May 15, 2002

Contents
1.       Revealed: the 582,000 animals that are genetically modified in
Britain's labs
2.       'Human' definition worries cloning foes
3.       No consensus on cloning regulation among experts
4.       Single gene failure "explains cloning deaths

1.
Revealed: the 582,000 animals that are genetically modified in Britain's
labs
Scientists condemn shock report by genetics watchdog as 'irresponsible'
John Vidal
Guardian
Wednesday May 15, 2002
British scientists are genetically modifying and cloning hundreds of
thousands of animals a year with little health or commercial advantage,
according to a report by genetics monitoring group GeneWatch.
The great majority of the 582,000 animals genetically altered in Britain in
2000 for medical or agricultural research were mice, but increasingly sheep,
goats, cattle, pigs, rabbits, birds, poultry and cats are being used.
The scale of the genetic experimentation on animals was previously unknown
and shocked the RSPCA and other animal welfare groups.
But the report, which drew on peer-reviewed scientific studies and patent
applications made by companies, was condemned by leading scientists as
"irresponsible".
The report, which covers the development of GM animal technologies
worldwide, says that many experiments are highly inefficient, wasteful of
animal lives and frequently involve suffering. "Abortion, premature death
and infertility are regular side-effects of these genetic technologies," it
says.
"The extent of animal suffering and the reasons for it are being hidden from
public scrutiny and debate", says Dr Sue Mayer, one of the report's authors
who also sits on the government's agriculture and biotechnology committee
which oversees biotechnology development.
Of more than 10,000 attempts at animal cloning worldwide so far, says the
report, there have been only 124 live births and just 65 animals have
reached maturity. Many of these showed serious physical defects. In one
peer-reviewed study of 40 cloned calves, 34 showed prenatal abnormalities,
several had limb deformities, and most were described as very slow or weak.
In another study of 80 GM lambs transferred to surrogate mothers, all but
three died inside 12 weeks with abnormal kidneys, brains or livers.
GM experiments and the cloning of animals have increased by 800% in the past
10 years and now include attempts in the US to clone pets and endangered
animals. The majority of experiments, however, are aimed at developing
pharmaceutical proteins from transgenic animals to counter multiple
sclerosis, infant diseases, hepatitis, and blood and growth disorders.
So far, says the report, at least 29 human therapeutic proteins have been
produced in transgenic animals, most in milk, but some in blood, urine or
sperm. While the companies argue that this could make drug production for
diseases such as diabetes cheap and readily available, GeneWatch questions
whether it is necessary to perform experiments on so many animals.
"The use of GM animals in medical research must undergo a complete review as
the science does not support the vast abuse of animals that is taking
place," says the report.
"These experiments should only be undertaken when there is no reasonable
alternative. Balancing the needs of people for drugs with the welfare and
integrity of animal species is a complex ethical dilemma."
Other animals, especially pigs, are being genetically modified to try to
produce whole organs for humans in xenotransplantation experiments. Because
of the huge gap between the numbers of organs needed and those available,
this branch of genetic manipulation has attracted millions of pounds of
investment, but has had little commercial or scientific success so far.
Eight companies, including two in Britain, are working on GM pigs to develop
livers, kidneys, hearts and pancreas.
Yesterday the Roslin Institute, which developed Dolly the sheep, the world's
first cloned animal, was highly critical of sections of the report. "All
experiments on animals need to be justified on a case by case basis. GM
animals will be increasingly important to advancing medical knowledge, the
testing of new drugs and to the production of treatments for cancer and
other diseases at a price society can afford," said Dr Harry Griffin,
assistant director of the institute.
"For GeneWatch to condemn a whole technology based on a few selected
examples is irresponsible and a gross disservice to the patients who will
benefit directly or indirectly in the future."
But he said that he agreed with GeneWatch when it criticised the development
of cloned pets or endangered species. "That is a nonsense, and not a
sensible way forward for the technology."
Dr Griffin also questioned the other major strand of GM animal research,
which is trying to develop increased food production. "It is very premature
to introduce cloning into agriculture and we need to look at improved
success rates," he said.
GeneWatch also says that governments and academic laboratories are
developing GM animals with increased agricultural productivity or disease
resistance. Genes coding for human growth hormones and vital proteins have
been inserted into a variety of animals.
The report says: "They have displayed enhanced growth, an increased meat/fat
ration and increased efficiency of feed conversion but there have been high
costs to the animals, including gastric ulcers, liver and kidney damage,
degenerative joint diseases, lameness, lethargy and damaged vision."
Two types of sheep are now being developed for increased wool production but
peer-reviewed scientific papers suggested that the small increases (6%) in
production in year one were not repeated later.
But other scientists reacted strongly. Dr Mark Matfield, director of the
Research Defence Society, which represents UK scientists in the debate about
use of animals in medical research, said: "GM animals are proving crucial in
the understanding of many serious and fatal diseases from cancer to cystic
fibrosis and motor neurone disease. Scientists take their responsibilities
towards all laboratory animals, including those that are genetically
modified, very seriously."
GeneWatch called for an independent inquiry into the use of GM and cloned
animals in medical research, an end to secrecy surrounding such experiments
and tighter regulations to prevent their use in agriculture, as pets, for
drug production or as organ donors.
"Scientists are getting carried away with gene hype and animals are
suffering. There is simply no justification for the genetic modification and
cloning of animals for use in agriculture, as drug factories or for organ
production," said Dr Mayer.
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2.
'Human' definition worries cloning foes
By Amy Fagan
THE WASHINGTON TIMES
 

