far more animal research would be
required before promising therapeutic ideas, such as embryonic stem cell
transplantation for leukemia, liver failure, or diabetes, could be
considered in humans. Thus cloning raises no pressing scientific reason
to reconsider current restrictions on federal funding for human embryo
research.
Bernard Lo, M.D.
521 Parnassus Ave.
Room C-126
University of California San Francisco
San Francisco, CA 94143-0903
Ph: 415-476-5370
Fax: 415-476-5020
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: [email protected] ([email protected] [ UNKNOWN
CREATION DATE/TIME:22-MAY-1997 07:27:55.00
SUBJECT: Ethics: Cellular Therapies
TO: [email protected] [email protected] [ UNKNOWN ])
READ:UNKNOWN
TEXT:
Bernie:
late in the ethics chapter you ask for examples of cellular therapies (in
addition to recombinant proteins).
all of this work is in early stages, in clinical trials. the efforts can
be grouped into 3 buckets.
1- Cells to Produce a Needed Protein: deliver the cells that produce the
needes hormone, enzyme, etc. as an alternative to delivering the protein
itself either for better health of the patient, ease of administration or
because the protein can't be effectively delivered (e.g., blood-brain
barrier problems. Examples are encapsulated human fetal or porcine
pancreatic insulin-producing beta islet cells, and human fetal (for
treatment of diabetes)or porcine or human fetal dopamine-producing
neuronal cells (for treatment of Parkinson's disease.
--Here, one would would like a continous human cell line, based on a stem
cell population, of such cells that was immunologically naive so that you
wouldn't need to encapsulate, would have a universal-donor cell line,
would not have to worry about immunological rejection, etc.. In virtue of
being a single source cell line (as opposed to individually based
therapies with a new population of cells each time)you would have enhanced
safety because of enhanced quality control. Research is going on the
derive such cell lines from the early embryo.
2- Cells to Replace Damaged/ Depleted Cells: the object here to provide
the lost multiple functions of the damaged or depleted cells. Most
advanced example is the reconstitution of the various hematapoeitic
lineages, e.g., after chemotherapy. Expansion of these lineages in vitro
(from autologously derived hematapoietic stem cells ) with transplantation
back to the autologous donor is already occuring in humans. Research,
earlier stage, is taking place with stem cells for additional cell
lineages, e.g.,
nerve cells (for nerve damage) and mesenchymal stem cells (for
carilage/bone damage).
--Again here, while the current work in clinicals with human cells starts
with somatically derived, autologous lineage specific (stem cell)
population, The ideal would be universal cells "in a bottle", as opposed
to an individualized procedure each time. The cutting edge research looks
to the embryo as the potential source of such universal donor cells.
3- Discovery of Novel Growth Factors: the developing embryo generates an
enormous number of signaling molecules/growth factors that orchestrate the
differentiation of the totipotent, and then pluripotent cells of the
embryo into the defined cell lineages that become the different parts of
the body.
Isolation of these factors, and understanding their roles and interplay,
could lead to new therapies in which we could direct cells to
differentiate into needed lineages (repair damage/replace deleted
lineages) or redirect cells (e.g., block/antagonize the factors to stop
proliferation in a cancer or, more starwars, dedifferentiate a
differentiated cell poplulation and redirect the newly created "stem cell
population" to another lineage).
Hope this helps,
-steve
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: [email protected] ( [email protected] [ UNKNOWN 1)
CREATION DATE/TIME:23-MAY-1997 14:26:48.00
SUBJECT: Re: Ethics chapter
TO: [email protected] [email protected] [ UNKNOWN
READ:UNKNOWN
TEXT:
Dear Bernie,
Thank you for the (FAST) revised version of the ethics chapter. I feel it
is much improved. I have made some suggestions to the text and I am
attaching the word 5.1 file with the suggestions. (I can later send other
file types but for the moment I do not have translators since my computer
crashed).
I do not understand Zeke's reservation with the new version of this
chapter. I don't think that the manner in which the issue of genetic
determinism is addressed weakens any argument. Rather it brings the
arguments into line with reality. Perhaps if Zeke were more specific about
what language he has a concern with I could find a way to address the
issue.
Below are a few of the more substantive comments that I have made.
1) you write:
This report does not discuss cloning of DNA sequences and somatic cell
lines and cloning research involving human embryos. Ethical questions
surrounding these issues have already received extensive analysis and
deliberation.
I don't know that ethical questions about cloning research involving human
embryos has been extensively deliberated.
I suggest this instead:
"This report does not discuss cloning of DNA sequences and somatic cell
lines. Ethical questions surrounding these issues have already received
extensive analysis and deliberation. In addition we do not discuss and
research involving human embryos as this area was the subject of a full
report by the embryo research panel."
2) I still feel that the section entitled: "Claims that cloning would
benefit society by reproducing an exemplary individual" should be
eliminated. (I still feel that the section is not necessary, we state in
the introduction that by reproducing an exemplary individual is science
fiction, not reality. I do not see the use in discussing this issue in
detail in an entire section.
I do understand the argument that some people THINK they can reproduce an
exemplary individual, and even this intention might be harmful. But that
is not how this section is written. The issue of a child being harmed by
the parent THINKING they can choose the person the child will be is
already discussed in a separate section.
3) You write:
In summary, Commissioners reached several conclusions on ethical
considerations to guide public policy regarding generating children
through nuclear transfer from somatic cells:
I can agree to most of the things that you say we all agree. I am not sure
however why is starts with several things that "all commissioners" agree
to and then goes to "some" commissioners agree and then back to all
commissioners. Perhaps this section could be restructured a bit.
4) Did you intend the section on cloning DNA sequence and cell lines and
Embryo research to be addendum separate from the ethics section? Althought
you said it was cut it was still after a page break in the document. I
still feel that we should not include this even as an addendum to the
ethics chapter. We have already mentioned these issues in the introduction
and said that we are not addressing them.
-
ethics5=22.CWG.doc
ATTACHMENT I
ATT CREATION TIME/DATE: 0 00:00:00.00
TEXT:
7#wvvvvv
@Y@Lxceimos
Need quote from RTL group
"Science is close to crossing some hor
rendous boundaries" Leon Kass in Time Magazine March 10, 1997
"If objectors to
cloning can identify no greater harm than a supposed affront to the dignity of
the human species, that is a flimsy basis on which to erect barriers to scient
ific research and its applications." Ruth Macklin, testimony.
"Enough good
uses can be imagined that it would be unwise to ban all cloning and cloning re
search because of vague and speculative fears." John Robertson, testimony.
"It's a horrendous crime to make a Xerox of someone" Jeremy Rifkin, Time Magazi
ne March 10, 1997
"A person who would want to clone himself is overwhelmingly
self centered"
Richard McCormick Newsweek Magazine March 10, 1997
"If research
into human cloning does move forward we must ensure that it does not seek know
ledge for its own sake or only to promote monetary gain or individual fame, but
to serve and protect the common good. Nancy Duff testimony.
As these quote
S illustrate, the birth of Dolly through nuclear transfer cloning technology, e
voked widespread public discussion. Many people expressed concerns and fears a
bout the generation of children using this technology, while others suggested t
hat cloning may be acceptable under some circumstances. In its deliberations,
NBAC attempted to understand these diverse reactions.
Many people resort to S
elf-evident philosophical principles, scriptural passages, or religious doctrin
e to justify their views on cloning. Often it is hard to articulate the precis
e nature of ethical concerns or objections about nuclear transfer cloning. Yet
in order to form public policy, we must try to express our moral concerns as c
learly and explicitly as possible, so that others can understand them and consi
der whether they are persuasive. We must realize that in a pluralistic society
, other people may not share our starting points. Furthermore, we must appreci
ate that even though our religious beliefs may be crucial in shaping our person
al views, because the First Amendment requires separation of church and state a
nd does not permit public policy to be based solely on explicitly religious bel
iefs.
This chapter has three goals. The first is to articulate and analyze t
he moral arguments that have been offered regarding generation of children thro
ugh nuclear transfer of somatic cells. Our second goal is to offer a framework
for further deliberation of the moral issues pertinent to public policies rega
rding such cloning. The third goal is to clarify which ethical considerations
should guide public policy about nuclear transfer cloning at this time.
We ha
ve structured this chapter in the following way. In the first two sections of
the chapter, we analyze the moral considerations that may be pertinent when an
individual person judges whether a particular act of nuclear transfer cloning i
S justified. We start by considering hypothetical cases in which a baby is pro
duced through nuclear transfer cloning. In daily life, people are accustomed t
o deliberating on whether an individual act is right or wrong. Examining speci
fic cases helps us to understand the moral dimensions of an issue and to articu
late the reasons for our judgments. In addition, careful reflection on particu
lar cases can suggest what general restrictions and limits might be appropriate
if public policy does not create an outright prohibition.
The various types of
moral considerations are organized into two broad groups. Some arguments exam
ine the consequences of generating a child through nuclear transfer cloning, wh
ich are alleged to be harmful or beneficial. Consequences may affect either in
dividuals or important shared social values. Other arguments do not refer to t
he consequences of nuclear transfer cloning, but instead allege that nuclear tr
ansfer cloning is wrong in itself or that people have a right to use this new t
echnology.
The third section of this chapter presents a framework for moral d
eliberation about public policies regarding nuclear transfer cloning. The Comm
ission was asked to consider whether public policy should permit, regulate, or
prohibit generation of children through nuclear transfer from a somatic cell.
We note that our views on whether cloning is acceptable as public policy may di
ffer from our views of whether specific acts of cloning are morally acceptable.
There are some actions that we consider morally wrong, but would not want to
prohibit through public policy. Even though we might try to persuade a relativ
e or friend that certain actions are wrong, we may not want the government to p
rohibit people from acting according to their own moral judgments. For example
, some people may disapprove of gambling or divorce, yet oppose a governmental
prohibition of these activities.
In the fourth section, the Commission indica
tes which arguments it believes should guide policy recommendations on generati
on of children through nuclear transfer of somatic cells at this time.
This r
eport does not discuss cloning of DNA sequences and somatic cell lines and clon
ing research involving human embryos. Ethical questions surrounding these issu
es have already received extensive analysis and deliberation. In addition we do
not discuss and research involving human embryos as this a area was the subjec
t of a full report by the embryo research panal.
Ethical arguments offered to
oppose acts of generating children through somatic cells nuclear transfer.
T
his section examines the arguments offered against generation of children throu
gh somatic cells nuclear transfer, starting with arguments claiming that such c
loning causes unacceptable harms or risks. Some of these alleged harms fall on
individuals, while others affect social values. Subsequently, we examine argu
ments claiming that cloning is wrong in itself, independent of any consequences
it causes.
Arguments that cloning of children through nuclear transfer of S
omatic cells is unethical because of harmful consequences.
Alleged harms to i
ndividuals
The risks to the child born after cloning are unacceptable at presen
t
The risks of attempting to clone a child through nuclear transfer from somati
c cells are prohibitive at the present time, compared to the likely benefits.
The technique that produced Dolly was successful in only one of 277 attempts.
The success rate of cloning human beings using the nuclear transfer technique m
ight also be extremely low (cite Science chapter). Nuclear transfer cloning in
volves significantly greater manipulation of genetic material than current form
S of assisted reproductive technologies, and such manipulations increase the ri
sk of birth defects. In addition, nuclear transplantation may transmit DNA tha
t has acquired genetic mutations or has been damaged by aging. The risk of can
cer or premature aging may be increased in the child that is born. The burden
of proof to justify an experimental technique that may cause physical harms to
children who will be born falls on those who would carry out the experiment. B
efore considering even the possibility of producing a child through nuclear tra
nsfer, we would require animal studies demonstrating a much higher success rate
that at present and long-term safety. We would never consider using a medical
drug or device on a human being after only one animal experiment. Without suc
h extensive animal research, no conscientious physician or Institutional Review
Board could approve of attempts to use nuclear transfer to generate a human ch
ild. Even if a person or couple requested cloning as a clinical intervention,
it would be unethical for a physician to provide it, in light of current limite
d knowledge about the feasibility and safety of the procedure. For these reaso
ns, the Commission unanimously supports prohibitions on all attempts to produce
children through nuclear transfer from a somatic cell at this time.
Critics
are concerned about psychological as well as physical harms to children born af
ter cloning. Such concerns are discussed in the following sections.
Claims t
hat children born after cloning through nuclear transfer from somatic cells wou
Id be subjected to inappropriate attempts at control
Some people have suggested
that cloning offers more control over the genetic makeup of the child than exi
sting methods of genetic selection, such as selecting a partner or using geneti
c screening to avoid serious illness, because the genes of the child would be t
he same as those of the nuclear donor rather than being a random combination of
genes from two parents. In addition, cloning allows positive selection of de
sirable genes, rather than negative avoidance of undesired genes. [This is alw
ays true, not unique to cloning, selction of a partnerallows selection of desir
able traits]
Novels and plays about cloning dramatize fears about such an abili
ty to duplicate the genes of an individual. Evil dictators are portrayed as ma
king multiple copies of a given individual to serve as warriors or drones to wo
rk in factories. Of course, even without making genetically identical individu
als it may already be possible to train a cadre of soldiers or workers through
existing techniques of social control. However, these stories reveal misunders
tandings that some people have about the role of genes in determining the indiv
idual. As described in the introduction and the science chapter, a child that
resulted from nuclear transfer cloning would have only the genes, not the chara
cteristics and behaviors of the nuclear donor.
Efforts to use nuclear transfe
r from a somatic cell to control the childs character are futile because they a
re based on a view of genetic determinism that is scientifically invalid. None
theless, critics fear that after birth the child would be subjected to the will
of the parent in inappropriate ways. Parents use their own nuclei to creat a
child who clone their genetic makeup may view these children as a younger vers
ions of themselves, whose interests and activities they control more strictly t
han with other children. Excessive attempts at control may harm the child, eve
n though the efforts are fruitless.
In rebuttal, others believe that parental
attempts to control children resulting from nuclear transfer cloning will not
be essentially different from what parents already do and indeed are expected t
o do when rearing children. Parents already try to mold their children through
selecting a partner, providing education, and bringing up the child in a chose
n religious faith. Children usually learn to handle excessive parental attempt
S to control them and are able to develop as individual persons.
Claims that
children born after cloning through nuclear transfer from somatic cells would h
ave inappropriately restricted future life scenarios
The generation of children
through nuclear transfer of somatic cells deliberately attempts to replicate t
he genetic composition of an existing person. Some critics fear that parental
expectations will then be very specific. The child may always be compared to t
he person who donated the nucleus, even if parents acknowledge that education a
nd environment will play a crucial role in who the child will become. Children
born using nuclear transfer may be judged in terms of how closely they match e
xpectations and may experience great pressure to live up to specific expectatio
ns. Hence, cloning might constrict a childs future and might compromise the ch
ilds freedom to make choices in life, to develop his or her talents and interes
ts, and to develop a unique identity.
Others do not find these concerns persu
asive, because having identical genes as another person need not restrict life
choices or compromise individual identity. Identical twins are genetically ide
ntical and look almost alike at any point in time, yet regard themselves and ar
e regarded by their families as unique persons who make their own choices in li
fe. In response, opponents of cloning point out that no one chose to create th
e twin and there was no pre-existing person whose qualities were to be duplicat
ed. For these reasons, opponents believe that the twin analogy does not apply
to cloning.
Claims that children born after cloning through nuclear transfer
from somatic cells would not be valued for their own sake
The intention of usin
g nuclear transfer cloning in many scenarios is to produce a child with specifi
c preselected characteristics. The resulting child may be intended to be like
a beloved child that is dying, to be a genetic match for another child needing
an organ transplant, or to express scientific or musical talent. Some critics
predict that catalogues of people willing to be cloned would appear, allowing p
arents to select a template based on characteristics of the donor. As explaine
d in Chapter 00 (Science), this intention to duplicate an existing person is ba
sed on a misunderstanding of the degree to which gens determine the individual.
serious scientific misunderstandings and fallacious ideas of genetic determini
sm.
Critics of nuclear transfer cloning fear that parents who hope to specify
the childs characteristics no matter how scientifically incorrect these hop
es might value the children by how closely they match the preselected specif
ications. Indeed, because such parental hopes are futile, their disappointment
may be greater. According to critics, objects may be evaluated by whether the
y meet certain standards, but children should be loved unconditionally and for
their own sake, not because they match a preselected phenotype. Children who f
eel they have not met parental expectations may lack a sense of security and se
If-confidence.
In some widely discussed scenarios, nuclear transfer cloning W
ould harm children by treating them as less then full persons. Such scenarios
include killing a clone to harvest a heart for transplantation or treating a cl
one as a slave. The Commission believes strongly that should any child born as
a result of cloning through nuclear transfer of somatic cells should be treate
d as a full person, like any other child. It would be immoral as well as illeg
al to treat a child born through cloning as a source of vital organs or as a sl
ave.
Claims that children would be harmed by confused social relationships
Th
e status of the child arising from nuclear transfer of somatic cells may be unc
ertain. For some, the disparity between the childs genetic and social identity
threatens the stability of the family. Is the child who results from nuclear
transfer cloning the sibling or the child of its parents? The child or the gra
ndchild of its grandparents? From this perspective the childs psychological an
d social well-being are in doubt or even endangered. Ambiguity over parental r
oles may undermine the childs sense of identity. It may be harder for a child
to achieve independence from a parent who is also his or her twin.
Others are
NOT persuaded by these objections. Children born through assisted reproductiv
e technologies may also have complicated relationships to genetic, gestational,
and rearing parents. Skeptics point out that there is no evidence that confus
ion over family roles has harmed children born through assisted reproductive te
chnologies, although the question has not been widely studied.
The risks to W
omen involved in cloning as oocyte donors or gestational mothers are unacceptab
le at present.
Harms may occur to the women involved as ooctye donors or gest
ational mothers as well as to the children born after nuclear transfer. The Co
mmission unanimously agrees that [I have not heard this argument at any commiss
ion meeting and I have not agreed to it] Some people say it would be ethically
unacceptable at the present time to subject oocyte donors and gestational mothe
rs to the risks of hormonal manipulation for the purposes of generating childre
n through nuclear transfer of somatic cells. The risks to these women are the
same as the risks associated with in vitro fertilization and include short-term
discomfort, ovarian hyperstimulation, and long-term risks of reduced fertility
and ovarian cancer. Ethically, experimentation with human beings is unaccepta
ble unless the risks are proportionate to the expected benefits. In the Dolly
experiment, 277 attempts were required before successful cloning. In view of t
he low likelihood that cloning of children through nuclear transfer of somatic
cells would be successful at present, the risks to women far outweigh the likel
y benefits of the experiment.
Alleged harms to important social values
Criti
cs fear that nuclear transfer cloning from somatic cells would cause harms to S
ocial values as well as alleged harms to individual persons.
Alleged harms to
values about children and parenting
Critics ask us to imagine a world in which
cloning through nuclear transfer from a somatic cell were permitted. What kin
d of people, parents, and children would we become in such a world? Opponents
fear that cloning to create children may disrupt the interconnected web of soci
al values, practices, and institutions that support the healthy growth of child
ren. Attempts to determine the characteristics of a child through the use of n
uclear transfer cloning are doomed to failure because they assume incorrectly t
hat the child is determined by the genes they rest on a discredited view of gen
etic determinism. But however misguided those attempts, they even just the int
iention itself may still harm important social values. Critics fear that the u
se of nuclear transfer cloning might undermine the view that children should be
encouraged to develop their own uniqueness as a person. In this view, the use
of cloning might also encourage the undesirable view that children are to be V
alued according to how much they meet parental expectations, rather than loved
for their own sake. In this way of looking at families and parenting, certain
values are at the heart of those relationships, values such as love, nuturing,
loyalty, and steadfastness. In contrast, a world in which cloning were permitt
ed would might give implicit approval to vanity, narcissism, and avarice. To t
hese critics, changes that undermine those deeply prized values should be avoid
ed if possible. At a minimum, such undesirable changes should not be fostered
by our public policies. Cloning to create children, to the extent that it disr
upts those values, therefore ought to be discouraged.
Others are not persuade
d by these objections. Skeptics point out that if strongly held moral values a
re in decline, there are likely many reasons, which would not be addressed by a
ban on cloning. Furthermore, skeptics argue that people can adapt to new tech
nologies. In their view, a child born after cloning can simply be loved and ac
cepted like any other child.
Alleged violations of justice and fairness
Criti
cs raise three objections to cloning based on justice. The first is an argumen
t from justice as equal opportunity: Creating a child through nuclear transfer
cloning would be wrong because it would be more available to the wealthy and po
werful than to the poor and powerless. Any advantages resulting from cloning W
ould exacerbate inequalities already present in the U.S. Even if there are no
actual benefits of creating a child through nuclear transfer cloning, because o
f the interplay of genetics, education, and environment in human behavior, the
mere perception of benefit may confer an advantage in terms of confidence or ex
pectations of others. The second argument considers the scarcity of resources.
The generation of children through nuclear transfer would divert scarce resou
rces, including money and the skills of researchers and clinicians, from more p
ressing social and medical needs. These considerations about allocation of res
ources are particularly pertinent if public funds would be involved. A third c
oncern rests on justice as equality of human worth. Critics fear that the abil
ity to select childrens appearance and physiogomy through nuclear transfer from
a somatic cell would lead to discrimination against persons who differ from th
e predominant social views of what appearance is desirable. Some fear that hum
an cloning would offer an opportunity to practice eugenics or heighten discrimi
nation based on race.
Historically there has been enormous strife based on ra
cial and ethnic differences, and critics believe that creating children through
nuclear transfer cloning will aggravate such divisions.
Arguments that clon
ing of children through nuclear transfer of somatic cells is wrong in itself.
