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Cloning
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PAGE
27
8TH STORY of Level 1 printed in FULL format.
Copyright 1997 Newsweek
Newsweek
March 10, 1997 UNITED STATES EDITION
SECTION: SOCIETY; Pg. 52
LENGTH: 3579 words
HEADLINE: Little Lamb, Who Made Thee?
BYLINE: BY SHARON BEGLEY, With STRYKER McGUIRE in Edinburgh, ANNE UNDERWOOD and
ADAM ROGERS in New York and MARY HAGER in Washington
HIGHLIGHT:
Dolly's was the birth heard round the world. The first mammal ever cloned from a
single adult cell, she was living proof that scientists had solved one of the
most. challenging problems of cell biology. Her creation raised a troubling
question: can humans, too, be cloned?
BODY:
KEITH CAMPBELL WASN'T THINKING, REALLY, ABOUT ROOMS full of human clones,
silently growing spare parts for the person from whom they had been copied. Nor
was he thinking about giving lesbians a way to bear a biological descendant
without visiting the sperm bank. And he certainly wasn't aiming to give pro-team
owners a tool to copy their greatest players, hospitals their best doctors or
parents their dying child. Campbell, a cell biologist at the Roslin Institute in
Scotland, was thinking
sheep. Lots of sheep, hillock upon hillock of
sheep, enough sheep (given enough fences) to put all the insomniacs in Scotland
to sleep. And all produced from a single cell of a single ewe.
Cloned.
Campbell knew that cloning from an adult mammal was, according to every
textbook, impossible. He knew that once a cell has decided what it's going to be
when it grows up -- part of bone, nerve, skin or any other organ -- it is like a
CD album that will play only a single track. Although every cell in every body,
from liver cells in a person to udder cells in a sheep, contains the complete
genetic blueprint for making the entire person or the entire sheep, only the
genetic melody for the liver cell or the udder cell is actually played. The
other tracks -- instructions for the complete organism -- have been silenced.
But Campbell would have none of that. He and his Roslin colleagues were going to
clone a lamb from an adult cell. Even though everyone said it couldn't be done.
At Roslin they stopped saying that in February 1995, after Campbell strode
down the hall to the professorially messy office of his colleague Ian Wilmut. He
had figured out, he told Wilmut, how to get adult cells to sound each and every
one of the genetic notes required to make a complete animal. The key was to make
the cell "quiescent," or inactive. In that state, all of its genes have the
potential of being played, Campbell realized. All that was needed was the
player. And Campbell had just the thing: a sheep oocyte -- egg cell -- contains
special proteins that turn on genes, playing all the tracks, one after another,
like the laser beam in a CD player. "We have to be very quiet about it,"
Campbell told Wilmut. "We can't tell anybody." And he didn't, until last week,
when the world learned of the arrival of Dolly, born last July, the first
PAGE
28
Newsweek, March 10, 1997
mammal cloned from an adult cell.
Cloning manipulating a cell from an animal so that it grows into an exact
duplicate of that animal -- is the forbidden fruit of biotechnology. Some
scientists were so sure it could not be done that, in the 1970s, they dissuaded
bioethicists from pondering its moral implications. Yet at the same time other
scientists, in out-of-the-way labs and under the cloak of secrecy, were getting
ever closer to making clones. What cloning is not, despite all the professions
of surprise in the wake of Dolly's birth announcement last week, is unexpected.
For 10 years scientists have been cloning sheep and COWS from embryo, though not
adult, cells. And the research hasn't stopped with the beasts of the field. In
1993, embryologists at George Washington University cloned human embryos: they
took cells from 17 human embryos (defective ones that an infertility clinic was
going to discard), all two to eight cells in size. They teased apart the cells,
grew each one in a lab dish and got a few 32-cell embryos -- a size that could
be implanted in a woman (though they weren't). So scientists' professed surprise
over Dolly rings somewhat hollow.
The real question, of course, was, wherever the lamb went, was Mary sure to
follow? In other words, how soon will scientists clone humans? Nature, the
scientific journal that published the Dolly paper, editorialized, "Cloning
humans from adults' tissues is likely to be achievable any time from one to ten
years from now. Cornell University biologist W. Bruce Currie estimates that
only 10 labs in the world (his not among them) can manipulate sheep cells the
way Dolly's makers did, getting them to become quiescent and producing clones
from them. But in principle "there is no difficulty at all in driving human
cells [in a lab dish] into [quiescence], says Currie. "All that's needed is to
take a culture of proliferating cells and deprive them of [nutrients] Last
week, as scientists cast about, almost desperately, for an obstacle to human
cloning, embryologist Colin Stewart of the National Cancer Institute came up
with one. In sheep embryos, the genes from the donor cell do not turn on until
the egg has divided three or four times, he pointed out. In humans, those genes
turn on after two divisions. That difference might be an insurmountable obstacle
to human cloning -- or it might not. But on the more profound question of what,
exactly, a human clone would be, doubters and believers are unanimous. A human
clone might resemble, superficially, the individual from whom it was made. But
it would differ dramatically in the traits that define an individual --
personality and character, intelligence and talents. "Here's the rule," says
psychologist Jerome Kagan of Harvard. "You will never get 100 percent identity
never -- because of chance factors and because environments are never exactly
the same."
That was small comfort to politicians, ethicists and pundits. President
Clinton, citing "serious ethical questions," ordered a federal bioethics panel
to report in 90 days on whether the United States should regulate human
cloning or ban it. (Britain, Denmark, Germany, Belgium, the Netherlands and
Spain already do.) Ethicists dusted off arguments they had mothballed in the
1970s, and thousands of trees gave their lives so dueling scholars could publish
articles arguing that cloning was a humane way for infertile couples to have a
child, joking that cloning made males superfluous or conjuring hideous images of
cloned humans raised for spare parts.
That prospect seems awfully remote from the Roslin Institute's mundane goal:
building a better glass of milk. The scientists, backed by PPL Therapeutics
P.L.C. of Edinburgh, wanted to genetically engineer sheep and COWS so that
PAGE
29
Newsweek, March 10, 1997
their milk contains human proteins. Not just any proteins, but those with
pharmacological uses medicines. Earlier this year PPL threw a coming-out
party for Rosie, a COW whose milk contains human alpha-lactalbumin. This protein
contains just about all the amino acids a newborn needs; the idea is to purify
the protein from Rosie's milk and sell it, in powdered form, for premature
babies who cannot nurse. Other companies are also banking on animals with human
traits, for everything from blood to hearts.
ROSIE MAKES A HUMAN protein because, when she was a mere embryo in a dish,
scientists slipped the gene for the protein into her cells. (The human gene is
rigged so that the protein is made only in milk glands and not in, say, the
retina.) When Rosie was born she carried the human gene; this makes her a
"transgenic" animal. But putting a human gene into each and every Rosie-to-be is
not only tedious but inefficient. It fails more often than it succeeds. Wilmut
figured that cloning offered a better way. His recipe: first make transgenic
sheep, which he preferred to COWS. When the lamb grows up, take one of its
cells, slip it into an egg cell from a different sheep, put the whole package
into a surrogate mother sheep and wait 150 days. Do this a few times and pretty
soon there is a flock of sheep making medicine-laced milk. After he built up a
flock of maybe 10 cloned sheep, Wilmut figured, he would breed the animals the
old-fashioned way. That way the flock would be more genetically diverse and thus
less vulnerable to viruses and disease.
The stumbling block to cloning had been that cells in an adult animal have
already chosen what they want to be when they grow up. They are liver cells, or
skin cells, or neurons, for instance. Any gene not needed in a cell is switched
off, though still present. As a result, skin cells do not make estrogen; brain
cells do not make insulin. Proteins, acting like a medieval chastity belt, seem
to block a cell's access to those genes. For this reason scientists had never
cloned an adult cell: like a frustrated knight, they couldn't get at all the
genes needed to make a complete animal.
The Scottish scientists' key discovery was making adult cells live up to
their full potential. First the researchers removed udder cells from a
6-year-old pregnant sheep. They grew the cells in lab dishes, immersing them in
nutrients. Then, in the eureka step that sent Campbell down the hall to Wilmut
two years ago, they dialed back the nutrients to one twentieth of what cells
need to grow. After five days the cells had become quiescent, stilled at exactly
that stage in their life cycle when their genes are open to what the Roslin
scientists call "reprogramming of gene expression." In other words, the genes
could receive signals from the ovum that they should start making a lamb embryo.
It is hardly a foolproof method -- of 277 adult cells fused with ova, only 13
pregnancies resulted and only Dolly was born alive but it is better than
anyone else has ever done.
The Roslin scientists had no sooner trotted out Dolly than they assured
everyone who asked that no one would ever, ever, apply the technology that made
Dolly to humans. Pressed to answer whether human cloning was next, scientists
prattled on about how immoral, illegal and pointless such a step would be. But
as The Guardian of London pointed out, "Pointless, unethical and illegal things
happen every day. " If society decided that it wanted to stuff the cloning genie
back into the bottle, could it? In the case of nuclear bombs, the five nuclear
powers have controlled proliferation, more or less, in part because the United
States showed, at Hiroshima and Nagasaki, what horrors the bomb can wreak. The
taboo on biological weapons has also held. And with the exceptions of the
PAGE
30
Newsweek, March 10, 1997
Iran-Iraq War of the 1980s and the Tokyo subway attack by the Aum Shinrikyo cult
in 1995, chemical weapons, too, have remained on the shelf, at least since the
horrific mustard-gas attacks of World War I. Will it take a few human-clone
disasters to bring a ban?
Technologies that require big capital investments and infrastructure, like
weapons, are easier to control than those that can be carried out by a couple of
graduate students in a basement lab. The United States, for instance, bans the
use of government money for research on human embryos. But in January a
biologist at George Washington University resigned after he was discovered doing
research on human embryos in an attempt to find a way to diagnose those with
genetic abnormalities. It is easy to imagine another researcher, also with
altruistic motives, attempting to clone humans despite a ban. It is equally easy
to imagine creepier reasons for cloning. The journal Nature reported that, just
before its Dolly issue went to press, it received an e-mail from a Harvard
University scholar, pleading that the paper be dropped because "abuse [of the
cloning technique] by extralegal or foreign groups is almost inevitable."
Alarmism? British futurologist and author Patrick Dixon claimed last week that
he had been contacted by a woman who wanted to clone her deceased father and
possibly carry the baby to term herself.
But who, exactly, would that baby be? Both the dreams and the nightmares of
cloning -- the thousands of Mother Teresas and the thousands of Pol Pots are
no closer to reality after Dolly than they were before. As far as anyone can
tell, Dolly is an exact copy of the ewe whose DNA she carries. But with sheep
it's kind of hard to spot differences anyway. When it comes to people, genes are
only the start, as even Hollywood recognized 19 years ago. In "The Boys From
Brazil, the 94 boys made from one of Hitler's cells were exposed to the same
traumatic and other formative experiences as Hitler, for the fictional plotters
knew that genes alone would not guarantee Fuhrers II through VC.
If Dolly had been born 10 years ago, the explanations would have ended there,
with comforting boilerplate about how people are more than their genes, how they
are complex products of their interactions with their parents, their friends,
their teachers, their culture and their times. But Dolly happened along just
when behavioral geneticists and psychologists have begun to figure out exactly
how genes -- nature -- are either turned up or turned down by their environment
nurture. "Environmental influences can alter the physical structure of the
brain, determining in part how genes express themselves in both biology and
behavior, notes psychiatrist Stanley Greenspan of George Washington University
in his new book "The Growth of the Mind."
Take shyness, considered the most heritable personality trait. Harvard's
Kagan has found that foetuses with fast heartbeats tend to become shy babies. In
other words, these children are biologically predisposed to be supercautious and
anxious. (The genes seem to have something to do with making the brain recoil
from stimulation and new experiences.) But if parents nudge their shy children
into situations that they would otherwise cringe from, like playing with other
kids, the biochemical systems that induced shyness in the first place may
somehow get dialed back. Which leads to lesson one for would-be cloners: if you
clone a sociable person but then protect the precious creation with the zeal of
Juliet's nurse, you may produce a quaking wallflower.
Achievement is under even weaker genetic control. "A Mozart born into a
primitive tribe in Papua New Guinea would never have written a symphony, says
PAGE
31
Newsweek, March 10, 1997
neurologist Harold Klawans of Rush Medical College in Chicago. But because
Mozart's father was a composer and his older sister took piano lessons, whatever
innate talent little Wolfgang possessed could be realized. Intellectual
revolutionaries are also made and not born, let alone cloned. Frank Sulloway of
MIT, who has made his reputation with studies showing how birth order influences
everything from political views to personality, argues that "if Darwin had been
his mother's firstborn, he would not have been an evolutionist." Based on data
from 600 of Darwin's contemporaries, Sulloway calculates that only 5 percent of
(conformist) firstborns were evolutionists, but 50 percent of
(establishment-challenging) later-borns were. Moreover, Darwin came from a
politically and religiously liberal family. "He's loaded to the gills with
everything that could have made someone a revolutionary," says Sulloway. Lesson
two: to clone an iconoclast, make him your second child.
Which is not to say that genes do not matter. They do. Genes gently nudge a
baby into certain behaviors, which then shape her world by, among other things,
eliciting from those around her certain kinds of reactions. But the reactions,
and the baby's experiences, are hardly predestined and outside human control.
Yes, a squalling baby can make his parents angry, even abusive; but parents can
recognize the destructive cycle that's beckoning and make a herculean effort to
hug, kiss, hold, talk to and COO at him. And the baby "genetically predestined"
to be emotionally cold may become a loving preschooler. Conversely, parents who
give in to the oversensitive baby, letting her play alone, only exacerbate
innate tendencies; parents who withdraw from the difficult baby exaggerate his
worst traits. Parents, says Greenspan, can "change the way their [children's]
nervous systems work and thus their personalities." Lesson three: genetic seldom
means immutable.
EVEN PHYSICAL TRAITS, such as risk for a disease, can be pumped up, damped
down or even snuffed out by life's experiences. About 15 percent of women who
inherit BRCA1, known as the breast-cancer gene, do not get the disease.
Something in their environment, perhaps dumb luck, protected them. Another gene,
related to skin cancer, is turned on by exposure to radiation; if the person
carrying the gene takes precautions against ultraviolet rays, he may never get
skin cancer, explains Mark Feinberg of Johns Hopkins University. More complex
diseases, such as heart disease and mental illness, are even less subject to
genetic control. One might clone what seems to be a well-adjusted, healthy
person only to find that the clone undergoes experiences that make him
hypertensive or schizophrenic. For example, the incidence of schizophrenia
doubled among Dutch children born in the Netherlands' "winter of famine" during
World War II. Maternal malnutrition can trigger the disease. But a clone of one
of these children, a genetic duplicate, might evade schizophrenia if borne by a
woman who ate normally during pregnancy. Lesson four: don't count on avoiding a
genetic disease just because you clone what seems to be a disease-free person.
What you clone may not be what you get for an even more basic reason: the
cell being cloned has undergone years of mutations. These changes in its genes
caused by radiation, chemicals or just chance might not have caused any
apparent problem. If a gene for a brain chemical is mutated in a skin cell, it's
not even detectable. But what if a lab happened to be unlucky enough to choose
that cell to clone? The baby would be born with horrible or even fatal defects.
" [Mutations are] a problem with every cell, and you don't even know where to
check for them, says reproductive biologist Ralph Brinster of the University of
Pennsylvania. Aging also affects the cloned cell, and perhaps the animal grown
from it. Although Dolly looks like an 8-month-old lamb (albeit a pudgy one,
PAGE
32
Newsweek, March 10, 1997
because her handlers have to keep feeding her to make her stand still for
photographers), is she, biochemically, really 6 years old, the age of the ewe
from whose cell she came?
If Dolly's creation offers any lessons, it is these. First, that which is not
absolutely prohibited by the laws of nature is possible. Second, science, for
better or worse, almost always wins; ethical qualms may throw some roadblocks in
its path, or affect how widespread a technique becomes, but rarely is moral
queasiness a match for the onslaught of science. Society, then, would do well to
face the fact that no known law of nature prohibits the cloning of humans. If it
wants a voice in whether adults clone themselves, either to raise as children or
to grow spare parts, the time to speak up is now.
Or maybe we shouldn't worry about it. After all, they say it won't be done.
Reproductive Rites
Technologies for reproduction started small, on the farm, but embryology and
genetics moved them from animals to humans to clones. The progress has been
steady -- both in science and science fiction.
1950
First successful freezing (at -79 degrees C) of bull semen for transport and
later insemination of COWS
1952
The first animal cloning: Robert Briggs and Thomas King make frogs from tadpole
cells
1962
John Gurdon also clones frogs, this time using cells from older tadpoles
1978
The film 'The Boys From Brazil' posits a plot to clone little Hitlers
1978
The birth of Baby Louise, the first child conceived through in vitro
fertilization. Midwives: Patrick Steptoe and R. G. Edwards of England.
1978
David Rorvik's book 'In His Image' alleges a human cloning
1983
First human mother-to-mother embryo transfer
1985
Ralph Brinster's lab creates the first transgenic livestock, pigs that produce
human growth hormone
1986
Artificially inseminated, surrogate mother Mary Beth Whitehead carries Baby M to
full term, then tries to keep her. She fails.
1993
*
'The X-Files' episode 'Eve' features psychotic clones
*
Human embryos cloned
PAGE
33
Newsweek, March 10, 1997
*
Jurassic Park's' cloned dinosaurs fill theaters
1994-96
Marvel Comics runs confusing 'Spider-Man' clone saga, in which our hero is
thought to be a clone, but turns out just to be a superhero
1996
*
Michael Keaton clones himself in 'Multiplicity'
*
Wilmut and colleagues announce birth of sheep cloned from embryonic cells,
presaging Dolly
Send in the Clones
Scientists once thought that cloning an animal from an adult cell was
impossible. Although every cell contains the complete genetic blueprint for
making a new animal, those instructions cannot be read in adult cells; they've
become specialists, producing cells only for a single body part. The Scottish
team figured out how to turn on all the genes needed to make a lamb from a
single adult sheep cell.
1 A Finn Dorset ewe provides the mammary cell for cloning.
2 A mammary cell contains copies of every gene needed to make a sheep, but only
genes for proteins required by mammary cells are active.
3 Cells grow and divide, making carbon copies of themselves. But if the cells
are starved of nutrients, they enter a quiescent state. At this point all of
their genes can be activated.
4 A Scottish Blackface ewe provides the egg.
5 The egg, or oocyte, is kept alive in a laboratory dish.
6 The nucleus is removed from the egg.
7 The mammary cell and the egg fuse with a spark of electricity. Molecules in
the egg then program genes in the mammary cell to produce the lamb embryo.