     The National Right to Life Committee is campaigning against a
Democrat-backed bill in the Senate that they say would leave the door open
to human cloning.
     The bill, introduced by Sen. Byron L. Dorgan, North Dakota Democrat,
would ban the cloning of human beings  so-called "reproductive cloning" 
but remains silent on the issue of therapeutic cloning, which is dividing
the Senate.
     The measure has been billed as a common-ground approach as the Senate
prepares to vote on cloning, with action expected by the end of the month.
     "We see it as a way to act upon what everyone agrees needs to be acted
upon," said Mr. Dorgan's spokesman Barry Piatt. "Everyone believes cloning a
human being should be illegal. So let's close that door right now and then
let's come to a sensible agreement on the other issues."
     Mr. Piatt said the bill's purpose is to prevent the therapeutic
procedure from being used to produce the first cloned infant.
     But Douglas Johnson, legislative director for the NRLC, said the bill
leaves the term "human being" open to interpretation. Because some do not
consider a fetus to be a human being, he said, that language could allow a
cloned human embryo to be implanted in a uterus and grown into a fetus for
experimentation.
     The Dorgan bill reads, "It shall be unlawful for any person to engage
in a human cloning procedure for the purpose of creating a cloned human
being."
     "So you've got a bill that has this additional condition, that
basically anything is OK unless it's done to produce a human being," Mr.
Johnson said.
     "If a 'fetus' is not a 'human being,' then the bill would allow a
cloned embryo to be implanted in a human or animal womb and grown for months
before being killed to obtain tissues or organs," the NRLC said in a press
release about the Dorgan bill.
     Mr. Dorgan call the NRLC's claim "absurd."
     "To say that [the bill] positively permits something to happen is
inaccurate," Mr. Piatt said. "This bill does not address the rest of the
issues, it addresses what we can agree on: that cloning a human being should
be illegal."
     However, the International Center for Technology Assessment, a
nonpartisan, nonprofit group that analyzes emerging technologies, agrees
with the NRLC assessment of the Dorgan bill. An ICTA analysis says the
Dorgan bill is "far from the Senate's 'common ground' and is the most
permissive piece of human cloning legislation introduced in the Senate."
     The ICTA analysis found that  unlike the other human cloning bills in
the Senate  the Dorgan bill would legalize the implantation of a cloned
human embryo into a woman's uterus.
     But Michael J. Werner, vice president of Bioethics at the Biotechnology
Industry Organization (BIO), said this is unlikely to happen. "I don't think
anyone is going to implant a blastocyst into a uterus for research purposes.
I don't know if that would be legal first of all, and I don't know who would
do it," he said.
     Two better-known cloning bills have been proposed in the Senate. One 
introduced by Sen. Sam Brownback, Kansas Republican, and favored by
President Bush  would ban the cloning of human embryos for any purpose. The
other  sponsored by Sens. Arlen Specter, Pennsylvania Republican, Dianne
Feinstein, California Democrat, and others  is favored by BIO. It would ban
the implantation of a cloned human embryo into a uterus but would allow the
human cloning procedure to be used to harvest stem cells for research.
     Mr. Dorgan's bill is co-sponsored by just two other Democrats  Sens.
Tim Johnson of South Dakota and Mark Dayton of Minnesota  but the NRLC said
there is an "active attempt to market this as a consensus measure."
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3.
 