Critics of cloning object that it is morally unacceptable, not only because it
produces harms but also because it is wrong in and of itself. That is, critic
S suggest that cloning violates fundamental moral principles, in ways we next d
iscuss.
Claims that cloning children through nuclear transfer from somatic ce
Ils treats violates human dignity
Critics fear that parents who use such nuclea
r transfer cloning are likely to have very specific expectations for their chil
d, even though those expectations are based on a mistaken view of genetic deter
minism. Thus children resulting from cloning may be valued for meeting predete
rmined specifications, not loved for their own sake. In this view, cloning vio
lates the dignity of children, by treating them like products and objects rathe
r than as human beings. Critics believe that viewing children in this way is m
orally wrong, even if it caused no psychological harms to the children. Howeve
r, others are not persuaded by this line of argument. In their view, whatever
their original expectations, parents are likely to love their children for thei
r own sake and cherish their individuality.
In certain situations, the clonin
g of creation of children through nuclear transfer from of somatic cells would
undermine human dignity to such a degree that it would indeed be morally unacce
ptable. One ethically unacceptable scenario is using children created through
nuclear transplantation solely as the means to achive someone elses goals, rath
er than respecting them as ends in themselves. An example is destroying a clon
ed child produced though nuclear transfer after birth in order to achieve such
goals as providing a heart for transplantation. A second unethical situation W
ould be commercialization of nuclear transfer cloning, with different prices pa
id to different persons willing to donate nuclei be cloned, according to their
perceived desirability. Buying and selling different combinations of genes nu
clei and thus gene sets from various individuals [avoid different conbinations
as it implies can choose the conbination when in fact it is fixed] that would
make having children tantamount to purchasing commodities and thereby violate h
uman dignity.
Claims that cloning may violate informed consent
Generation of
a child through nuclear transfer cloning would be ethically unacceptable if it
occurred without informed consent of the person whose DNA was used. Lack of co
nsent would undermine human dignity because it violates a persons bodily integr
ity, autonomy, and freedom not to reproduce. Using a persons nucleus as a donor
for nuclear transfer cloning Cloning without consent wrongs a person even if h
er or she is not physically harmed in any way. (In this line of thinking, it W
ould also be improper to use a child as a nuclear donor clone children. Childr
en are not capable of giving informed consent. Even if their parents consent t
o having them cloned, the child may wronged by becoming a parent without having
agreed to do so.)
Claims that cloning violates moral boundaries
Critics asse
rt that cloning tempts human beings to transgress moral boundaries that should
not be crossed and to grasp for powers that are properly outside human control.
Ancient Greek literature and many Biblical interpretations emphasize that hum
an beings are between animals and the divine neither driven by instinct nor
omnipotent over nature. In this view, respecting limits is to respect this pla
ce of mankind in the universe and to ensure that technology is used in morally
acceptable ways and not allowed to run out of control. This view need not be t
ied to a particular religious doctrine, view of God, or even a belief in God.
However, these objections are often expressed in religious terms: cloning temp
ts human beings to seek immortality, usurps the role of God, or violates divine
commands. Many religious traditions consider procreation divinely ordained be
cause it symbolizes the limits of any individual human being, the inevitability
of death, and the necessity of human interdependence and cooperation. Two ind
ividuals must join to procreate; neither alone is sufficient. Parents are awed
that their child is both similar to and different from each of them, in unpred
ictable ways. Such wonder reinforces the need for human beings to be humble an
d to recognize their limitations.
Ethical arguments offered to support acts
of cloning of children through nuclear transfer of somatic cells.
The followi
ng sections examine the moral arguments offered in favor of nuclear transfer cl
oning, first examining the alleged benefits of cloning to individuals and to im
portant social values and subsequently rights-based arguments for cloning.
Ar
guments that cloning of children through nuclear transfer of somatic cells resu
Its in beneficial consequences.
Some people argue that generation of a child t
hrough nuclear transfer cloning is ethically acceptable in some circumstances b
ecause it leads to benefits for individuals or for society as a whole.
Claims
that cloning could benefit to a person with a fatal illness.
In some cases,
cloning may offer the only hope of curing a fatal illness. Suppose that a two-
year old boy develops aplastic anemia, a disease in which the body fails to pro
duce blood cells. This condition is fatal, but the child can be kept alive for
months with transfusions and treatment for complications such as infection. T
he most effective treatment is bone marrow transplantation. Suppose, however,
that no donor can be found who matches the sick child, either among the childs
relatives or in a bone marrow registry.
In similar situations, parents have t
ried to conceive another child, hoping that the new child will be a match for t
he older sibling. Suppose, however, that in this case the parents are now unab
le to conceive. Cloning offers the only possibility of saving the childs life.
The parents are determined that they will love the new child for its own sake
, even though he will also serve as a bone marrow donor for his brother. The n
ew child will not suffer any serious or permanent physical harm from serving as
a bone marrow donor. In this hypothetical case, the parents are motivated to
save the life of their son. They are trying to replicate the genes that contro
1 transplant rejection. They do not intend to duplicate other characteristics
of the son. Because the two children will be close in age, the younger son wou
Id likely face few expectations to duplicate the characteristics of his older b
rother. Admittedly, the family relationships after transplantation may be comp
licated. However, the parents believe the possibility of such complications is
worth the opportunity to save their sons life.
Some members of the Commissio
n believed such a situation justified cloning and avoided many objections to cl
oning. This scenario appears to reinforce important shared values regarding he
lping, compassion, altruism, and sacrifice for family members. Even those memb
ers who regarded cloning as unacceptable in all cases were sympathetic to the p
light of the child and the wishes of the parents in such a tragic situation.
Claims that cloning would benefit the child who will be born.
Some proponents
argue that the generation of a child through nuclear transfer cloning can be a
net benefit to the child. This argument takes two forms. One argument builds
on the view that genetics has some effect on a persons characteristics and acc
omplishments. While Even if they reject rejecting a rigid view of genetic dete
rminism, some parents may simply want to take advantage of whatever propensitie
S genetics may confer. Realizing that the complex characteristics actual pheno
type of the child will depend on the interaction of genetics with environment a
nd education, the parents may nonetheless seek to determine some aspects of the
childs makeup give the child a good start in life through selecting a genotype
through nuclear transfer cloning. For example if one parent were a carrier fo
r a potentially serious genetic disease, the parents might choose to not pass o
n that gene and thus give their child what they perceive as a better chance in
life. Such parents may, after considerable soul searching, conclude that they W
ill be able to refrain from excessive attempts to control the child and love th
e child for its own sake, whether or not it meets their hopes. In this view, a
decision to use nuclear transfer cloning might benefit the child and would not
harm him or her if the parents indeed are flexible and moderate. In rebuttal,
critics question whether parents will actually be able to moderate their expec
tations about the child born after cloning and to refrain from trying to mold t
he child to conform to their expectations.
Another form of argument argument
compares existence, even with substantial impairments, with non-existence. Pro
ponents conclude that even a severely constrained existence is better than none
at all, and that therefore cloning, even though it resulted in grievous harm t
o the child, nevertheless is as a net benefit to that child. Such reasoning ha
S been criticized on several grounds. First, it makes the wrong comparison. R
ather than comparing existence with non-existence, we ought to compare the choi
ce to bring a child into the world with substantial burdens with the alternativ
e of bringing a child into the world without those same burdens. If a child co
uld be conceived without the risks associated with cloning, then that alternati
ve would count as a strong ethical reason against cloning. The second critique
of this argument claims that it misses the point and does not address the conc
erns about harm to children born of the procedure. A third rebuttal is that th
is argument is unacceptable because it would excuse any actions or decisions by
the parents, even those that resulted in serious, avoidable harms to the child
who was born.
Claims that cloning would benefit the parents.
Some have arg
ued that in some scenarios the parents would benefit from cloning. For example
, an infertile woman whose husband and only child are near death after an autom
obile accident seeks to clone the child. In such situations, the intention may
not be to replicate the existing person but to have some genetic link to offsp
ring. The motives of the people seeking cloning in such tragic scenarios evoke
sympathy. However, others question whether cloning will be effective in achie
ving the parents goals. Even if cloning might benefit individual parents, some
question whether these benefits outweigh the alleged harms to social values di
scussed previously. These critics question whether such dramatic but unusual c
ases should be the basis for public policies regarding cloning.
(I still fee
I that the section below is not necessary, we state in the introduction that th
is is science fiction, not realit. I do not see the use in discussing this issu
e in detail as is is discussed here)
Claims that cloning would benefit society
by reproducing an exemplary individual
Some suggest that society would benefi
t if the remarkable achievements of Einstein, Madame Curie, Mahatma Gandhi, or
Mother Theresa could be replicated through generating children containing the g
enes of tehse people. However, this suggestion rests on false assumptions abou
t role of genetics in determining complex human traits. Having the genes of Ma
dame Curie woiuld not generate another Madame Curie. Individual identity is th
e result of complex interactions between genes and environment during the devel
opment of a child.
Some individuals may be relucatant to abandon their faith
in genetic determinism. For them, it may be useful to point out other objectio
ns to efforts to clone exemplary persons, however scientficially misconceived.
If we were to try to replicate exemplary individuals, who should be cloned? W
hile many Americans might agree that it would be desirable to replicate a great
scientist or a great humanitarian, would there be agreement that society would
benefit if an athlete or a movie star were cloned? Even assuming we could dec
ide which exemplary individuals should be cloned, there is no way to restrict c
loning to persons whom society deems to be exemplary. Anyone who can pay for t
he procedure would be able to clone anyone they deem worth cloning.
Argument
S based on moral rights.
Other arguments in favor of cloning children through
nuclear transfer claim that people have a moral right to use cloning. This al
leged right can be characterized in various ways.
Claims of a moral right to
make decisions about having children free from government interference.
Decis
ions to choose a spouse or partner and to have children through coital reproduc
tion are intimate personal decisions. Many people support a right to make such
decisions free of government interference. Such a moral right has been claime
d to include the right to marry, the right to marital privacy, the right to con
traception, the right to abortion, and the right to be free of forced steriliza
tion by the state. Some argue that people also have a moral right to use assis
ted reproductive technologies or to avoid serious genetic anomalies through pre
natal testing. Proponents of cloning claim that there is a similar right to us
e this technique.
In some circumstances, a person or couple may want to repro
duce by using nuclear transfer cloning. For some infertile couples, cloning ma
y be the only means for them to have a child that has a genetic link to one of
them. Genetic lineage may be particularly important, for example to an inferti
le person whose relatives were all killed in the Holocaust. In these circumsta
nces, the options of adoption or sperm or egg donation may seem undesirable.
For other couples, cloning may offer an opportunity to have genetically related
offspring who are free of a serious genetic illness. For instance, a couple m
ay both be carriers for Tay Sachs disease. They have a 25% chance of conceivin
g a child with a genetic illness that is usually fatal within one or two years.
Dave Cox, Arturo Brito can you comment on the clinical prognosis here? Do we
need a better example? Furthermore, suppose the couple is opposed to pre-impl
antation genetic diagnosis or selective abortion after prenatal genetic testing
They may wish to be spared the anguish of terminating a pregnancy, or they m
ay be morally opposed to abortion under these circumstances. Furthermore, the
couple may reject the option of sperm or egg donation from someone who is not a
Tay Sachs carrier. In these circumstances, cloning may be the only means to a
chieve their reproductive goals.
Proponents of a right to make decisions abou
t having children may believe that people may exercise that right even if other
S think they are wrong or misguided. In the extreme, proponents believe that p
eople should have a right to make decisions based on views of genetic determini
sm that scientific experts believe are mistaken.
However, many people deny th
at there is a right to cloning. Critics argue that cloning through nuclear tra
nsfer from a somatic cell is essentially different from procreation or reproduc
tion. In their view, cloning can be distinguished clearly from coital reproduc
tion or assisted reproductive technologies because passes on all the genes of o
ne parent and thus does not involve equal genetic input from a male and female
progenitor. Furthermore, critics point out that policies that restrict or proh
ibit creation of a child through nuclear transplantation would not implicate an
y rights that are strongly recognized, such as the right to marry or have acces
S to contraception.
Claims of a moral right to rear children.
In the U.S.,
parents have the freedom to raise their children according to their values and
aspirations, without government interference. Moreover, it is considered appro
priate and morally desirable for parents to rear their children to try to meet
certain expectations. In this line of argument, parents should be free to try
to have a child with a specific set of genes, if they hope that this will give
the child a predisposition to develop in certain ways.
Critics point out that
parental rights are not absolute and may be restricted to protect the best int
erests of the child or important social values. Critics believe that the alleg
ed harms of cloning, discussed previously in the Chapter, justify restriction o
n parental rights.
Claims of a moral right to free scientific inquiry
Permit
ting free scientific inquiry shows respect for human achievement and flourishin
g. Allowing researchers to advance scientific knowledge may also lead to benef
icial applications. However, scientific inquiry must respect other ethical val
ues. For example, experimentation with human subjects is regulated by society,
and there are several precedents for moratoria or bans on certain types of bio
medical research out of concern for health, safety, or human dignity.
Framew
ork for moral deliberation about public polices regarding cloning of children t
hrough nuclear transfer of somatic cells.
In this section we first discuss th
e differences between the ethical analysis of individual acts and ethical analy
sis of public policies. Subsequently we develop a framework for moral delibera
tion about public policies. Finally, we indicate what ethical considerations t
he Commission believes should guide public policy regarding cloning of children
through nuclear transfer of somatic cells.
Moral deliberation about public p
olicies differs from moral deliberation about individual actions
Moral delibera
tion about public policy to allow, prohibit or regulate generation of children
through nuclear transfer cloning differs from moral reasoning about individual
cases of cloning. When individuals make moral judgments, they may rely on many
sources of moral wisdom and knowledge, including their religious faith and mor
al intuitions. People will use their understandings of morality to decide what
they should and should not do, as well as judge the actions of others.
In mo
ral discourse about public policy, we try to provide reasons that will persuade
our fellow citizens. In deciding upon public policy, we must balance respect
for moral beliefs that may be held by a minority, with moral considerations tha
t are broadly accepted by the American people. Generally moral convictions can
be formulated in ways that most people can understand and reflect upon. We ha
ve tried throughout this report both to respect moral beliefs in their original
form, and also to reframe them if necessary in order to make them more accessi
ble.
Some moral considerations will have more weight in public policy debate
than in judgments about individual cases. The burdens of enforcing public poli
cies must be considered. It is extremely intrusive to monitor reproductive dec
isions by individuals and couples. This has several policy implications. Firs
t, it is impractical to have a policy that allows some reasons for cloning, whi
le prohibiting others, even though we make such judgments privately about indiv
idual actions. On the policy level, attempts to distinguish acceptable from un
acceptable reasons will be intrusive and will lead people to misrepresent their
true reasons to fit the acceptable criteria. Second, strict enforcement of re
strictions or bans on cloning of children may be burdensome or ineffective. So
me people fear that establishing policies that cannot be consistently enforced
invites hypocrisy, cynicism about the law, and selective or unfair enforcement.
Third, the likelihood that a prohibition will be violated is no reason to eli
minate it. For example, violent crimes like murder continue to be perpetrated,
yet no one argues that laws against murder should not be enacted. Finally, an
d most important, because the Commission strongly believes that generation of c
hildren through nuclear transfer from somatic cells would be unethical at this
time because of unacceptable physical risks, public policy should be crafted th
at provides a strong deterrent to even a single attempt of such cloning.
Ethi
cal issues regarding research on human subjects also need to be considered in p
olicy discussions. If generation of children through nuclear transfer of somat
ic cells were ever attempted, it would be such a radical departure from usual c
linical practice that it would need to be considered research. Informed consen
t would be required from donor of transferred nucleus, oocyte donor, and gestat
ional mother. Indeed, informed consent for such cloning would need to be stric
ter than usual in clinical research. Several questions of research ethics woul
d need to be resolved before cloining could be considered: What level of risk
should be permitted when research is carried out on an embryo that will be impl
anted, carried to term, and become a child? What level of oversight should be
applied to such innovative research? Is approval by a local IRB sufficient, or
should stricter review from a national committee with more expertise be requir
ed?
Finally, pragmatic considerations may carry great weight in determining p
ublic policies. Widespread, strong opposition to a practice after full elabora
tion of opposing views, education about the scientific aspects, and deliberatio
n carries great weight in policy decisions. In a democracy, public opinion abo
ut generation of children through nuclear transfer cloning is one indication of
what arguments and reasons are persuasive. Furthermore, opponents of a contro
versial policy may link it to other issues in the political process; continued
advocacy of that policy may lead overall to more harm than good, if other desir
able policies are thwarted. For example, opponents of generation of children t
hrough nuclear transfer cloning might link a ban on cloning to continued public
support for unrelated basic scientific and clinical research.
Framework fo
r moral deliberation about public polices.
The Commission was asked to consid
er whether public policy should permit, regulate, or prohibit generation of chi
Idren through nuclear transfer cloning from a somatic cell. In the U.S., gover
nmental policies that prohibit or regulate human actions require justification
because of a general presumption against governmental interference in individua
I activities. Obviously, this presumption can be rebutted under various circum
stances for a variety of reasons. Governmental interference may be warranted,
for example, to prevent individuals from harming others and to protect importan
t social institutions and values. Many critics of generation of children throu
gh nuclear transfer cloning are concerned that this initial presumption of no i
nterference with individual actions will lead to unwise policies regarding clon
ing. Indirect and long-term harms may be discounted, because they are difficul
t to detect or measure.
There is no easy way to determine when and which gove
rnmental interventions are warranted. No algorithm clearly indicates whether t
he moral arguments for governmental interventions in a particular situation are
stronger than the moral arguments against such interventions. Instead, we mus
t engage in moral discourse, debate, and argument in a process of public delibe
ration. Closure must be reached, and decisions made, even if there is no conse
nsus.
Moral deliberation about governmental policies can only proceed by crit
ically examining (1) how to characterize the reasons why some people might clon
e themselves or others and the moral values that might be threatened by such cl
oning, and (2) how much weight to assign to these different interests and value
S.
There is a close connection between how we characterize various interests
and values and how much weight we assign to them. For instance, in our society
, decisions about procreation are generally shielded from governmental interven
tion. Much of the argument about whether to allow or prohibit cloning of child
ren may thus depend on whether genetic replication through cloning falls within
the sphere of reproductive or procreative freedom. The issue is whether gener
ation of children through nuclear transfer cloning is similar, in morally relev
ant ways, to reproduction or procreation, with or without technological assista
nce. However, even if society recognizes and assigns considerable weight to pr
ocreative freedom, it is not absolute. It may be justifiably overridden or out
weighed in some circumstances in order to protect other important moral values.
The difficult task is to determine when those conditions are met.
Our socie
ty has only just begun to reflect seriously on the possibility of generation of
children through nuclear transfer cloning and its implications -- it was hard
to sustain serious moral reflection when human cloning was deemed possible only
in science fiction or in the very distant future. It may premature to come to
closure on some issues because so little time has been devoted to the issue.
Our society will need to continue to reflect on the moral issues surrounding hu
man cloning in order to formulate defensible policies as the science develops.
One goal of this chapter is to help build a framework for sustained moral refl
ection and deliberation.
Which ethical considerations should guide public po
lices regarding generation of children through nuclear transfer cloning from so
matic cells.
We now discuss which ethical considerations should guide public
regarding cloning of children using nuclear transfer from somatic cells. We n
eed to answer a series of three questions.
The first question is how strong a
re the objections to a policy allowing generation of children through nuclear t
ransfer cloning. In the context of public policy, we need to reconsider the et
hical concerns discussed previously regarding individual acts of cloning.
The
Commissioners strongly agree that the unacceptable risks of physical harms to
the child and to the women undergoing oocyte donation and gestation justify a m
oratorium or ban on such cloning at the present time. Indeed, these possible p
hysical risks are currently so unacceptable that the Commission believes public
policy must offer a strong deterrent to even a single attempt at such nuclear
transfer cloning.
If we consider whether a policy permitting such nuclear tra
nsfer cloning might ever be acceptable at some future time, deliberations are m
ore controversial. Let us assume for the sake of argument that research on nuc
lear transfer cloning of animals suggests that the risk of using such technique
S on human beings is comparable to accepted risks of assisted reproductive tech
nologies. Under this assumption, are there moral concerns that would justify a
public policy prohibiting cloning?
On this question the Commission was divid
ed. Some Commissioners were persuaded that various of the harms and wrongs des
cribed earlier in this chapter were ethically compelling, and would be decisive
reasons never to permit nuclear transfer cloning. Other Commissioners were le
SS certain about the significance of the objections, and were unwilling to conc
lude that nuclear transfer cloning would be ethically impermissible, if and whe
n the risks could be shown to be minimal. A comparable range of views is refle
cted in the testimony, letters, and commissioned papers we have reviewed.
Peopl
es views on nuclear transfer cloning cannot be separated from their world view,
a web of values regarding human nature, families, and the good society. There
are several contrasting positions. One view holds that moral attitudes toward
the challenges posed by modern biology -- of which nuclear transfer cloning is
only one example should be rooted in traditional values regarding life, int
erpersonal relations, the family, and the natural order. This position, while
evolving to remain consistent with a changing world, is also based in deeply he
Id conceptions about what is natural. These conceptions are believed to provid
e a bulwark against shifting trends or untried ideas. As an example are the vi
ews of many Roman Catholic and Protestant theologians about the need to engage
in reproduction within the context of what is natural and ordained (intercourse
within a monogamous, heterosexual marriage). A second view believes in the fl
exibility of social structures and the mutability of persons. In this perspect
ive, change is not merely something that happens in the face of events such as
nuclear transfer cloning, but desirable because of the potential for human impr
ovement or perfectibility. Yet a third view is a pragmatic perspective arising
from the acceptance of modern life. In this view, the social impact of scient
ific developments can be something to be absorbed into life lived around, on
e might say. Many technological innovations were feared at the onset as underm
ining traditional moral values, yet have been absorbed into modern culture. Th
ese conflicting views of the issues in cloning by nuclear transfer rest on fund
amentally different perspectives that have been in opposition for centuries.