8 Clusters of embryonic cells are grown.
9 Embryos are implanted into a surrogate mother.
10 The lamb that results is a clone of the donor ewe.
GRAPHIC: Cover Photo Illustration, no caption, by Tom Haynes. Computer
retouching by David Terban -- Shoot Digital. ; Picture 1, THE COVER: Dolly's
birth was heard round the world. The first mammal ever cloned from a single
adult cell, she raised a troubling question: can humans be cloned, too? A look
at the science -- and the ethics. ; Picture 2, Derived from mammary cells, she
surely made her namesake, Dolly Parton, proud; Pictures 1 and 2 by CHRIS BUCK;
Picture 3, Dr. Ian Wilmut, in his Roslin Institute lab, was just looking to
build a better glass of milk -- containing medicine for premature babies, NAJLAH
FEANNY -- SABA; Pictures 4 through 14, no caption, DAN MCCOY -- RAINBOW, JEAN
CLAUDE REVY -- PHOTOTAKE, ROBIN SMITH -- TONY STONE IMAGES, EVERETT COLLECTION,
REX USA, COURTESY AMERICAN RED CROSS -- VIRGINIA POLYTECHNIC INSTITUTE, RICKI
ROSEN -- SABA, KOBAL COLLECTION, (c) MARVEL ENT. GROUP; Picture 15, The key
PAGE 34
Newsweek, March 10, 1997
was getting a single cell to grow into an entire sheep. Above, an embryo cell
before manipulation. REPRINTED BY PERMISSION FROM NATURE, VOL. 385, 1997;
Diagram, no caption, BLUMRICH -- NEWSWEEK; Pictures 16 and 17, It's All
Happening at the Zoo, Cloning might be one way to protect endangered species,
but ZOOS are using other reproductive methods. At the Louisville Zoo, a
surrogate mother horse gave birth to a zebra that had been conceived in a lab
dish. Last year the world's first test-tube gorilla, Timu, was born at the
Cincinnati Zoo. SYGMA, (c) CINCINNATI ZOO
LANGUAGE: ENGLISH
LOAD-DATE: March 11, 1997
PAGE
22
16TH STORY of Level 1 printed in FULL format.
Copyright 1997 The Time Inc. Magazine Company
Time
March 10, 1997
SECTION: SPECIAL REPORT; MONEY IN MOTION; Pg. 72
LENGTH: 551 words
HEADLINE: BEARISH ON BIOTECH ;
LAYMEN SHOULD STAY AWAY LEST THEY GET FLEECED
BYLINE: DANIEL KADLEC
BODY:
Dormant for years, the biotech bug is once again infesting stocks. This nasty
man-made microbe, hatched in the labs of Wall Street, surfaces every few years
to prey on susceptible (i.e., gullible) investors. Symptoms include feverish
optimism followed by cold chills of reality.
The cyclical critter was due to hatch again anyway, but last week's
revelation that Scottish scientists had succeeded in cloning a sheep amounted to
a final whack at the snooze button. Now investors are wide awake to the
potential wonders of biotechnology for the first time since a euphoric rally in
those stocks in 1991. If you're a doctor or scientist, go ahead and take your
best shot. Biotech certainly holds great promise, and you may well understand
enough to pick the few stocks that will thrive. But overall the industry has
been SO consistently disappointing that laymen should stay away lest they get
fleeced.
Consider that of the 300 or so publicly traded U.S. biotech firms, only about
a dozen stirred up a profit last year. Many are one-drug research outfits in a
field where only 1 in 10 drugs gets approved. In many cases, three or four
one-note companies are working on the same basic treatment, like wound healing.
It's a dicey business.
Recall the Flavr Savr, a tomato bioengineered to ripen on the vine and last
months on the shelf. It might have been a huge moneymaker if only the thing had
tasted like a tomato. Its maker, Calgene Inc., traded above $ 20 a share in
1992, but the stock subsequently rotted to $ 5, and Monsanto Co. has offered to
buy the company for $ 7.25 a share.
That is by no means the most devastating loss stemming from a biotech failure
in the '90s. Centocor Inc. fell from $ 60 to $ 5; Xoma Corp., from $ 32 to $ 1;
Synergen Inc., from $ 73 to $ 4--all because of hyped septic-shock drugs that
didn't work. Inject those babies into your 401 (k), and you'll never retire. And
these aren't isolated cases. Viren Mehta, a biotech expert at Mehta and Isaly,
keeps track of biotech bombs. He says there have been 14 major disasters this
decade. But even if you avoid specific product failures, it isn't enough.
Biotech stocks fly in swarms. The whole group gets clipped when a few failures
surface. In the three years that ended in December 1994, the average biotech
stock fell 63%.
The average biotech stock has doubled in two years and reached a four-year
high. Following the cloning news out of Scotland, investors indiscriminately
PAGE 23
Time, March 10, 1997
bid up stocks of cloning companies. Shares of PPL Therapeutics of Edinburgh,
which helped fund the sheep-cloning research, jumped 16% in a day. There have
been some genuine commercial successes, such as Biogen Inc. 's drug Avonex,
approved last year to treat multiple sclerosis. Still, a dangerous froth is
forming. "During the next six months you're going to see quite a few disasters,"
predicts Evan Sturza of Sturza's Medical Investment Letter.
There are lots of reasons to root for these companies. High stock prices
raise more money to seek important treatments. But after much exposure, I've
been able to develop a resistance to the biotech bug. And until the gene-bending
gods can separate the hype from the glory, they're not getting any of my
savings.
Daniel Kadlec is TIME's Wall Street columnist. Reach him at [email protected]
GRAPHIC: COLOR CHART, HOT AGAIN, American Stock Exchange Biotechnology Index,
weekly closings [Chart not available--index illustrated in line graph from 1990
to 1997}
LANGUAGE: ENGLISH
LOAD-DATE: March 3, 1997
PAGE
25
10TH STORY of Level 1 printed in FULL format.
Copyright 1997 Newsweek
Newsweek
March 10, 1997 / UNITED STATES EDITION
SECTION: SOCIETY; Pg. 60
LENGTH: 844 words
HEADLINE: Today the Sheep
BYLINE: BY KENNETH L. WOODWARD, With ANNE UNDERWOOD in New York
HIGHLIGHT:
Tomorrow the shepherd? Before science gets there, ethicists want some hard
questions asked and answered.
BODY:
TWENTY YEARS AGO, WHEN only the lowly tadpole had been cloned, bioethicists
raised the possibility that scientists might someday advance the technology to
include human beings as well. They wanted the issue discussed. But scientists
assailed the moralists' concerns as alarmist. Let the research go forward, the
scientists argued, because cloning human beings would serve no discernible
scientific purpose. Now the cloning of humans is within reach, and society as a
whole is caught with its ethical pants down.
Today the sheep -- tomorrow the shepherd? Whether the cloning of human beings
can be ethically justified is now firmly, perhaps permanently, on the nation's
moral agenda. President Clinton has given an advisory panel of experts just 90
days to come up with proposals for government action. The government could
prohibit the cloning of human beings or issue regulations limiting what
researchers can do. But the government cannot control the actions of individuals
or private groups determined to clone humans for whatever purpose. And science
has a way of outdistancing all ethical restraints. "In science, the one rule is
that what can be done will be done," warns Rabbi Moses Tendler, professor of
medical ethics at Yeshiva University in New York.
Some ethicists regard the cloning of humans as inherently evil, a morally
unjustifiable intrusion into human life. Others measure the morality of any act
by the intention behind it; still others are concerned primarily with the
consequences -- for society as well as for individuals. Father Richard
McCormick, a veteran Jesuit ethicist at the University of Notre Dame, represents
the hardest line: any cloning of humans is morally repugnant. A person who would
want a clone of himself, says McCormick, "is overwhelmingly self-centered. Once
Richard McCormick is enough." But why not clone another Einstein? Once you
program for producing superior beings, he says, you are into eugenics, "and
eugenics of any kind is inherently discriminatory. What's wrong with
duplicating a sibling whose bone marrow could save a sick child? That, he
believes, is using another human being merely "as a source for replaceable
organs." But why shouldn't an infertile couple resort to cloning if that is the
only means of having a child? "Infertility is not an absolute evil that
justifies doing any and every thing to overcome it," McCormick insists.
Other ethicists see possible exceptions to a general rule against cloning.
Tendler opposes cloning on Biblical grounds. But if a sterile
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Newsweek, March 10, 1997
second-generation Holocaust survivor wanted a male heir to continue an otherwise
doomed family line, the rabbi says he might advise the man to clone rather than
use donor sperm. Boston College moral theologian Lisa Sowhill Cahill is "not yet
convinced that cloning human beings is inherently evil. II The mother of identical
twins, Cahill questions whether creating a clone necessarily violates the
dignity of the original or of the genetic copy. As with other ethicists, what
most concerns Cahill is the commodification of human beings and their genes.
Forget hubris, consider commerce. What's to prevent the transfer of a dollop of
DNA to a wealthy bidder who wants an especially beautiful, swift or smart child?
Beyond the arguments of experts, the nation's religious communities "will
play an important role in the national debate over cloning," says Quaker
ethicist James Childress, a member of the president's advisory panel. All
theologians agree that a clone would have a soul like everyone else. Although
the pope has yet to address the cloning issue, the Vatican has repeatedly
condemned the use of human embryos for nontherapeutic purposes -- which is what
cloning requires. Islamic courts have not ruled on cloning, either, but Muslim
scholar Abdulaziz Sachedina, a medical ethicist at the University of Virginia,
worries about the long-term implications of separating reproduction from human
relationships. "Imagine a world with no need for marriage,' he asks. Protestant
ethicist Allen Verhey of Hope College in Holland, Mich., warns that cloning
would program parents to "think of their children as products.' And Buddhist
scholar Donald Lopez foresees real problems for the theory of karma. Would the
clone inherit the karma of the original person? And, he wonders, "what did the
sheep do in a previous life that resulting in its being cloned in this one?"
But to judge by what American society currently permits, the nation is
already far along the road toward tacit acceptance of cloning. "In our society
there are two values which will allow anyone to do whatever she wants in human
reproduction," observes ethicist Daniel Callahan of the Hastings Center in
Briarcliff Manor, N.Y. "One is the nearly absolute right to reproduce -- or not
- - as you see fit. The other is that just about anything goes in the pursuit of
improved health.' Perhaps the message of Dolly is that society should reconsider
its casual ethical slide toward assuming mastery over human life. Do we really
want to play God?
GRAPHIC: Picture, Andy Warhol cloning around in 'The Twenty Marilyns', (c) 1997
ANDY WARHOL FOUNDATION FOR THE VISUAL ARTS -- ARS N.Y. -- ART RESOURCE
LANGUAGE: ENGLISH
LOAD-DATE: March 11, 1997
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Copyright 1997 The Time Inc. Magazine Company
Time
March 10, 1997
SECTION: SPECIAL REPORT; Pg. 62
LENGTH: 1764 words
HEADLINE: THE AGE OF CLONING;
A LINE HAS BEEN CROSSED, AND REPRODUCTIVE BIOLOGY WILL NEVER BE THE SAME FOR
PEOPLE OR FOR SHEEP
BYLINE: J. MADELEINE NASH, WITH REPORTING BY HELEN GIBSON/ROSLIN AND DICK
THOMPSON/WASHINGTON
BODY:
Even now, a week after news of the achievement first flew around the globe,
traces of astonishment linger in the air like a contrail. The landmark paper
published late last week in the journal Nature confirmed what the headlines had
been screaming for days: researchers at the Roslin Institute near Edinburgh,
Scotland, had indeed pulled off what many experts thought might be a scientific
impossibility. From a cell in an adult ewe's mammary gland, embryologist Ian
Wilmut and his colleagues managed to create a frisky lamb named Dolly (with
apologies to Ms. Parton), scoring an advance in reproductive technology as
unsettling as it was startling. Unlike offspring produced in the usual fashion,
Dolly does not merely take after her biological mother. She is a carbon copy, a
laboratory counterfeit so exact that she is in essence her mother's identical
twin.
What enabled the Scottish team to succeed where so many others have failed
was a trick so ingenious, yet so simple, that any skilled laboratory technician
should be able to master it--and therein lies both the beauty and the danger:
once Wilmut and his colleagues figured out how to cross that biological barrier,
they ensured that others would follow. And although the Roslin researchers had
to struggle for more than 10 years to achieve their breakthrough, it took
political and religious leaders around the world no time at all to grasp its
import: if scientists can clone sheep, they can probably clone people too.
Without question, this exotic form of reproductive engineering could become
an extremely useful tool. The ability to clone adult mammals, in particular,
opens up myriad exciting possibilities, from propagating endangered animal
species to producing replacement organs for transplant patients. Agriculture
stands to benefit as well. Dairy farmers, for example, could clone their
champion cows, making it possible to produce more milk from smaller herds. Sheep
ranchers could do the same with their top lamb and wool producers.
But it's also easy to imagine the technology being misused, and as news from
Roslin spread, apocalyptic scenarios proliferated. Journalists wrote seriously
about the possibility of virgin births, resurrecting the dead and women giving
birth to themselves. On the front page of the New York Times, a cell biologist
from Washington University in St. Louis, Missouri, named Ursula Goodenough
quipped that if cloning were perfected, "there'd be no need for men."
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Time, March 10, 1997
Scientists have long dreamed of doing what the Roslin team did. After all, if
starfish and other invertebrates can practice asexual reproduction, why can't it
be extended to the rest of the animal kingdom? In the 1980s, developmental
biologists at what is now Allegheny University of the Health Sciences came
tantalizingly close. From the red blood cells of an adult frog, they raised a
crop of lively tadpoles. These tadpoles were impressive creatures, remembers
University of Minnesota cell biologist Robert McKinnell, who followed the work
closely. "They swam and ate and developed beautiful eyes and hind limbs, he
says. But then, halfway through metamorphosis, they died.
Scientists who have focused their cloning efforts on more forgiving embryonic
tissue have met with greater success. A simple approach, called embryo twinning
(literally splitting embryos in half), is commonly practiced in the cattle
industry. Coaxing surrogate cells to accept foreign DNA is a bit trickier. In
1952 researchers in Pennsylvania successfully cloned a live frog from an
embryonic cell. Three decades later, researchers were learning to do the same
with such mammals as sheep and calves. "What's new, observes University of
Wisconsin animal scientist Neal First, "is not cloning mammals. It's cloning
mammals from cells that are not embryonic."
Embryo cells are infinitely easier to work with because they are, in the
jargon of cell biologists, largely "undifferentiated." That is, they have not
yet undergone the progressive changes that turn cells into skin, muscles, hair,
brain and SO on. An undifferentiated cell can give rise to all the other cells
in the body, say scientists, because it is capable of activating any gene on any
chromosome. But as development progresses, differentiation alters the way
DNA--the double-stranded molecule that makes up genes--folds up inside the
nucleus of a cell. Along with other structural changes, folding helps make vast
stretches of DNA inaccessible, ensuring that genes in adult cells do not turn on
at the wrong time or in the wrong tissue.
The disadvantage of embryonic cloning is that you don't know what you are
getting. With adult-cell cloning, you can wait to see how well an individual
turns out before deciding whether to clone it. Cloning also has the potential to
make genetic engineering more efficient. Once you produce an animal with a
desired trait--a pig with a human immune system, perhaps--you could make as many
copies as you want.
In recent years, some scientists have speculated that the changes wrought by
differentiation might be irreversible, in which case cloning an adult mammal
would be biologically impossible. The birth of Dolly not only proves them wrong
but also suggests that the difficulty scientists have had cloning adult cells
may have less to do with biology than with technique.
To create Dolly, the Roslin team concentrated on arresting the cell
cycle--the series of choreographed steps all cells go through in the process of
dividing. In Dolly's case, the cells the scientists wanted to clone came from
the udder of a pregnant sheep. To stop them from dividing, researchers starved
the cells of nutrients for a week. In response, the cells fell into a slumbering
state that resembled deep hibernation.
At this point, Wilmut and his colleagues switched to a mainstream cloning
technique known as nuclear transfer. First they removed the nucleus of an
unfertilized egg, or oocyte, while leaving the surrounding cytoplasm intact.
Then they placed the egg next to the nucleus of a quiescent donor cell and
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Time, March 10, 1997
applied gentle pulses of electricity. These pulses prompted the egg to accept
the new nucleus--and all the DNA it contained--as though it were its own. They
also triggered a burst of biochemical activity, jump-starting the process of
cell division. A week later, the embryo that had already started growing into
Dolly was implanted in the uterus of a surrogate ewe.
An inkling that this approach might work, says Wilmut, came from the success
his team experienced in producing live lambs from embryonic clones. "Could we do
it again with an adult cell?" wondered Wilmut, a reserved, self-deprecating man
who likes gardening, hiking in the highlands and drinking good single-malt
Scotch (but who was practical enough to file for a patent before he went
public).
It was a high-risk project, and in the beginning Wilmut proceeded with great
secrecy, limiting his core team to four scientists. His caution proved to be
justified; the scientists failed far more often than they succeeded. Out of 277
tries, the researchers eventually produced only 29 embryos that survived longer
than six days. Of these, all died before birth except Dolly, whose historic
entry into the world was witnessed by a handful of researchers and a
veterinarian.
Rumors that something had happened in Roslin, a small village in the green,
rolling hills just south of Edinburgh, started circulating in scientific circles
a few weeks ago. It was only last week, when the rumors were confirmed and the
details of the experiment revealed, that the real excitement erupted. Cell
biologists, like everybody else, were struck by the simple boldness of the
experiment. But what intrigued them even more was what it suggested about how
cells work.
Many scientists had suspected that the key to getting a donor cell and egg to
dance together was synchronicity--getting them started on the same foot. Normal
eggs and sperm don't have that problem; they come pre-divided, ready to combine.
An adult cell, though, with its full complement of genes, has to be coaxed into
entering an embryonic state. That is probably what Wilmut did by putting the
donor cell to sleep, says Colin Stewart, an embryologist at the National Cancer
Institute. Somehow, in ways scientists have yet to understand, this procedure
seems to have reprogrammed the DNA of the donor cell. Thus when reawakened by
the Roslin team, it was able to orchestrate the production of all the cells
needed to make up Dolly's body.
Like most scientists who score major breakthroughs, Wilmut and his colleagues
have raised more questions than they have answered. Among the most pressing are
questions about Dolly's health. She is seven months old and appears to be
perfectly fine, but no one knows if she will develop problems later on. For one
thing, it is possible that Dolly may not live as long as other sheep. After all,
observes NCI's Stewart, "she came from a six-year-old cell. Will she exhibit
signs of aging prematurely?" In addition, as the high rate of spontaneous
abortion suggests, cloning sometimes damages DNA. As a result, Dolly could
develop any number of diseases that could shorten her life.
Indeed, cloning an adult mammal is still a difficult, cumbersome business--so
much so that even agricultural and biomedical applications of the technology
could be years away. PPL Therapeutics, the small biotechnical firm based in
Edinburgh that provided a third of the funding to create Dolly, has its eye on
the pharmaceutical market. Cloning, says PPL's managing director Ron James,
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Time, March 10, 1997
could provide an efficient way of creating flocks of sheep that have been
genetically engineered to produce milk laced with valuable enzymes and drugs.
Among the pharmaceuticals PPL is looking at is a potential treatment for cystic
fibrosis.
Nobody at Roslin or PPL is talking about cloning humans. Even if they were,
their procedure is obviously not practical--not as long as dozens of surrogates
need to be impregnated for each successful birth. And that is probably a good
thing, because it gives the public time to digest the news-and policymakers
time to find ways to prevent abuses without blocking scientific progress. If the
policymakers succeed, and if their guidelines win international acceptance, it
may take a lot longer than the editorial writers and talk-show hosts think
before a human clone emerges--even from the shadows of some offshore renegade
lab. "How long?" asks PPL's James. "Hopefully, an eternity.
--With reporting by Helen Gibson/Roslin and Dick Thompson/Washington
GRAPHIC: COLOR ILLUSTRATION: ILLUSTRATION FOR TIME BY TIM O'BRIEN, [Drawing of
cloned men walking away from gum-ball machine containing additional clones];
COLOR PHOTO: WILLIAM RITCHIE--ROSLIN INSTITUTE, DELICATE OPERATION Researchers
at the Roslin Institute use a hair-thin pipette to pierce an egg cell and remove
its nucleus and DNA [Magnified image of pipette and egg cell]; FIVE COLOR
ILLUSTRATIONS: TIME DIAGRAM BY JOE LERTOLA, [Drawing of Finn Dorset ewe and
donor cell; drawing of Blackface ewe and egg cell with DNA highlighted; drawing
of donor cell fusing with egg cell; drawing of embryo and Blackface ewe; drawing
of Finn Dorset lamb]
LANGUAGE: ENGLISH
LOAD-DATE: March 3, 1997
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Time
March 10, 1997
SECTION: SPECIAL REPORT
LENGTH: 64 words
HEADLINE: If you had the chance, would you clone yourself?