The second question to address in moral deliberations about public policy is ho
W to weigh these objections and concerns against restrictions on the freedom of
individuals to make decisions about having children without government interfe
rence. Those who regard nuclear transfer cloning as a form of reproduction bel
ieve it should be strongly protected, like other forms of reproductive freedom.
On the other hand, those who regard nuclear transfer cloning as essentially d
ifferent from reproduction would grant it no more protection than other human a
ctions. Again, these differences cannot be decided at this time, and further d
eliberation is surely needed.
The third policy-relevant question is whether t
here are countervailing ethical considerations that favor a policy of allowing
creation of children through nuclear transfer of somatic cells. There are exce
ptional scenarios of cloning, as described previously, that evoke sympathy. Ho
wever, people disagree on whether these unusual situations outweigh the potenti
al harms of a policy allowing nuclear transfer cloning. The Commission believe
S that many arguments offered in support of nuclear transfer cloning, such as b
enefiting children and society by cloning exemplary individuals, are based on a
seriously mistaken belief that replicating a persons genes will lead to duplic
ation of the persons traits or accomplishments. Again, further public discussi
on is needed to clarify our understanding of how genes interact with environmen
t and education in shaping human behavior. The Commission believes that it is
essential that public deliberations be based on a sound science. As citizens,
we must understand not only how some newly discovered genes are strongly associ
ated with certain serious inherited diseases but also how complex human behavio
rs depend on much more than our genetic inheritance.
In summary, Commissione
rs reached several conclusions on ethical considerations to guide public policy
regarding generating children through nuclear transfer from somatic cells:
All
Commissioners agree that generating children through nuclear transfer from som
atic cells is unethical at this time because of insufficient evidence that it i
S effective and safe.
All Commissioners agree that even if concerns about saf
ety could be resolved, cloning should be prohibited in certain circumstances.
These include paying people to be cloned and cloning a person without his or he
r informed consent. Furthermore, the Commission agrees that any children born
after cloning need to be treated as full persons. They could not be used as sl
aves or killed as sources of organs for transplantation. ALTHOUGH WE DID NOT V
OTE ON THESE, ARE THEY NOT POINTS OF AGREEMENT? DOES ANYONE DISAGREE?? I WE S
HOULD TRY TO ARTICULATE ANY SITUATIONS IN WHICH WE BELIEVE CLONING WOULD BE WRO
NG EVEN IF SAFETY ISSUES ARE RESOLVED.
All Commissioners agreed that many sce
narios of cloning human beings through nuclear transfer from somatic cells were
based on the serious misconception that selecting a childs genetic makeup woul
d be equivalent to selecting the childs traits or accomplishments. A benefit o
f widespread discussion of cloning would be a clearer recognition that a person
S traits and achievements depend heavily on education, training, and the social
environment, as well as on genes.
Some Commissioners believe that cloning wo
uld always be unethical because it undermines important social values and cause
S harms to the child born after cloning. On the other hand, other Commissioner
S found that many objections to cloning were not persuasive because people were
likely to adapt to new reproductive technologies and because cloning was unlik
ely to be widespread.
Some Commissioners thought that certain individual acts
of cloning might be justified. However, no Commissioners believed that many S
cenarious proposed for cloning to be compelling (I do not understand what the i
ntension here is ). Moreover, some scenarios seemed clearly unethical.
All C
ommissioners believe that deep public opposition to cloning through nuclear tra
nsfer from somatic cells should be given great weight, even though they might n
ot personally share all those concerns. Attempts to achieve a policy allowing
cloning may cause more overall harm than good, by putting at risk public suppor
t for important, unrelated scientific research.
All Commissioners agree on th
e need for further public deliberation on the serious moral concerns about clon
ing. As we proceeded in our work, we learned from listening to members of the
public who addressed us and from each other. Many important issues remain uncl
ear or unresolved, such as whether there is a moral right to freedom to make de
cisions about procreation that includes a right to cloning. The Commission bel
ieves that it is essential to try to understand the diverse reactions to clonin
g and the ethical arguments for and against various policies regarding cloning
human beings. Our work is only the beginning of moral deliberation about the i
mpact of this new technology. We urge that during the moratorium or ban on clo
ning, the public continue to discuss the ethical issues we have sketched in thi
S chapter.
Cloning of DNA sequences and cell lines.
The Commission was ch
arged with examining the ethical issues regarding cloning of human beings throu
gh nuclear transfer from somatic cells. However, because the term cloning is
used in various ways, it is important to comment briefly on other uses of the t
erm.
Cloning of DNA sequences and somatic? (YES) cell lines are well-establis
hed scientific techniques that are widely used in basic scientific research. T
hese techniques do not lead to embryos that have the potential to develop into
human beings. These research tools have already led to important new treatment
s, such as improved forms of insulin for the treatment of diabetes, vaccines ag
ainst hepatitis, new drugs for the treatment of heart attack and stroke (recomb
inant TPA), as well as better diagnostic tests for such conditions such as tube
rculosis and cystic fibrosis. Carol Greider, Steve Holtzman, and David Cox, ca
n we give some examples of clinical advances due to cell cloning? ( Cell cloni
ng is used in recombinant DNA work thus the advances are the same) Further pro
gress in medical research will require continued use of these techniques, subje
ct to existing requirements for peer review for federal funding of research and
regulations about biosafety.
Cloning of animals, as in the Dolly experiment,
offers the promise of increasing our understanding of fundamental biologic pro
cesses, such as the growth, development, and differentiation of cells into spec
ialized organs. Such knowledge also holds the promise of important medical adv
ances that will relieve human suffering, as discussed in Chapter 00, Scientific
Issues. Like all animal research, cloning of animals must be carried out in a
humane manner, in accordance with established federal and state regulations, a
nd with review and approval by institutional animal welfare committees.
In vi
ew of the important benefits of this research, the Commission strongly recommen
ds that research using cloning of DNA sequences, somatic cell lines, and animal
S continue to be permitted and receive federal funding, subject to existing reg
ulations and peer review for scientific merit. Any moratoria, regulations, or
prohibitions that might be proposed or enacted with regard to the cloning of hu
man beings or cloning research involving human embryos must not restrict clonin
g research on DNA sequences, cells, and animals.
Cloning research involving
human embryos.
Any research on cloning human beings through nuclear transfer
from somatic cells would involve human embryo research. The fusion of a human
somatic cell and a oocyte whose nucleus has been removed would produce a human
embryo, with the potential to be implanted in utero and develop to delivery.
Currently, federal funding for human embryo research is severely restricted. C
ongress has inserted restrictions on embryo research into the 1996 and 1997 App
ropriations Bills. Congress forbids human embryo research that leads to the de
struction or discarding of human embryos. Furthermore, research may not presen
t more than minimal risk to the embryo. In addition, a 1994 Presidential direc
tive forbids federal funding for the creation of human embryos expressly for th
e purpose of research. Although federal support for human embryo research is h
eavily restricted, there are few restrictions of human embryo research carried
out in the private sector, using nonfederal funds.
From a scientific viewpoin
t, progress in understanding molecular genetics and cellular differentiation cu
rrently can proceed through research using animal cells, human somatic cells, a
nd animals. Far more animal research would be required before promising therap
eutic ideas, such as embryonic stem cell transplantation for leukemia, liver fa
ilure, or diabetes, could be considered in humans. Thus cloning raises no pres
sing scientific reason to reconsider current restrictions on federal funding fo
r human embryo research.
//
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.1! @
uy=/Bxd "Science is close to crossing some horr
endous boundaries" Leon Kass in Time Magazine March 10, 1997
Carol Greider.New
Century Schlbk
END ATTACHMENT
1
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: [email protected] ( [email protected] [ UNKNOWN ])
CREATION DATE/TIME:25-MAY-1997 21:23:42.00
SUBJECT: Re: Science Chap Edits
TO: [email protected] [email protected] [ UNKNOWN 1)
READ:UNKNOWN
TEXT:
NBACers:
I thinks that Steve's edits to the science section are very helpful. They
help make the wording more precise.
The only thing among all the changes that I disagree with is the
suggestion that we removes the papagraph that reads:
"Apart from the fact that embryonic stem cell lines have not yet been
produced from farm animals, the other argument for using nuclear transfer
to introduce germ line genetic alterations in farm animals is that it
avoids one generation of breeding from the initial chimeric animals. This
is an important time and cost saving factor in farm animals with long
generation times and small litter size. This factor, however, might not
be as important as once thought. In mice, it turns out, embryonic stem
cells can also be used to generate cloned animals carrying gene
alterations directly without the initial generation of chimeric
animals
"
Although it may seem technical, for those who did not know about this, and
are interested in the details, (and paying attention) it is an important
point.
Thanks again for your detailed comments Steve. I do not have the
electronic document, so it is up to Kathi and Harold if they want these
changes made.
Carol
Carol Greider, Ph.D.
Cold Spring Harbor Laboratory
P.O. Box 100
Cold Spring Harbor, NY 11724
Phone: (516) 367-8808
Fax: (516) 367-8815
E-mail: [email protected]
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: [email protected] ( [email protected] [ UNKNOWN ])
CREATION DATE/TIME: 3-AUG-1997 17:22:15.00
SUBJECT: Adhoc: Varmus Denies CellPro Petition
TO: [email protected] ( [email protected] [ UNKNOWN )
READ:UNKNOWN
TEXT:
NIH Director Harold Varmus this afternoon announced that he has denied the
petition of CellPro, Inc. that the NIH initiate "march-in" procedures
under the Bayh-Dole Act. The NIH release on Dr. Varmus's decision follows.
Tony Mazzaschi
AAMC
NIH Decision Regarding Petition from CellPro, Inc.
NIH Director Harold Varmus, M.D., today denied the petition of CellPro,
Inc. (CellPro) that the NIH initiate "march-in" procedures under the
Bayh-Dole Act in order to give CellPro a license to certain patents owned
by the Johns Hopkins University and licensed to Baxter Healthcare
Corporation (Baxter).
CellPro asserted that march-in was necessary to alleviate health needs
that arise because a Federal District Court found the stem cell separation
device developed by CellPro to infringe the patents. The Court has issued
an order in that case allowing CellPro to keep its product on the market
until an alternative is approved by the Food and Drug Administration and
made available for sale.
Dr. Varmus concluded that the initiation of march-in procedures is not
warranted based on the available information, but that the NIH will
continue to monitor the situation until a comparable alternative product
becomes available for sale in the United States. Although the petition was
originally sent to DHHS Secretary Donna Shalala, the authority for
march-in is delegated to the head of the funding agency, in this case, Dr.
Varmus at the NIH.
"The patient care implications of this matter were our first priority and
concern," said Dr. Varmus. "Our review indicated that patient needs would
be met as long as one or the other cell separation device is available to
people in treatment or clinical research programs. Since both devices are
currently available under the terms of the Court Order, I do not believe
march-in proceedings are warranted." Dr. Varmus added, "The NIH will
continue to follow the situation to ensure that patient access to this tec
hnology is not compromised."
The NIH recognizes that its decision today will not resolve the legal
dispute between CellPro and Baxter, which has been the subject of complex
patent litigation. It is the position of the NIH that these companies have
full power and authority to resolve this dispute on their own. The NIH has
encouraged and will continue to encourage them to negotiate a resolution.
For more information, please read the accompanying backgrounder at
(http://www.nih.gov/news/pr/aug97/niha-01.htm). The full text of the
determination is available via the Internet at
(http://www.nih.gov/news/pr/aug97/nihb-01.htm). or through the NIH Office
of Communications at (301) 496-8740.
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: [email protected] [email protected] [ UNKNOWN ])
CREATION DATE/TIME:10-FEB-1998 13:37:52.00
SUBJECT: Administration's position on S.1601
TO: [email protected] [email protected] [ UNKNOWN ])
READ:UNKNOWN
TEXT:
>From: "Ellis, Gary" <[email protected]>
>To: "r. alta charo" <[email protected]>
>Subject: Administration's position on S.1601
>Date: Tue, 10 Feb 1998 11:23:44 -0500
>X-Mailer: Internet Mail Service (5.5.1960.3)
>
>The Feb. 9, 1998 Congressional record contains a message from the
>Administration regarding S. 1601
>
>
>S. 1601 HUMAN CLONING PROHIBITION ACT
>
>On June 9, 1997, the President transmitted to Congress legislation
making it
>illegal for anyone to
>create a human being through cloning. The President believes that
using
>somatic cell nuclear transfer
>cloning techniques to create a human being is untested, unsafe,
and morally
>unacceptable. The
>Administration, however, believes S. 1601, as introduced, is too
>far-reaching because it would
>prohibit important biomedical research aimed at preventing and
treating
>serious and life-threatening
>diseases. Therefore, the Administration would not support passage
of the
>bill in its current form. The
>Administration looks forward to working with the Congress to
address these
>concerns. Specifically,
>the Administration supports amendments to S. 1601 that would:
>
>Include a five-year sunset on the prohibition on human somatic
cell nuclear
>transfer technology. The
>sunset provision would ensure a continuing examination of the
risks and
>benefits of this, while being
>free from the concern that someone will use it prematurely.
>
>Permit somatic cell nuclear transfer using human cells for the
purpose of
>developing stem cell
>(unspecialized cells capable of giving rise to specific cells and
tissue)
>technology to prevent and treat
>serious and life-threatening diseases and other medical conditions,
>including the treatment of cancer,
>diabetes, genetic diseases, and spinal cord injuries and for basic
research
>that could lead to such
>treatments.
>
>Strike the bill's criminal penalties and instead make any
property, real or
>personal, derived from or
>used to commit violations of the Act subject to forfeiture to the
United
>States.
>
>Strike the bill's provisions establishing a new Commission to
Promote a
>National Dialogue on
>Bioethics. The new Commission would needlessly duplicate the
mission of the
>President's National
>Bioethics Advisory Commission.
>
>The President's proposal, which in many ways is reflected in S. 1602
>sponsored by Senators
>Feinstein and Kennedy, would prohibit any attempt to create a
human being
>using somatic cell
>nuclear transfer, provide for further review of the ethical and
scientific
>issues associated with the use
>of somatic cell nuclear transfer, and protect important biomedical
research.
V
>
r. alta charo, j.d.
senior fellow, stanford center for biomedical ethics
701a welch road, suite 1005
palo alto, ca 94304
650-723-5760 (tel)
650-725-6131 (fax)
415-661-9987 (home)
[email protected]
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: robin alta charo <[email protected]> ( robin alta charo <[email protected]> [
UNKNOWN ])
CREATION DATE/TIME:12-NOV-1998 09:49:30.00
SUBJECT: Re: FW: NEW YORK TIMES
TO: NBAC Members E-list <[email protected]> (NBAC Members E-list <nbac-
[email protected]> [ UNKNOWN]
READ:UNKNOWN
TEXT:
fyi, neal first, here at univ of wisconsin, announced last january at a
meeting in boston, that he had successfully mixed nuclei from one animal
species with enucleated eggs from another species, working with a variety
of non-human species. a key finding from his work is that normal cell
division only goes on for a period of days (maybe a week?) before the cells
begin to divide in an unorganized fashion. in other words, his hybridized
egg/embryos did NOT have the potential to become fetuses of any species.
also fyi, with regard to the embryo stem cell technology developed by jamie
thomson at univ of wisconsin, announced last week: our newly formed
university bioethics advisory commission has advised the chancellor that
stem cells be licensed to researchers at other universities only under
certain conditions of use. one of those conditions is that the stem cells
or their derivatives not be used with the intent to transfer them into a
uterus for development into a human being.
thus, for neither of these technologies is there a risk that a baby could
be born from the experiment.
At 09:20 11/12/98 -0500, you wrote:
>To consider with your morning coffee.
V
>Eric M. Meslin, Ph.D
>Executive Director
>National Bioethics Advisory Commission
>6100 Executive Blvd. Suite 5B01
>Rockville, Maryland 20892-7508
>Tel: (301) 402-4242
>Fax: (301) 480-6900
>Email: [email protected]
>http://www.bioethics.gov
Original Message
>From: Skirboll, Lana (OD)
>Sent: Thursday, November 12, 1998 5:22 AM
>To: '[email protected]'; Patterson, Amy (OD); Meslin, Eric (OD);
Emanuel,
>Ezekiel (CC); 'Howard Garrison'; 'mazzaschi,tony'; '[email protected]';
Knorr,
>Debra (OD); '[email protected]
>Subject: NEW YORK TIMES today
>Importance: High
>
>If you thought the news last week was replete with ethical problems, read
below.
>Now we have a combination of cloning, totipotent embryonic stem cells and
>human/animal chimeras! The founder of Geron, Michael West, now head of
Advanced
>Cell Technology, alleges he has created a totipotent embryonic cell line
using
>SCNT in which he transferred the nucleus from one of his own somatic cells
into
>an enucleated cow egg - now we have human-animal chimeras to deal with!
This has
>not been confirmed or even published, but Dr. West decided to begin the
public
>debate! Yikes!
>
>
>NEW YORK TIMES November 12, 1998
>
>
>
Human Cells Revert to Embryo State, Scientists Assert
>
>
>
>
By NICHOLAS WADE
>
Venturing deep into uncharted realms of ethics and
medicine, a
>small biotechnology company
V
said Wednesday that its scientists had for the first time
made
>human cells revert to the
>
primordial, embryonic state from which all other cells develop,
by
>fusing them with cow eggs and
>
creating a hybrid cell.
>
V
The research comes from biologists who are well known in their
field,
>but has yet to be confirmed or
>
even published in a scientific journal. Their company, Advanced
Cell
>Technology of Worcester,
>
Mass., said the method could eventually be used to grow
replacement
>body tissues of any kind from
>
a patient's own cells, sidestepping the increasing scarcity of
organs
>available for transplant and the
>
problems of immune rejection.
>
>
The technique is likely to concern and perplex ethicists
because it
>involves the creation of an
>
embryonic cell that is part human and part cow, consisting of a
human
>cell's nucleus inside a cow egg
>
whose own nucleus has been removed. The company said the hybrid
cell
>quickly became more
>
human-like as the human nucleus took control and displaced cow
>proteins with human proteins.
>
Creation of the embryonic cells is an important component of a
>strategy that in principle offers high
>
medical benefits if it can overcome a doubtless high barrier to
public
>acceptance.
>
>
The technique involves creating an embryo of uncertain moral
status,
>and one that crosses the barrier
>
between humans and other species. Even though the hybrid is in
the
>form of cells, not a whole
>
organism, the concept of half-human creatures arouses deeps
anxiety,
>as is evident from the
>
unfriendly powers ascribed to werewolves, centaurs, mermaids,
>Minotaurs and other characters of
V
myth and folklore.
V
>
"Many people are going to be horrified by this scenario, others
will
>say 'So what?' said Thomas
V
Murray, director of the center for biomedical ethics at Case
Western
>Reserve University in
V
Cleveland and a member of the National Bioethics Advisory
Commission.
>"This is the sort of thing
V
that makes me very uncomfortable. I think we are likely to get a
very
>powerful reaction to it, and I
>
would like for all of us to have a breathing space here to
articulate
>our moral concerns."
V
>
Another serious uncertainty is the preliminary nature of the
company's
>work. No article has yet been
>
submitted for peer review and publication in a scientific
journal, an
>essential touchstone of credibility.
>
Scientists asked about the company's work said they would
require much
>more proof before
>
believing that human embryonic stem-like cells had been created
as
>claimed, and some were
>
skeptical the technique would work at all.
>
>
The company said it had achieved the feat announced Wednesday
with one
>cell three years ago.
>
Michael West, Advanced Cell Technology's chief executive
officer, said
>he was announcing the
>
work done to date in order to test its public acceptability He
said
>the company, which is privately
>
held, was not planning to go public or raise money at this time
but
>needed to decide whether to
>
commit investment to development of the technique.
>
>
Some scientists praised West's decision to make his work public
but
>others are critical, saying he has
>
invited an emotional public debate on a slender basis of fact.
>
>
West is the founder of Geron, a biotechnology company that has
had two
>spectacular successes this
>
year in its research on aging. In January, the company
developed a
>method for "immortalizing" human
V
cells grown in the laboratory by making them leap the supposedly
>immutable barrier at which cells
>
usually lapse into senescence. Last week, two university teams
>financed by Geron said they had
V
isolated and cultivated human embryonic stem cells, the
all-purpose
>cells from which the fetus
>
develops. West lay the foundations for these developments by
financing
>leading scientists in the two
V
fields.
V
>
Advanced Cell Technology, which West joined in October, has
focused on
>cloning and genetically
>
improving cows, a technology developed by James Robl and
colleagues at
>the University of
>
Massachusetts in Amherst. West said he hoped to use the
technology to
>further the founding concept
>
of Geron: delving into the mystery of human aging and
sidestepping
>some of its processes.
>
>
The company said work with human cells was performed in 1996 by
Jose
>Cibelli, a colleague of
>
Robl at the University of Massachusetts. Using 52 of his own
cells,
>some of them white blood cells
>
and others scraped from the inside of his cheek, Cibelli fused
each
>one with a cow egg whose own
>
nucleus and DNA had first been removed, the company said. Most
failed
>to thrive but one embryo
>
grew and divided five times, generating cells resembling
embryonic
>stem cells. Cibelli and West say
>
the method can be made more efficient with present technology.