BODY:
Yes 7%
No 91%
Is it against God's will to clone human beings?
Yes 74%
No
19%
Should the Federal Government regulate the cloning of animals?
Yes 65%
No 29%
From a telephone poll of 1,005 adult Americans taken for
TIME/CNN on Feb. 26-27 by Yankelovich Partners Inc. Sampling
error +/- 3.1%. "Not sures" omitted.
LANGUAGE: ENGLISH
LOAD-DATE: March 3, 1997
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Copyright 1997 The Time Inc. Magazine Company
Time
March 10, 1997
SECTION: SPECIAL REPORT; Pg. 60
LENGTH: 814 words
HEADLINE: A SPECIAL REPORT ON CLONING
BYLINE: CHARLES KRAUTHAMMER
BODY:
One doesn't expect Dr. Frankenstein to show up in wool sweater, baggy parka,
soft British accent and the face of a bank clerk. But there in all banal
benignity he was: Dr. Ian Wilmut, the first man to create fully formed life from
adult body parts since Mary Shelley's mad scientist.
The creator wore chinos. Wilmut may not look the part, but he plays it. He
took a cell nucleus from a six-year-old ewe, fashioned from it a perfect
twin--adding the nice Frankenstein touch of passing an electric charge through
the composite cell to get it growing--and called it Dolly.
Dolly, the clone, is an epochal- cataclysmic--creature. Not because of the
technology that produced it. Transferring nuclei has been done a hundred times.
But because of the science. Dolly is living proof that an adult cell can revert
to embryonic stage and produce a full new being. This was not supposed to
happen.
It doesn't even happen in amphibians, those wondrously regenerative little
creatures, some of which can regrow a cut-off limb or tail. Try to grow an
organism from a frog cell, and what do you get? You get, to quote biologist
Colin Stewart, "embryos rather ignominiously dying (croaking!) around the
tadpole stage."
And what hath Wilmut wrought? A fully formed, perfectly healthy mammal--a
mammal!-born from a single adult cell. Not since God took Adam's rib and
fashioned a helpmate for him has anything so fantastic occurred.
What, then, was the reaction to this breakthrough of biblical proportions?
There is a mischievous story (told mostly in England) that a leading Scottish
newspaper reported the Titanic sinking with the headline GLASGOW MAN LOST AT
SEA. Well, here was a story that deserved the headline MAN CREATES LIFE. And how
does it play? A Wall Street Journal headline urgently asks, WHO WILL CASH IN ON
BREAKTHROUGH IN CLONING? (Answer: "Tiny company could emerge a big winner ") The
President of the U.S. calls for a committee of experts to gather and pull their
beards.
And the New York Times, in a lovely coda to its editorial titled CLONING FOR
GOOD OR EVIL, advises that "society will need to sort through what is acceptable
and what is the nightmare beyond."
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Time, March 10, 1997
Well, yes. The most portentous scientific achievement since Alamogordo will
need a weighing of pros and cons. No kidding.
And, no doubt, the pro-and-con weighing, the pontificating and the chin
pulling will now go into high gear. Wilmut will spawn more ethics conclaves than
cloned sheep. No matter. There is nothing to stop cloning, not even of humans.
What the politicians do not understand is that Wilmut discovered not so much
a technical trick as a new law of nature. We now know that an adult mammalian
cell can fire up all the dormant genetic instructions that shut down as it
divides and specializes and ages, and thus can become a source of new life.
You can outlaw technique; you cannot repeal biology. And even the outlawing
of this technique--Britain for example, forbids the cloning of humans--will
fail. It is too simple, too replicable. No amount of regulation by the FDA or
the NIH or even the FBI will stop it.
Why? Not just because it is SO easy, but because its potential for good is so
immense. The study of cloning can give the world deep insights into such puzzles
as spinal cords, heart muscle and brain tissue that won't regenerate after
injury, or cancer cells that revert to embryonic stage and multiply
uncontrollably. Replicating Wilmut's work will elucidate what he along the way
did right that nature, in these pathologies, does wrong.
Of course, the potential for evil is infinitely greater. But there will be no
stopping that either. Ban human cloning in America, as in England, and it will
develop on some island of Dr. Moreau. The possibilities are as endless as they
are ghastly: human hybrids, clone armies, slave hatcheries, "delta" and
"epsilon" sub-beings out of Aldous Huxley's Brave New World.
But you don't have to be mad to be tantalized. Being human will do. Think of
it: what Dolly--fat, insensible Dolly--promises is not quite a second chance at
life (you don't reproduce yourself; you just reproduce a twin) but another
soul's chance at your life. Every parent tries to endow his child with the
wisdom of his own hard-earned experience. Here is the opportunity to pour all
the accumulated learning of your life back into a new you, to raise your exact
biological double, to guide your very flesh through a second existence.
Oh, the temptation to know what might have been. Or to produce an Einstein, a
Dr. King, for every generation. Or to raise a Jefferson in a clearing, a cross
between Jurassic Park and Williamsburg, an artificial environment re-creating
18th century Virginia. Create, nurture and wait. Then bring him out one day,
fully grown, to answer the question of the ages: What would Jefferson do today?
-CHARLES KRAUTHAMMER
GRAPHIC: COLOR PHOTO: DIGITAL PHOTOMONTAGE BY ARTHUR HOCHSTEIN. DOLLY,
PHOTOGRAPHED FOR TIME BY ROBERT WALLIS--SABA, COVER, Will There Ever Be Another
You? A SPECIAL REPORT ON CLONING, [Multiple image of cloned sheep Dolly]; COLOR
PHOTO: ROBERT WALLIS--SABA FOR TIME, Good or Baa-ad? Cloning a sheep sets off a
worldwide debate on ethics (see SPECIAL REPORT) [Sheep--T of C]; COLOR PHOTO:
REUTERS, [Ian Wilmut and sheep]
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Time
March 17, 1997
SECTION: SCIENCE; Pg. 60
LENGTH: 1011 words
HEADLINE: NETI AND DITTO;
TWO CUTE NEW CLONES ARE TOO CLOSE FOR COMFORT
BYLINE: CHRISTINE GORMAN
BODY:
It was bad enough when Scottish researchers cloned a sheep named Dolly and
commentators started writing about virgin births and Frankenstein. But then one
week later, researchers at the Oregon Regional Primate Research Center let it be
known that they had cloned a pair of rhesus monkeys, named Neti (for nuclear
embryo transfer infant) and Ditto, that squinted in the glare of the TV lights
and clung to each other for dear life.
It was two clones too many--or, more to the point, clones too close to human
for comfort. Politicians- with one eye on re-election and another on the polls
(a TIME/CNN survey reported that 3 out of 4 Americans believe such research is
"against the will of God") -wasted no time. The President, proclaiming that
"each human life is unique, born of a miracle that reaches beyond laboratory
science, banned the use of federal funds for human cloning, while Republican
Representative Vernon Ehlers of Michigan introduced not one but two anticloning
measures.
Lost in the rush of legislative activity was the fact that Neti and Ditto
were not so much a step toward a brave new world as a diversion. They were
produced from embryos, which makes them clones only in the way that identical
twins or triplets are clones. The same technique has already been used with
sheep, cattle, rabbits, pigs and even humans--although in the last case the
embryonic clones were destroyed. What makes Dolly special is that she was cloned
from an adult sheep, not from an embryo. She is the only mammal ever born that
is identical to her biological mother.
She may not be the last, however. As NIH director Dr. Harold Varmus told a
congressional subcommittee last week, it could take just one infertile couple,
arguing that cloning provides their only chance to bear a child, to turn public
opinion around.
--By Christine Gorman
GRAPHIC: COLOR PHOTO: JACK SMITH--AP, LAB MATES: Making monkeys of politicians
[Monkeys Neti and Ditto]
LANGUAGE: ENGLISH
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79TH STORY of Level 1 printed in FULL format.
Copyright 1997 Information Access Company, a Thomson Corporation Company;
IAC (SM) Industry Express (SM) ;
Copyright 1997 American Health Consultants
BIOWORLD Today
March 31, 1997
SECTION: VOL. 8; No. 61
LENGTH: 732 words
HEADLINE: BIO LETTER TO PRESIDENT CLINTON URGES CAUTION IN CLONING LEGISLATION
BYLINE: Seachrist, Lisa
BODY:
By Lisa Seachrist Washington Editor WASHINGTON While lauding President
Clinton's decision to declare a moratorium on research into cloning humans until
the National Bioethics Advisory Commission (NBAC) weighs in at the end of May,
the Biotechnology Industry Organization (BIO) urged Clinton to oppose hastily
drafted legislation that could threaten biotechnology research. In a letter
delivered to the president on March 27, BIO recognizes the spiritual and ethical
dilemmas raised by the sheep clone, Dolly, but warns that poorly thought out
legislation could jeopardize important medical research.
"The board wanted to get on record as having similar concerns to the public,"
Carl Feldbaum, president of BIO, said. "But we also wanted to state very
graphically the risks of bad legislation."
In the letter, BIO notes that Dolly "raises new prospects for which we are
not so adequately prepared." And, BIO continues, "these new prospects challenge
some of the most fundamental concepts we hold about ourselves as social and
spiritual beings.'
Nevertheless, the organization points out that cloning the duplication of
genes is an essential tool in biotechnology. BIO goes on to say that the
cloning of certain human tissues could produce replacement skin, cartilage and
bone tissue for burn and accident victims as well as potentially produce cells
for cancer therapy. In addition, research into cloning human cells could result
in ways to regenerate diseased retinas and severed spinal cords.
"The good news about all of this is that legislators and people in general
understand the value of biotech research and they don't want to put it in
jeopardy,' Feldbaum said. "We just want to make sure that no legitimate research
is deterred in the process of creating laws to address human cloning.'
BIO said it intends to circulate the letter to both houses of Congress, the
NBAC as well as to state legislators in order to educate them about the need for
a cautious approach to legislation. "Our position is Let's wait. Let's not jump
ahead until we have heard from the president's bioethics commission, Feldbaum
said.
Already three bills have been introduced in the 105th Congress to prohibit
cloning human beings. In the Senate, Christopher Bond (R- Mont.) sponsored S.
368 stating that "no federal funds may be used for research with respect to
PAGE
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BIOWORLD Today March 31, 1997
the cloning of a human individual." Bond goes on to define the term cloning to
mean "the replication of a human individual by the taking of a cell with genetic
material and the cultivation of the cell through the egg, embryo, fetal and
newborn stages into a new human individual.
Rep. Vernon Ehlers (R-Mich.) introduced two bills in the House. H.R. 922
dictates that "none of the funds made available in any Federal law may be
expended to conduct or support any project of research that involves the use of
a human somatic cell for the process of producing a human clone." H.R. 923 opens
the door to civil penalties for using "a human somatic cell for the process of
producing a human clone."
While all of these bills are well meaning, Feldbaum noted that Ehlers' bills
leave the door open to interpretations that could stymie biotech research
because they don't provide a definition of what is meant by producing a human
clone. The Bond bill, while clearer about what is meant by cloning a human, is
still under scrutiny, and BIO has not taken a position on it, Feldbaum said.
Even if Congress proceeds cautiously, biotech research faces a threat from
state initiatives designed to prohibit human cloning. To date, BIO counts 12
bills that address human cloning in states as varied as Alabama, California and
Florida.
"The worst bill is in Florida, where the proposed legislation bans the
cloning of human DNA. " Feldbaum said that, should such a bill become law, it
would effectively eliminate medical research in the state. "This is a bill that
we are going to oppose categorically.'
"Cloning is not an issue for grandstanding," Feldbaum said. "State
legislators need to know that if they enact a poorly written law they could
drive biotech and medical research from their state."
The U.S. isn't the only country struggling with the challenge of crafting
appropriate legislation. Feldbaum said that he has been informed of a Canadian
bill in the Canadian House of Commons that could stymie research in that
country.
LANGUAGE: ENGLISH
LOAD-DATE: April 1, 1997
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IAC (SM) Industry Express (SM) ;
Copyright 1997 American Health Consultants
BIOWORLD Today
April 1, 1997
SECTION: VOL. 8; No. 62
LENGTH: 1195 words
HEADLINE: MOVE OVER, YACS; HERE COME THE HACS CASE WESTERNERS CONSTRUCT FIRST
ARTIFICIAL HUMAN CHROMOSOMES
BYLINE: Leff, David N.
BODY:
By David N. Leff Science Editor
The
hourglass-shaped centromere, which pinches the midriff of every human
chromosome, carries no genes. Its job is to honcho the proper divvying up of
chromosomal DNA during cell division.
"While it's been known since the early years of this century that chromosomes
carry genes,' said geneticist Huntington Willard, "until now the complexity and
size of normal chromosomes has limited our ability to analyze their structure
and function."
One of the most complex parts of that overall complexity is the centromere.
"Our successful creation of functional centromeres and incorporation of them
into human artificial chromosomes HAC Willard observed, "were the critical
achievements enabling the stability and normal behavior of the chromosomes
during cell division."
Willard, who chairs the department of genetics at Case Western Reserve
University, in Cleveland, is senior author of a paper in the April issue of
Nature Genetics, titled: "Formation of de novo centromeres and construction of
first-generation human artificial chromosomes."
Molecular geneticists have been frustrated in their efforts to create human
artificial chromosomes. Instead, they must make do with yeast artificial
chromosomes (YAC) in cloning experiments. These are patterned on the genomic DNA
of Saccharomyces cerevisiae baker's yeast.
"YACs have been instrumental in allowing the Human Genome Project to move
forward," observed cancer biologist John Harrington, the article's lead author.
"They've been used to date largely as a cloning vector. Until very recently, he
pointed out, "YACs have been the only vector that allowed very large pieces of
human DNA to be cloned. By large, I mean from several hundred kilobases up to,
and perhaps exceeding, a million bases in size."
Why HACs Lagged Behind YACs
Human chromosomes, which range from about 50 to 250 megabases in size, are
100-fold larger than their yeast-cell counterparts.
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BIOWORLD Today April 1, 1997
"One of the major obstacles confronting people interested in cloning human
artificial chromosomes,' Harrington told BioWorld Today, "has been an inability
to clone a functional human centromere.' He counted the reasons why:
"First, it's extremely large, unlike the yeast centromere, which is only 125
base pairs in length.
"Second, the human centromere is made up of extremely repetitive sequences of
alpha-satellite DNA. This consists of a 171-base-pair, head-to-tail tandem
repeat, iterated over and over again for several thousand base pairs long."
Harrington pointed out that "the exact function of this class of DNA is largely
unknown, because until now we've never had a system that allowed us to dissect
the function associated with these centromeric repeats."
A principal goal of Case Western's two-year HAC-building effort was to
provide vectors for gene therapy free of the drawbacks that hamper viral and
non-viral DNA vehicles. "Viral vectors,' Harrington pointed out, "suffer from
serious limitations, such as unstable gene expression, unwanted immune
responses, occasional generation of infectious viral particles, and stringent
size restrictions, which allow only small genes to be placed in the viral
plasmid and delivered to the target tissue."
If genes are the "software" of chromosomes, then their "hardware" consists of
the gene-free, wasp-wasted centromere near their middle, and telomeres at each
end. The latter are far-out (literally) repetitive regions of DNA, capping both
tips of every chromosome. Telomeres act like boundary markers or bumpers to
protect the chromosome from unwanted hook-ups, end-to-end, with other
chromosomes.
As Harrington recounted, to construct their human artificial chromosomes, he
and his co-authors first synthesized arrays of alpha satellite DNA. Then, to
this centromeric genetic material, they added telomeres and large fragments of
random human genomic DNA. The latter presumably contained origins of replication
sequences that regulate the controlled copying of a chromosome's total DNA
during cell division. They kick-start the replication process, and thus
constitute the business part of a gene-therapy vector.
"This approach, Harrington explained, "simply allowed us, in essence, to
make a DNA library within the cells we transfected."
Finally, they inserted this mix into human tumor cell lines. There, like
building blocks, these independent elements assembled into miniature versions of
human chromosomes.
As for the actual assembly of the HACs inside those cells, Harrington said,
"Once we introduced the several DNA ingredients into the cell, they found their
way to the nucleus, where they assembled into various HAC combinations. Genes
present in both the genomic DNA and in our constructs were then expressed. At 24
to 48 hours after that transfection took place, we put the cells under drug
selection, which killed off the vast majority of them.
"Among the survivors," Harrington went on, "were putative human
microchromosomes, which persisted inside dividing cells for more than six months
of culture. At that point they had all the characteristics of normal human
chromosomes, except for size. These HACs are only a tenth as large as native
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BIOWORLD Today April 1, 1997
human chromosomes. II
Readying HACs For Gene Therapy Vector Duty
To bring their HACs to the clinic, and to market, three of the paper's
co-authors founded Cleveland-based Athersys Inc. in 1994.
Harrington is the company's vice president for research and development.
"Athersys was a spin-off of Case Western," he explained, "but is now an
independent, privately financed company, which has a very good working
relationship with the university."
Geneticist Gil Van Bokkelen is the firm's president and CEO and Willard is a
member of its scientific advisory board. All three are inventors on an allowed
U.S. patent which, Harrington said, "covers methods of cloning long
alpha-satellite DNA sequences up to about 200 kilobases in length, then
expanding them in vitro to a megabase long.'
Two other patent applications are pending.
Once their prototype synthetic microchromosomes (HACs) are refined for use,
Harrington said, "the first thing we'd want to demonstrate is that they can be
introduced into primary, freshly isolated human cells. Next, to show that they
could go into stem cells, which can be used in various ex vivo gene therapy
applications."
The project leaders are also "very interested in developing animal models
that would allow us to determine the safety and efficacy of our prototype HACs
in a non-human system."
Harrington foresees their use "in gene therapy human clinical trials the
ultimate goal we hope, in the next couple of years. " The first such
applications, he concluded, "are expected to be in treating disorders such as
AIDS, sickle-cell anemia, beta-thalassemia, cystic fibrosis and muscular
dystrophy."
An editorial accompanying the Case Western paper in Nature Genetics called it
"an important landmark in terms of constructing HACs. This is the first time
that a mitotically and cytogenetically stable artificial chromosome derived from
transfected DNA has been generated.' n
LANGUAGE: ENGLISH
LOAD-DATE: April 2, 1997
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Copyright 1997 Information Access Company, a Thomson Corporation Company;
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BIOWORLD Today
April 15, 1997
SECTION: VOL. 8; No. 72
LENGTH: 1208 words
HEADLINE: CLOCK TICKS FOR NATIONAL BIOETHICS COMMISSION AS CLONING ISSUE IS
SCRUTINIZED
BYLINE: Seachrist, Lisa
BODY:
By Lisa Seachrist Washington Editor WASHINGTON With its deadline for makings
ome recommendations on cloning to President Clinton looming six weeks ahead,
the National Bioethics Advisory Commission (NBAC) is leaning toward proposing a
federal ban on research efforts that would result in producing a cloned human
baby The commission, however, appears hesitant to weigh in on research in human
tissues that stops short of implanting a cloned embryo the types of research
on human eggs and DNA that could result in new cell and tissue therapies for
fear of simply renewing the human embryo research debate.