>
>
Considering this work was sufficient to describe an invention,
Robl
>and Cibelli filed a patent
>
application and then set the research aside to focus on the more
>immediately practical field of cow
>
cloning. Only two others besides himself and Robl knew what had
been
>done, Cibelli said. The
>
patent has not yet been issued but West said he was confident of
>receiving "important intellectual
V
property" in the field. He said he is making the hybrid cell
technique
>public now "because I want to
>
be very open and level with everyone. We need to get the
ethicists to
>talk about it so as to
V
encourage a rational response to these new technologies."
V
V
Cibelli said he regarded any embryos obtained in this way as
"not a
>separate individual, just a
>
de-differentiated cell from a patient." Differentiation is the
process
>whereby the all-purpose cells of
V
the very early embryo, known as human embryonic stem cells,
become
>committed to their roles as
>
the various specialized tissues of the body. The process is
>irreversible in nature but egg cells
>
apparently have the ability to de-differentiate, or reset to
default
>mode, the settings in a specialized
>
cell's nucleus. This is presumably what happened in the
experiment
>reported in July when mice were
>
cloned by transferring the nucleus of an adult mouse cell into
another
>mouse's egg cell.
>
>
Cibelli, who trained as a veterinary doctor in Argentina, said
he
>believed that he and his colleagues
>
"were the first to de-differentiate a human cell by nuclear
transfer."
>
>
>
Asked if he was concerned about destroying, in principle, 52
potential
>twins of himself, he said, "I
>
never thought about it, it's a good question. But if you use
your own
>cells to treat a disease you may
>
have, you are not taking cells from another person selfishly."
>
>
West and Cibelli said they had no intention of transferring the
>embryos to a uterus, a step they
>
consider unethical and unsafe for it. The embryos would be
created
>solely for the purpose of tissue
>
culture. "Any technology can be abused but once the public
understands
>how these cells can be used
>
to treat any disease caused by loss or malfunction of cells,
from
>Parkinson's to diabetes to heart
V
disease, the concerns will be overshadowed," West said.
V
V
Whether or not West's prediction will be borne out depends on
two
>major sets of factors, the
>
scientific validity of the proposed method and the ethical and
legal
>questions that related work has
>
already raised.
>
V
From discussions with scientists, ethicists and lawyers in the
past
>few days, several concerns have
>
emerged.
>
>
Scientists are particularly critical of the lack of supporting
>evidence accompanying Advanced Cell
>
Technology's announcement, saying in essence the claim could be
true
>but there was no compelling
>
reason yet to accept it. Even if the claim is valid, biologists
note a
>serious uncertainty relating to an
>
important part of the cells known as the mitochondria,
components that
>produce the energy the cell
>
needs and that are, in essence, the cell's batteries. If the
bovine
>mitochondria should prove
>
incompatible with their humanized environment the cells will
not be
>viable.
>
>
Ethicists believe the mixing of species is likely to trouble the
>public severely, at least at first. Lawyers
>
who specialize in issues of human reproduction note that the
moral and
>legal status of the human
>
embryo is undecided in American law, a fact pointed up by the
>isolation of the human embryonic
>
stem cells announced last week. The new entity adds further
>complexity.
V
>
If Advanced Cell Technology can produce viable hybrid cells,
those
>cells will offer a new route to
>
grow tissue for transplant. This is the same goal held by the
>scientists who announced last week they
>
had grown human embryonic stem cells in the laboratory. It is
widely
>accepted in principle that
>
embryonic stem cells can be directed to develop into any desired
>tissue, with enormous potential for
>
medicine, even though this has yet to be achieved in practice.
V
>
West said the advantage of the Advanced Cell Technology method
was
>that embryonic cells derived
>
from the patient being treated would generate entirely
compatible
>tissues. The two methods reported
V
last week, by James Thomson of the University of Wisconsin and
John
>Gearhart of Johns Hopkins
>
University, derive stem cells from human embryos or fetuses.
Tissues
>made from these cells would
>
be incompatible with the patient, a problem that has yet to be
>resolved.
V
>
In support of its claim, Advanced Cell Technology supplied a
patent
>application and a photograph
>
taken of its embryonic cells under a microscope. The patent
>application describes how the cells are
>
made but provides no proof that they possess the properties to
be
>expected of human embryonic
>
stem cells. Robl said his laboratory was not set up to perform
the
>required tests at the time the hybrid
>
cells were made.
>
>
Shown the photograph of the hybrid cells, John Gearhart of Johns
>Hopkins University, author of one
>
of the two methods reported last week, said that "they certainly
could
>be embryonic stem cells" but
>
that no scientific journal would publish the result without
further
>proof. "It's not that I don't believe
>
this biologically. I just think they could have given a little
bit
>more assurance as to what was done
>
here."
>
>
Roger Pedersen of the University of California at San Francisco,
who
>also works on human
>
embryonic stem cells, said he doubted the hybrid cells would
last long
>enough to develop into useful
>
tissue because of their cow-derived mitochondria.
>
>
Mitochondria, former bacteria enslaved by cells eons ago, have
their
>own genes but operate in close
V
cooperation with genes from the cell's nucleus.
V
V
Pedersen cited a recent experiment showing that within the
>human-ape-monkey family, each species'
V
mitochondria is subtly different, the more so the longer the
>evolutionary distance between the species
>
in question. The mitochondria of chimpanzees and gorillas work
well
>enough in human cells but those
>
of primate species that diverged more than 10 million years ago
from
>the human line, do not work.
V
>
Because cows and humans last shared an ancestor so long ago, cow
>mitochondria are very unlikely
>
to work well with a human nucleus, in Pedersen's view, and asmost of
>the mitochondria in the hybrid
>
cells are contributed by the cow egg, the cells would probably
not
>remain viable for long. "It's hard
>
to say this is a total sham, but I smell a sham here," he said.
>
>
Citing the same data, Gearhart said the mitochondria in the
hybrid
>cell had clearly carried it through
>
its first few divisions but might not sustain it in further
>development, unless the few human
>
mitochondria that were also present somehow took over.
>
>
Pedersen said Advanced Cell Technology should be held to a high
>standard of proof "because of
>
what the implications are for upsetting people unnecessarily
if you
>cry fire in a crowded auditorium
>
you may be liable if it's a false alarm."
>
>
The human embryonic stem cells announced last week have already
pushed
>against the frontiers of
>
ethical acceptance. Experts in biomedical ethics say the public
is
>likely to be alarmed by the new
>
technique, particularly because of the mingling of species.
Murray of
>Case Western Reserve
>
University said that the hybrid embryo "escapes our usual
categories."
>When biologists first learned
>
to transfer genes from one species to another, "The idea of
>human-animal hybrids was often raised as
>
the kind of monstrosity that no morally perceptive person would
ever
>create," he said.
V
>
"Even if it's only to create tissue, the minute you start mixing
>species you raise all kinds of red flags in
>
people's minds," said Barnie Steinboch, a moral philosopher at
the
>State University of New York in
V
Albany. But she noted that pig valves are now seen as acceptable
>replacements in human hearts.
V
>
Rebecca Dresser, a law professor at Washington University in St.
>Louis, noted, as did several
>
biologists, that distinctions between humans and other animals
are
>less clear in nature than they are in
>
people's minds. "Biologically a lot of this research is showing
us
>similarities and the upshot in a
>
hundred years may be that the lines between humans and
non-humans will
>be viewed as a little bit
>
grayer," she said.
>
>
A perplexing feature of the hybrid embryo is that it starts off
mostly
>bovine and then becomes mostly
>
yet not entirely human. But some legal experts have no doubt
that it
>should be regarded from the
>
start as a human embryo. "It doesn't matter that the
mitochondria come
>from a cow, it also has
>
human mitochondria and so has all the potentials of a human
embryo,"
>said Lori Andrews of the
>
Chicago-Kent College of Law in Chicago.
>
>
"Once it's gone through that first division it has gone from
being a
>somatic cell to a thing with potential
>
life," she said, referring to the ordinary specialized cells of
the
>human body. If transferred to a
>
woman's uterus the embryos may or may not come to term, "but
under
>state laws it doesn't matter
>
whether the fetus is going to be born or not - it doesn't make
them
>less human."
>
>
The human body consists of 100 billion cells. Should embryos
created
>from them by the cow egg
>
method be regarded as having special status when they can be
made so
>easily and plentifully? Ms.
V
Andrews said that human embryos are not so hard to make the
usual way,
>and the fact that an
>
embryo is easily made, by whatever means, is irrelevant to
arguments
>about its status.
>
>
The moral status of the human embryo "is not clearly
established in
>U.S. law," Dresser said. The
>
embryo can be regarded as mere property, as a person, or as
something
>in between but deserving of
V
special respect. Congress, in banning the use of federal funds
for
>research on human embryos, has
>
favored the view that they are in the category of people. But in
>custody battles over fertilized
>
embryos, courts have favored the special respect status. Dresser
said
>the hybrid cells could be seen
>
as somewhere between the property and special-respect status.
>
>
The hybrid cells were made by Cibelli in Robl's laboratory in
the
>University of Massachusetts at
>
Amherst. Michael Weinberg, executive secretary of the
university's
>human subjects committee, said
>
the experiment was given administrative approval, without
review by
>the committee or any major
>
discussion. Cibelli was using his own cells, not experimenting
on
>other people, and
>
self-experimentation does not require special consent. "If
someone
>wants to inoculate themselves
>
they can do that," Weinberg said.
>
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: "Meslin, Eric (OD)" <[email protected]> ("Meslin, Eric (OD)" <[email protected]> [
UNKNOWN
CREATION DATE/TIME:13-NOV-1998 11:32:22.00
SUBJECT: FW: more on human/cow cell breakthrough
TO: NBAC Members E-list <[email protected]> ( NBAC Members E-list <nbac-
[email protected]> [ UNKNOWN 1)
READ:UNKNOWN
TEXT:
Commissioners, et al.
You will all have seen this, by now.
Let me inform you that after discussions with Harold, he has decided that,
if
asked by the administration, NBAC would be prepared to offer its
assistance.
Should this occur (and it has not), I will share the request with you and
discuss any potential action on our part.
Eric
Eric M. Meslin, Ph.D
Executive Director
National Bioethics Advisory Commission
6100 Executive Blvd. Suite 5B01
Rockville, Maryland 20892-7508
Tel: (301) 402-4242
Fax: (301) 480-6900
Email: [email protected]
http://www.bioethics.gov
Original Message
From: Hull, Randolph Everson (OD)
Sent: Friday, November 13, 1998 10:09 AM
To: Andrew Siegel; Deborah McCurry; Elisa Eiseman; elisa2; Emma
Codrington;
Eric Meslin; Evadne Hammett; Feinstein, Emily; Freeman, Bill; Hull,
Randolph
Everson; Hyatt-Knorr, Henrietta; LaShell Gaskins;
[email protected];
Melissa Goldstein; Norris, Patricia; Quinlan, Margaret; Simon, Sean;
Tanner,
Rob; Temp NBAC
Subject:
more on human/cow cell breakthrough
Mass. Firm Says It Created Embryo Out of Human, Cow Cells
By Rick Weiss
Washington Post Staff Writer
Friday, November 13, 1998; Page A01
Scientists, ethicists and federal regulators scrambled yesterday to sort
out the
many controversial issues raised by a small biotechnology company's
announcement
that it had used cloning techniques to create an embryo out of human and
cow
cells.
The work, conducted in 1995 and 1996 at Advanced Cell Technology of
Worcester,
Mass., but not made public until yesterday, was part of an effort to make
medically useful tissues but also appears to be the closest that anyone
has come
to cloning a human being.
Among the many questions raised by the revelation was whether the research
broke
a ban on the use of federal funds for embryo research; whether it bypassed
Food
and Drug Administration rules on research; and how the work passed muster
with
the ethics review board at the University of Massachusetts in Amherst,
where the
company-supported work was done.
Those and other uncertainties led several experts yesterday to call upon
Congress and the White House to clarify the regulatory framework within
which
human embryo research and other high-tech human studies are conducted.
"We will be contacting the White House today to ask that the president
have the
National Bioethics Advisory Commission examine these issues," said Carl
Feldbaum, president of the Biotechnology Industry Association, who said he
was
excited by the findings but was concerned by the lack of regulatory
clarity.
The Worcester company produced one cloned human embryo - perhaps the first
ever
made - and performed the unprecedented cross-species hybridization of a
human
cell and a cow egg.
Michael West, president of the company, said in an interview yesterday that
although the technique was very similar to that used to clone Dolly the
sheep,
he had no intention of cloning adult humans. Rather, the project's goal
was to
grow replacement cells and tissues for transplantion into people with
diseases.
West said he had recently reopened the files on the dormant experiment and
concluded that it was largely successful. He was publicizing the findings,
he
said, because the company had the moral responsibility to get feedback
from the
public before going any further.
Several critics, however, said they suspected the company had made a
business
decision to ride a new wave of interest in cultured embryonic cells,
spurred by
recent promising reports published in scientific journals. In contrast to
those
recent studies, West's company has not submitted its findings for review
and
publication in a research journal. Instead it released its findings to the
New
York Times, which ran a report about it yesterday. That suggested to some
that
the company was primarily trying to position itself to make an an
intellectual
property claim on cell transplant technology.
"What do they have? They've got no publication, they've got nothing," said
George Annas, a professor of health law at Boston University. "All they
have is
the opportunity to tag along with the other stem cells in the news. They're
saying, 'Let's cash in.""
West said the company's team had fused a human skin cell to a cow's egg
whose
genes had been removed. The fluids that remained in the gutted cow egg
caused
the genes in the human cell to revert to their primordial state, as though
they
were back in a developing human embryo. The fused cell divided several
times,
and microscopic examination indicated that some of the resulting cells
resembled
stem cells, which scientists hope to harness for medical purposes and for
which
the company has submitted a patent claim.
Other scientists disputed West's conclusions, however, saying the
Worcester team
never did the basic tests used to see if cells are really stem cells. West
confirmed those tests were never done.
Roger A. Pedersen, a stem cell researcher at the University of California,
San
Francisco, said the company's claim of having isolated stem cells shocked
him.
"One must be very circumspect about such a fanciful notion without good
data to
support it," he said.
Moreover, Pedersen and others said, experiments in other species have
shown that
hybrid embryos made from divergent species grow poorly and suffer many
defects
because of an incompatibility between the newly transferred genes (in this
case
human) and so-called mitochondrial genes that are left behind in the fluid
of
the gutted egg.
"There's a carefully choreographed dance between nuclear DNA and
mitochondrial
DNA," Pedersen said, saying he doubted the Massachusetts team's cells
would have
much medical value.
John Gearhart, who last week published a scientifically reviewed report
showing
he had isolated human embryonic stem cells from fetuses, agreed, saying
the new
report reminded him of the much ballyhooed and ultimately disproved claims
of
"cold fusion" earlier in this decade.
Experts also questioned the legal and ethical basis of the work. Congress
has
banned federal funding for human embryo research, and Gearhart, Pedersen
and
others work in labs from which federally purchased equipment has been
scrupulously excluded.
West said the company's embryo work was done using only corporate funds,
but
officials at the University of Massachusetts said they were unaware that
any of
the labs in the building where the work was done had been specially
cleared of
all equipment purchased with federal grant money. "We don't have an NIH
room and
an NSF room and so on," said Michael Weinberg, special assistant to the
vice
chancellor for research. "Faculty members get funded and they go from room
to
room."
The role of the FDA also remained unclear yesterday. Acting FDA
Commissioner
Michael Friedman said that if the work was basic research then the company
was
under no obligation to get approval from the agency, but if it was done
with the
intention of developing a cellular therapy for use in humans then the
company
should have filed for an Investigational New Drug application. With only a
newspaper report to describe what the team did, he said, it remained
unclear to
him which category the work belonged in.
Others questioned how the university's institutional review board could
approve
the species-mixing research. Weinberg, who heads that committee, said the
group
only considered whether it posed a risk to the researcher who donated his
skin
cells. But other experts said such committees are clearly required by
federal
law to consider the full range of scientific and ethical issues raised by
proposed research. They said the committee's quick approval gives credence
to a
recent federal report that called for a major overhaul of the nation's
local
research review system.
"What this whole business shows is that we are in a regulatory nightmare,"
said
Glenn McGee, a professor of bioethics at the University of Pennsylvania.
"It's
going to be impossible to state whether these things are really human, let
alone
how to protect them."
ïᵢ½ Copyright 1998 1998 The Washington Post Company
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RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: Tony Mazzaschi <[email protected]> ( Tony Mazzaschi <[email protected]> [ UNKNOWN ]
)
CREATION DATE/TIME:15-NOV-1998 09:58:06.00
SUBJECT: Adhoc: Clinton Requests NBAC Review of Stem-Cell Research Issues
TO: [email protected] ( [email protected] [ UNKNOWN 1)
READ:UNKNOWN
TO: [email protected] ( [email protected] [ UNKNOWN ])
READ:UNKNOWN
TO: [email protected] ( [email protected] [ UNKNOWN )
READ:UNKNOWN
TO: [email protected] ( [email protected] [ UNKNOWN )
READ:UNKNOWN
TO: [email protected] ( [email protected] [ UNKNOWN ])
READ:UNKNOWN
TEXT:
According to Sunday*s NY Times, the President on Saturday wrote to the
chair of the National Bioethics Advisory Commission asking that the panel
review at its Tuesday meeting the ethic issues raised by embryonic
stem-cell
research. The Times* article on the President*s request follows.
Tony Mazzaschi
AAMC
November 15, 1998
Effort to Make Part-Human, Part-Cow Cells Troubles Clinton
By NICHOLAS WADE
Saying that he is "deeply troubled" by the creation of part-human, part-cow
embryonic stem cells, President Clinton has directed the National Bioethics
Advisory Commission to consider the implications of the research at its
meeting Tuesday in Miami and to report back to him "as soon as possible".
In a letter sent Saturday to the chairman of the commission, Harold Shapiro
of Princeton University, Clinton also asked for a review of embryonic
stem-cell research in general, including the all-human embryonic stem cells
whose isolation was reported earlier this month. These cells -- the
primordial, all-purpose cells from which all tissues of the body develop --
were derived from very early embryos or blastocysts and from tissues of
aborted fetuses.
While the president signaled concern about the "mingling of human and
non-human species," he was more positive about the all-human embryonic stem
cell research, noting that it "may have real potential for treating such
devastating illnesses as cancer, heart disease, diabetes and Parkinson's
disease."
But he also stressed the ethical concerns raised by the research, telling
the commission that he wanted a "thorough review, balancing all ethical and
medical considerations."
The letter was sent after the president had consulted with the White House
Domestic Policy Council and the president's science adviser, Neal Lane,
"because he wanted the broadest views possible -- the policy people,
medical
ethicists, as well as the scientists," an administration official said.
A political issue that lies in the background of the commission's
deliberations is the ban on federal financing of fetal research. The ban,
imposed by Congress, has created the situation that university scientists,
who mostly depend on federal money, cannot work on the human embryonic stem
cells whereas the private sector may conduct whatever research it pleases.
A group of scientists and ethicists known as the Human Embryo Research
Panel said in 1994 that research on human embryonic stem cells should be
federally financed, provided that the cells were derived from excess
pre-implantation embryos created for infertility treatments. This was the
source of some of the human embryonic stem cells isolated earlier this
month.
In response to the panel's report, Clinton said in December 1994, "I do not
believe that federal funds should be used to support the creation of human
embryos for research purposes." The statement did not rule out research on
excess embryos created in infertility clinics but subsequent action by
Congress banned all research in which a human embryo is destroyed.
Referring to this history, the president said in his letter Saturday that
the ethical issues of human embryonic stem cell research had not diminished
since his statement of 1994 but that the benefits had become less
hypothetical.
Lane said the implications of human embryonic stem-cell research had been
under review but news of the human-cow hybrid cells, reported last week,
"clearly raised urgent ethical, medical and legal issues that the president
wants addressed and that's why he asked for the commission to give it
immediate attention."
Human embryonic stem cells can develop into any of the body's 210 types of
cells, a process that happens naturally during fetal development.
Biologists
at Geron, the company that supported the research, hope to grow the cells
in
the laboratory and guide them to develop into heart cells, blood cells and
other tissues.
The cells would then be injected into the patient and integrate with
tissues under the control of local body signals.
In principle, the method could address a range of otherwise untreatable
degenerative diseases, as well as relieving the severe shortage of organs
available for conventional transplants.
Many serious technical problems remain to be resolved, including finding
ways to guide the stem cells down desired paths of development and ways to
prevent immune rejection.
The ethical problems are also important because of the source of the
embryonic stem cells. In one case the cells came from excess
pre-implantation embryos created in infertility treatments, and in the
other
from aborted fetal tissue. Both sources were legal, but research using the
first would have been ineligible for federal money.
The human-cow hybrid cell also complied with all laws, said Michael West,
chief executive of Advanced Cell Technology of Worcester, Mass., the
company
that supported the research. In the hybrid cell, the cow cell's nucleus is
first removed and the cow proteins are expected to be rapidly replaced with
human proteins as the human nucleus takes over the cell.
Although the mingling of species raises many questions, scientists at
Advanced Cell Technology regard the operation as one in which the cow egg
is
used simply to make the human cell's nucleus revert to its embryonic state.
As the human cells can be provided by the patient himself, from blood or
skin, there is no immune rejection when developed cells grown from his
embryonic state cells are injected back into the body.
Advanced Cell Technology performed its cow-human hybrid experiment only
once, three years ago, and took the study only to a very preliminary stage.
Other scientists say more evidence is needed to verify whether embryonic
stem-like cells were created.
West said he was announcing the research now to test its public
acceptability before making further investments in the technique.