"We have a lot to do here, said NBAC chairman and Princeton University
President Harold Shapiro. "But, for a wide variety of reasons, everyone seems to
be saying they want a barrier to human cloning now. Here is an easier area to
reach a conclusion."
NBAC entertained religious, legal, scientific and ethical points of view at
its meeting in March. Shapiro divided the issues into three "buckets" to contain
the various questions that will come to play in any policy recommendations and
assigned the commissioners to participate in one of the discussion "buckets.'
Bernard Lo, a medical ethicist at the University of California, San
Francisco, lead the ethical discussion, which focused on which consideration was
strong enough to continue the moratorium: whether those who wished to clone or
those who wished to prevent cloning had the burden of proof, and what arguments
would justify a permanent ban.
"We had a lot of support for continuing the moratorium," Lo said, "but we
couldn't pinpoint any one objection that was telling. Instead, it was a
cumulative effect that may justify a continuation of the moratorium. And we
didn't begin to touch upon the research that would lead up to cloning a human.
The ethical "bucket,' however, did try to assess whether there was an
inherent right to reproduction and, if there was, whether these were limits to
that right. They weighed that view against concerns discussed during the
religious perspectives meeting in March, which include undue expectations of a
cloned human, disruption of the family unit as well as problems in identifying
one's genetic parents.
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BIOWORLD Today April 15, 1997
Nevertheless, the ethical discussion found some difficulty incorporating
religious views because they weren't stated in secular language.
"Some people said that is demeans our belief to ask us to state it in secular
terms,' Lo said. "It is difficult because many of these objections do have
weight, but many religious representatives feel it shows disrespect to ask for
different language. II
Thomas Murray, an ethicist at Case Western Reserve University, in Cleveland,
who asked several of the speakers in the March meeting to state their objections
in secular terms, pointed out that the commission "can't just give veto power to
anyone with a strong belief. We don't do that with blood transfusions even
though some find that procedure offensive."
Attempting To Regulate That Which Doesn't Exist
Even though these types of considerations will be important in developing
policy actions for the committee, several members questioned whether it was
necessary to address human cloning when cloning as yet doesn't exist. Stuart
Orkin, professor of pediatric medicine at Harvard Medical School, and Janet
Rossant, senior scientist at Mount Sinai Hospital, in Toronto, served as
cloning experts and presented some of the scientific issues to the committee.
Rossant noted that species differences may prevent human cloning from ever
happening. In addition, she pointed out that there are completely differentiated
cells in most tissues and it is unclear that the donor cell used to create the
cloned sheep "Dolly" was indeed a fully differentiated cell.
"It is possible that imprinting may result in developmental problems,"
Rossant said. "There is also some risk to the cloned human as a result of using
old DNA it may result in a shortened life and they have begun to accumulate
mutations that could cause problems."
Orkin presented the list of steps that good science would follow before
attempting to create a human clone. Orkin maintains that science today is in
phase one basic research into animal cloning and the cellular mechanisms
controlling reprogramming of the DNA. Phase two, which is not yet happening,
would include experimentation on early embryos not intended for implementation.
Phase three would include generating differentiated cells as cellular therapies
and phase four would be implanting an embryo produced by nuclear transfer in
order to produce a human being.
"At this time period, implanting, in addition to ethical concerns, is just
bad science, Orkin said. "We need more information from animal experiments."
Ezekial Emmanuel, professor of medicine at the Dana-Farber Cancer Institute,
in Boston, asked whether, for the time being, animal research provides enough
information. Rossant responded, "For now, there is a great deal of animal
research that needs to be done. But I don't see how any cellular therapies are
going to arise without moving to experiments with human eggs and producing a
human embryo. "
Because of a ban on human embryo research written into the appropriations
legislation for the National Institutes of Health, there is no government
funding for, and consequently no oversight of, human embryo research. For that
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BIOWORLD Today April 15, 1997
reason, the legal "bucket" explored all of the policy options for two different
activities that Alta Charo, professor of law at the University of Wisconsin,
Madison, described as "baby-making and everything else.'
For "everything else, Charo described the policy options as total
permission, including federal funding, permissibility without federal funding,
conditional permissibility without federal funding and rules that restrict use
in humans, until adequate information in animals is obtained, or a total
prohibition.
"It is important to realize that federal funding may slow down the
introduction of this technology into the clinic, " Charo said.
In the "baby-making" scenario, Alexander Capron described the policy options
as full federal funding, conditional permissibility without federal funding and
protections in place for the gestating woman and consent to using DNA, or a
total prohibition.
"We all agree about baby-making. III Eric Cassell, professor of public health
at Cornell Medical College, in New York, said. "But how do we get at the private
sector?"
Charo noted that with the current ban on human embryo research, some doctors
in the fertility field have patients pay for services that are basically
unproven experimental therapies that take place outside of clinical protocols
without any outside review.
Charo advocates the extension of basic human subject protections informed
consent and outside protocol review to all citizens in the U.S. Currently,
human subject protections apply for those participating in research funded by
the National Institutes of Health, those participating in studies that will be
reviewed by FDA and those participating in research sponsored by a few other
government agencies.
NBAC plans to meet twice in May in order to prepare policy recommendations
for the president.
LANGUAGE: ENGLISH
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ASAP
Copyright 1990 Atlantic Monthly Company
The Atlantic
June, 1990
SECTION: Vol. 265 i No. 6 ; Pg. 40; ISSN: 0276-9077
LENGTH: 3736 words
HEADLINE: Getting the bugs out; agricultural use of genetically altered bacteria
BYLINE: Baskin, Yvonne
BODY:
IN THE SPRING of 1987 California scientists removed the lids from a few
petri dishes, scraped out yellowish-white blotches that smelled like sweaty
feet, diluted the material in water, and sprayed it on a tiny patch of potatoes
and another of strawberries. With the spraying, genetically engineered microbes
made their much delayed debut in the environment.
The blotches were colonies of bacteria, nicknamed "ice minus, that had been
altered in a laboratory so that they would protect plants from mild frosts.
Boosters of biotechnology predicted that ice minus would soon be joined by
microbes genetically altered to kill caterpillars and weevils, supply nitrogen
to the roots of plants, and eliminate the increasing and undisputed menace to
the environment of chemical pesticides and fertilizers.
Alternatives to farm chemicals are hardly a new dream, In her landmark 1962
book Silent Spring, Rachel Carson urged the nation to take "the other road, to
seek biological solutions, based on understanding of the living organisms they
seek to control, and of the whole fabric of life to which these organisms
belong.' The dream, however, remains largely unfulfilled. Researchers have
identified some 1,500 microorganisms or microbial toxins with the potential to
control insects. But in their naturally occurring forms most have proved too
short-lived, too slow to kill, and too narrowly specific in their effects to
oust chemicals from the farm. Only nineteen microorganisms-eleven bacteria, four
viruses, three fungi, and one protozoan-have been registered as pesticides by
the Environmental Protection Agency, as compared with some 640 chemicals, used
in 24,000 pesticide products. In some areas the introduction of wasps and other
predators has successfully controlled insect pests. Altogether, however, only
one percent of the world's 10,000 crop pests can now be controlled effectively
by natural biological methods.
With the advent of genetic-engineering techniques, in the mid-1970s,
biologists held out the hope that many of the drawbacks to pest control by
microbes could be overcome. But in the early 1980s, when agricultural
researchers began trying to enhance the efficiency of biological agents through
genetic engineering, not everyone perceived it as the fulfillment of Carson's
dream. Indeed, when the plant pathologist Steven Lindow first sought permission,
in 1982, to field-test ice minus, he aroused the nation's misapprehensions, not
only about genetic engineering but also about technology in general. It took
five years of congressional scrutiny, public hearings, lawsuits, ever-shifting
regulatory hurdles, and even vandalism of the fields before Lindow and
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The Atlantic, June, 1990
Advanced Genetic Sciences, a small Oakland, California, biotech firm that had
license to use his concept, were allowed to spray their microbes outdoors.
To those of us who gathered for the events, near Brentwood, in California's
Central Valley, and at Tulelake, California, on the Oregon border, the signs of
the nation's anxiety were unmistakable. Both patches of land were surrounded by
metal towers and stakes laden with EPA air-monitoring equipment. By regulatory
fiat the researchers wore "moonsuits" and respirators as they sprayed, creating
an ominous tableau for the television cameras.
These dramatic precautions were abandoned within months. Regardless, only
half a dozen live, genetically engineered microorganisms have followed ice minus
out of the lab. None is available to farmers. The technique remains, as one
biotech executive put it, in an "intellectual cul-de-sac," trapped there by
public perceptions and a formidable regulatory scheme.
Just what is this ice-minus bacterium? Where does it come from? How does it
work? How do we know whether it poses any threat at all to the environment?
FARMERS IN THE northern half of the United States spend millions of dollars
a year on frost protection: smudge pots to heat the air, sprinklers to wet the
crop, wind machines and helicopters to mix the cold ground layer with warmer air
aloft, and artificial fogs or foam blankets to prevent heat loss from the
ground. Still, they lose as much as $ 3 billion a year in direct damage from
mild frosts. Perhaps more important, the threat of frost limits both the growing
season and the northern range of crops.
Traditional plant breeders, who engineer the genes of crop plants simply by
selecting successful strains, have pushed back some of these limits. Since the
turn of the century they have extended the northern range of corn on this
continent by 200 miles and brought wheat to the northern Canadian prairies.
Plant biologists are now trying to pinpoint the genes that confer
frost-hardiness or rapid maturation, in order eventually to enhance them or to
endow more-vulnerable crops with their powers.
Genetic engineering of hardier crops seems to farmers I have spoken with to
be a natural extension of plant breeding. Designing bacteria to control frost,
however, strikes them as bizarre and unnatural. Yet this concept, too, had its
beginnings in a cornfield. It was the serendipitous spinoff, in an odd,
backwards sort of way, of a traditional plant-breeding experiment.
The story begins with Paul Hoppe, a U.S. Department of Agriculture corn
pathologist at the University of Wisconsin, who was laboring during the 1940s
and 1950s to breed new strains of fungus-resistant corn. To ensure that his
plants were challenged by fungal epidemics, he would grind up infected corn
leaves from. the previous Year's crop and sprinkle them on the field. He did this
as usual in June of 1961. Two weeks later a late freeze hit the Midwest. The
plants. sprinkled with dried corn leaves were killed. The rest survived.
When Steven Lindow arrived at Wisconsin twelve years later to work on his
doctorate, "this weird thing about corn plants," as he now describes it, was
presented to him. Was there something about the infected leaves that enhanced a
plant's sensitivity to cold? He pursued the matter first as a biochemistry
problem, making active extracts from the old leaves and searching for a chemical
that made young leaves vulnerable. Then one day he added a bactericide to the
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The Atlantic, June, 1990
extracts and the frost-enhancing activity stopped. He began isolating and
testing dozens of strains of bacteria from his leaf extracts, trying to find
which ones somehow increased a plant's susceptibility to low temperatures. In
early 1975 his thirty-first isolate gave him an answer.
Lindow had a refrigerator loaded with test tubes full of water and colonies
of bacteria that he had isolated from the corn leaves. When he went to the
refrigerator one day, he found that the temperature had dipped a little below
freezing. Every tube of bacterium No. 31 had frozen. None of the others had.
Water doesn't necessarily turn to ice at 32 degrees F Small amounts of pure
distilled water can remain liquid at temperatures as low as -40 degrees C a
phenomenon called supercooling. Even large amounts of pure water readily
supercool to 14 degrees Drop a catalyst-a nucleating agent that helps orient
the water molecules into an ice-like lattice-into a flask of supercooled water
and the water will instantly, dramatically, crystallize into ice. Or lower the
temperature further and random groupings of water molecules will trigger this
phase shift spontaneously.
Lindow soon established that bacterium No. 31, a strain of common leaf
bacteria called Pseudomonas syringae, has a protein in its cell membrane that
can nucleate ice. In fact, this so-called ice-plus microbe has turned out to be
one of the most effective ice nucleators known.
Plants are 90 percent water, and water in plant tissues can supercool.
Lindow began to wonder: do the ice-nucleating bacteria that live on plants'
stems and leaves limit supercooling and allow damaging ice crystals to form
inside the plants' tissues at warmer temperatures? In a greenhouse he grew
plants under aseptic, or microbe-free, conditions, and found they could tolerate
temperatures as low as 23 degrees When he sprayed the plants with
ice-nucleating P. syringae, they froze at 28 degrees Lindow began washing
bacteria from the leaves of dozens of plant species, both crops and weeds; he
found ice-nucleating strains on leaf surfaces everywhere. Anywhere from a tenth
of a percent to ten percent of the bacteria on a leaf surface may be capable of
nucleating ice, he discovered. Of all the ice-plus strains, P. syringae turned
out to be the most common. You probably eat it in every salad, he told me.
In growth chambers and field plots Lindow began testing various ways of
manipulating the microbial populations on corn leaves: killing off all microbes
with antibiotics, for example, or coating the leaves with detergents and heavy
metals, such as zinc and copper, to inhibit ice nucleation. He also tried
something else: spraying plants with bacteria that are naturally ice-minus-that
is, bacteria that are essentially neutral and do not possess an ice-nucleating
capability-to make sure that plant surfaces were too full to support
later-arriving ice-nucleating cousins.
The results confirmed that frost damage declines as the ice-plus population
shrinks. But detergents, heavy metals, and antibiotics either are toxic to
plants or provide frost protection too short-lived to be widely practical on the
farm. And the natural ice-minus bacteria competed poorly with the ice-nucleating
ones. Not until he had completed his in 1978, and accepted a faculty post
at the University of California-Berkeley, did Lindow begin to consider the
possibility of genetic manipulation of P. syringae.
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The Atlantic, June, 1990
For every protein an organism makes, it must carry a gene that encodes the
blueprint for it. Knock out the so-called ice gene and the bacterium would be
unable to make the ice-nucleating protein. Lindow's team made its first
ice-minus mutants not by genetic engineering but by the more traditional (and
still largely unregulated) technique of exposing bacteria to mutagenic
chemicals. A decade ago, with no fanfare or need for federal approval, they
sprayed these mutant bugs on potatoes in a field near Tulelake.
But chemicals-and radiation, which is also sometimes used-are crude. They
mutate multiple genes, not just the targeted trait, and leave the bugs "sick in
subtle ways, Lindow explained to me. So in 1981, when genetic-engineering
techniques became available for manipulating P. syringae, his team set out to
locate the ice gene and remove it precisely, without causing other, haphazard
damage. They started with no idea where among the bacteria's 3,000 genes the ice
gene might be, or what its protein product looked like. In the lab one day
Douglas Gurian-Sherman, a graduate student, walked me through the process they
used.
"THINK OF THE bacteria as plastic bags filled with DNA and other stuff, he
said. "You want to break them open and then separate the DNA from the other
components." The terminology-breaking, loading, cutting, splicing,
inserting-suggests a dramatically mechanical, almost surgical operation. In
truth, I found, genetic engineering is a chemical and enzymatic process, to the
naked eye a seemingly endless mixing and separating of clear liquids. First
enzymes, detergents, and acidic compounds are added to a bacterial suspension to
lyase, or cat away, the outer membranes of the bacteria. The resulting liquid is
spun in a centrifuge to separate out the DNA, which differs in weight and
density from other organic molecules inside the bacterial cell.
Once the DNA of P. syringae was isolated, the next step was to chop it into
fragments, one of which would carry the ice gene. The chopping was done with
restriction enzymes, popularly referred to as "chemical scissors.' Like most of
the tools of genetic engineering, these enzymes had originally been isolated
from microbes, which use them to disable invading viruses or to cut and splice
their own DNA for replication and repair. Researchers now buy dozens of kinds of
these enzymes off the shelf.
It is the specificity of the various restriction enzymes that gives genetic
engineering its precision. DNA is formed in a linear sequence composed of four
chemical bases-adenine, thymine, guanine, cytosine (ATGC) - strung along two
complementary strands. A is always found paired with T, G with C. The sequence
of bases GAATTC on one strand, for example, will always be paired with CTTAAG on
the other, the pairs linked like the teeth of a zipper, the whole zipper-like
sequence twisted into a double helical shape. When a restriction enzyme called
EcoR1 recognizes the six-base-pair pattern GAATTC and its complement, it will
make a staggered cut in the double strands, slicing each strand between the A
and the G. This leaves an AATT tail on one cut end and a TTAA tail on the
other-so-called "sticky ends," single-stranded and eager to link up with a
complementary match.
"Often the whole thing is done in a test tube about this big,"
Gurian-Sherman said. He was holding up a one-inch vial. "You might have a
solution of DNA that's half the tube, and then you might add a tiny bit of this
enzyme. A tiny bit of another. And usually a buffer solution.' Once the DNA is
chopped, the researchers generate thousands of copies of each fragment by
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The Atlantic, June, 1990
inserting each into a bacterium for cloning. The first step toward cloning is
splicing each fragment onto a small segment of viral DNA called a cosmid. "From
a supplier you buy what are called right and left arms, Gurian-Sherman said.
"You just take your fragments and your cosmid arms and mix them. Both need to
have been cut with the same restriction enzymes, SO that they have sticky ends,
ready to link up. II
To begin to create an ice-minus version of P syringae, Lindow's team took
these cosmid-linked fragments of P. syringae DNA and presented them to tiny
viruses, called phages, that attack bacteria and use the bacteria's cellular
machinery to produce multiple new viruses. "The phage sees the cosmid DNA,
recognizes it, and pulls it in just as if it were winding string onto a spool,'
Gurian-Sherman said. The phages were then allowed to infect Escherichia coli, a
bacterium that has become the white mouse of genetic engineering. Inside E. coli
the viral DNA multiplied freely, making thousands of clones of the P. syringae
fragments with the cosmid DNA.
Which bacterial colonies carried the fragments with the ice gene? E. coli
are naturally ice-minus, and so Lindow's team picked out the ones that now
nucleated ice. Then, to isolate the gene further, the researchers did what is
called subcloning. Essentially, they removed the fragment and started over,
repeating the whole process several times, using ever smaller lengths of DNA. In
mid-1982 the team announced the isolation of the ice gene itself-the smallest
fragment of P. syringae DNA that could turn an ice-minus bug ice-plus.
Once they had the gene, the researchers gutted it by cutting a chunk out of
the center with restriction enzymes and rejoining the ends. Their next move was
to insert this crippled gene into the parent strains of P. syringae that still
carried full copies of the ice gene. This was done by encouraging mating and
"conjugal transmission" of the crippled gene from the E. coli to P. syringae.
Putting the two strains of bacteria together on a. petri dish for several hours
is encouragement enough for mating to occur.
By manipulating the environment in the petri dish, Lindow also made it
impossible for these P syringae to survive unless they not only accepted the
crippled ice gene but also inserted it into their own chromosomes next to their
good ice gene. For the few that survived this test, a final manipulation
awaited. Lindow shifted the environment of the dish again, relieving the
pressure on the bacteria to keep the new gene. He hoped that in a few of them
the new gene would detach itself from the chromosome a little sloppily, taking
along a chunk of the bug's own ice gene.
A few colonies of ice-minus P syringae, identical to their parents except
for a single gene, were all that remained: yellowish-white blotches that smelled
like sweaty feet and were no longer able to nucleate ice.
SINCE ITS inception, amid a barrage of frightening headlines in the
mid-1970s, genetic-engineering research had been subject to guidelines laid down
by the National Institutes of Health. Strict containment of all lab-altered
creatures was the goal. No crises occurred, and gradually both public anxiety
and federal oversight relaxed. Then, in 1982, Lindow proposed to field-test ice
minus.
Congress called hearings. The Washington activist Jeremy Rifkin, an opponent
of virtually every application of genetic engineering, filed the first in a
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The Atlantic, June, 1990
series of procedural lawsuits. Ecologists emphasized the problems created by
non-native species such as gypsy moths and kudzu vines. In 1983 the EPA entered
the fray by declaring ice minus a pesticide under the jurisdiction of the
Federal Insecticide, Fungicide and Rodenticide Act. The rationale went like
this: ice-plus bacteria encourage plants to freeze and thus are pests; ice
minus, if it arrives first, blocks this pestiferous activity and thus is a
pesticide. At the same time, the EPA ended its practice of exempting from
scrutiny small-scale (under ten acres) field trials of microbial agents. To get
permission to spray ice minus on a quarter-acre potato patch, Lindow faced an
enormous array of lab tests and paperwork previously required only for products
at well-advanced stages of commercialization.
By the time his experiment was approved, Lindow had filed more than 1,300
pages of applications and data with federal and state agencies. In labs and
greenhouses he had tested ice minus for pathogenicity on seventy-five plants,
from zinnias to sugar beets. He had run an extensive battery of "product
identity" tests and scrutinized the bug's life-style preferences, all to make
sure that it had no novel powers that might cause it to run amok.
Two seasons in the field-1987 and 1988-confirmed the bacterium's staid
behavior, and also its ability to protect crops: potato seedlings coated with
ice minus received only a third as much frost damage as unprotected plants.
Lindow chose not to conduct a third field test last summer. Faced with
regulatory uncertainty, ice minus's future on the farm is far from assured.
A few other lab-altered creatures did go to the fields last summer.
BioTechnica Agriculture, of Overland Park, Kansas, tested several genetically
modified strains of rhizobia, nitrogen-fixing. bacteria that have long been used
to foster the growth of alfalfa, soybeans, and other legumes. Crop Genetics
International, of Hanover, Maryland, tested bacteria designed to protect against
rice stem borers and European corn borers. These bacteria, which live inside the
vascular systems of plants, had been outfitted with toxin genes taken from
another bug, Bacillus thuringiensis, or BT, a natural microbial pesticide sold
in the United States since 1961.
None of the tested bugs have ventured away from their release sites or
persisted in the environment. Undoubtedly they have changed for a time the mix
of microbial populations in the soil or on leaves, but so do chemical pesticides
and herbicides, and farm practices such as tilling, irrigation, and crop
rotation. In May of 1988 a Congressional Office of Technology Assessment report
concluded, "With adequate review none of the small-scale field tests proposed or
probable within the next several years are likely to result in an environmental
problem that would be widespread or difficult to control."
HERE is still no consensus, however, on what constitutes "adequate review.
A draft proposal for revising the EPA regulations was circulated in the last
months of the Reagan Administration, but it drew criticism from all sides and
finally died at the Office of Management and Budget. A key provision would have
created a number of local environmental-biosafety committees to assume some
unspecified oversight role. The EPA also proposed to broaden the scope of the
Toxic Substances Control Act to oversee work with naturally occurring organisms.
Industry argued that the EPA should move in the opposite direction, exempting
all or most small-scale research with microbes. Environmentalists oppose such an
exemption but also don't want the EPA squandering its regulatory energies on
bugs commonly found in compost heaps or sewage ponds.
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The Atlantic, June, 1990
The EPA and the White House are currently working out the Bush
Administration's position. No one, however, expects any dramatic shifts in the
regulations. With major environmental legislation like the Clean Air Act under
review, genetically engineered microbes have not been a priority on anyone's
agenda this year.
Many in the biotech industry echo the sentiments of Jerry Caulder, the
president of Mycogen Corporation, who believes that the current regulations
would work well "if we didn't have people coming along playing what-if to the
nth degree on every release." He adds, "The EPA is in a terrible position. The
regulations are supposed to be scientifically reasonable, and yet the public
wants an assurance of absolute safety. You really can't do both.' The EPA has no
equivalent of the medical-research community's clinical trial, in which new
therapies are evaluated in relation to standard ones, allowing the better of two
often imperfect alternatives to be determined.
The 1988 OTA report stated,
In evaluating the potential risks associated
with these new technologies,
the appropriate question is not
"How can we reduce the potential
risks to zero?" but "What are the relative
risks of the new technologies
compared with the risks of the technologies
with which they will compete?"
Furthermore, What are the
risks posed by over-regulating, or
failing to develop fully the new
technologies? How do we weigh
costs and benefits? How much review
is enough?
Until such questions have been answered satisfactorily and the answers guide
our regulatory strategies, we will have little choice but to keep relying on the
chemical pesticides and fertilizers whose harmful effects are already apparent.
- Yvonne Baskin
GRAPHIC: Photograph
PAGE
2
7TH STORY of Level 1 printed in FULL format.
Copyright 1997 Information Access Company, a Thomson Corporation Company;
IAC (SM) Industry Express (SM) i
Copyright 1997 IMS World Publications Ltd.
R & D Focus Drug News
May 5, 1997
LENGTH: 176 words
HEADLINE: gene discovery, metabolic disease, deCODE genetics deCODE genetics
licensing offer, Worldwide
BYLINE: Smarason, Hannes T
BODY:
A gene discovery program is under way with deCODE genetics (Iceland) to find
genes associated with metabolic diseases such as diabetes, utilizing access to
Iceland's uniquely homogeneous population. The company is constructing an
anonymous database (GGPR) comprised of genotypes, genealogy, phenotypes and
resource information in conjunction with the Icelandic government, and will use
the database along with a proprietary bioinformatics platform to rapidly
identify the genetic basis of diseases. Potential disease-causing genes will
be cloned using positional cloning techniques. deCODE genetics hopes to
establish corporate collaborations for gene discovery and characterization,
product development, and nonexclusive licensing rights to the GGPR database.
Data on the company's research activities were presented at the 5th European
Life Sciences Conference, 20-22 April 1997, Amsterdam (Netherlands) gene
discovery, metabolic disease, deCODE genetics, A10X, Other Drugs Used In
Diabetes, deCODE genetics, licensing-offer, Worldwide, new-drug.
LANGUAGE: ENGLISH
LOAD-DATE: May 5, 1997
PAGE
11
1ST STORY of Level 1 printed in FULL format.
Copyright 1997 New Scientist IPC Magazines Ltd
New Scientist
April 26, 1997
SECTION: Forum, Pg. 47
LENGTH: 4827 words
HEADLINE: Promises, promises
HIGHLIGHT: From extra cash to better access to the Net, all three parties claim
to be on the side of science. Here's how they measure up in New Scientist 's
1997 election call
BODY:
Sweden dedicates 3.3 per cent of its GDP to research and development, Japan
2.9 per cent and the US 2.5 per cent. France and Germany spend 2.4 and 2.3 per
cent respectively. At 2.2 per cent, Britain spends below them all. What
percentage of the nation's GDP do you think should go to science ? If you think
Britain has it right, does that mean the others are just being inefficient ?
Conservatives: The key indicator is not R&D expenditure, but its impact, and
it is clear that British science punches well above its weight. With only 1 per
cent of the world's population we generate 6 per cent of its research, 8 per
cent of science publications and 9 per cent of citations. We are the most
cost-effective producer of research among the G7 countries, many of which are
now restraining their science budgets.
Labour: The percentage of GDP spent on science and technology is only one of
several indicators of the underlying strength of a nation's science base. Once
in government, Labour will develop criteria to assess the quality as well as the
quantity of investment.
Liberal Democrats: Britain spends far too little on its science base. The
current percentage of GDP spent on science is far too low. Liberal Democrats
would immediately increase it by shifting funds from the military R&D budget to
civilian research. For far too long other countries have been ahead of us in
their investment; our scientists must be enabled to compete on a level footing.
Do you believe that labs set up to give impartial advice, such as the
Institute of Animal Health and the Laboratory of the Government Chemist, should
operate in the private sector ? If they do operate in the private sector, what
steps should be taken to ensure their impartiality ?
Conservatives: Whether in the public or private sectors, laboratories have a
professional duty to be impartial. The prior options review process has
rigorously evaluated the individual status of each of the public sector research
establishments (PSREs) In some cases, it was clear that they should continue to
be in the public sector, in others that they should enjoy agency status and in
yet others that they can best flourish in the private sector. Such decisions are
made after full consultation, to secure the best future for each establishment.
Labour: The government's prior options review of government labs was driven
more by Conservative privatisation ideology than by what is best for our
PAGE
12
New Scientist April 26, 1997
nation's science base. The PSREs are a major national resource and a source of
crucial research expertise, and they have a vital role to play in offering
independent, impartial advice to government and the private sector. We welcome
the fact that the government's prior options review concluded that most PSREs
should remain in the public sector.
We will work with the new management in establishments such as the
Laboratory of the Government Chemist, which have already been transferred into
the private sector, and ensure that the channels to offer impartial advice to
ministers remain open.
Liberal Democrats: It is only in the public sector that we can be sure of
absolute impartiality. A laboratory set up to investigate food safety but funded
by a supermarket chain might be serving an agenda not in the public interest.
The end of the prior options review, designed to privatise government
laboratories, was good news. Constant reviews damage morale and often waste
time.
Should government research funding be more concentrated within a
"superleague" of universities ?
Conservatives: It is only fair, as well as efficient, that university
departments which achieve excellence in their research should be rewarded with
further funds. That encourages success and international excellence. But all
departments are able to enter into research contracts, including with the
private sector, and many are doing so successfully.
Labour: Labour will await the conclusions of the Dearing inquiry into the
future of higher education before deciding policy in this area.
Liberal Democrats: The issue of selectivity and direction of resources in
science is highly contentious. Some element of selectivity is inevitable: there
is never going to be enough to satisfy all demands. Rationing therefore has to
take place and priorities have to be set.
The increasing expense of research means that it makes sense to concentrate
a fair amount of funding on a limited number of well-equipped centres. However,
there has been large-scale government neglect of funding for equipment.
Liberal Democrats would make annual grants to eliminate the backlog of
obsolete buildings and equipment as part of our proposed increase in the science
budget. Under Liberal Democrat policy all universities would get more funding.
According to the last "R&D Scoreboard", an international league table of
corporate research spending, companies worldwide spent on average 4.4 per cent
of their total sales revenue on research. British firms on average devoted only
2.5 per cent. What should government do to encourage British firms to spend more
on research ?
Conservatives: It was the Conservatives who initiated the R&D Scoreboard to
show up the relative efforts of British companies. The government has encouraged
British firms to spend more on research by working to improve the links between
business and the science base. The Foresight programme is a prime example of how
businesses and academics can come together to mutual advantage. The Teaching
PAGE
13
New Scientist April 26, 1997
Companies Scheme also reinforces links. In addition, specific programmes such as
SMART, SPUR and the Crusade for Biotechnology provide direct incentives for
companies to increase their investment in R&D.
Labour: It is a matter of concern that there is only one British company in
the R&D Scoreboard top 50. Labour has already set up a corporate tax review to
examine obstacles to all types of private sector investment, including R&D. We
want to encourage a longer-term view of investment by industry. We will
encourage the Design Council's work in promoting best practice in the private
sector. This will increase the awareness within management of the importance of
a carefully structured programme of research, design and development. Companies
should publish details of their R&D expenditure to focus the minds of managers
and aid comparison between firms.
Liberal Democrats: We would set up regionally based development agencies to
bring together the functions of Department of Trade and Industry regional
offices. The agencies would operate as regional organisations responsible to
local authorities and, eventually, as part of our programme for regional
government.
Liberal Democrats would develop a new pool of seed-corn funding to be
administered by the regional development agencies and used either on its own or
as leverage for other public (EU, City Challenge, and SO on) or private-sector
(banks, business angels) funding. Links with universities would also encourage
companies to invest in research because they could see what was available and
invest in research projects which interested them.
How will you measure the impact of Foresight ?
Conservatives: The impact of Foresight will be measured by the extent to
which it influences corporate policy and investment decisions. There is already
evidence that Foresight is embedding new thinking into companies'
decision-making.
Labour: Labour will undertake a comprehensive audit of the Foresight
programme to re-examine the way in which government should be involved in the
funding of basic research activity. Labour will put in place effective
mechanisms to ensure that there is a coordinated approach across all government
departments in the dissemination and understanding of the Foresight findings.
The remit of the work done by the Foresight panels will be broadened to
encompass quality of life issues as well as wealth creation. Environmental,
ecological and ethical issues would be taken more into account than has been the
case to date.
Technology Foresight will be judged on the way in which it generates a
significantly increased level of R&D spending within the economy; by the
creation of new spin-off companies in the high-tech, high value-added sector of
the economy; through the effectiveness of technology-transfer activity between
the public and private sectors and within the private sector; and, in the closer
and more deeply embedded relationship between our university research base and
industry.
Liberal Democrats: The impact of Foresight can be measured by the number of
research projects started through it and the number of companies more able to
compete as a result of it. If companies start to invest in research through
PAGE
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New Scientist April 26, 1997
Foresight and continue to do so then it will have succeeded.
Will you create a food safety authority, separate from agricultural
interests and with statutory powers, along the lines of the American Food and
Drug Administration ?
Conservatives: The Prime Minister has indicated that he will consider the
possibility of introducing an independent food safety authority, but is inclined
to believe that the current system of direct ministerial accountability provides
greater safeguards for the public than this alternative.
Labour: Yes. Labour's agriculture, fisheries and food team, headed by Gavin
Strang, has made a clear commitment to setting up an independent food standards
agency, which will see itself as the consumer's champion. Its overriding
priority will be the safety and quality of our food, all the way through the
production and transportation process, from plough to plate. Food labelling will
also come within its remit. It will monitor the enforcement of food safety
regulations and will provide advice to the government on long-term food policy
issues and research.
We will transfer resources from existing government departments, including
the Ministry of Agriculture Fisheries and Food (MAFF), to the independent
agency. Its advice and recommendations will be made public. It would report to
Parliament and to the secretaries of state for health and for food and
agriculture. It will act as one point of contact for government, consumers and
industry - as opposed to the 43 different quangos across various departments
that currently cover these issues.
Tony Blair has already asked Philip James, director of the Rowett Research
Institute in Aberdeen and a renowned authority on food standards and nutrition,
to begin work on the agency's remit.
Liberal Democrats: It has long been Liberal Democrat policy to create an
independent food commission accountable to Parliament to separate the
representation of producer and consumer. It is ridiculous that MAFF represents
both producer and consumer, farmer and general public. The different functions
of MAFF and the Department of Health should be separate to prevent a conflict of
interest.
In the US, many scientific advisory meetings are conducted in public. In
Britain, very few are. Would you make more such meetings, for example, those of
the new Human Genetics Advisory Commission, open to the public ?
Conservatives: This is a matter for the committees themselves. We have
agreed that their reports should be published, but it has to be for them to
determine which parts, if any, of their deliberations need to be held in
confidence.
Labour: Labour is committed to improving the public understanding of science
and greater awareness of the importance of scientific progress to our quality of
life. One of the ways to do this is to encourage a greater level of informed
debate about the ethical implications of scientific advance. We are currently
investigating ways in which to improve the level of informed debate on science
in Britain.
PAGE
15
New Scientist April 26, 1997
Consensus conferences, where selected members of the public are brought
together to deliberate then come.to a consensus on a difficult issue, such as
the ethics of cloning, are used to good effect elsewhere in Europe, and have now
been introduced here through an initiative of the Biotechnology and Biological
Sciences Research Council.
Liberal Democrats: Liberal Democrats would introduce a Freedom of
Information Bill and encourage openness in all areas. By holding meetings in
public, we will make sure that advisory committees are accountable to the
public. We will also publish all results so that everyone is aware of important
findings.
Would you support an international tax on aviation fuel as part of a
programme to curb global warming ? Do you believe that taxation has a role in
meeting any future environmental targets, domestic or international ?
Conservatives: We do not support an international tax on aviation fuel, as
fiscal matters must be the responsibility of national governments.
Domestically, however, we have given taxation a central role in promoting
environmental objectives. We increased the level of fuel duty specifically to
promote more environmentally conscious transport choices, and introduced the
landfill tax, which goes directly to reduce employers' national insurance
contributions.
Labour: Labour's environmental policy document In Trust for Tomorrow states
that we are committed to a long-term, gradual change in the way the economy is
organised, to ensure that it encourages "goods" such as employment, value-added
production, investment and savings and discourages "bads" such as pollution and
resource depletion. There are various different policy tools that can be used to
achieve this, but each needs to be considered carefully.
Liberal Democrats: Liberal Democrats believe that taxation has a role to
play in cutting down pollution. We would cut Vehicle Excise Duty on smaller,
more fuel-efficient cars to only pounds 10, from the current pounds 145, by
raising fuel duty by about 3p. This would encourage people to drive less
polluting cars. Combined with investment in public transport, pursuing this
policy would cut down on pollution significantly.
All parties have talked of money for computer equipment for schoolchildren.
But the real costs will be in training teachers, maintaining the equipment and
upgrading it regularly. Which department will this money come from and how much
will you pledge ?
Conservatives: Departments across government share a responsibility for
investing in computers. Only the US has a comparable ratio of personal computers
to pupils. This year, pounds 132 million has been made available for information
technology in schools within the Grant for Education Support and Training
scheme. In addition, we have announced that after the millennium, all the
proceeds of the National Lottery currently given to the Millennium Fund will go
to a new pounds 300-million Information and Communication Technology Fund to
invest in IT, including in schools.
Labour: There are four pillars of Labour's pledge to deliver to every pupil
the educational benefits of the new information technologies. First, we agreed
with British Telecom in September 1995 that as part of the phased
PAGE
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New Scientist April 26, 1997
liberalisation of the home entertainments market they would connect every
school, college, university and library to the information superhighway. The
cable companies have indicated that they will also do this.
Second, we are in discussions with BT and other telecoms providers to ensure
that their commitment to keep the costs of access to the Internet as low as
possible.
Third, Tony Blair announced in October 1996 that we will establish a
National Grid for Learning by providing high-quality content and access to
software to make the superhighway work for schools, colleges and universities in
the near future.
We envisage that this would be run as a public-private partnership, with
government licensing the provider. The right to establish and run the service
will be awarded to the consortium best able to bring together relevant software
and educational experience along with financial backing.
The service will be free to schools, and self-financing, raising revenues
from charging software companies and possibly from advertising and sponsorship.
The fourth pillar concerns hardware and teacher training. David Blunkett has
pledged that Labour's University for Industry will include a Teachers' Centre
for professional development.
Liberal Democrats: Liberal Democrats are committed to investment in
education. Our policy of putting an extra penny on the basic rate of income tax
is long-established. Some of the money raised would be spent on computer
equipment for schools. Primary schools with over 250 pupils would receive pounds
16 000 for books, computers and equipment.
Teachers would be trained in information technology while they were at
teacher training college and would be able to go back for refresher courses to
make sure that they were up to speed on the latest technology. Local authorities
would employ computer consultants to maintain and upgrade the equipment and
buying in bulk would keep the price down.
Many small biotechnology and high-tech firms starve in their infancy for
lack of funds. Would your government consider sponsored loans schemes to give
them a fighting chance ?
Conservatives: The government's Biotechnology Means Business programme has
been established specifically to encourage firms to exploit the potential of
biotechnology. The SMART and SPUR schemes provide substantial assistance to
small firms making use of new technology. In addition, the government's Small
Firms Loan Guarantee Scheme provides biotech and high-tech firms with
underwritten loans.
Earlier this year, we announced that we will encourage more investors with
experience of high-tech businesses to lend their expertise to the scheme to
boost further the take-up by such firms.