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: Sean Tipton <[email protected]> ( Sean Tipton <[email protected]> [ UNKNOWN 1)
CREATION DATE/TIME:30-NOV-1998 10:31:07.00
SUBJECT: Adhoc: Stem Cell Research
TO: [email protected] ( [email protected] [ UNKNOWN )
READ:UNKNOWN
TEXT:
Disclaimer: The Ad Hoc Group has not taken a stance on stem cell
research.
As many of you know, the Labor Health and Human Services subcommittee of
the Senate Appopriations Committee is holding a hearing to discuss
advances in stem cell research and their implications. The hearing is
set for Wednesday Dec 2 at 9:30 am in Dirksen 192.
As recent studies have shown, the promises of dramatic therapies using
stem cells may be closer than had been thought. It is vitally
important that this work be allowed to progress.
Hopefully many of you are signing on to a letter being circulated by BIO
urging that stem cell research be allowed to progress free of barriers
that would impede progress.
Unfortunately there are those who would oppose stem cell research in
order to make larger political points. I hope the research community can
send them a message that this work is important, and that we will work
to ensure it can continue.I think it is important that the research
community be heard on this and be heard early.
The American Society for Reproductive Medicine will be issuing a
statement on Wednesday supporting stem cell research and opposing
attempts to curtail it for political reasons.
I urge you to sign on to the BIO letter, and/or issue your own.
If anyone has any questions, please feel free to get in touch with me.
Sean Tipton
American Society for Reproductive Medicine
[email protected]
202-863-2494
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: Tony Mazzaschi <[email protected]> ( Tony Mazzaschi <[email protected]> [ UNKNOWN ]
)
CREATION DATE/TIME: 2-DEC-1998 16:39:58.00
SUBJECT: Adhoc: Varmus' Statement on Stem Cell Research
TO: [email protected] ( [email protected] [ UNKNOWN 1)
READ:UNKNOWN
TEXT:
For those unable to attend this moning's Senate hearing on stem cell
research, a copy of Dr. Varmus' prepared statement follows. The complete
hearing was broadcast live on C-SPAN II and is likely to be repeated on
either C-SPAN I or II.
Tony Mazzaschi
AAMC
Statement of
HAROLD VARMUS, M. D.
Director
National Institutes of Health
before the Senate Appropriations Subcommittee on Labor, Health and Human
Services, Education and Related Agencies
December 2, 1998
Mr. Chairman and Members of the Subcommittee, I am Harold Varmus, Director
of the National Institutes of Health. I am pleased to appear before you to
discuss recent published reports on the isolation and propagation of the
first human pluripotent stem cell lines. These findings, reported by Drs.
John Gearhart from Johns Hopkins University and James Thomson from the
University of Wisconsin, bring medical research to the edge of a new
frontier that is extraordinarily promising. The development of human
pluripotent stem cell lines deserves close scientific examination, further
evaluation of the promise of the research, and careful consideration and
open discussion of the ethical and legal issues. I want to thank you for
the opportunity to discuss this important issue with you and the Members of
this Subcommittee.
Why the excitement? For the first time, scientists have obtained human
stem cells that can give rise to many types of cells in our body. Let me
briefly describe these experiments. Dr. Thomson and coworkers derived stem
cell lines from embryos donated by couples undergoing in vitro
fertilization
(IVF) as part of treatment for infertility. These cells were grown in
culture and found to divide indefinitely and have the ability to form cells
of the three major tissue types endoderm (which goes on to form the lining
of the gut), mesoderm (which gives rise to muscle, bone and blood) and
ectoderm (which gives rise to epidermal tissues and the nervous system).
The ability of the cells to specialize into the three major tissues types
is
an important indicator that these cells are pluripotent. Dr. Gearhart and
his coworkers derived pluripotent stem cells from fetal gonadal tissue
destined to form germ cells. When grown in culture, these cells resemble
other types of pluripotent stem cells in that they, like the cells from Dr.
Thomson's work, also can develop into cells of the three major tissue
types.
What Are Stem Cells?
As policy makers proceed to consider the scientific, ethical and societal
issues raised by this research, it is absolutely essential to clarify terms
and definitions. There are many types of stem cells. In general, they all
have the ability to divide (and self renew) and to commit to a more
specialized function. There is a hierarchy of stem cell types. Some stem
cells are more committed than others. Some stems cells - the pluripotent
stem cell we are discussing today - have the ability to become many, but
not
all, of the cells types in the human body.
Through processes we are only beginning to understand, primitive stem cells
can be stimulated to become specialized, so that they are precursors to any
one of many different cell types such as muscle cells, skin cells, nerve
cells, liver cells. Unlike the stem cells from which they are derived,
these specialized cells are "committed" to a particular function.
All stem cells have the capability of self-renewal, i.e., they can
continually reproduce themselves. Cells from the very earliest embryo (up
to
about the 16 cell stage) are totipotent stem cells. They are "totally
potent" or totally capable of forming all cells of the body, including the
cells required to support embryonic and fetal development. Each cell of
this early embryo has the potential to develop into a human being.
After a few days of development, the early embryo forms a hollow ball of
cells, called a blastocyst. This is the next stage of embryonic
development.
The clustered cells within this ball are called the inner cell mass. The
cells in the inner cell mass are not totipotent. Rather, they are
pluripotent. Pluripotent stem cells are more "committed" than totipotent
stem cells. Unlike the fertilized egg, or the early embryo, or the intact
blastocyst, neither the disaggregated inner cell mass nor the pluripotent
stem cells derived from it (nor the pluripotent stem cells derived from
fetal germ cells) will produce a human being even if returned to a woman's
uterus. These cells do not have the potential to form a human being,
because
they do not have the capacity to give rise to the cells of the placenta or
other extraembryonic tissues necessary for implantation, nor can they
support fetal development in the uterus.
During fetal development, pluripotent stem cells become even more
committed, i.e, they have the capacity to form only one or a few different
kinds of cells. For example, hematopoietic stem cells can form all the
blood cells, but no other tissue types. The adult human being continues
to
harbor many types of stem cells responsible for the body's ability to
repair
some but not all tissues. Stem cells that permit new skin growth and
renewal of blood cells are two examples.
Potential Applications of Pluripotent Stem Cells
There are several important reasons why the isolation of human pluripotent
stem cells is, indeed, important to science and for the future of public
health. At the most fundamental level, pluripotent stem cells could help
us to understand the complex events that occur during human development.
A
primary goal of this work would be the most basic kind of research -- the
identification of the factors involved in the cellular decision-making
process that determines cell specialization. We know that turning genes on
and off is central to this process, but we do not know much about these
"decision-making" genes or what turns them on or off. Some of our most
serious diseases, like cancer, are due to abnormal cell differentiation and
growth. A deeper understanding of normal cell processes will allow us to
further delineate the fundamental errors that cause these deadly illnesses.
Human pluripotent stem cell research could also dramatically change the way
we develop drugs and test them for safety and efficacy. Rather than
evaluating safety and efficacy of a candidate drug in an animal model of a
human disease, these drugs could be tested against a human cell line that
had been developed to mimic the disease processes. This would not replace
whole animal and human testing, but it would streamline the road to
discovery. Only the most effective and safest candidate would be likely to
graduate to whole animal and then human testing.
Perhaps the most far-reaching potential application of human pluripotent
stem cells is the generation of cells and tissue that could be used for
transplantation, so-called cell therapies.
Many diseases and disorders result from disruption of cellular function or
destruction of tissues of the body. Today, donated organs and tissues are
often used to replace the function of ailing or destroyed tissue.
Unfortunately, the number of people suffering from these disorders far
outstrips the number of organs available for transplantation. Pluripotent
stem cells stimulated to develop into specialized cells offer the
possibility of a renewable source of replacement cells and tissue to treat
a
myriad of diseases, conditions and disabilities including Parkinson's and
Alzheimer's disease, spinal cord injury, stroke, burns, heart disease,
diabetes, osteoarthritis and rheumatoid arthritis. There is almost no
realm
of medicine that might not be touched by this innovation. Let me expand on
two of these examples.
- Transplant of healthy heart muscle cells could provide new hope for heart
attack victims. The hope is to develop heart muscle cells from human
pluripotent stem cells and transplant them into the failing heart muscle in
order to augment the function of the heart. Preliminary work in mice and
other animals has demonstrated that healthy heart muscle cells transplanted
into the heart successfully repopulate the heart tissue and integrate with
the host cells. These experiments show that this type of transplantation is
feasible.
- In the many individuals who suffer from Type I diabetes, the production
of insulin by the pancreas by specialized cells called islet cells is
disrupted. There is evidence that transplantation of either the entire
pancreas or isolated islet cells could mitigate the need for insulin
injections. Islet cell lines derived from human pluripotent stem cells
could be used for this critical research and, ultimately, for
transplantation.
While I have taken this opportunity to outline the promise of this
research, there is much to be done before we can realize these innovations.
First, we must do the basic research to understand the cellular events that
lead to cell specialization in the human, so that we can direct these
pluripotent stem cells to become the type(s) of tissue needed for
transplantation in great numbers. And before we can use these cells for
transplantation, we must overcome the well-known problem of immune
rejection. Because human pluripotent stem cells derived from embryos or
fetal tissue would likely be genetically different from the recipient,
future research would need to focus on modifying human pluripotent stem
cells to minimize tissue incompatibility. Technological challenges remain
before these discoveries can be incorporated into clinical practice. These
challenges, though significant, are not insurmountable.
How Are Pluripotent Stem Cells Produced?
There are several ways to produce human pluripotent stem cells. These
methods have been developed over the past 17 years by researchers working
with animals. The work you will hear about today builds on this important
basic animal research.
As I mentioned earlier, one method of creating these pluripotent stem cells
was described by Dr. Thomson and his coworkers. The techniques they used
were initially developed using mice. Dr. Thomson first made stem cells
from
non-human primates. In the most recent work, they used inner cell mass
cells from blastocyst stage human embryos that were created in the course
of
infertility treatment and donated by couples for research to derive stem
cells. The researchers allowed cell division to continue in culture to the
blastocyst stage and then removed the inner cell mass, which was cultured
to
derive pluripotent stem cells.
Pluripotent stem cells can also be derived from fetal tissue, as was first
done using primordial germ cells from mouse fetal tissue. Dr. Gearhart and
coworkers isolated human primordial germ cells, the cells that will go on
to
become eggs and sperm, from 5-9 week old fetal tissue obtained after
pregnancy termination. When grown in culture, these stem cells appear to
be
pluripotent.
It may also be possible to make human pluripotent stem cells by using
somatic cell nuclear transfer the technology that received so much
attention with the announcement of the birth of the sheep, Dolly. Although
there has been no scientific publication of this to date, presumably any
cell from the human body (except the egg or sperm cell) could be fused with
an enucleated egg cell and stimulated to return to highly immature,
pluripotent and possibly totipotent state.
The Role of the Federal Government
Federal funds were not used in either of the experiments that you will hear
about today. First, let me first address Dr. Thomson's work in which cells
were derived from embryos created by in vitro fertilization but not used
for
infertility treatment. This work falls clearly within the Congressional ban
on human embryo research. NIH could not, and did not, support Dr.
Thomson's
recent work developing this cell line.
The same restrictions do not apply to Dr. Gearhart's work, although it may
be governed by other laws and regulations. Dr. Gearhart derived his
pluripotent stem cells from fetal tissue from terminated pregnancies. The
Public Health Service Act authorizes Federal funding of human fetal tissue
research and provides safeguards for its conduct. The department may
conduct or support research on the transplantation of human fetal tissue
for
therapeutic purposes if a number of statutory requirements are met. Thus,
if Dr. Gearhart's research falls within these boundaries, NIH could have
supported his recent work deriving pluripotent stem cells from fetal
tissue,
as long as he followed these Federal statutes and regulations. For the
record, NIH did not, however, support any of this research.
Ethical Issues
I have just described the science and the medical promise of research on
the pluripotent stem cell. But the realization of this promise is also
dependent on a full and open examination of the social and ethical
implications of this work. The fact that these stem cells were produced
from embryos and fetal tissue raises a number of ethical concerns
including,
for example, the need to ensure that stem cell research not encourage the
creation of embryos or the termination of pregnancies for research
purposes.
In strict accordance with the President's 1994 directive, no NIH funds
will
be used for the creation of human embryos for research purposes. We also
will continue to abide by relevant statutes.
The ethical and social issues associated with stem cell research are
complex and controversial and require thoughtful discourse in public fora
to
reach resolution. To this end, the President has asked the National
Bioethics Advisory Commission to undertake a thorough review of the issues
associated with human stem cell research, balancing all ethical and medical
considerations.
Summary
The development of cell lines that may produce almost every tissue of the
human body is an unprecedented scientific breakthrough. It is not too
unrealistic to say that this research has the potential to revolutionize
the
practice of medicine and improve the quality and length of life.
Mr. Chairman, I am grateful to you for providing a forum to present
information about this promising arena of science and medicine. I would be
pleased to answer any questions you might have.
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: "Meslin, Eric (OD)" <[email protected]> ("Meslin, Eric (OD)" <[email protected]> [
UNKNOWN ])
CREATION DATE/TIME: 9-DEC-1998 10:20:28.00
SUBJECT: Human Genetic Advisory Commission (UK) Report on cloning (includi ng stem cells)
TO: NBAC Members E-list <[email protected]> (NBAC Members E-list <nbac-
[email protected]> [ UNKNOWN]
READ:UNKNOWN
TEXT:
Everyone has no doubt seen the report of the Japanese cow cloning story
today.
In addition, today's Washington Post contains a story about the UK Human
Genetics Advisory Commission's latest report "Cloning Issues in
Reproductive
Medicine and Science (December 1998)" which discusses their views on human
stem
cell research. The report is available on the HGAC website:
www.dti.gov.uk/hgac. I have also ordered hard copies for all
Commissioners. We
may invite Sir Colin Campbell (HGAC Chair) to our January meeting.
We'll keep you posted.
Eric
Eric M. Meslin, Ph.D
Executive Director
National Bioethics Advisory Commission
6100 Executive Blvd. Suite 5B01
Rockville, Maryland 20892-7508
Tel: (301) 402-4242
Fax: (301) 480-6900
Email: [email protected]
http://www.bioethics.gov
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: "Dr. Lawrence H. Miike" <[email protected]> ("Dr. Lawrence H. Miike"
<[email protected]> [ UNKNOWN
CREATION DATE/TIME:11-DEC-1998 16:41:30.00
SUBJECT: capacity report
TO: NBAC Members E-list <[email protected]> ( NBAC Members E-list <nbac-
[email protected]> [ UNKNOWN 1)
READ:UNKNOWN
TEXT:
I'm okay, and won't be submitting an individual statement. some minor
edits will be sent to eric. look forward to finishing the tissue sample
report, and forging ahead with the stem cell report.
larry
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: "Van Eyck, Laila" <[email protected]> ("Van Eyck, Laila" <[email protected]>
UNKNOWN ])
CREATION DATE/TIME:18-DEC-1998 13:56:29.00
SUBJECT: CGA Conference Call Summary: Dec. 10, 1998
TO: [email protected] ([email protected] [ UNKNOWN
READ:UNKNOWN
TEXT:
>CGA Conference Call Summary
>December 10, 1998
>CGA EVENTS:
>The CGA Executive Committee will meet in Tucson, AZ on Jan. 8 and
9,1999 with >dinner hosted by Margie McGonagill, University of Arizona.
The meeting of the Committee will take place on Saturday morning.
Members will be invited to attend some of the Working Group meetings of
the AAU Council on Federal Relations. Katrina >Briscoe has sent
detailed information to Executive Committee members.
>
>The CGA Winter Meeting is tentatively planned for March 3-5, 1999 in
>Washington D.C. Howard Gobstein, Michigan State University will serve
>as chair of the planning committee. The CARET reception on the Hill is
>scheduled for March 2. Possible session topics: budget presentations
by
>agencies; Nethercutt study on NIH; Teacher education; Graduate
>education; and EPSCOR.
>
>The CGA Summer Meeting is scheduled for August 8-10, 1999 in Monterey,
>California. John Hamilton will serve as chair >of the planning
committee.
>
>In 1999, Bob Samors chair of CGA subcommittee >on Research Issues will
begin holding monthly conference calls on >research issues.
V
V
>CURRENT ISSUES:
NIH Study in the HOUSE: Bev Lingle reported that Speaker Livingston is
not supporting a separate study of the NIH by Congressman Nethercutt.
It is not endorsed by Congressman Bliley, chair of the Commerce
Committee, either. The reason given was that it was outside the
traditional committee structure. The NIH study was designed to
replicate the Ehlers study for biomedical research. Nethercutt may
continue to conduct a review under the aegis of the Science Committee.
HEA Regulations: The proposed regs on Campus Crime are out now. Others
are coming out in bits and snatches. Regional hearings are scheduled
for information purposes. NASULGC will keep CGA members up to date on
the latest developments.
>Circular A-110 - April Burke prepared a report in her capacity as Chair
of the Regulatory Affairs Committee about proposed changes in management
circular A-110. Language was included in the omnibus spending bill
>directing OMB to revise Circular A-110 to require federal agencies to
>ensure that all data produced under grants are made available pursuant
>to Freedom of Information Act. AAU and COGR have sent a letter to OMB
>expressing concerns with this provision. Paul Sweet requested that
>NASULGC send a similar letter.
>
>HUD Community Outreach Partnership Centers Program - John Hamilton
reported that HUD is requesting a >doubling of their grant budget from
$7.5 to 15 million. It is seeking >the support of universities. This
program may benefit universities that >work with urban communities. This
will be raised in the context of the reauthorization of HUD.
>
>Digital Millenium Copyright Act - Cindy Bank reported that universities
in their role as on-line >service providers seeking certain exemptions
or limitations in Copyright >law must register with the copyright office
to designate agents for >notification of claims of infringement. Forms
and background information >are located at
http://www.leweb.loc.gov/copyright
>
>Stem Cell Research - Rhonda Norsetter reported that Senator Specter
recently held a hearing on the >recent breakthroughs and ethical
questions surrounding Stem Cell
>Research. In his testimony at the hearing, NIH Director Varmus
>recommended that NIH be involved in the study. The House Science
>Committee may also look at the use of human embryos in research.
>
>Immigration - If universities are experiencing any problems or concerns
>with the implementation of the Immigration Provision in the 1998
Omnibus >Bill, please contact Sang Han at AAU. He is especially
interested in >items related to the honorarium issue.
>
>Sallie Mae and Direct Lending - Reportedly, Sallie Mae is contacting
>some direct lending institutions and trying to provide them with
>incentives to leave the direct lending program.
>
>Agriculture Research Funding - Stu Hadley reported that full funding
for the authorized Ag research program remains a top priority, and they
will be seeking up to $600 million. He suggested CGA members should
impress this priority on their Appropriations members.
>RECENT CGA CHANGES AND ADDITIONS:
>Craig Piercy has recently joined Wayne State University and will be the
>federal relations representative in their Washington office. The
University of Maine has recently opened an office in Washington D.C.
>Heather Almquist-Jacobson is the federal relations representative.
Both offices are at 499 South Capitol Street, SW, Suite 500B,
Washington, DC 20003.
Also, Louisiana State University also has an office in the Washington
area. Paul Gravel is the Executive Director. His offices are at 2300
Clarendon Blvd, #300, Arlington, VA 22201. His phone is 703-276-7101.
>
>
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: "Meslin, Eric (OD)" <[email protected]> ("Meslin, Eric (OD)" <[email protected]> [
UNKNOWN )
CREATION DATE/TIME:21-DEC-1998 17:51:21.00
SUBJECT: Capacity update...and dates for 1999
TO: NBAC Members E-list <[email protected]> (NBAC Members E-list <nbac-
[email protected]> [ UNKNOWN )
READ:UNKNOWN
TEXT:
Commissioners:
We sent the capacity report to the editor for final copy editing. Many
thanks to
all of you who sent in comments, found typos, suggested edits. I should
note
that both Jonathan Moreno and Jack Schwartz provided a very helpful
read-through.
I need to point out 3 minor changes in the recommendations that were made.
I
assume you agree with these:
1. Recommendation 1: The word "irregularly" was changed to "occasionally".
2. In Recommendation 2: the title of the panel should be:
Special Standing Panel on research involving persons with mental disorders
that
may affect decisionmaking capacity.
3. In Recommendation 2 (A), we had intended to repeat the phrase omitted
the
phrase "that cannot otherwise be approved under the recommendations
described in
this report" just as it appears in 2(B). Therefore, 2(A) should read:
reviewing individual protocols, that cannot otherwise be approved under the
recommendations described in this report, that have been forwarded by IRBs
to
the SRP for its consideration.
We will try to have the full report available on the web within the next
two
weeks, and then hard copy will be available a few weeks alter (depending
on the
printing schedule).
1999 Schedule
Following discussions with Harold, we have decided to schedule further
meetings
for 1999 in order to complete the Stem Cell Project.
Some months ago, you received an email from Henrietta which listed the
following
1999 dates:
Jan 19-20; (DC)
March 2-3 (DC)
April 17-18 (listed as provisional)
May 11-12 (Madison)
June 29-30 (listed as provisional)
July 13-14 (Cambridge)
Sept 16-17 (DC)
We've decided to try to hold additional meetings in February, April, and
June
as follows. Please let me know at your earliest convenience whether you can
attend these meetings.
February 2-3 (in Princeton, NJ); 1 1/2 days (First day would start at
1:00pm,
second day would be a full day).
April 15-16, or April 18-19 (in Charlottesville, VA) as you know, a
conference
has been scheduled on April 16-18 at UVA on the Belmont Report. This is
not a
commission meeting. However, since all commissioners will be invited to
attend
the conference, and many will no doubt be coming--we can try to arrange
for a
commission meeting immediately before or after this conference. If the
commission meeting occurred on April 15-16, it would be full day 15, half
day
16. If it occurred on April 18-19, it would be half day (afternoon), and
full
day 19.