Labour: The Labour Party is supportive of the European draft directive on
gene patenting which, if adopted, will help provide the stable regulatory
environment within which essential biotechnology investment can take place
PAGE 17
New Scientist April 26, 1997
throughout the European Union.
Labour also supports the Biotechnology Means Business initiative belatedly
launched by this government, although we fear that it is more concerned with
window-dressing than providing effective support. The biotech sector is an area
where Britain has a distinct lead over other European countries and ranks second
only to the US. Labour's corporate tax review will be examining obstacles to
investment in this sector as in many other areas of cutting-edge technology.
Liberal Democrats: The regional development centres, as mentioned earlier,
would use a new pool of funding to help developing companies with the cost of
employing scientists and engineers.
We would also encourage banks to establish regional investment funds to help
small businesses at the local level, for instance, by lending on the basis of
individuals and their records, rather than on the value of their property.
For more science news see http://www.newscientist.com
LANGUAGE: English
TYPE: Forum
LOAD-DATE: April 25, 1997
PAGE
18
12TH STORY of Level 1 printed in FULL format.
Copyright 1997 U.S. News & World Report
U.S. News & World Report
March 17, 1997
SECTION: U.S. NEWS; U.S. NEWS IN BRIEF; Pg. 36
LENGTH: 751 words
HEADLINE: Keeping snoops out of health files; Cloning a flap over research; A
disputed story threatens a trial; Who's to judge?
BYLINE: By Dana Hawkins; Traci Watson; Ted Gest; Gordon Witkin
HIGHLIGHT:
Privacy; Science; Terrorism; Courts
BODY:
PRIVACY
Keeping snoops out of health files
When a new mother comes home from the hospital these days, the bundle of mail
awaiting her about cribs and diapers may outweigh her bundle of joy. How did the
infant industry find out so fast?
Easy. Electronic medical records are now standard, and insurers, employers,
researchers, and even marketing firms and creditors are collecting them for
profit. Among the targets are detailed accounts of patient treatment and
expenses, sought by HMOs in an effort to stem health costs. Many insurers
formerly asked only for basic information on diagnoses.
Citing the increasing vulnerability of medical records, a National Research
Council panel called last week for special software, encrypted passwords, and
other measures to deny unauthorized outsiders access to sensitive files.
Democratic Sen. Patrick Leahy of Vermont will propose limiting access to medical
data and allowing patients to see and correct their records.
SCIENCE
Cloning a flap over research
It didn't take long for the cloning controversy to spread from biology to
politics. Ethical alarms about the cloning of a sheep from one adult cell and of
monkeys from embryo cells prompted President Clinton last week to ban federal
funding for human-cloning research and some lawmakers to propose forbidding the
process. With 87 percent of Americans saying they're against human cloning,
politicians saw a rare chance to take a seemingly bold stand without alienating
anyone.
The debate may lead to a repeat of the 1994 fuss over human embryo research.
Clinton cut off federal funding, and Congress soon followed suit. As a result,
there's no federal oversight of several studies that began without help from
:
PAGE
19
U.S. News & World Report, March 17, 1997
Washington. "The great falsehood here is that research will go away,' says David
Adamson of the Society for Assisted Reproductive Technology. "It won't.
Funding squeeze. Even noncontroversial research has experienced a decline in
federal support. A coalition of more than 20 scientific societies protested last
week that the United States is shortchanging its research labs. When inflation
is factored in, only two of the 10 federal agencies with large research
portfolios have more science dollars this year than they did in 1994. Scientists
want each agency's research budget to grow 7 percent next year. Yet White House
aides and legislators note that science has won modest increases in austere
times. "The government has an important role in science," says Tim Newell, a
senior White House science adviser. "It's also important to balance the budget. "
Despite concerns that science is being stifled, it is likely that fiscal
concerns will prevail.
COURTS
Who's to judge?
President Clinton is battling Senate Republicans over how best to fill nearly
100 vacancies in the 837-seat federal judiciary. Conservatives say he picks too
many judicial activists; liberals want more gender and ethnic diversity. Clinton
has named more women and minorities than his predecessors. Presidents Reagan and
Bush averaged 11.8 percent women and 3.2 percent African-Americans.
TERRORISM
A disputed story threatens a trial
Can Oklahoma City bombing suspect Timothy McVeigh get a fair trial? That
question hung in the crisp Colorado air last week amid fallout from a Dallas
Morning News story claiming he had confessed.
The inflammatory impact on potential jurors could hardly be overstated; the
article said McVeigh bombed the Murrah Federal Building during the day to ensure
a "body count" that would grab the federal government's attention. (The April
1995 blast killed 168 and injured more than 500 others.) The story appeared soon
after letters had been sent to about 700 prospective jurors from 23 counties in
northeastern Colorado.
The trial, which could last two to four months, starts March 31. Meanwhile,
McVeigh attorney Stephen Jones argues that the "confession" actually was a
defense investigator's ruse to lure a potential witness into talking. The News
stands by its story.
Judges appointed by Clinton
By gender
Males
139
68.8 percent
Females
63
31.2 percent
By race
Whites
146
72.3 percent
Blacks
38
18.8 percent
PAGE
2
3RD STORY of Level 1 printed in FULL format.
Copyright 1997 The McGraw-Hill Companies, Inc.
Biotechnology Newswatch
March 3, 1997
SECTION: Pg. 1
LENGTH: 1131 words
HEADLINE: Cloning clamor aside, long leap seen from lamb to lad
BYLINE: MS, MP, MB
BODY:
Well, Hello Dolly.
While the little lamb's story is inspiring a flood of fantastic visions,
from doomsday scenarios of thousands of Hitler clones to whimsical ways to
create your better self, life on planet earth is a little more humdrum.
Despite all the hoopla about the possibility of cloning humans now that
Dolly is among us, some scientists think the obstacles may well be
insurmountable. Of course, nobody knows until the experiments are done, but
there may be some technical reasons for profound skepticism regarding human
cloning.
Colin Stewart, a biologist with the National Cancer Institute, suspects that
sheep embryos may possess some characteristics that are unique in the animal
kingdom.
In an editorial accompanying the report from Scotland's Roslin Institute on
the lamb clone in the journal Nature, Stewart writes that the genetic material
in sheep embryos start to replicate at the 8-16 cell stage, far later than the
DNA in the embryos of other mammals, including humans.
The time lag may permit the DNA from an adult sheep to remodel itself into
an embryonic state, forming a clone, but the process is unlikely to occur in
other animals, he said in a telephone interview.
''It may not be possible to produce the same kind of results in other
animals, said Stewart. DNA transcription begins at the 2-cell stage in mice
and about the 4-cell stage in humans.
Of course, scientists had long dismissed the notion that it was possible to
clone an animal from an adult cell.
But as one biologists quipped: ''Who would want to make a clone of
themselves anyway? This is an applied technology that will have some industrial
applications, but as far as basic research is concerned, I don't think it will
be very useful.
Other scientists battling in the trenches of research had a different take
on the prospect of cloned animals.
PAGE
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Biotechnology Newswatch, March 3, 1997
'That kind of stuff is going to be great for us because we can have a
uniform tissue to work on and we can study them in much better detail, said
Nick Rampino, a cancer researcher at The Burnham Institute, of La Jolla, Calif.
Rampino, who is attempting to find out how tumor regulating genes work said
that, ''a lot of the problem we have is that genetically we don't work with the
same thing all the time. Even with genetically similar mice, you breed them and
get genetic drift. It kind of puts a sense in this.
The stunning display of technological prowess generated a whirlwind of press
coverage about Dolly, Ian Wilmut, the 53-year-old embryologist who cloned her
from a cell from another sheep's udder and PPL Therapeutics, the tiny,
low-profile biotechnology company that owns the rights to the technique.
But financial analysts did not see the news sparking an immediate stampede
of investors to the sector as a whole.
''This is very important scientific work; it maybe lends itself a little bit
more to public imagination than other kinds of discoveries, said Meg Malloy, a
biotech analyst with Hambrecht & Quist. ''But people should invest in the sector
because of positive fundamentals.
Malloy, who follows Genzyme, one of the companies developing transgenic
animals that produce human proteins in milk, said that there would be no
advantage to using the cloning technique at this time. Transgenic technology as
a whole is still in the proof-of-principle stage, she said, and several steps
removed from cloning.
Other companies working in this area include Novartis AG, Nextran and
Alexion, which are developing transgenic animals that can be used as organ
donors.
''Most of the public companies today are working so far afield from
cloning technologies, I just don't see it really impacting. A lot of other
issues go into biotech investing, she said.
Another analyst, Edward Hurwitz of Robertson, Stephens & Co., said that the
achievement, and ''the fact that it happened as quickly as it did, when people
thought it couldn't be done, is largely consistent with the way most of the
field and this science has played out, which is the that discoveries have
happened at an accelerated pace beyond anybody's expectations.
He thinks progress in biotechnology will ''continue to surprise people,
but the investors view cloning as a long-term issue.
'What drives these stock prices has to do more with clinical data, and
revenue protections in the near-term, and this is too far out, he said.
The public and politicians reacted, for the most part, with fear about the
chance the technology will be used to create human clones.
Sen. Christopher Bond (R-Mo.) called on the federal government to 'send a
clear signal'' that cloning ''is something we cannot and should not tolerate.
PAGE
4
Biotechnology Newswatch, March 3, 1997
At the same time President Bill Clinton asked the National Bioethics
Commission to examine the issue and report to him within 90 days on the legal
and ethical ramifications of cloning, especially on what it means for humans.
The president and congress will also be interested in recommendations on what,
if anything should be done with legislation to control cloning.
In 1995 Clinton signed an executive order banning government funding for the
creation of human embryos. At that time the target was in vitro fertilization,
now it may be extended to human cloning.
Clinton spokesman Mike McCurry called cloning a very troubling subject and
said White House polls showed 87 percent of Americans believed cloning of humans
should be banned outright.
Carl Feldbaum, president of the Biotechnology Industry Organization, said
that he ''can think of no ethical reason to apply this technique to human
beings, if in fact it can be applied.
Feldbaum believes that strict attention must be paid to the ethical
implications of the discovery.
The biotechnology industry exists to use genetic information to cure
disease and improve agriculture. We opposed human cloning when it was a theory.
Now that it may be possible, we urge that it be prohibited by law, he said in
a statement.
France's farm minister Philippe Vasseur conjured up horror movie critters.
'Even if countries like France, Italy, Spain Germany and others have
rigorous rules
about using science, what you can and cannot do, tomorrow
someone could well invent sheep with eight feet or chickens with six legs,
Vasseur said.
Long-time biotech foe Jeremy Rifkin sent out a terse press release, stating
that the ''prospect of potential cloning of human beings marks one of the most
significant scientific events of all time, challenging our most basic concept of
reproduction on earth.
He said his organization, The Foundation on Economic Trends, is 'determined
to mount a global effort in opposition to human cloning, and will seek
legislation to outlaw this technology in every nation.
LANGUAGE: ENGLISH
LOAD-DATE: March 25, 1997
PAGE
6
8TH STORY of Level 1 printed in FULL format.
Copyright 1992 Information Access Company, a Thomson Corporation Company
ASAP
Copyright 1992 American Association for the Advancement of Science
Science
November 13, 1992
SECTION: Vol. 258 i No. 5085 ; Pg. 1216; ISSN: 0036-8075
LENGTH: 1813 words
HEADLINE: Black colleges cultivate scientists; includes related articles on
enrollment boom and on 3 success stories; Special Section: Minorities in Science
BYLINE: Culotta, Elizabeth
BODY:
In the spring of 1981, North Carolina native B. Lee Stackhouse left
all-black Hampton University in Hampton, Virginia, with at least two newly
acquired assets: an M.S. in biology and the confidence that he could do a Ph.D.
at a major university. Stackhouse, whose B.S. in biology is also from Hampton,
decided to spend the summer as a research assistant in a cardiovascular research
lab at Boston University, his initial foray into a mostly white environment. But
his first taste of the world of big-time research was sour--so sour that he has
never returned full-time to a majority institution.
He says that in the Boston lab, faculty members-and even his fellow
students--treated him like a child, offering to write down the simplest
instructions. In the city itself, security guards perked up when he entered
grocery stores and followed him through the aisles. "If I'd gone to a majority
undergrad institution I might have been accustomed to it," Stackhouse says. "But
this hit me like a ton of bricks. I thought: 'Is this the way the country really
is?'"
Stackhouse lasted out the summer, but in the fall, he headed back to
Hampton, where he taught as an instructor for 2 years. Then he decided to get
that Ph.D. after all--at historically black Howard University.
Like Stackhouse, an increasing number of black students are choosing black
colleges. Overall enrollments have surged, especially at the undergraduate
level, and the top black schools are flooded with applications. But how well do
these schools teach science? Few can afford state-of-the-art instrumentation,
and even fewer have a research tradition, scientists both inside and outside
these schools agree. And the historically black colleges and universities
(referred to as HBCUs) vary greatly in quality, with some small schools little
better than junior colleges. Yet on the plus side, HBCUs provide a welcoming
environment, personal attention from professors, and a plethora of role models
who expect students to excel.
Howard grad Roosevelt Johnson, program director for graduate and postdoc
programs at NSF, sums up the education at the best black colleges this way: "You
come out with a very strong academic experience, but possibly a limited research
experience."
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Science, November 13, 1992
Black pride. For many scientifically inclined students, the HBCU advantages
apparently pay off. Although most blacks enter majority schools, black schools
graduate more than their share of black scientists. In 1989, with less than 20%
of black students, HBCUs awarded 40% of all black B.S. degrees in natural
science, according to the National Science Foundation (NSF). At the bachelor's
level, the top five producers of black biologists are all historically black
schools (see table on page 1218).
And graduates from many of these schools go on to make the grade in Ph.D.
programs at mainstream universities, suggesting that at least some HBCUs offer a
good grounding in science. For example, of the roughly 700 blacks who received a
Ph.D. in science and engineering between 1986 and 1988, 29% earned their
bachelor's degree at a black college, according to NSF. In some fields the
figure was much higher: 42% of black Ph.D. biologists and 36% of black Ph. D.
engineers received undergraduate degrees from black schools.
Fans of the HBCUs say the numbers reflect what they do best: teach
undergrads. Students are routinely showered with personal attention. At Clark
Atlanta University, for example, biology professor Isabella Finkelstein keeps
track of the academic profiles of students in her class. "I see a kid with 1200
SAT scores who gets a 30 on my first test, I put a note on there: 'YOU CAN DO
BETTER.
Psychological boost. Black colleges' chief advantage--an environment that
nurtures self-confidence--is hard to measure. But most HBCU grads insist the
advantage is there. They say that at mostly white schools, simply being in the
minority exacts a psychological toll. Spelman grad Sharon Neal, now assistant
professor of chemistry at the University of California, Riverside, attended a
white prep school in Philadelphia. The school "did more for me intellectually
than any other experience," she says. "But it was at a great personal price in
my youth. I got SO sick of people being your friend in school and then not
knowing you when we met in a department store." Other graduates of white high
schools remember never getting dates and feeling pressure to live up to
stereotypes like knowing the latest dance steps. Neal turned to Spelman because
she wanted a place where "race just wasn't an issue."
Such social concerns may seem irrelevant to what ought to be a primary
concern in college: making the grade. But when blacks--or any other group--are
in the minority in school, they tend to work in isolation. And in tough science
courses, the savvy strategy is to band together. "The minute I didn't understand
something in biochemistry the first thought in my head was, 'I'm the only one
who doesn't understand this, remembers NSF's Johnson. "It took group study to
realize the other guys didn't understand it either.'
Working in concert with classmates is key, agrees mathematician Gloria
Gilmer, who runs an educational consulting company in Milwaukee, Wisconsin, and
has taught at six HBCUs as well as several mostly white universities. "I tell
students to go where they give Ph.D.s to people who look like you. Don't go to
some school and sit in a class where you're not even taking the same course as
the rest because you're isolated and they're working together."
And at majority schools, the lone black chemistry major may feel that his
every move must prove that black people can make it. The pressure not to make
mistakes is huge. "People forget that freshmen are 18-year-olds. They're still
kids," says Johnson. "They need to be able to be young, and do silly, foolish
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Science, November 13, 1992
things, and not be under a microscope."
Working alone makes hard problems nearly impossible; maybe that's part of
the reason blacks at majority schools tend to drop out of tough hard science
courses and major in "softer" social sciences. Mainstream universities enrolled
about 80% of black students and produced 74% of the black B.S. social scientists
in 1989-and only 63% of the computer scientists, according to NSF.
Walter Pattillo Jr., chair of the biology department at historically black
North Carolina Central University, complains: "The way we see it, the majority
schools are wasting large numbers of good students. They have black students
with admissions statistics that are very high, tops. But these students wind up
majoring in sociology or recreation or get wiped out altogether." As a result,
Pattillo is somewhat skeptical of majority schools who come calling: "These
white schools come here asking for graduate students, and we say, 'What are you
doing with the students you already have?' One of my colleagues says they got
the cream, now they come back for the skim milk."
Coddling students? Others, however, point out the dangers of coddling
students. Campuses devoted to nurturing may not be as academically rigorous as
majority universities that expect students to "sink or swim.' Upon arriving as
an assistant professor at a well-regarded HBCU about 10 years ago, one black
scientist recalls thinking that the school was more like a high school or junior
college than a university. Professors were expected to call the roll before each
class.
And students at black schools may be inadequately exposed to the research
world: "Science is a culture, says Bertram Fraser-Reid, a Jamaican-born black
chemistry professor at Duke. In his lab, he says, undergrads soak up chemistry
simply by socializing with grad students and postdocs. If you choose a black or
inexpensive private college, says Fraser-Reid, "You may be gaining one culture
at the expense of the other."
In science, a good undergraduate education means research, or at least some
ambitious lab courses--and that takes money. Financially strapped HBCUs may not
be able to provide those courses. "Undergraduate teaching in science is an
extraordinarily expensive business. People these days can't learn about
molecular modeling, they need to learn how to do it,' says Fraser-Reid.
At Pattillo's university, North Carolina Central University in Durham, for
example, students--including master's students--had no access to many of the
tools of modern molecular biology. Only last year, after one young faculty
member won outside funding for a new lab course, did the university offer
training in cloning, the polymerase chain reaction, and other basics.
This has long been a problem at black colleges. "I was poorly prepared,"
says Kenneth Olden, director of the National Institute for Environmental Health
Sciences, who got his B.S. from Knoxville College in 1960. "I learned science
from a descriptive point of view. I wasn't very quantitative. I hadn't done much
lab work." As a result, Olden now believes that for many minority students,
major universities are the way to go. "When you really get down to it, if you
say, 'What I really want for my child is a serious rigorous academic training,
then you're probably talking about a majority school.'
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Science, November 13, 1992
Tradeoff. Maybe the best solution, some say, is an education that combines
the best of both worlds. Says Meredith Williams, a Yale-educated young
physicist, now in grad school at North Carolina State University, a majority
school, "In my dream world I'd go to an HBCU for 2 years and then transfer to
Yale. Because I've seen how people come out of those black schools. They exude
the message, 'I'm capable.
The ability of black colleges to keep turning out such confident students,
however, will depend on whether they can continue to recruit outstanding
faculty. Thirty years ago, that task was easy: All top black scientists went to
schools like Howard and Tuskegee, since they were unwelcome elsewhere. No
longer. Many HBCU fans worry that their faculty ranks are filling with foreign
professors, instead of minority role models. And in the long run, HBCUs will
have to rely on more than a sense of commitment to attract faculty.