June 28-29 (DC)
We intend to finalize the 1999 dates as soon as possible, and to respect
the
wishes of the west-coasters who would prefer to have at least one of the
DC-area
meetings to be near Dulles airport. Thanks very much for your patience.
Best wishes for the holidays
Eric
Eric M. Meslin, Ph.D
Executive Director
National Bioethics Advisory Commission
6100 Executive Blvd. Suite 5B01
Rockville, Maryland 20892-7508
Tel: (301) 402-4242
Fax: (301) 480-6900
Email: [email protected]
http://www.bioethics.gov
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: "Dr. Lawrence H. Miike" <[email protected]> ("Dr. Lawrence H. Miike"
<[email protected]> [ UNKNOWN
CREATION DATE/TIME:22-DEC-1998 15:35:19.00
SUBJECT: Re: Capacity update...and dates for 1999
TO: NBAC Members E-list <[email protected]> (NBAC Members E-list <nbac-
[email protected]> [ UNKNOWN])
READ:UNKNOWN
TEXT:
I should be able to make the scheduled and proposed meetings.
larry miike
Meslin, Eric (OD) wrote:
>
> Commissioners:
>
> We sent the capacity report to the editor for final copy editing. Many
thanks to
> all of you who sent in comments, found typos, suggested edits. I should
note
> that both Jonathan Moreno and Jack Schwartz provided a very helpful
> read-through.
>
> I need to point out 3 minor changes in the recommendations that were
made. I
> assume you agree with these:
>
>
1. Recommendation 1: The word "irregularly" was changed to
"occasionally".
>
> 2. In Recommendation 2: the title of the panel should be:
> Special Standing Panel on research involving persons with mental
disorders that
> may affect decisionmaking capacity.
>
> 3. In Recommendation 2 (A), we had intended to repeat the phrase omitted
the
> phrase "that cannot otherwise be approved under the recommendations
described in
> this report" just as it appears in 2(B). Therefore, 2(A) should read:
V
> reviewing individual protocols, that cannot otherwise be approved under
the
> recommendations described in this report, that have been forwarded by
IRBs to
> the SRP for its consideration.
V
> We will try to have the full report available on the web within the next
two
> weeks, and then hard copy will be available a few weeks alter (depending
on the
> printing schedule).
>
> 1999 Schedule
>
> Following discussions with Harold, we have decided to schedule further
meetings
> for 1999 in order to complete the Stem Cell Project.
> Some months ago, you received an email from Henrietta which listed the
following
> 1999 dates:
>
> Jan 19-20; (DC)
> March 2-3 (DC)
> April 17-18 (listed as provisional)
> May 11-12 (Madison)
> June 29-30 (listed as provisional)
> July 13-14 (Cambridge)
> Sept 16-17 (DC)
>
> We've decided to try to hold additional meetings in February, April,
and June
> as follows. Please let me know at your earliest convenience whether you
can
> attend these meetings.
>
> February 2-3 (in Princeton, NJ); I 1/2 days (First day would start at
1:00pm,
> second day would be a full day).
>
> April 15-16, or April 18-19 (in Charlottesville, VA)--as you know, a
conference
> has been scheduled on April 16-18 at UVA on the Belmont Report. This is
not a
> commission meeting. However, since all commissioners will be invited to
attend
> the conference, and many will no doubt be coming--we can try to arrange
for a
> commission meeting immediately before or after this conference. If the
> commission meeting occurred on April 15-16, it would be full day 15,
half day
> 16. If it occurred on April 18-19, it would be half day (afternoon), and
full
> day 19.
>
> June 28-29 (DC)
>
> We intend to finalize the 1999 dates as soon as possible, and to respect
the
> wishes of the west-coasters who would prefer to have at least one of the
DC-area
> meetings to be near Dulles airport. Thanks very much for your patience.
>
> Best wishes for the holidays
>
> Eric
>
> Eric M. Meslin, Ph.D
> Executive Director
> National Bioethics Advisory Commission
> 6100 Executive Blvd. Suite 5B01
> Rockville, Maryland 20892-7508
> Tel: (301) 402-4242
> Fax: (301) 480-6900
> Email: [email protected]
> http://www.bioethics.gov
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: [email protected] ( [email protected] [ UNKNOWN ])
CREATION DATE/TIME:12-JAN-1999 11:42:29.00
SUBJECT: Adhoc: Workshop on NIH Grants Stats
TO: [email protected] ( [email protected] [ UNKNOWN 1)
READ:UNKNOWN
TO: [email protected] ( [email protected] [ UNKNOWN 1)
READ:UNKNOWN
TEXT:
Yes, I will attend.
Thanks for the follow-up, I wouldn't want to be left out.
I RSVPed via fax to Micketa Brooks mid last week. It seems there have
been breaks in communication over the last two weeks. Two weeks ago
my colleagues, Suzanne Tomlinson and Nancy Bradish Myers, RSVPed (via
fax) to the AAMC Stem Cell briefing held last week and the faxes never
got through.
Please let us know what we can do to prevent this from happening in
the future.
Call with any questions. Thanks.
C. Brett Karcher
Government Relations Assistant
Biotechnology Industry Organization
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: Alexander Capron <[email protected]> ( Alexander Capron <[email protected]> [ UNKNOWN ]
)
CREATION DATE/TIME:12-JAN-1999 19:22:01.00
SUBJECT: HESC Topic
TO: NBAC Members E-list <[email protected]> ( NBAC Members E-list <nbac-
[email protected]> [ UNKNOWN )
READ:UNKNOWN
TEXT:
Harold's memo does a nice job of framing the options regarding scope of
our project on human embryonic stem cells. He may well be correct that we
should raise our sights to encompass #3 (which takes in general "research
use of human embryonic and/or fetal material"), but I will wait for the
debate on this point at the meeting, as I would hate to see us expend
effort on what may be a sure "nullity" before we even begin. Several
points from history bear examining, as it is the wise man who learns from
experience. and the wiser man who learns from the experience of others.
In that regard, I'll look forward to hearing from the members of the NIH
Embryo Research Panel before resolving that issue in my own mind.
Moreover, since Harold also includes "fetal material" under #3, I think it
would be useful for staff to send
along the recommendations of the earlier (Reagan/Bush era) panel on fetal
tissue research and a description (from the media?) of the eventual fate
of those recommendations. (I believe Jim Childress was a member of that
committee, though my memory may be playing tricks on that question.) My
general impression is that both committees, which carved out categories of
permissible research, saw their conclusions disregarded, as was also true
for the major report of the short-lived Ethics Advisory Board which it
recommended that the Secretary of then-DHEW permit federal funding of
certain types of in vitro research creating (and then disposing of)
fertilized human eggs; in May we will "celebrate" the 20th anniversary of
the delivery of that report, which has been gathering dust on the desk of
about 7 or 8 subsequent Secretaries of HHS.
I also want to make sure that somewhere in options I or 2 is consideration
of the issue of embryonic stem cells being capable of being turned into
embryos. This is probably at least a three-part question: what is the
probability of this happening; if it occurred, is that good or bad; and if
bad, do technical means of preventing it exist that wouldn't destroy the
utility of the stem cell as a research tool?
See you soon,
Alex
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: "r. alta charo" <[email protected]> ( "r. alta charo" <[email protected]> [ UNKNOWN
])
CREATION DATE/TIME:12-JAN-1999 20:11:07.00
SUBJECT: alex's query
TO: NBAC Members E-list <[email protected]> (NBAC Members E-list <nbac-
[email protected]> [ UNKNOWN )
READ:UNKNOWN
TEXT:
alex wrote:
"I also want to make sure that somewhere in options 1 or 2 is consideration
of the issue of embryonic stem cells being capable of being turned into
embryos. This is probably at least a three-part question: what is the
probability of this happening; if it occurred, is that good or bad; and if
bad, do technical means of preventing it exist that wouldn't destroy the
utility of the stem cell as a research tool? "
i'd like to urge people to take advantage of jamie thomson's appearance as
an opportunity to explore this. as i understand it from conversations with
jamie here in wisconsin, stem cells by themselves cannot develop into
embryos, only into unorganized masses of cells. the only way to turn a
stem cell into an embryo is to do what one would do with any ordinary cell
of the body -- use cloning techniques, e.g. nuclear transfer or cell fusion
or cytoplasmic injection. but certainly we should confirm that this
understanding is correct.
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: National Marfan Foundation <[email protected]> (National Marfan Foundation <[email protected]> [
UNKNOWN 1)
CREATION DATE/TIME:13-JAN-1999 12:23:26.00
SUBJECT: Adhoc: Workshop on NIH Grants Stats
TO: [email protected] ( [email protected] [ UNKNOWN 1)
READ:UNKNOWN
TEXT:
>From: [email protected]
>Date: Tue, 12 Jan 99 09:47:01 -0500
>To: <[email protected]>, <[email protected]>
>Subject: Adhoc: Workshop on NIH Grants Stats
>Content-Description: "cc:Mail Note Part"
>Sender: [email protected]
>Reply-To: [email protected]
>
V
>
Yes, I will attend.
V
>
Thanks for the follow-up, I wouldn't want to be left out.
>
I RSVPed via fax to Micketa Brooks mid last week. It seems there
have
been breaks in communication over the last two weeks. Two weeks ago
my colleagues, Suzanne Tomlinson and Nancy Bradish Myers, RSVPed (via
fax) to the AAMC Stem Cell briefing held last week and the faxes
> > > > > > > > > > > > never >
got through.
Please let us know what we can do to prevent this from happening in
the future.
Call with any questions. Thanks.
C. Brett Karcher
Government Relations Assistant
Biotechnology Industry Organization
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: Carol Greider <[email protected]> ( Carol Greider <[email protected]> [ UNKNOWN ])
CREATION DATE/TIME:13-JAN-1999 08:19:59.00
SUBJECT: ES cells/embryos
TO: NBAC Members E-list <[email protected]> ( NBAC Members E-list <nbac-
[email protected]> [ UNKNOWN])
READ:UNKNOWN
TEXT:
Alta Wrote:
>
>i'd like to urge people to take advantage of jamie thomson's appearance as
>an opportunity to explore this. as i understand it from conversations
with
>jamie here in wisconsin, stem cells by themselves cannot develop into
>embryos, only into unorganized masses of cells. the only way to turn a
>stem cell into an embryo is to do what one would do with any ordinary cell
>of the body -- use cloning techniques, e.g. nuclear transfer or cell
fusion
>or cytoplasmic injection. but certainly we should confirm that this
>understanding is correct.
My understanding is similar to Alta's. Currently in animals, to use ES
cells to create an embryo they are injected into a blastocyst (early
embryo). This creates a chimeric animal with contributions from both the
donor (injected ES cells) and host cell types. Thus there is additional
'embryo research' involved to use ES cells to create an embryo.
Carol
Carol W. Greider, Ph.D.
Associate Professor
Department of Molecular Biology and Genetics
Johns Hopkins University School of Medicine
617 Hunterian Building
725 N. Wolfe Street
Baltimore, MD 21205
e-mail: [email protected]
phone: (410) 614-6506
fax: (410) 614-2987
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: "Bernard Lo, M.D." <[email protected]> ( "Bernard Lo, M.D." <[email protected]> [ UNKNOWN
1)
CREATION DATE/TIME:13-JAN-1999 16:48:53.00
SUBJECT: Additional thoughts on stem-cells and embryos
TO: NBAC Members E-list <[email protected]> ( NBAC Members E-list <nbac-
[email protected]> [ UNKNOWN )
READ:UNKNOWN
TEXT:
I agree that it would be very useful to get on the record and in the report
the types of manipulations required in order to covert stem cells into
embryos. We might also want to think about the question of provenance:
does it matter that stem cells are derived from the manipulation of and
non-implantation of human embryos. This will be the source of the most
heated opposition to stem-cell research. Many people accept a gradation:
it is more problematic to intentionally create embryos for the purpose of
research than to use embryos that would not be implanted in any case. Is
there an argument that using already existing stem cell lines is less
problematic than creating a stem cell line de novo? This is what might be
a new twist on the human embryo research debate. Additionally, what
important scientific work could not be addressed by using existing stem
cell lines or creating new lines from embryos that were to be discarded.
In other words, the policy options are to allow creation of "research
embryos," to allow research on embyos that were to be discarded, and to
allow research on stem cells that are no longer titpotent and hence do not
have the same moral status as embyos. It would be useful to clarify the
ethical differences and the scientific implications of using one source of
material rather than another.
Bernard Lo, M.D.
Professor of Medicine
Room C-126
521 Parnassus Ave.
University of California San Francisco
San Francisco, CA 94143-0903
Ph:
415-476-5370
Fax: 415-476-5020
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: alta charo <[email protected]> ( alta charo <[email protected]> [ UNKNOWN
CREATION DATE/TIME:13-JAN-1999 16:51:54.00
SUBJECT: harold's fax on stem cell project
TO: NBAC Members E-list <[email protected]> NBAC Members E-list <nbac-
[email protected]> UNKNOWN])
READ:UNKNOWN
TEXT:
in anticipation of next week's meeting, i'd like to throw out some
reactions to harold's memo, which nicely lays out possible project
parameters going from the most narrow to the most broad.
harold's first option, to focus only on use of existing stem cells, raises
two major areas of analysis:
(a) is work on them morally distinguishable from work on embryos?
on
this point, the recent emails, emphasizing the biological distinction
between embryos and stem cells in terms of their intrinsic potential to
develop into babies, seems on point. of course, as the argument from
potential has many logical inconsistencies within it, one might conclude
that this distinction between stem cells and embryos is unimportant, but
then the distinction between embryos and all other somatic cells becomes
equally unimportant.
(2) assuming for the sake of argument that work on embryos is morally
suspect, is work on the stem cells tainted by their derivation from
privately financed embryo research? here there is good literature on the
debates surrounding use of data from the nazi experiments in the death
camps from which we can develop our own ideas.
thus, there certainly is plenty to talk about on just this topic.
nonetheless, it is my understanding that the existing stem cells in jamie's
lab cannot supply all the researchers indefinitely with their need for
research material, despite the fact that he can replicate the stem cells.
this is due to the inherent problem of spontaneous mutations developing
when the stem cells reproduce, rendering the supply unusable at some point
in time. thus, if we wish to really deal with the question of research
just on stem cells, we will have to tackle the question of how one obtains
adequate supplies of stem cells on which to work. this, it would seem,
means tackling either embryo research or fetal tissue research or both --
i.e., harold's categories (2) and (3). and since there are some questions
about the usefulness of stem cells derived from fetal germ cells (jamie
explained this to me but i fear i have already forgotten the explanation),
it would appear that we would have to tackle embryo research in order to
tackle the question of stem cell supplies.
as for (4), i.e. the making of new embryos for research and stem cell
collection, i'd suggest that we get a very firm understanding of exactly
how far down the road we can go with stem cell research before we need to
get into this. for example, i understand that for stem cells to be used for
cell-based transplant therapies, we may well need to have them
immunologically matched to the recipient, thus necessitating the use of
cloning to generate a de-differentiated somatic cell (otherwise seen as an
embryo by many people) that can be developed to the stage where it can
become a source of stem cells for auto-transplantation. at the senate
hearings, some of the scientists thought this kind of experimental therapy
was no more than 5-7 years away for parkinson's disease. if that's the
case, one would hope there would be federal policy on this technique
sometime in the next three years, so that researchers have time to figure
out if they can rely on public funds, will need to seek private funds, or
will be faced with state or federal prohibitions that forestall the work
altogether.
r. alta charo, j.d.
professor of law and medical ethics
university of wisconsin law school
975 bascom mall
madison, wi 53706
tel: 608-262-5015
fax: 608-262-5485
[email protected]
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: Alexander Capron <[email protected]> ( Alexander Capron <[email protected]> [ UNKNOWN
)
CREATION DATE/TIME:13-JAN-1999 16:21:06.00
SUBJECT: Re: ES cells/embryos
TO: NBAC Members E-list <[email protected]> (NBAC Members E-list <nbac-
[email protected]> [ UNKNOWN
READ:UNKNOWN
TEXT:
On Wed, 13 Jan 1999, Carol Greider wrote:
> Alta Wrote:
> >
> >i'd like to urge people to take advantage of jamie thomson's appearance
as
> >an opportunity to explore this. as i understand it from conversations
with
> >jamie here in wisconsin, stem cells by themselves cannot develop into
> >embryos, only into unorganized masses of cells. the only way to turn a
> >stem cell into an embryo is to do what one would do with any ordinary
cell
> >of the body use cloning techniques, e.g. nuclear transfer or cell
fusion
> >or cytoplasmic injection. but certainly we should confirm that this
> >understanding is correct.
>
V
> My understanding is similar to Alta's. Currently in animals, to use ES
> cells to create an embryo they are injected into a blastocyst (early
> embryo). This creates a chimeric animal with contributions from both the
> donor (injected ES cells) and host cell types. Thus there is additional
> 'embryo research' involved to use ES cells to create an embryo.
Thanks to you both for the clarification. My question arose both from
some of the responses that Thompson et al made to the press at the time of
their recent announcements on stem cells and from the comments made when
Wilmut first announced Dolly and some scientists speculated that the sheep
had been created NOT from a normal somatic cell but either from a
fertilized egg or from a stem cell present in the mammary tissue (where,
it seemed to be suggested, one would have a greater likelihood of finding
a stem cell than in the epithelium). The upshot of those comments seemed
to be that performing "cloning" with a nucleus from an embryo or stem cell
was less of a "big deal" than with a normal somatic cell---so I was just
wondering if that perspective would lead to the conclusion that an
embryonic stem cell is really very close to being an embryo (that is
easily triggered into becoming an embryo). I understand the answer to be
"No; it would still have to be subject to nuclear transfer, etc. and hence
is basically not that different than any other cell that can provide a
nucleus for transfer." If this is right, then we should get it discussed
on the record and plan to have a clarification on this point in the
report, as a way of making clear what issues the development of human
embryonic stem cells DOESN'T implicate.
Alex
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: "Bernard Lo, M.D." <[email protected]> ("Bernard Lo, M.D." <[email protected]> [ UNKNOWN
])
CREATION DATE/TIME:14-JAN-1999 13:02:59.00
SUBJECT: First reactions to briefing book
TO: NBAC Members E-list <[email protected]> ( NBAC Members E-list <nbac-
[email protected]> UNKNOWN
READ:UNKNOWN
TEXT:
After reading the materials in briefing book, I have several
observations and suggestions to share.
1. Historically, the debate over embryo research has been dominated by
issues of the moral status of the embryo and whether certain answers
preclude embryo research, or at least the federal funding of it. I wonder
if we can think about how me might broaden the terms of the debate, because
if we go down the same tracks, I fear we will reach the same impasse.
Perhaps two considerations are pertinent today, which were not salient at
the time of the NIH panel deliberations in 1994. First, the prospective
therapeutic benefits of stem cell research seem much less speculative today
than in 1994. As with the fetal tissue debate, the prospect of important
therapeutic benefit may substantially alter the policy discussion. Second,
the discussion surrounding non-heart beating cadaver donation for organ
transplantation suggests that the public is willing to consider the idea
that persons who will not have a long life trajectory, considerations of
benefit to others may assume greater moral weight. In some discussions,
embryos that are considered to be full persons are given greater respect
than live-born persons who are imminently dying on life support and whose
relative wish to donate organs. This discrepancy may deserve more
attention and analysis.
2. When faced with apparently unprecedented situations, we all tend to
draw analogies to other situations. Recognizing the limitations of all
such analogies, we might consider the potential transplant donor (for
non-heart beating cadaveric donation) as another analogy.
3. When we consider the policy options for providing oversight of
research, I would like to learn more about the RAC model for gene therapy.
How did it work, from the perspectives of scientists, ethicists, etc. It
seems that the scientists thought it was too restrictive/intrusive, whereas
some ethicists believed that protocols were approved that didn't give a
balanced view of the nature of the prospective benefits. While I
personally find a RAC model attractive, it may be one of those good ideas
that didn't work out well in practice, at least in its previous
configuration.
Bernard Lo, M.D.
Professor of Medicine
Room C-126
521 Parnassus Ave.
University of California San Francisco
San Francisco, CA 94143-0903
Ph: 415-476-5370
Fax: 415-476-5020
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: "r. alta charo" <[email protected]> ( "r. alta charo" <[email protected]> [ UNKNOWN
1)
CREATION DATE/TIME:14-JAN-1999 20:42:14.00
SUBJECT: bernie's email
TO: NBAC Members E-list <[email protected]> ( NBAC Members E-list <nbac-
[email protected]> [ UNKNOWN )
READ:UNKNOWN
TEXT:
i agree with bernie that another circuit around traditional arguments
focusing on the status of the embryo based on its intrinsic characteristics
would be at high risk of simply re-stating the case for an impossible
divide in public thinking. the "snark" piece of mine that was included in
the briefing book lays out (at somewhat tedious length) my own
post-embryo-panel efforts to argue for shifting the debate to different
grounds, to wit, an approach i called "political ethics" which sets forth
moral arguments about how to balance public interests by supporters and
opponents of embryo research, focusing on the distributive justice
questions of how the benefits and burdens of the research would be handled.
i'd be very interested in others' reactions to the proposals therein, as
the piece occasioned little comment after it was published.
At 10:02 1/14/99 -0800, you wrote:
>
>
After reading the materials in briefing book, I have several
>observations and suggestions to share.
>1. Historically, the debate over embryo research has been dominated by
>issues of the moral status of the embryo and whether certain answers
>preclude embryo research, or at least the federal funding of it. I wonder
>if we can think about how me might broaden the terms of the debate,
because
>if we go down the same tracks, I fear we will reach the same impasse.
>Perhaps two considerations are pertinent today, which were not salient at
>the time of the NIH panel deliberations in 1994. First, the prospective
>therapeutic benefits of stem cell research seem much less speculative
today
>than in 1994. As with the fetal tissue debate, the prospect of important
>therapeutic benefit may substantially alter the policy discussion.
Second,
>the discussion surrounding non-heart beating cadaver donation for organ
>transplantation suggests that the public is willing to consider the idea
>that persons who will not have a long life trajectory, considerations of
>benefit to others may assume greater moral weight. In some discussions,
>embryos that are considered to be full persons are given greater respect
>than live-born persons who are imminently dying on life support and whose
>relative wish to donate organs. This discrepancy may deserve more
>attention and analysis.
>2. When faced with apparently unprecedented situations, we all tend to
>draw analogies to other situations. Recognizing the limitations of all
>such analogies, we might consider the potential transplant donor (for
>non-heart beating cadaveric donation) as another analogy.
>3. When we consider the policy options for providing oversight of
>research, I would like to learn more about the RAC model for gene therapy.
>How did it work, from the perspectives of scientists, ethicists, etc. It
>seems that the scientists thought it was too restrictive/intrusive,
whereas
>some ethicists believed that protocols were approved that didn't give a
>balanced view of the nature of the prospective benefits. While I
>personally find a RAC model attractive, it may be one of those good ideas
>that didn't work out well in practice, at least in its previous
>configuration.
>
>
>Bernard Lo, M.D.
>Professor of Medicine
>Room C-126
>521 Parnassus Ave.
>University of California San Francisco
>San Francisco, CA 94143-0903
>Ph: 415-476-5370
>Fax: 415-476-5020
>
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: Carol Greider <[email protected]> ( Carol Greider <[email protected]> [ UNKNOWN 1)
CREATION DATE/TIME:14-JAN-1999 10:04:51.00
SUBJECT: Re: ES cells/embryos
TO: NBAC Members E-list <[email protected]> ( NBAC Members E-list <nbac-
[email protected]> [ UNKNOWN])
READ:UNKNOWN
TEXT:
Alex Wrote:
> The upshot of those comments seemed
>to be that performing "cloning" with a nucleus from an embryo or stem cell
>was less of a "big deal" than with a normal somatic cell---so I was just
>wondering if that perspective would lead to the conclusion that an
>embryonic stem cell is really very close to being an embryo (that is
>easily triggered into becoming an embryo). 1 understand the answer to be
>"No; it would still have to be subject to nuclear transfer, etc. and hence
>is basically not that different than any other cell that can provide a
>nucleus for transfer." If this is right, then we should get it discussed
>on the record and plan to have a clarification on this point in the
>report, as a way of making clear what issues the development of human
>embryonic stem cells DOESN'T implicate.
There are two issues here:
what is a "BIG DEAL" from the scientific stand point of what is going on
during "reprogramming of the nucleus" and what is a "BIG DEAL" from the
ethical concern standpoint.
We should not confuse these.
>From the scientific standpoint it is less of a 'big deal' to get an early
fetal cells to "de differentiate" than is is to get a fully determined
adult human cell to "de-differentiate". so scientist might say this is less
of a big deal but be talking about something differetn than ethisists.
>From the ethical view point, as you know, some people have a concern about
any research that uses any human enbryo or fetal material. Thus for those
people it matters not a bit what kind of nucleus is tranfered if the
transfer involves a human oocyte and creation of a (possibly?) viable
embryo.
Second from the ethical standpoint regarding cloning, as we all know, if
people are concerned about "babymaking" it is very different in the public
mind to clone from and existing person thatn from an embryo that is not an
existing person.
Finally regarding the discussion that others have raised about "already
existing ES cells". If you read some of the reviews that came in the
breifing book it is apparent that many of the proposed uses of ES cells are
to get around immune rejection of tissue transplants. To do this NEW ES
cells must be created using nuclear transfer from the person who will
receive the transplant. thus limiting the discussion to "already existing
ES cells" misses much of the point of proposed the medical benifits.
Carol
Carol W. Greider, Ph.D.
Associate Professor
Department of Molecular Biology and Genetics
Johns Hopkins University School of Medicine
617 Hunterian Building
725 N. Wolfe Street
Baltimore, MD 21205
e-mail: [email protected]
phone: (410) 614-6506
fax: (410) 614-2987
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: [email protected] (Gregory Aharonian) ( [email protected] (Gregory Aharonian) [
UNKNOWN 1)
CREATION DATE/TIME:15-JAN-1999 09:56:18.00
SUBJECT: PATNEWS: Boycott against RiceTec; NIH testifies about techtran/stem cells
TO: [email protected] ( [email protected] [ UNKNOWN 1)
READ:UNKNOWN
TEXT:
!19990115 Boycott against RiceTec; NIH testifies about techtran/stem
cells
-- A boycott is being organized against Rice Tec
-- NIH official testifies about technology transfer and stem cells
-- Country study: India - Local species (turmeric, neem and basmati)
Greg Aharonian
Internet Patent News Service
AUTHOR: Nandita Sharma and Allison Campbell, Basmati Action Group
TITLE: North American Boycott against Rice Tec called
DATE: 29 November 1998
PLACE: Vancouver, Canada
NOTE: Please contact the Basmati Action Group for more information, to
indicate your support to their campaign or to share ideas on explanding
the campaign to other countries.
BASMATI ACTION GROUP (BAG)
c/o 1957 Kitchener St. Vancouver, B.C. Canada V5L 2W6
Tel. (1-604) 255-4910 E-mail: [email protected]
Website: http://www.eciad.bc.ca/~lolin/basmati/
NORTH AMERICAN BOYCOTT AGAINST RICE TEC CORPORATION CALLED
November 29, 1998
The Basmati Action Group (BAG) has launched a North American boycott
against
the products of Rice Tec Corporation of Alvin, Texas, USA. Rice Tec claims
to have invented the basmati rice they sell under the trade name, "Texmati"
(Rice Tec products also include "Jasmati" and "Kasmati" rice). The purpose
of the boycott is to heighten awareness of the issue of life-patents,
organize public condemnation of this process and demonstrate that the
patenting of life will be costly - not profitable - to those that pirate
indigenous knowledge and nature's creative capacities. We ask that you
support the Basmati Action Group in our boycott of all Rice Tec products.
Why support a boycott on Rice Tec?
Basmati rice has been grown in the Punjab region of India and Pakistan for
centuries. Working with nature's own creative capacities, farmers in this
area have, over time, cross bred and cultivated this distinct form of rice
known for its fragrant aroma and unique taste. For the farmers of India
and
Pakistan, basmati rice is a vital subsistence food and source of income.
In 1997, the powerful United States Patent and Trademark Office accepted
Rice Tec's application to patent basmati rice (patent # 5,663,484). By
cross-breeding two basmati rice varieties, this corporation insists that it
has "invented" a "novel" variety of basmati and has patented it as "basmati
867." The Rice Tec patent covers any basmati variety crossed with a
semi-dwarf strain grown anywhere in the western hemisphere. Despite Rice
Tec's claims of 'novelty', "basmati 867" has been derived from Indian and
Pakistani basmati rice lines crossed with semi-dwarf varieties. The basmati
varieties used to "invent" Rice Tec's "basmati 867" are farmers' varieties
bred over centuries in South Asia. What Rice Tec has done with its patent
is to pirate what until now had been communally shared and claimed it as
their own private property.
The crux of the issue is not whether the basmati rice variety bred by Rice
Tec is "novel" and therefore patentable or not because the facts show that
it is not. The real issue is that no one should be able to hold a patent
over a life form. By taking out a patent on "basmati 867" Rice Tec is
participating in what has been described as "biopiracy."
Biopiracy is the theft of indigenous knowledge, the theft of the creative
capacities of nature and the false claim by patent holders - mostly
corporations - that they created the life form they have pirated. Biopiracy
lays the groundwork for the colonization of creation - of life itself - by
scientists and, ultimately, the corporations they work for.
Life-patents further the power of corporations. Imagine a world where
nothing is grown except crops that a corporation has claimed 'invention' of
and can profit by. Imagine if nothing is grown without farmers having to go
to corporations to buy back seeds stolen from them in the first place. Or a
world where nothing can even grow without the permission of corporations
(i.e. the "Terminator Technology" that prevents plants from reproducing
themselves). This is the world that biopirates, and patents like the one on
"basmati 867" are already helping to bring about!
We need to fight against this trend. BAG is part of a world-wide movement
of
people who are protesting the corporate claims of "invention" that patents
on life represent. We are not resigned to living in a world where the
creative capacities of nature, of women and of communities of people are
systematically denied and pirated. BAG calls for an end to patents on life
forms that is currently being sanctioned by the World Trade Organization
and
enshrined in both national and international law.
Victories have been won against corporations that have patented life forms!
The US National Institutes of Health "disclaimed" its notorious US patent
on
the human cell line of a Hagahai Indigenous person from Papau New Guinea
(patent # 5,397,696) after popular outrage was organized. The Indian
government revoked the W.R. Grace Corporation's "species patent" on
transgenic cotton. In other words, this boycott against Rice Tec can work!
Who is the Basmati Action Group (BAG)?
BAG is a grassroots organization that values life in all its diversity. BAG
is opposed to the patenting of any life forms, anywhere, by anyone. This
means supporting actions that value and procect ecological integrity,
indigenous knowledge and lands, women's rights, the autonomy and
self-determinacy of people and community-based action. Food forms the
natural link between community and life. For this reason, recent
developments in world trade and agricultural policy, life-patenting and
genetic engineering strike us as attacks on the essence of those things
we value most.
BAG has been formed to raise awareness about biopiracy, life patents and
on-going acts of colonialism - and to work to end these practices. Along
with many others, we see biopiracy as the "third wave of colonialism" and
an entrenchment of sexist and racist practices. We recognize that women
in the South ("Third World Women') continue to bear the brunt of acts of
colonialism. For over 500 years, the North (the 'First World') has been
enriched by stealing from nature and the people's of the South (the 'Third
World'). This is maintained by present global economic and political
relations. Most of the world's biodiversity is located in the South and
biopiracy is an attempt by corporations to privatize and 'own' what is the
common heritage of people in the South. BAG is also working to show that
biopiracy is a form of class conflict with corporations trying to eliminate
communal property, destroy farmers' control and supplant nature's creative
capacities in order to increase their own private profits.
How can I support the boycott on Rice Tec?
Please circulate this notice within your organization and to your
membership. Talk about biopiracy and the Rice Tec boycott whenever
possible.
Spread the word to your contacts across North America. Support local
actions
against biopiracy. Ask your local stores to stop carrying Rice Tec
products.
Boycotting Rice Tec and its products is one action in the movement to
resist
corporate control over life forms. Raising awareness of biopiracy and
developing ways of producing and distributing food that are ecologically
sound and socially just is something we can all contribute to in different
ways. BAG has also initiated a petition campaign trying to get the Canadian
government to refuse Rice Tec's US patent on basmati rice and enacting
strong legislation that prevents the patenting of life forms in Canada.
This struggle cannot be won without global solidarity - a victory in Canada
is impossible without simultaneous victories against the World Trade
Organization, NAFTA etc. BAG is working in coalition with people's
organizations in both the South and North to revoke Rice Tec's U.S. patent
on basmati rice and to stop biopiracy.
Please let us know if we can use your name as a supporter of our campaign
in
our future work.
Any suggestions towards strengthening our objectives and resistance is
greatly appreciated.
For more information, check out our Web Site.
http://www.eciad.bc.ca/-lolin/basmati/
or call and ask for Nandita Sharma or Allison Campbell at (1-604) 255-4910.
Mailing and e-mail addresses are listed above.
In Struggle,
Nandita Sharma for the
Basmati Action Group
Letter to Stores Carrying Rice Tec Products:
November 29, 1998
NORTH AMERICAN BOYCOTT AGAINST RICE TEC CORPORATION CALLED
The Basmati Action Group (BAG) has launched a North American boycott
against
the products of Rice Tec Corporation of Alvin, Texas, USA. Rice Tec claims
to have invented the basmati rice they sell under the trade name, "Texmati"
(Rice Tec products also include "Jasmati" and "Kasmati" rice). The purpose
of the boycott is to heighten awareness of the issue of life-patents,
organize public condemnation of this process and demonstrate that the
patenting of life will be costly - not profitable - to those that pirate
indigenous knowledge and nature's creative capacities. We ask that you
support the Basmati Action Group in our boycott of all Rice Tec products.
There are three things you can do to support the boycott on Rice Tec.
1) Remove all Rice Tec products from your shelves immediately, and let
us know that you have done so.
2) Stop ordering Rice Tec products. Tell your Rice Tec distributor that
you are not willing to support biopiracy in this or any form.
3) Tell your customers that you are boycotting Rice Tec and why.
To facilitate your cooperation, we are holding an information evening on
TUESDAY, JANUARY 26, 1999 from 7 to 9 p.m. at Room #4 at the Mount
Pleasant
Neighbourhood House (800 E. Broadway - near Fraser St. in Vancouver, B.C.).
This meeting will be designed to give store-operators and staff more
targeted information so that you may better explain the boycott to your
customers. Also at this meeting we will distribute copies of a letter for
your customers, explaining biopiracy and the reasons for the Rice Tec
boycott.
Please notify us as soon as you decide to support the boycott.
Included in this call for support (sent to those in Canada) is the petition
BAG is circulating within Canada. Please photocopy and distribute it.
Remember, it is important to return completed petitions to the return
address printed on the bottom.
Any suggestions towards strengthening our objectives and resistance is
greatly appreciated.
For more information check out our web site.
http://www.eciad.bc.ca/~lolin/basmati/
or call Nandita Sharma or Allison Campbell at (1-604) 255-4910.
Mailing and e-mail addresses are listed above.
In Struggle,
Allison Campbell for the
Basmati Action Group
BASMATI ACTION GROUP (BAG)
c/o 1957 Kitchener St.
Vancouver, B.C. Canada V5L 2W6
Tel. (1-604) 255-4910
E-mail: [email protected]
Web: http://www.eciad.bc.ca/~lolin/basmati/
Earlier this week, NIH OTT Director, Maria Freire was one of the panelists
called for testimony before the Senate Appropriations Subcommittee on
Labor,
Health and Human Services, Education & Related Agencies. As an follow-on
of
earlier hearings on the Hopkins/WARF/Geron stem cell projects, the
committee
members have become increasing interested in how patent rights & licensing
affect basic research product development. For federally-funded technology
this means, of course, patenting & licensing practices of universities and
Federal labs derived from the Bayh-Dole Act & the Federal Technology
Transfer Act.
The NIH testimony on this subject at the hearing (which included a
discussion
of the potential adverse effects of restrictive licensing/MTA practices for
research tools) is appended below.
Regards,
Steve Ferguson
NIH Office of Technology Transfer
Statement of Maria C. Freire, Ph.D
Director - Office of Technology Transfer
National Institutes of Health
before the Senate Appropriations Subcommittee on Labor, Health and
Human Services, Education and Related Agencies
January 12, 1999
Mr. Chairman and members of the subcommittee, I am Maria Freire, Director
of the Office of Technology Transfer at the National Institutes of Health
(NIH). I am pleased to appear before you today to address how intellectual
property considerations affect basic science and the future development of
products for public benefit.
I understand that the subcommittee is particularly interested in how patent
rights and commercialization strategies operate in the context of the
recent
findings on pluripotent stem cells reported by Drs. John Gearhart from
Johns
Hopkins University and James Thomson from the University of Wisconsin. You
have previously heard from a panel of experts, including the Director of
NIH, Dr. Harold Varmus, on the scientific implications of these findings.
Given the complexity of these issues, it is important to understand how the
transfer of federally funded technology from the not-for-profit sector --
be it university or Federal laboratory to the private sector, is
accomplished. To do so, I direct you to the successful process established
by Congress in the 1980's that governs the commercialization of federally
funded biomedical research.
The Bayh-Dole Act, Stevenson-Wydler Technology Innovation Act of 1980, and
amendments, including the Federal Technology Transfer Act of 1986 (FTTA)
Nearly twenty years ago, Congress enacted a series of laws that encourage
government owned and government funded research laboratories to pursue the
commercialization of the results of their research. These laws are the
Bayh-Dole Act of 1980, the Stevenson-Wydler Innovation Act of 1980,
including
one of its amendments, the Federal Technology Transfer Act of 1986 (FTTA).
The Bayh-Dole Act addresses intellectual property rights in federally
funded
grants, contracts and cooperative agreements, while Stevenson-Wydler and
the
FTTA address intellectual property of government laboratories. The goal of
these laws is to promote economic development, enhance U.S. competitiveness
and benefit the public by encouraging the commercialization of technologies
that might otherwise not be developed into products due to the lack of
incentives. Generally, these laws allow government laboratories and the
recipients of government funding to elect to retain title to their
inventions. They also impose certain obligations: promoting utilization,
encouraging commercialization and ensuring public availability of these
technologies.
I am pleased to say that these goals have been achieved and expectations
havebeen surpassed. Indeed, in the biomedical arena, the impact of these
statutes
has been dramatic. Many experts believe that the biotechnology industry
was
spawned from the close interaction between academia and industry. The
Bayh-Dole Act and the FTTA continue to contribute to the global leadership
of the U.S. biomedical enterprise. New products developed under this
system
benefit patients daily and provide hundreds of scientists with the tools
required for further discovery in support of our public health mission.
The NIH intramural program alone has over 150 products on the market,
including diagnostic kits, vaccines, therapeutic drugs and dozens of
antibodies, cell lines and other research tools. Statistics on the
remarkable success of university-based technology transfer activities are
also available and I have submitted a recent survey for the record.
To accomplish the transfer of technology, universities have relied on
authorities granted to them by the Bayh-Dole Act. The Act permits the
grantee
to retain title to intellectual property developed with federal funds and
to
license its rights to for-profit entities. Patents provide the right to
exclude others from making, using, or selling a new invention for the life
of the patent. This is society's reward to the owner for teaching others
how to make and use the invention claimed in the patent. In the biomedical
field, patents are extremely valuable to companies, particularly small
companies. They provide a means of securing investment income by
establishing the company's preeminence in a particular area of technology.
Parties interested in practicing an invention, in which they have no
ownership, may obtain rights to the invention by entering into a licensing
agreement with the patent owner. A license is a contract with binding
commitments on each party, usually involving compensation. A license does
not grant title to the invention. Licenses can be exclusive, when only
one party is permitted to benefit from the use of the technology, or
non-exclusive, when more than one party is allowed to benefit from such
rights.
As this subcommittee well knows, new drugs and vaccines are costly to
develop;
companies will not invest in further research and development without some
promise of future product exclusivity. When Congress gave federal grantees
the ability to patent and exclusively license government-funded inventions,
the private sector turned its attention toward publicly supported research
as a new source of potential products. The value to the public resides in
the generation of new drugs, vaccines, and medical devices. These
activities
have also stimulated economic development and the creation of new jobs in
the United States.
The University of Wisconsin provides us with a good example of how the
Bayh-Dole Act is implemented. Early work by Dr. Thomson on non-human
primates, such as Rhesus monkeys, was federally funded and therefore, the
patent obtained on stem cells arising from this work is governed by this
Act. In accordance with the law, the invention was disclosed to the NIH,
a patent application was filed by the University, through the Wisconsin
Alumni Research Foundation (WARF), and WARF licensed the technology to a
small company (Geron). Because federal funds were used for this non-human
primate work, the government has a non-exclusive, royalty-free right to
use the patented cells by or on behalf of the government. This would allow
the government laboratories and contractors the right to use the patented
cells for further research. In addition, in handling this invention the
University must ensure that the goals of the Bayh-Dole Act -- utilization,
commercialization, and public availability -- are implemented.
When research is funded entirely by the private sector, the government has
no license, and it is strictly a private matter whether, and under what
terms, new intellectual property is made available to others for commercial
or research purposes. This is the case for the Geron sponsored work
conducted by Dr. Gearhart on human pluripotent stem cells derived from
fetuses.
It is usually not the existence of a patent that raises concern for the
biomedical research community. The concern arises when the patent holder
chooses to exercise its rights through licensing in a manner inconsistent
with
the advancement of basic research. For example, many new inventions are
not
final products. The discovery may be a research material or a new method
or
procedure, primarily useful as the means to conduct further research. Such
discoveries are commonly known as research tools. There is little doubt
that
these research tools may be patentable and that they are of economic value
to
the holder of these rights. There is also little doubt that the value to
society is greatest when such research tools are widely available to
scientists.
Mr. Chairman, I cannot emphasize this point strongly enough. Preserving
research uses is extremely important to the advancement of science. A
license that provides complete exclusivity to a technology that is also a
research tool may result in some product development in the short- term,
but it will close off opportunities to advance science and develop other
products in the long-term. The only way to maximize the benefit to the
public is to ensure that both research use and the potential for commercial
development are preserved.
The professionals working in the specialized field of biomedical licensing
strive to promote a balance between commercial interests and the public
interest. In those instances where a research tool can also become a
therapeutic product, licenses can be, and are, carefully crafted by scope,
application and field to allow use by the research community without
destroying a company's commercial incentive to develop the product. Careful
licensing that preserves this balance, however, has not always been the
case. The NIH has been concerned for some time about the potential adverse
effects of restrictive licensing practices on access to research tools.
Dr. Varmus convened a national workgroup to study the issue and make
recommendations to the NIH. The report of the workgroup is on the NIH web
site:
www.nih.gov./news/researchtools/index.htm,
and NIH expects to publish guidelines for NIH supported investigators this
spring, in accordance with the report.