For example, Stackhouse, who received three degrees from black schools, now
teaches at one, Winston-Salem State University. "If we don't return to minority
institutions, who will?" he asks. He keeps a research connection alive through
summer programs but wonders if that will be enough. In his own university, he's
frustrated by heavy teaching loads and lack of lab space and equipment. But like
many black college alumni, he is passionate about keeping black schools alive so
students have a choice. In his view, until integration works in both spirit and
practice, some black students will benefit from learning science in a place
where, for a few years at least, they are the majority.
GRAPHIC: Photograph; Table
IAC-NUMBER: IAC 13217814
IAC-CLASS: Magazine
LANGUAGE: ENGLISH
LOAD-DATE: August 28, 1995
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7TH STORY of Level 1 printed in FULL format.
Copyright 1994 Information Access Company, a Thomson Corporation Company
ASAP
Copyright 1994 Hastings Center
The Hastings Center Report
March, 1994
SECTION: Vol. 24 i No. 2 ; Pg. 6; ISSN: 0093-0334
LENGTH: 8311 words
HEADLINE: The question of human cloning.
BYLINE: Robertson, John A.
BODY:
Accustomed though we are to advances in medical technology, a 24 October
1993 news report that human embryos had been cloned astonished many persons. A
New York Times story, "Researcher Clones Embryos of Humans in Fertility Effort, 11
was the feature that Sunday morning in many newspapers throughout the country.
Media coverage continued for several days, with debates about cloning on
editorial pages, Nightline, and Larry King Live.
Within a week the issue had faded from media consciousness, aided in part by
Time and Newsweek stories that stressed the huge gap between die reported
research and the Jurassic Park-type fears of cloned human beings that initially
spurred national coverage. Bioethicists and law makers, however, must still
contend with the ethical and policy issues that even limited cloning of humans
presents. Should researchers be free to continue cloning research? May infertile
couples and their physicians employ cloning to form families? Or should
government prevent cloning research or discourage some or all of its later
applications?
As with many biomedical developments, these questions present a mix of
issues that need careful sorting. They involve, among others, questions of the
propriety of embryo research, the validity of deliberately creating twins, and
the importance of nature versus nurture in forming human beings. They also raise
slippery slope concerns: should otherwise seemingly valid uses of a new
technique be stopped to prevent later undesirable uses from occurring? To
address those issues we must first describe the cloning research that has
touched off the furor and the concerns that it presents.
Two Types of Cloning
The research that put cloning on the public agenda was a long way from
Huxleyian fantasies of identical babies, mass produced in laboratories, and did
not involve cloning as conventionally understood at all. To clone means to
create a genetic copy or replica. Perhaps due to science fiction fantasies, it
has been assumed that cloning would occur by removing the nucleus from the cell
of one person, placing it in an egg that has had its nucleus removed, and then
implanting it in a laboratory incubator or a woman who would bring to term a
child with the identical genetic characteristics of the person providing the
cell nucleus. Although this procedure has worked with frogs, it has never
succeeded with mammals and appears highly unlikely to be accomplished in even
the mid-range future. If this form of cloning were possible, scientists could
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The Hastings Center Report, March, 1994
fabricate as many copies as one wished of any available human genome, subject
only to the limits of uterine or artificial gestation.
A second and more limited way to create clones is to split the cells or
blastomeres of an early multicelled embryo before the cells have begun to
differentiate. Because each blastomere at this stage is in theory totipotent
(that is, capable of producing an entire organism itself), die separated cells
can become new embryos, all of which which have the same genome. This form of
cloning is now practiced to some extent in the cattle industry. Cloning by
blastomere separation is limited to the number of cells that can be separated
before cell differentiation, which destroys totipotency, occurs.
The study that generated the recent interest in cloning involved a small but
essential step toward cloning human beings by embryo splitting. Researchers at
George Washington University Hospital in Washington, D.C., separated cells or
blastomeres from seventeen two- to eight-celled preembryos and showed that, to a
limited extent, they would divide and grow in culture. The cells had been
obtained from polyspermic embryos that had no chance of implanting in the uterus
and that ordinarily would have been discarded.
The separated blastomeres were coated with an artificial zona pellucida and
placed in the culture medium used for in vitro fertilization (IVF).
The researchers obtained forty-eight blastomeres from the seventeen
polyspermic embryos (eight two-cell, two three-cell, five four-cell, and two
eight-cell), or theoretically forty-eight new totipotent embryos. A similar
percentage of embryos cleaved for each stage of the embryo from which they were
taken. While morulas (thirty-two-celled embryos) were achieved when blastomeres
from two-celled embryos were cultured, blastomeres from four-celled embryos
developed only to the sixteen-cell state, and no blastomeres derived from the
eight-cell stage grew past eight cells in culture. These results suggest that
splitting embryos at the two-cell stage appears to be more conducive to further
development than does separation at the four-cell or eight-cell stage. However,
the maximum stage at which a single blastomere can be reprogrammed to exhibit
totipotency by itself or with cellular materials transplanted from other cells
is unknown. 2
The study thus demonstrated that experimental cloning or twinning of human
embryos is potentially feasible as an aid to relieving infertility, though much
additional work remains before offspring are produced, and there is uncertainty
whether the technique will ever work at all. To produce a child by this method
would first require showing that excised blastomeres from normal embryos would
grow in culture to the point at which transfer to the uterus would ordinarily
occur. Such research should also show the optimal stage for splitting normal
embryos. It would then be necessary to place embryos that appear to be
developing normally from split blastomeres into the uterus to show their
potential for implantation and a successful pregnancy.
Some experts, however, are dubious that infertile couples would ever benefit
from cloning by blastomere separation.3 They view the higher pregnancy rate
after transfer of several embryos as due to the genetic heterogeneity of the
embryos transferred, not to numbers alone. On this view, placing several
genetically identical embryos in the uterus will not increase the chances of
pregnancy if one embryo with that genome would not have implanted. If this view
is correct, there will be little incentive to use blastomere separation to
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The Hastings Center Report, March, 1994
treat infertility, and the ethical issues discussed below will have little
practical significance. The following discussion, however, assumes that
blastomere separation could provide certain advantages in treating infertility,
and examines the ethical and policy issues that then arise.
Fears and Concerns
Some commentators saw nothing particularly unethical or disturbing in the
George Washington research. This was simply another step toward improving the
efficacy and efficiency of IVF, particularly for those couples who produce too
few eggs or embryos to initiate pregnancy.
Many news reports, however, highlighted the disturbing or possibly unethical
features of cloning and quoted ethicists who found the practice troubling. They
described hypothetical scenarios in which embryos would be cloned for sale or to
produce organs and tissue for existing children who needed transplants. One
ethicist termed cloning as "contrary to human values"; others saw it as "an
opportunity for mischief " that called for "governmental and societal debate
and, perhaps, prohibitions and restraints.' 4 The Vatican newspaper termed it a
step into "a tunnel of madness,' while the United Methodist Church called for an
executive order banning cloning in all federally financed institution. 5 A poll
a week after the first story reported that 60 percent of Americans opposed
cloning. 6
The fears and concerns about cloning have several strands. Some of them
arise from the artificial nature of assisted laboratory reproduction. Others are
tied to discomfort with the manipulation and destruction of embryos that cloning
research, if not the procedure itself, will inevitably cause. The most prevalent
ethical concern, however, arises from the dangers that intentional creation of
identical twins or multiples of one genome might pose to resulting offspring.
The fear is that cloning will violate the inherent uniqueness and dignity of
individuals, as well as create unrealistic parental expectations for their
children. It also opens the door to identical embryos being created and sold
because of their genetic desirability, as cattle embryos now are sold to
increase animal yield and profitability. A worst-case scenario envisages the
mass production of identical embryos to be sold to persons seeking desirable
children. Finally, there are fears that embryos will be created to provide
organs and tissue for existing children who need transplants.
Despite these reservations, research into the feasibility of splitting
embryos will undoubtedly continue. Cloning by blastomere separation is basically
a mechanical procedure that requires only the ability to micromanipulate
fertilized eggs and embryos and a few hundred dollars' worth of culture medium.
7 No DNA analysis or genetic expertise is necessary. It is likely that the next
research steps - separating and culturing single blastomeres from normal embryos
and then placing those that grow well into the uterus - and the actual birth of
children as a result of embryo splitting might well occur in the next two to
five years. As micro- manipulation of eggs and embryos is a rapidly growing
practice, the ability to excise blastomeres from an embryo will easily be within
the reach of many IVF physicians and embryologists. If shown to be safe and
effective, physicians in many fertility centers will then offer the procedure to
patients.
These possibilities engender a recurring disquietude about new reproductive
technologies. Scientific zeal and the profit motive combine with the desire of
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The Hastings Center Report, March, 1994
infertile couples for biologic offspring to create an enormous power to
manipulate the earliest stages of human life in infertility centers across the
country. Even before one innovation is fully assimilated, the largely
unregulated billion-dollar infertility industry presents another improvement,
which separately or together threatens disturbing consequences for offspring,
families, and society.
Some persons would argue that the idea of creating exact replicas of other
human beings is so novel that there should be a moratorium on further research
and development until a national consultative body evaluates the ethical
acceptability of the procedure and develops guidelines for research and use of
the technique. At the very least, to prevent abuses there should be strict rules
about the circumstances in which cloning by embryo splitting occurs, and about
the uses made of cloned embryos.
A closer look at the issues, however, suggests that the most likely uses of
cloning are neither SO harmful nor so novel that all research and development
should now stop until the ethics of the practice are fully aired, or that
governmental restrictions on cloning research or applications are needed.
Indeed, there may be no particular need for guidelines beyond the full and
accurate disclosure of risks and success rates that should always occur in
assisted reproduction.
To assess the ethics of embryo splitting and the need for regulation, we
must first ask who would use this technique if it were available and why, and
then analyze the ethical issues that the likely demand for cloning would
generate. We can then address the need for regulation of the embryo research
that is essential if cloning by blastomere separation is to occur, and of the
uses to which cloning techniques will be put.
The Demand for Cloning
The news accounts of the George Washington University research emphasized
many speculative uses of cloning, thereby slighting the most likely uses of the
technique. The immediate impetus to develop cloning - and its most likely future
use - is to enable infertile couples going through IVF to have a child.
To Increase the Number of Embryos Transferred. Initially the main demand for
embryo splitting would come from couples undergoing IVF who cannot produce
enough viable embryos to initiate pregnancy. In basic IVF practice, the highest
rates of pregnancy occur with transfer of three to four embryos. Often more than
that number of eggs has to be fertilized to produce enough viable embryos for
transfer, with the excess frozen for use during a later cycle. Couples who
produce only one or two embryos may thus have undergone an expensive and, for
the woman, onerous procedure that has little chance of success.
Cloning by blastomere separation appears to be a reasonable step for such
couples, if genetic heterogeneity of transferred embryos turns out not to be a
key determinant of pregnancy success rates. Their goal is the birth of at least
one child. If the prospective parents produce only two embryos, they would face
the difficult choice of transferring those two in the hopes that a single
pregnancy would result, or increasing their chances of having one child by
splitting the blastomeres of one or both embryos.
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The Hastings Center Report, March, 1994
If they produce only one embryo and embryo splitting has been shown to be
safe and effective, they may opt to divide that embryo. Depending on the
embryonic stage at which splitting is most successful, this could produce two
embryos (if split at die two-cell stage), four (if split at the four-cell
stage), or even eight (if two embryos are both split at the four-cell stage).
The number of embryos they end up with will affect the number of embryos
placed in the uterus at any one time, and also whether cloned embryos remain
available for transfer on a later cycle. If their efforts yield only two
embryos, it is likely that both will be transferred to the uterus. (If both
implant and come to term, embryo splitting will have produced identical twins).
If they produce four or more viable embryos by blastomere separation, three
or four might then be transferred to the uterus in the hopes of having one
child, with the rest frozen for later use. 8 Assuming two cycles of transfer
with two to four embryos transferred in a given cycle, several possibilities
arise. No children could be born from transfer in either cycle, or one or two
could be born from the first transfer, and none from the second, or vice versa.
In any given case, no child, one child, or deliberately created twins would have
been born as a result of blastomere separation.
However, this scenario also opens the door to having "twins" (or even
triplets" or "quadruplets") born several years apart. This would occur if one or
two children were born as a result of the first transfer cycle. Three years
later, perhaps, the couple wishes to have a second child, and rather than go
through IVF again, opts to have the remaining cloned embryos thawed and
transferred to the wife's uterus. The period between births of children with the
same genome could vary from a year or two to several years.
Embryo Splitting to Avoid Subsequent Egg Retrieval. Other scenarios
involving embryo splitting as a treatment for infertility can also be envisaged.
Perhaps the next most likely scenario if cloning by blastomere separation is in
fact effective would arise with a couple undergoing IVF who produce a sufficient
complement of viable embryos to initiate a pregnancy - three or four - but who
wish to avoid the expense and burdens of subsequent egg retrieval cycles. Not
many IVF candidates are likely to find themselves in this position, since
ovarian stimulation often produces ten or more eggs. Because the couple would
need to splitt only one or two of the three or four viable embryos that they
have produced, it is conceivable that many couples who produce only four embryos
would opt for this procedure. Indeed, the demand for embryo splitting from this
group might arise even if it turned out that successful implantation requires
genetic heterogeneity of embryos and the procedure thus was not sought by the
group that produces very few eggs.
If some of their embryos are split but only noncloned embryos are
transferred during the first or subsequent cycles, couples may satisfy their
need for offspring without having to resort to cloned embryos. However, if
uncloned embryos do not produce (enough) children, some of the cloned embryos
may be thawed and transferred during a later cycle. In that case deliberately
created twins could result at the same time, or at a point separated in time
from the first child born with that genome. A third or fourth cycle using cloned
embryos could result, with genetic replicas of earlier children born separated
in time.
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The Hastings Center Report, March, 1994
In either scenario, cloned embryos that are no longer needed by the couple
that produced them might be discarded or donated to other infertile couples.
Twins or triplets of an existing child might then be born to and reared by
another couple. Because embryo donation is ordinarily anonymous, neither the
children nor the genetic or rearing parents are likely to know the identity of
the others.
Embryo Splitting as a Form of Life or Health Insurance. An often cited
though highly unlikely demand for embryo cloning could arise from couples
seeking insurance against disaster for any children that they have. That is, a
couple might request that one or more blastomeres be split from embryos that
will be transferred, so that the resulting clone can be frozen for later use in
case the child born from the source embryo later dies or needs an organ or
tissue transplant. In that case, embryos that are genetically identical to the
child already born can be thawed and implanted in the mother (or a surrogate) to
produce a genetically identical child to replace the dead child, or to serve as
an organ or tissue donor for an existing child.
This scenario could occur, but it is unlikely for several reasons. First,
few couples not otherwise undergoing IVF would choose to do so just to gain the
hypothetical protection that identical backup embryos might provide. Second,
couples that experience the death of a child may not, because of the sadness
that it will engender, want to replace that child with a genetic twin, much less
plan even before the first child is born to create a replica for that purpose.
Third, couples undergoing IVF who produce enough embryos for transfer may not
want to risk their viability by separating blastomeres for hypothetical
insurance purposes. Fourth, a genetic replica of an existing child might not be
necessary to provide needed organs or tissue, or there may not be sufficient
time once organ failure in a child occurs to thaw, implant, and bring to term
the cloned embryo to serve as an organ or tissue donor. Fifth, there may be
medical reasons why a genetic twin will not be suitable as a donor, though in
some cases, such as bone marrow or kidney transplantation, genetic homogeneity
could provide an advantage.
Because SO few couples - even those otherwise going through IVF - will
request embryo splitting for this purpose, the use of cloned embryos as backup
protection for existing children is likely to arise only with embryos that were
created to enhance the efficiency of IVF. In situations of this kind, where the
embryonic clones were not produced with the specific intention of insuring
against disaster, parents might occasionally be glad of the opportunity to avail
themselves of the stored cloned embryos to obtain tissue for transplant for an
existing child, or to replace a child who has already died. Such scenarios are
not impossible, but for the reasons stated above, they are not likely to be
frequent.
Embryo Splitting to Obtain a Desirable Genome. Ethicists have speculated
that cloning by embryo splitting might occur to facilitate, or might result in,
the selection of stored embryos deemed to be particularly desirable. They
envisage scenarios whereby parents will try to sell clones of desirable children
to other couples, or where an attractive or successful couple will clone many
embryos for later sale or dissemination.
These speculations are highly fanciful. Most couples are not in the market
for other peoples' genetic offspring, but prefer to have their own. If so, they
can exercise some control over the genetic characteristics of offspring by
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The Hastings Center Report, March, 1994
mate or gamete selection, or by preimplantation or prenatal genetic analysis.
Few couples who can have their own children would be so obsessed with having a
perfect child that they would eschew their own reproduction in order to obtain a
cloned embryo that appears to have a desirable genome.
Of course, if cloning by embryo splitting is perfected, one could routinely
excise and store a cell from every embryo that is produced and transferred to
the uterus (assuming that this will not impair the embryo's development). The
children born of the source embryo could then be followed, and the excised cells
of those that turn out to have good genomes or healthy lives might then be
sought by persons in quest of donor embryos. The mere description of the
procedure shows how complicated and unwieldy it would be as a means to produce
particularly desirable embryos.
However, couples who cannot produce genetic offspring might wish to have
some say in the characteristics of embryos donated to them. In addition to
choice of hair and eye color, and assurances that there are no genetic defects,
they might want to see what the embryo they choose would look like as a child or
youth, if such information were available. But there is no particular reason why
it would be available, or why it would necessarily have to be provided.
In any event, providing information about cloned embryos to prospective
recipients would not itself lead to embryo splitting specifically for purposes
of genetic selection. The couple undergoing IVF might clone to enhance IVF
efficiency, but there would be no particular point in cloning embryos just to
enable genetic selection of donor embryos to occur at some later time. If the
sale of embryos is also prohibited, the financial incentives necessary to induce
embryo splitting for later sale would not exist.
Ethical Issues: Destruction of
Embryos
Cloning by blastomere separation raises a number of ethical issues. Some
ethical concerns derive from the stark interference with natural reproduction,
or the manipulation and destruction of embryos that cloning necessarily entails.
However, those concerns are not unique to cloning, and have been voiced about
embryo research, freezing, and discard, and about IVF generally. Since they are
not deemed sufficient to justify banning or restricting those accepted forms of
assisted reproduction, they should not be sufficient to ban cloning either.
Yet persons who believe that fertilized eggs and embryos are already persons
with rights will object that embryo splitting goes beyond the manipulations
ordinarily involved in IVF. In this case a new unique individual will be
intentionally split to serve other ends. The very process of blastomere
separation could destroy embryos that would have developed normally, thus
denigrating and undermining the value of human life. Because human life at all
stages is a preeminent value, cloning by blastomere separation is an unethical
procedure that should be banned.
There may be no way to answer the objections of persons who think that
embryos are themselves persons and must be protected at all costs. The fact that
embryo cloning might yield additional human lives will not assuage their
concerns, for one is ordinarily not justified in killing one person in order to
save several. 9 One can only point to the prevailing moral and legal consensus
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The Hastings Center Report, March, 1994
that views early embryos as too rudimentary in neurological development to have
interests or rights. 10 On this view, splitting embryos can no more harm them
than freezing or discarding them can. Nor is splitting embryos to enable one or
more of them to implant and come to term inherently degrading or disrespectful
of human life. Cloning embryos thus poses no greater harm to embryos than other
IVF practices and should be permitted to the same extent that they are.
Ethical Issues: Deliberate Twinning
Ethical objections that are unique to cloning arise from a concern that the
intentional creation of genetic replicas of an existing person denies the
uniqueness of resulting offspring. This could occur from causing more than one
child with the same genome to be born simultaneously. It could also occur from
causing more than one child with the same genome to be born at different points
in time.