Stem Cell Research
How does this relate to pluripotent stem cells? Pluripotent stem cells
provide the research community a springboard to launch numerous inquiries
into the most fundamental processes of cellular growth and differentiation
that underlie human development. Elucidating these mechanisms provides
the foundation for the next generation of biomedical discovery. Such
discoveries will be directed toward treatment of human developmental
abnormalities, regulation of uncontrolled cellular growth associated with
cancer, a source of differentiated cells and tissues for transplantation
therapy, and a means to identify new drug targets and test potential
therapeutics, among others. Realizing the fullest potential from this new
stem cell technology for the American people deserves and requires
further inquiry.
Stem cells are a research tool today; hopefully, they will also be
developed
into therapeutic products in the future. The issuance of patents on these
new discoveries by the Patent and Trademark Office may not necessarily have
an adverse effect on continuing research, provided that the patent owners
devise a licensing strategy that will allow basic research to continue
unencumbered while preserving commercial value. We understand that both
the Johns Hopkins and Wisconsin licenses to Geron are exclusive at this
time, but may allow for the use of these cells by non-profit researchers
under certain terms and conditions. These terms and conditions would be
set forth in an agreement commonly called a Material Transfer Agreement,
or MTA.
MTAs are vehicles used to transfer proprietary materials between and among
the for-profit and not-for-profit sectors. While most MTAs are simple,
1 to 2-page agreements, MTAs can sometimes pose problems due to the type
of obligations or restrictions imposed by the provider of a material on
the recipient. Such obligations can stifle the broad dissemination of
new discoveries, slow the technology transfer process and limit future
avenues of research and product development. Examples of such obligations
include so-called "reach-through" provisions that may: 1) give the
provider
of a material ownership of new inventions developed by the recipient; 2)
require royalty payments by the recipient to the provider on inventions
discovered by the recipient that are not covered by the provider's patent;
or, 3) require options to exclusive rights to any new intellectual property
arising from recipient's use of the material. The NIH has minimal
authority
with regard to the stem cell patent and patent applications at issue today,
and it would be inappropriate for me to try to comment on specific terms
and conditions that may be imposed by these parties under the MTAs
contemplated.
At NIH, our view is that conditions imposed by patent owners - whether in
a license or an MTA - can be crafted to ensure both research uses and
commercial development. For example, our strategy is to negotiate
non-exclusive licenses whenever possible. This allows more than one
company
to develop products using a particular technology, products that may
ultimately compete with each other in the marketplace. We recognize that
companies need an exclusive market to offset the risk, time, and expense
of developing biomedical diagnostic or therapeutic products. However,
companies do not necessarily need to achieve that position solely by
exclusively licensing a government technology used to develop the product.
Instead, companies are frequently able to add their own proprietary
technologies to the invention licensed from the government to ultimately
achieve some level of uniqueness and exclusivity for the final product.
If non-exclusive licensing does not provide enough incentive for the
company
to develop a product, and it often does not for a potential therapeutic
application, NIH will award exclusivity for specific indications or fields
of use, based on the license applicant's commercial development plans at
the
time of the application. NIH also requires exclusive licensees to grant
sublicenses to broaden the development possibilities when necessary for
the public health. Finally, NIH insists on the continuing unencumbered
availability of the licensed technology to not-for-profit scientific
community for further research.
Experience over the last 20 years has shown that to maximize public health
benefit, the balance between exclusivity and access must be carefully
maintained and research uses of new technologies must be preserved.
These concepts form the basis for the licensing policies of the NIH, as
well as for the proposed guidelines for our grantees mentioned above.
Summary
Congress has enacted legislation for recipients of federal funding that
encourages the utilization, commercialization and public availability of
federally funded inventions. Grantees have exercised broad discretion and
appropriately seek to achieve these goals through the patenting and
licensing
of new inventions that arise through the use of federal funds. If the
research is entirely funded by the private sector, the government has no
license and is not involved in patenting or licensing decisions. Exclusive
licensing, without regard to research uses, can impede rather than enhance
utilization and public availability of certain types of inventions, such
as research tools. Strategic licensing can alleviate potential problems.
Indeed, many grantees provide for the continuing availability of
exclusively
licensed subject matter to researchers in order to ensure progress of
biomedical research. The NIH has urged, and will continue to urge, patent
owners and exclusive licensees to ensure continuing availability under
terms that do not limit basic research or encumber future products.
Mr. Chairman, I am grateful to you for providing a forum to present
information about the effects of patents and licenses on this promising
new area of science and medicine. I would be pleased to answer any
questions you may have.
AUTHOR: Siddartha Pradesh, WTO consultant
TITLE: Country study: India - Local species (turmeric, neem and basmati)
IN: Information Technologies for Development website
DATE: beta version, 1998
URL: http://www.itd.org/issues/india6.htm
NOTE: The Trade and Development Centre is run jointly by the World Trade
Organization and the World Bank's Economic Development Institute, under a
programme called Information Technologies for Development (ITD). A wide
range of sectoral studies, essays, book reviews, links & other research
tools is being posted on this website (http://www.itd.org) about
development
aspects of the global trade system. Some of the material deals with issues
like genebanking and farmers' rights, protecting indigenous biodiversity
knowledge, etc. The case study below, meant to counter-argue claims of
"bio-piracy", contains many direct links to patents, newspaper articles,
NGO websites and other sources.
World Trade Organization & World Bank
Trade and Development Centre
COUNTRY STUDIES: INDIA
PART 6: LOCAL SPECIES - TURMERIC, NEEM AND BASMATI
Some of the biggest controversies on intellectual property rights in India
are about patents involving local plant species. Three plants in particular
have been the focus of attention: turmeric, neem and basmati rice. In each
case, the patents were granted in the United States. But there is some
confusion about the exact implications of these cases.
The outcry against patents involving plants that have traditionally been
used in India for medicinal or agricultural purposes is based on three
broad concerns:
* that farmers will no longer be able to use these products without paying
royalties
*
that consumers will also be deprived of cheap medicines
*
that local communities should receive a share of the commercial gains:
after all - the argument goes - the companies owning the patents
learnt the value of the species through local knowledge, so they have
a debt to repay.
There are also strong counter-arguments. They take the form of a defence
of the intellectual property protection (patents, or some other form of
protection for plant varieties, for example) in these areas as a means of
promoting development through research. They also reject some of the
assumptions and conclusions of the criticisms =97 for instance, that
patenting means higher costs.
What the cases presented here show is this: whatever you believe about themerits or costs of protecting intellectual
property, it is important to
understand exactly what is being protected and whether the protection does
or does not have broader implications for the use of the species. There is
a lot of confusion and misunderstanding in this area.
One point is clear. By definition, a product or a process that has been
used
publicly and traditionally is not new and therefore it cannot be patented.
In at least one case, a patent was withdrawn because Indian objectors were
able to prove successfully that the idea was not new.
TURMERIC
What is turmeric?
Turmeric (Curcuma longa) is a plant of the ginger family yielding
saffron-coloured rhizomes used as a spice for flavouring Indian cooking.
Its unique properties also make it an effective ingredient in medicines,
cosmetics and as a colour dye. As a medicine, it is traditionally used to
heal wounds and rashes.
A turmeric patent
In March 1995, two expatriate Indians at the University of Mississippi
Medical Centre, Jackson, (Suman K Das and Hari Har P. Cohly) were granted a
US patent (patent number 5,401,504) for turmeric to be used to heal wounds.
The Indian Council for Scientific and Industrial Research (CSIR) filed a
case with the US Patent Office challenging the patent on the grounds of
"prior art", i.e. existing public knowledge. CSIR said turmeric has been
used for thousands of years for healing wounds and rashes and therefore
its use as a medicine was not a new invention.
The claim had to be backed by written documentation claiming traditional
wisdom. CSIR went so far as to present an ancient Sanskrit text and a paper
published in 1953 in the Journal of the Indian Medical Association. The US
Patent Office upheld the objection and cancelled the patent.
Why was the patent withdrawn?
Inventions can only be patented if they satisfy three criteria:
* novelty - only inventions that are genuinely new, and not part of
existing knowledge, can be patented.
* non-obviousness - if the new invention is obvious, i.e. anyone familiar
with the subject could easily anticipate the invention, then it cannot
be patented.
* utility - the invention has to work in practice The turmeric case failed
to meet the novelty criteria.
What are the social implications?
In this case, there was no threat to Indian farmers and consumers once the
patent was cancelled. This case shows that unjustified patents can be
challenged.
Some concern remains, however. The fact that the patent was initially
granted shows the difficulty of checking in one country (in this case the
United States) whether public knowledge about an idea already exists in
another country (in this case India).
Often the check involves a search (by the patent office) for written
evidence =97 for example in an existing patent or an academic journal.
Searching for existing patents in other countries is becoming easier, even
among developing countries, with computerized databases, pooled
information,
and international or regional cooperation.
P.S. That's not the only turmeric patent
The US Patent Office database reveals some nine patents using turmeric, the
latest for treating degenerative musculoskeletal diseases such as
rheumatoid
arthritis and osteoaarthritis.
NEEM
What is neem?
Neem (Azadirachta indica) is a tree from India and other parts of South and
Southeast Asia. Growing to 7=AD20 metres tall, it is now also planted in
Africa, Central America, the Caribbean and Hawaii. One of the world's
largest plantations is in Saudi Arabia, where approximately 50,000 trees
have been planted on the Plains of Arafat.
Because of its properties as a natural medicine, pesticide and fertilizer,
the neem tree has attracted a considerable amount of international
interest.
As a pesticide, neem extracts can be used against over 250 pests including
whiteflies, aphids, mealybugs, mites, and termites. It is also effective
against fungus diseases such as rusts and powdery mildew that attack the
leaves of ornamental plants and food crops.
Its properties are used to cure common colds and flu. The oil extracted
from
its seeds can be used to cure various diseases. Mixed in soap, it offers
cheap and easy relief from malaria, skin diseases and even meningitis. Neem
is grown in semi-arid regions and during droughts, when most crops fail,
its leaves provide fodder for livestock.
Neem patents
Numerous neem products have received patents. Several of these have been
granted to Indian companies for a range of products including a
contraceptive (patent granted to the National Institute of Immunology in
1993) and an environmentally safe pesticide (for Godrej Soaps in 1994).
But the most controversial patents are those granted to the US company WR
Grace & Co for extraction and storage processes. They are:
* US patent No 4946681, granted in 1990 for improving the storage stability
of neem seed extracts containing azadirachtin (a substance obtained from
Azadirachta (neem). (The inventor is named as James F Walter of Ashton,
Maryland.)
* US patent No 5124349, 1994 for storage of stable insecticidal composition
comprising neem seed extract. The major contribution was increasing the
shelf-life stability of azadirachtin solution. (Four people are named as
the inventors.)
The WR Grace patents provoked a national outcry. Under pressure from these
groups, the Indian government filed a complaint to the US Patent Office
accusing WR Grace of copying an Indian invention. However, in the end, the
government withdrew its complaint as it realized that the US-based company
had in fact created a new invention for the neem extraction process, and
the patent was not based on traditional knowledge.
Are the fears valid?
The neem patents aroused a number of complaints. Farmers protested that the
patents would prevent them from using neem as a source of home-made
pesticide. Non-government organizations used the incident to challenge
European and US patents on the grounds of =93bio-piracy=94. A coalition of
200 non-governmental organizations from 40 countries have challenged the
patents, fearing they would put pest control costs out of reach for farmers
who are now using the extracts in underdeveloped nations.
In fact, the patents granted to WR Grace & Co are quite specific.
The 1990 patent is for a method of producing neem extract that can be
stored
well. The abstract says: 'Storage stable pesticide compositions comprising
neem seed extracts which contain azadirachtin as the active pesticidal
ingredient wherein the compositions are characterized by their
non-degrading
solvent systems. In a first embodiment, the pesticide compositions contain
solvent systems characterized as having greater than 50% by volume aprotic
solvents and less than 15% by volume water. In a second embodiment, the
pesticide compositions contain solvent systems characterized as having
greater than 50% by volume alcohol and less than 5% by volume water. The
pesticide compositions contain surfactant concentrations of at least about
1.0%, up to 10%.'
The 1994 patent is for a specific method of extracting and treating active
substances from neem seeds so that the resulting solution is stable enough
to store. The abstract says the patent is for a =93process for the
production
of stable azadirachtin solutions comprising extracting ground neem seeds
with a solvent having azadirachtin solubility to produce an
aqueous-containing azadirachtin extract solution and then adding an
effective amount of 3=AD4 Angstrom molecular sieves to selectively remove
water from the extract to yield a storage-stable azadirachtin solution
having less than 5% water by volume=94.
It is only these specific newly invented processes that are covered by the
patents. Farmers always have and will continue to be free to use neem in
any traditional way they desire.
The use of neem extract, or its seeds or leaves, cannot be patented, since
they have been used for centuries. Its properties can only be patented if
they are considerably modified. For instance, any synthetic variation of a
naturally occurring product is patentable, as it does not occur in nature
in that form.
BASMATI
What is basmati?
Basmati is a top-quality rice from the Punjab provinces of India and
Pakistan. The word means 'fragrant earth', and the rice is a slender
aromatic long grain variety that originated in this region and is a
major export crop for both countries.
What is protected?
There are two distinct issues here, involving three aspects of intellectual
property rights.
1. The patent. In September 1997, the US Patent Office granted a patent to
US firm RiceTec Inc (patent number 5,663,484) covering 'novel' varieties of
basmati rice, their plants and seeds, a method of breeding them and a
method
for selecting rice grains (by examining their starch content) so that the
cooked rice has the same qualities as traditional basmati.
It is important to be clear that the patent does not (and cannot) cover the
use of the name 'basmati' or any other name. It simply deals with the
varieties and various methods of dealing with them. Fears that the patent
would give RiceTec exclusive right to use the word 'basmati' in the United
States are therefore entirely incorrect.
2. The name. Various reports have referred to the US company's use of such
names as 'basmati', 'Kasmati', 'Texmati' and 'Jasmati'. See for example an
item in Scientific American magazine.
In fact, the company has used the brand names Kasmati, Texmati and Jasmati
in the United States and United Kingdom since before the patent was issued.
It has been using the term 'basmati' as a generic term for considerably
longer: 'RiceTec has produced and marketed Texas basmati and American
basmati rice - and labelling it as such - for 20 years and exporting the
products for 15 years with no objection ever previously raised', a
company statement says.
In other words, the name and the patent are completely separate issues; and
there is also a distinct difference between the use of basmati as a generic
term, and the use of brand names such as Texmati and Jasmati.
('Jasmati' is a combination of 'basmati' and 'jasmine' - the latter term
originally used to describe a Thai variety of fragrant rice that is quite
different from 'basmati'.)
Two types of intellectual property are involved with the names: trademarks
and geographical indications (the use of place names or words associated
with a place to identify the origin, type and quality of a product - for
example 'champagne'). Since the word 'basmati' is not a place name, its
validity as a geographical indication would depend on whether 'basmati'
can be shown to be closely and exclusively associated with a geographical
area.
The debate
1. The criticisms
Three broad complaints have been raised by critics of the Rice patent
and the separate issue of the use of names such as Texmati and Jasmati.:
* that the collective intellectual and biodiversity heritage of Indian and
Pakistani farmers is being 'stolen'
* that the patent and/or trademark allow(s) the US company to 'steal' the
markets of Indian traders and exporters by describing US-grown rice as
'basmati'
* that consumers are being misled because the word basmati is being used
for
an American-grown rice which is derived from Indian rice but not grown
in India, and hence not of the same quality.
2. The patent
The Indian government has protested that the patent could affect annual
basmati exports worth $277m and thus threaten the livelihood of thousands
of
Punjabi farmers. But so far it has not formally challenged the patent, and
therefore the question of whether a significantly novel step has been taken
to justify the patent remains unchallenged in law.
Critics also claim that US law allows patents to be issued for inventions
made in the US even if the same inventions have been made in other
countries
- but this is untrue as the turmeric case shows.
3. The name
First the generic term 'basmati'. Critics in India and Pakistan say the
term
should not be used for rice grown outside the Punjab region. But for many
years 'basmati' has been grown elsewhere, and not only in the United
States.
In Thailand, a company called Siamati has been trying for several years to
produce basmati commercially. Basmati is also grown in Uruguay.
Under international agreements such as the WTO's intellectual property
pact,
a name associated with a geographical region can be used elsewhere if the
name has become generic. For this reason =93cheddar=94 cheese is produced
all over the world, and not just in the part of the United Kingdom
identified by the name.
For basmati, the debate about whether it is geographic or generic
continues.
For the American industry, the position is clear. On 9 July 1998 the USA
Rice Federation declared that 'the terms basmati and jasmine refer to types
or generic classes of aromatic rice and that these terms cover many
varieties and a broad range of qualities. Additionally, these terms are
not restricted to products or varieties produced in any specific country
or groups of countries.'
RiceTec also observes that Indian researchers have used the term 'basmati'
to describe fragrant rice from countries other than India and Pakistan.
But that view is questioned in India.
Second, the trademarks. RiceTec's trademarks registered in the United
States
have not been legally challenged although some critics have suggested that
the names could mislead consumers.
RiceTec has applied for trademark registration in the United Kingdom. In
February 1998, the Indian Agricultural and Processed Foods Development
Authority (APEDA) said it would oppose RiceTec=92s trademark application
for basmati in the United Kingdom.
APEDA says the UK has established a Code of Practice for rice which allows
the term basmati to be used only for the long grain aromatic rice grown in
India and Pakistan. Therefore, APEDA believes that the case is winnable in
favour of India, but the case remains unsettled.
RiceTec says that despite the opposition, there have been no lawsuits or
other legal actions in the UK. 'The fact is that RiceTec has not sold any
product in the United Kingdom due to the European Union import levy which
discriminates against US specialty rice products in favour of India and
Pakistan', RiceTec says.
4. Theft and deception?
As to the accusations of 'theft' and deception, RiceTec says it 'invented
a way to produce basmati rice in the United States comparable to the best
basmati grown in India and Pakistan and we received a patent to protect our
breeding method and seeds. Those countries do not have such laws and, thus,
few people there understand what they [the patents] do and don't do.'
RiceTec denies that it took germplasm (the genetic material) from India or
Pakistan or that it used biotechnology or genetic transformation to producethe patented new basmati lines. The
germplasm 'came partly from the World
Collection of Germplasm in Aberdeen, Idaho, which is operated by the
Agricultural Research Service of the US Department of Agriculture', RiceTec
says, adding that it used 'traditional, classical' breeding techniques
over a period of 10 years.
RiceTec says its production of high quality products and the new breeding
methods it has developed 'help feed a hungry world and reduce land
requirements'.
AND FINALLY, BIO-PIRACY?
The questions of whether local communities have a right to a share of
intellectual property royalties, or even whether substances found in nature
should be patentable, is complicated.
It partly depends on one's judgement of whether a particular invention
represents a big enough leap into new knowledge - knowledge that is far
removed from local or traditional wisdom. It also depends on views of
how best to deal with biodiversity.
These issues are being discussed in a number of international forums,
including the WTO's Committee on Trade and Environment.
Some countries have reached agreement with commercial firms, allowing the
companies to undertake research into local species on condition that
payment
is made to the host country or that there is some technology transfer to
allow local scientists to take over the research later.
Opinion is also likely to continue to differ on whether intellectual
property protection such as patents help or hinder a community's ability
to discover new medicines or agricultural materials. Similarly, for the
question of the best way to handle biodiversity.
But while the issue continues to rage in India, it is notable that the
Indian government has come some way towards endorsing the view that
intellectual property protection is beneficial - in areas where Indians are
strong, such as computer software, movie-making and some areas of design,
the government is keen to enforce protection.
Written and researched by Siddhartha Prakash, WTO Consultant
Edited by WTO Information and Media Relations Division
Copyright 1998 World Trade Organization, Geneva, Switzerland
RECORD TYPE: FEDERAL (NOTES MAIL)
CREATOR: Alex Capron <[email protected]> ( Alex Capron <[email protected]> [ UNKNOWN
CREATION DATE/TIME:15-JAN-1999 14:01:26.00
SUBJECT: Re: First reactions to briefing book
TO: NBAC Members E-list <[email protected]> ( NBAC Members E-list <nbac-
[email protected]> [ UNKNOWN])
READ:UNKNOWN
TEXT:
In reply to Bernie's suggestions/queries:
1. I urge us to stay away frm the nonheartbeating cadaver analogy. It is
itself an enormously controversial area. I for one believe that the usual
protocol for using such donors violates the letter and spirit of the
determination of death statutes and would be rejected by many people if
they understood that. Trying to construct a tortured analogy from there
to embryos (i.e. if we're willing to terminate life of person with little
prospect of long life so that he/she can be used as organ donor shouldn't
we be willing to terminate life of embryo so he/she can be used as stem
cell donor?) is not only problematic in itself but runs the risk of
importing an additional controversy. I hope we can keep it off the table.
2. In my view, the RAC worked well in both scientific and ethical terms
for many years; the problem arose (in HArold Varmus' view) when companies
that were not, strictly, required to seek RAC review (because no federal
$) sought it anyway (which had a virtuous implication) rather than only
going with FDA; as I understood Varmus' view, a lot of the science
involved wasn't very good and it was not only a waste of RAC time to
review it but was really being used by the companies to hype their
"cutting edge" new "therapies" (which was useful in venture capital
terms, compared to the behind-closed-doors FDA review). From the
viewpoint of those of us on the RAC, there was also the sense that a lot
of what we were doing was repetitive and that kept us from looking at the
truly unresolved issues, such a transfers that might lead to germ-line
changes. LeRoy Walters has written about the RAC and could be asked to
come talk about it.
Alex