Is the intentional creation of twins who are born simultaneously morally
objectionable? Identical twinning occurs naturally and is not generally thought
to be harmful or disadvantageous to twins. If anything, being a twin appears to
create close emotional bonds that confer special advantages. If this is true,
then having twins as a result of embryo splitting should be no more harmful to
offspring than having twins naturally.
Suppose, however, that having twins does sometimes pose rearing problems or
even psychological conflicts for children. For example, some families may have
trouble rearing two infants simultaneously. Or asymmetrical relations with
parents or intense rivalry between twins may occur, resulting in psychological
harm to one or both of the pair. Still, the fact that undesirable outcomes might
occur for some twins is no basis for concluding that all embryo splitting is
unethical and should be discouraged.
The greatest chance that twins would result from embryo splitting would
arise with a couple who produce too few embryos to have a reasonable chance of
establishing even a single pregnancy. Their goal in embryo splitting is to have
one child (or sometimes possibly two), but they know there is the risk that a
twin pregnancy will result. If they knowingly accept the risks of twins, they
will most likely be in a good position to handle the special burdens posed in
rearing them. In any event, the risk of psychological harm from being a twin is
neither so likely nor so severe that merely being born in this situation could
constitute a harm. Twinning, whether natural or intentional, hardly amounts to a
wrongful life. Neither child can reasonably claim that she has been wronged
because, but for her parents' choice, she would have been born without a twin.
What, however, if triplets or even quadruplets are born simultaneously as a
result of cloning by blastomere separation? If a four-cell embryo is split into
four, and all separated blastomeres grow in culture and then are placed
simultaneously in the uterus, the risk of a multifetal pregnancy increases.
Multiple gestation does pose physical risks to the mother and to fetuses. Thus
women who have multifetal pregnancies as a result of IVF or fertility drugs
often use selective abortion to reduce the pregnancy to twins or triplets to
improve the chances of a healthy outcome for all concerned. If multifetal
pregnancies due to cloning occur, it is likely that they will also be
selectively reduced to protect the health of mother and offspring.
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Suppose a woman who is pregnant with triplets or quadruplets in virtue of
transfer of four cloned embryos refuses to reduce the pregnancy to twins. Will
she harm her offspring as a direct result of the cloning decision? Two different
harms must be distinguished here. One is the potential harm of having three or
four genetically identical siblings rather than just one, as occurs with twins.
The second is the physical harm from prematurity that all offspring in such a
multiple gestation might experience.
With regard to the first harm, it is not at all clear that identical
triplets (or rarely, even quadruplets) suffer unique or inordinate psychological
problems because they have identical siblings. If being an identical twin is
generally a good thing, then it may be that being an identical triplet also has
advantages and specialness that outweigh whatever disadvantages exist. At the
very least, it would appear difficult to argue that these disadvantages are so
great that the triplet should never have been born. Given that this is the only
way for this individual to be born, its birth hardly appears to be a wrongful
life that never should have occurred.
The risk of physical dangers of prematurity from a triple (or quadruple)
pregnancy raises somewhat more complicated questions. Suppose the pregnancy ends
prematurely at seven months. All three infants spend several weeks in intensive
care and end up with permanent learning and physical disabilities. Have they
been harmed by the cloning that produced a multifetal pregnancy, which their
mother refused to reduce to twins? The child who would have been aborted would
not appear to have been wronged by the mother's refusal because it had no other
way of being born but in a triplet situation subject to the very risks that have
eventuated.
But two of the three infants (there is no way to identify the two that would
not have been aborted) are worse off than they would have been if the pregnancy
had been reduced to twins. Presumably they would then have been born healthy,
without the physical and mental deficits they now have. One could reasonably
argue that they have been hurt by their mother's refusal to reduce the
pregnancy, even though there is no way to tell which two they are.
If the disabled offspring have been wronged, the wrong is not due to embryo
splitting but rather to their mother's refusal to reduce the pregnancy from
triplets to twins. The same arguable wrong would occur if the triple pregnancy
occurred naturally or as a result of assisted reproductive techniques that did
not involve cloning. Because the possibility of this wrong to the injured
offspring is not unique to cloning, it is not an argument against all embryo
splitting, any more than it is an argument against all use of fertility drugs or
IVF, which also can produce multifetal pregnancies that are not reduced.
Ethical Issues: Later Born Twins
The second ethical issue unique to cloning by embryo splitting is the
possibility of genetically identical siblings being born years apart in the same
or different families. Are later born children harmed because a twin or triplet
already exists? The claim rests on the notion that the later born child lacks
the uniqueness or individuality that we deem essential to human worth and
dignity, and that human individuality is largely determined by nature or genome
rather than by nurture and environmental factors. Because phenotype and genotype
do diverge, and because the environment in which the child will be raised will
be different from that of his older twin, the child will still have a unique
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The Hastings Center Report, March, 1994
individuality. Physical characteristics alone do not define individuals, and
there is no reason to think that personal identity will be wholly controlled by
having an older twin.
Still, there could be special problems faced by such a child. Its path
through life might be difficulty if the later born child is seen merely as a
replica of the first and is expected to develop and show the skills and traits
of the first. This might be a special danger if the later born child is used as
a replacement for an earlier born child who has died. However, it will be some
years before the later born child is even aware of his genetic identity relative
to an older sibling and the special expectations his parents might have.
But it is also as likely that the later born child will be loved and wanted
for his own sake. His status as a later born twin (or triplet) could be seen as
a special status, indeed, a unique or novel status that confers attention and
love. It could also lead to close ties with the older twin, if the special bond
that twins feel is genetically based. However, it could also lead to unique
forms of sibling rivalry. Will the older twin feel that he is deficient because
his parents wanted a newer version of him, or will he feel special and proud
that his parents wanted another child like him? In any event, it is difficult to
conclude that later or earlier born twins or triplets are likely to have such
serious psychological problems that they should never be born at all. Even if
one did so conclude, this would counsel against implanting cloned embryos only
when a twin already exists, not against implanting two cloned embryos
simultaneously or splitting embryos at all.
Ethical Issues: Cloning as Life or
Health Insurance
Although cloning for the explicit purpose of providing parents with a
replica for a lost child or as a source of organs or tissue for transplant for
an earlier born child will not frequently occur, couples who have split embryos
to treat infertility might occasionally be faced with thawing a cloned embryo
for those purposes. Consider, for example, parents who request cloning to
protect against the loss or death of a child, or who wish to thaw a cloned
embryo to replace a dead child. Wanting a child to replace one who has died is
not itself unethical. Nor does it become so merely because the new child will be
a twin of the first. Although the parents may hope that the new child will
develop and show the same traits as her deceased twin, they should very rapidly
learn that the second child is different in some respects and similar in others,
and would ordinarily come to treat and accept her as the individual that she is.
The use of cloned embryos as insurance against organ and tissue failure in
an existing child presents a different set of issues. Here the concern is that
the cloned embryo will be treated as an instrument or means to serve the needs
of an older twin and will not be loved or respected for his own sake. As the
Ayala case in California showed, however, a family can be motivated to have
another child to provide an existing child with bone marrow and still treat the
subsequent child with the love and respect that children deserve.
If this is so, thawing cloned embryos to provide tissue or organs for an
existing child should also be ethically acceptable. The key is whether the child
will be loved and accepted by the family that brings her into the world, not how
or why she was conceived, nor even whether she was cloned for that purpose. As
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The Hastings Center Report, March, 1994
long as the child's interests are protected after birth occurs, it is hard to
see how being cloned or thawed to provide organs for a twin is any worse than
being conceived for that purpose. Even if it were, the risk that some cloned
embryos might be used to provide tissue to existing children would not justify a
ban on embryo splitting to treat infertility.
Ethical Issues: Embryo Splitting
for Genetic Selection
Scenarios involving embryo splitting for genetic selection are, as discussed
above, extremely unlikely as long as overall demand for embryo donation is low
and the buying and selling of embryos is not permitted. Since it is highly
unlikely that a market in embryos will develop, there will be little incentive
for couples going through IVF to clone embryos in order to sell them in the
future. This is true even if recipients of donated embryos are permitted to pay
some of the costs of embryo production.
It is true that the small subset of infertile couples who are candidates for
embryo donation might wish to know the actual characteristics of existing twins
or triplets of the embryos they seek to "adopt." However, neither having nor
satisfying this wish is itself immoral. Indeed, the right of adoptive parents to
receive as full information as possible about the children whom they seek to
adopt is increasingly recognized. There is no reason why the same principle
should not apply to embryo "adoptions. Even though the couple seeking the
embryos will be choosing them on the basis of expected characteristics, such a
choice is neither invalid nor immoral. As long as the parents are realistic
about what the information signifies, do not have unrealistic expectations about
the child's perfection, and love the child for itself, seeking and providing
such information prior to embryo donation should be ethically acceptable. If it
were not, providing such information could be banned without requiring that
embryo splitting to treat infertility also be banned.
Regulatory Issues
This account of cloning by embryo splitting and the ethical issues it poses
suggests that, contrary to initial impressions, there is no major ethical
barrier to proceeding with further research in embryo splitting as a treatment
or adjunct to IVF. Given the great utility that embryo splitting could have for
infertile couples, a moratorium on embryo splitting research is both unnecessary
and unjustified. Such moratoria have occurred only when research appeared to
pose great danger to others, as occurred with the brief moratorium on
recombinant DNA research declared at Asilomar in 1975 because of the fear that
genetically engineered pathogens might escape from the laboratory. By contrast
the risks of embryo splitting are no different from the risks that now exist in
IVF laboratories and should be treated accordingly.
Even if a moratorium on cloning research is not justified, persons leery of
embryo splitting argue for close regulation of the research that could perfect
the practice, and then of its application. The most immediate policy questions
concern whether there should be any restriction on research with embryos
designed to improve or perfect techniques of embryo splitting. If research
establishes the safety and efficacy of embryo splitting, then the question of
regulatory limits on the use of the technique must be addressed.
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The Hastings Center Report, March, 1994
The issue concerning the ethics of embryo research has several parts. One is
whether research on normal embryos that will otherwise be discarded is ethically
acceptable for any purpose. The second is whether embryos created by splitting
blastomeres may ethically be placed in the uterus and brought to term. Such
questions should be answered in terms of risks to the human subjects directly
involved. As we have seen, the use of cloned embryos to treat infertility
appears to be ethically acceptable. One should not deny investigators the right
to carry out research otherwise respectful of human subjects because one
disagrees with the utility or worth of eventual applications.
Research with Normal Embryos.
The most immediate question is whether researchers should be permitted to
split and culture blastomeres from normal embryos in order to replicate the
results obtained at George Washington with polyspermic embryos. Although no
authoritative American guidelines exist for research on normal embryos, there is
a strong basis in the ethical literature and in practices of other countries for
holding that such research is ethically acceptable. 11 Because early
preimplantation embryos have no differentiated organs or nervous system, they
cannot be harmed by splitting or other research manipulations and thus may
ethically be used as the objects or vehicles of medical research.
As long as the research is for a valid scientific purpose, embryos that
would otherwise be discarded can, with the informed consent of the couple whose
gametes produced the embryos, ethically be used in research. Indeed, it should
also be ethically acceptable to create embryos solely for research purposes when
needed, even if there is no intent to place them in the uterus. Thus neither the
lack of guidelines, the moral objections of some to any embryo research, or
fears about where cloning research might lead justify forbidding researchers to
take this next step. Researchers may not have the right to receive governmental
or private funds for cloning, but if they are otherwise funded, their research
should not be stopped because of objections to the use of embryos or to cloning
itself.
Embryo Transfer after Splitting.
Harder questions will arise if research shows that blastomeres separated
from healthy embryos develop normally in culture to the point where they may
implant in the uterus and go to term. Universities and IRBs might legitimately
demand that implantation of manipulated embryos not occur until there are
reasonable assurances that resulting offspring will not be physically harmed by
the experiment. But if the embryos have developed normally in culture, this
condition should be satisfied, just as it has been with embryos that were
experimentally frozen and thawed before transfer, and with embryos that have
been experimentally biopsied for preimplantation genetic analysis. When no
physical harm appears likely, transfer to the uterus is ultimately beneficial
for the resulting child (who has no other way to be born) and should be
permitted. Again, neither the lack of clear guidelines, the fact that embryos
will be manipulated and transferred, nor speculative fears of where blastomere
separation ultimately could lead would be valid grounds for blocking this
research.
Such a conclusion is consistent with the recommendations of commissions and
advisory boards in the United States and abroad that have examined embryo
research. Although they have not addressed cloning research directly, they do
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The Hastings Center Report, March, 1994
approve of transfer of embryos to the uterus after experimentation when the
research is designed to aid or treat the resulting child. Transfer after
experimental embryo splitting is designed to enable a child produced from
blastomere separation to be born, and thus might be said to advance its
interests. Just as the first embryo transfers after IVF were ethically
acceptable because they enabled children to be born, so these should be as well,
for there is no reason to think that if they implant and come to term they will
have physical defects or otherwise be harmed.
Embryo Splitting Applications.
Once it is shown that embryo splitting can produce normal offspring, the
relative ease of the procedure and competition for parents will lead many IVF
centers to offer it. Will it be necessary to restrict the uses to which embryo
splitting is then put?
As the previous analysis suggests, the case for banning or greatly
restricting embryo splitting as a treatment for infertility is extremely weak.
The right of married and arguably even unmarried persons to procreate is a
fundamental constitutional right that cannot be restricted unless clearly
necessary to protect compelling state interests. 12 Because a ban on embryo
splitting to treat infertility would directly interfere with the ability of
infertile couples to have offspring, it would have to meet the compelling
interest standard. Yet the prospect of great harm from intentional twinning,
from twins born years apart, or from other possible uses of the technology does
not appear to be SO likely that governmental restrictions that go beyond
assuring informed consent could be justified.
As with other forms of assisted reproduction, medical professionals who
offer the service may be left largely to regulate themselves. IVF programs that
engage in embryo splitting will have to decide at what stage embryos will be
split, how many clones will be made, how many will be transferred at any one
time, and how great a gap in time may, occur between the birth of one child and
another whose origin was the same embryo. They mill have to develop procedures
for counseling couples, particularly when twins are born months or years apart.
Professional organizations, such as the American Fertility Society, might
develop practice guidelines, as they have done with donor sperm and other
reproductive technologies. 13 As long as the interests of couples and offspring
are well served, there will be no need for governmental restrictions on the
decisions made by medical professionals and their patients.
Nor do the more exotic scenarios imagined with cloned embryos necessarily
warrant governmental intervention. The use of cloned embryos to replace a lost
child or to provide tissue or organs for an existing child should be decided on
the merits and ethics of those practices independently of creating or using
cloned embryos for those purposes. If families may otherwise have children to
serve as tissue donors for existing children, there is no basis for banning the
use of cloned embryos for that purpose. Such uses are likely to be rare, and in
any event, should not stop the use of cloning to treat infertility.
Similarly, couples seeking embryo donations should be entitled to as much
information about the genetic characteristics of prospective offspring as is
available. Wanting healthy, talented, attractive children is not per se immoral
and should not in itself bar the use of the technique. Of course if it did, that
would not bar other uses of cloned embryos.
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The Hastings Center Report, March, 1994
Laws that restricted trade or commerce in cloned embryos would be an
acceptable public policy. Athough it is highly unlikely that demand for cloned
embryos would lead to a market in them, it may be desirable to symbolize the
unique value of incipient human life by banning the sale of embryos, whether
cloned or not. Such a ban would not prevent infertile couples from getting
access to infertility treatments or otherwise forming families, and thus would
not limit or interfere with their procreative liberty. The ban need not prevent
persons receiving embryo donations from sharing in some of the costs of embryo
production.
The Permissibility of Cloning
The idea of cloning human beings initially sounds so bizarre and dangerous
that one would think that such practices should be closely regulated, if
permitted at all. Yet this survey of ethical and policy issues in cloning by
embryo splitting suggests that the procedure has fewer risks and more benefits
than first appeared and would be ethically permissible in most cases. The most
unappealing appealing applications of the technique are highly speculative and
could be restricted without also stopping more valid uses.
Cloning by embryo splitting thus presents a regulatory situation that often
arises with new reproductive technologies. An immediate step that seems
justified to meet the legitimate needs of infertile couples could open the door
to future applications that are much less defensible. If we ban the immediate
steps in order to prevent potentially harmful future applications, infertile
couples lose the benefits of the procedure without a clear showing that future
harms would necessarily have occurred.
The temptation in such situations is to defer further research and
development until a national commission or ethics advisory body puts its
imprimatur on the practice. While such bodies, however, have been absent from
bioethical debate in the United States for some time, there now appears to be an
increased willingness to confront such issues. For example, an advisory panel on
embryo research has been created to recommend guidelines for federal funding. 14
However, it remains uncertain when any such body will consider the complicated
issues of human cloning.
As a result, we are left to elucidate and resolve on a retail basis the
ethical dilemmas that each new innovation presents. Cloning by embryo splitting
is another example of this policymaking process. Unless there are greater risks
from its use than are now apparent, the case for adding the technique to the
armamentarium of infertility treatments is a reasonable one. Its novelty will
not prevent parents from loving and acting in the best interests of children
born in this way.
References
1. "Cloning Humans, Time, 5 November 1993 (cover story); "Clone Hype,' II
Newsweek, 8 November 1993, p. 60. 2. J. L. Hall et al., "Experimental Cloning
of Human Polyploid Embryos Using an Artificial Zona Pellucida," The American
Fertility Society conjointly with the Canadian Fertility and Andrology Society,
Program Supplement, 1993 Abstracts of the Scientific Oral and Poster Sessions,
SI. 3. Howard Jones, Robert Edwards, and George Seidel, "On Attempts at Cloning
in the Human, Fertility and Sterility, March 1994 (forthcoming). 4. Michael
Waldholz, "Scientists Halt Research to Duplicate Human Embryos after Furor
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Erupts, Wall Street Journal, 27 October 1993; Gina Kolata, "Cloning Human
Embryos: Debate Erupts over Ethics, New York Times, 26 October 1993. 5. Time,
5 November993; "Cleric Asks President for a Curb on Cloning,' New York Times, 30
October 1993. 6. New York Times, 1 November 1993. Fifty-eight percent of
respondents believed that "it was morally wrong to clone a human being.
Sixty-three percent believed cloning was against God's will. Fewer than one in
five respondents thought that cloning should be allowed to continue. 7.
Statement of Dr. Robert Stillman on Larry King Live, 25 October 1993. 8.
However, it is possible that three or even all four embryos transferred will
implant. In that case, the couple will face the issue of selective reduction of
the pregnancy to twins. Depending on the number of children who are born,
cloning by separation could lead to twins or even triplets as a result of
intentional cloning. 9. Judith Thomson, "The Trolley Problem," Yale Law Journal
94 (1985) : 1395-1415 10. American Fertility Society, "Ethical Considerations of
the New Reproductive Technologies," special supplement, Fertility and Sterility
46 (1986); John A. Robertson, "In the Beginning: The Legal Status of the Early
Embryo,' Virginia Law Review 76 (1990) : 437-517, at 440-50. 11. John A.
Robertson, "Embryos Research, Western Ontario Law Review 24 (1986) : 15-37. 12.
John A. Robertson, "Embryos, Families, and Procreative Liberty: The Legal
Structure of the New Reproduction, Southern California Law Review 59 (1986) :
939-1041. 13. American Fertility Society, "Ethical Considerations of the New
Reproductive Technologies. 14. Federal Register 59, no. 10 (14 January 1994)
2414. See also, Joseph Palca, "A Word to the Wise," in this issue (p. 5).
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