No consensus on cloning regulation among experts

Copyright ) 2002
United Press International
 

By JENNIFER LORD, United Press International
WASHINGTON (May 14, 2002 9:50 p.m. EDT) - It is a good thing that in the
future, parents will be able to predetermine the physical traits of their
children - providing that current anti-cloning legislation before Congress
does not pass - Reason magazine science correspondent Ronald Bailey said
recently at the New America Foundation.
Speaking at a packed brown-bag luncheon on May 9, Bailey discussed current
genetic testing technology that allows parents to prevent passing on genetic
diseases to their children and said that in the future, reproductive cloning
will go even farther by allowing parents to bear children with pre-chosen
chromosomes, which will allow them to determine their offspring's looks,
intelligence and other traits. All these applications of human genetic
science are to the good, he said.
"Respecting the sanctity of human life does not require that we accept all
the horrors that nature chooses to dish out," said Bailey, who has written
many articles in favor of genetic engineering and is a strong supporter of
Congress granting complete freedom to research scientists to explore new
possibilities in the field. His most recent article appears in Reason
magazine, which is published by the libertarian Reason Foundation.
Many of his colleagues in the think tank world disagree with him, however.
For a variety of reasons, other analysts at both conservative and
liberal-leaning think tanks call for either total or partial regulation of
human cloning and of other human genetic research that may lead to
experimental medical treatments.
Eric Cohen, a resident scholar at the Ethics and Public Policy Center, said
that bioengineering experiments can't be done in a way that is consistent
with the ethics of human experimentation, so they should be banned.
"Human beings are not animals - there's something fundamentally different
about human beings, and we ought not to be treated as animals who are bred
to specifications," said Cohen.
He said that the "tragic results" of animal cloning - cloned animals appear
to develop health problems (Dolly the sheep, the first surviving clone, has
severe arthritis), and cloned animals frequently die at birth or soon
afterward, and seem to have very short life spans generally - should be a
strong indicator that the science is not ready to be tried on humans.
At the meeting, Bailey spoke out against the bipartisan Brownback-Landrieu
Human Cloning Prohibition Act, a bill that banned all human cloning. He said
repro-genetic technologies do not violate the rights of the unborn and those
opponents of cloning attempt to frighten lawmakers with unverified
predictions of future genetic mutations.
Bailey also said that the future should not be viewed with fear, but instead
with great expectation, because reproductive cloning would prevent many
negative attributes of natural human genetics, such as inherited diseases,
from surfacing.
Daniel Callahan, director of International Programs at the New York-based
Hastings Center disagrees. Picking out your child's personality traits is a
bad and hazardous business, Callahan said.
"We have no idea how it is going to turn out, and it's very hard to imagine
that in most cases it will be beneficial for the child," Callahan said.
"Show me that those (genetically engineered) children will actually be
better off than they would if we had left them untouched."
Callahan maintains that the government should step in now and begin
regulating the industry.
"Someone like Ronald Bailey seems to think that anything science wants to do
is almost de facto a good thing, and are opposed to any form of
interference, but I think that is a naive view of science. Science can do
good things and it can do bad things, and one of our human tasks is to make
some distinctions and say that there are certain things that science ought
not to do," Callahan said.
Ruy Teixeira, a senior fellow at the Century Foundation, a leftward-leaning
think tank, agreed that Congress should pass measures to regulate the
industry but not to ban it completely.
"Right now we are just at the point where we are going to need to develop
some sort of regulatory regime for it. I think that's what the public really
wants, and I think that's what the reality of the technology demands,"
Teixeira said.
Steve Buckstein, president of the Cascade Policy Institute, an Oregon-based,
free-market think tank, is completely against any regulation of the cloning
industry.
"I don't think that 100 senators and 400-some Congress people should be
making the rules about this," said Buckstein. "I think that science has
helped more than it's hurt the human race, and genetic engineering and
cloning and all of these new technologies have far more potential for good
than for harm. Obviously there are risks involved, and it's good to look at
those, but to stop progress because of this would be unfortunate."
Other free-marketers also supported further developments in human
biotechnology, but thought the issue should be decided by future
generations.
Patrick Stephens, a research fellow at the Objectivist Center, a
philosophical think tank that endorses author Ayn Rand's principals of
individualism, said bioengineering humans would not happen in the near
future.
"The science is not there yet and probably won't be for decades and decades
at least. I think that on the whole, genetic engineering will be a very
positive thing for mankind," Stephens said. "The ability to select out
diseases like Alzheimer's, autism, Parkinson's and various other genetic
defects has the potential to be an enormous medical device. Most of modern
medicine is curative, whereas this would be preventative."
Bailey was similarly optimistic about the future. He said government
regulation was the main obstacle to future innovation.
Lack of government regulation in the past, Bailey said, was the main reason
why the field of genetic science is so successful today.
"If we had regulation of fertility treatments by the Food and Drug
Administration, we would still be waiting for the first test-tube baby,"
Bailey said. "Fortunately, our descendants will have at their disposal even
more technologies. And the benefit of our own bad experiences now to guide
them in their future reproductive decisions. They will in no way be
prisoners of our decisions now."
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4.

Single gene failure "explains cloning deaths

22:00 14 May 02
NewScientist.com news service

The catastrophic failure of a single gene's regulation seems to explain the
early death of most cloned embryos, of most cloned embryos, suggests a new
study in mice.
Hans Schvler of the University of Pennsylvania and his colleagues found that
the gene that encodes the protein Oct4 was mis-regulated in about 90 per
cent of clones from somatic or adult cells.
Oct4 is a transcription factor protein responsible for switching on other
genes. Because the gene for Oct4 known is crucial for embryonic development,
its failure alone could account for the majority of clone deaths.
The work should be an additional warning to self-proclaimed human cloners
such as the controversial Italian fertility doctor Severino Antinori, says
Schvler. "Antinori has said he'll be able to pick only good embryos for
human cloning. Our embryos can look very nice. But they are ticking time
bombs."
"This is top notch, brilliant work," says Robert Lanza at the
Massachusetts-based company Advanced Cell Technology.

Sensitive barometer
In cloning, a donor cell is fused with or injected into an egg stripped of
its own genetic material. Unknown factors in the egg are then able to
"reprogram" the cell to begin life again as an embryo.
But only a few per cent of cloned embryos survive to birth and some of the
survivors are unhealthy or develop illnesses later in life.
Experts suspect that part of the trouble is that the reprogramming is
sometimes incomplete. But they have not been able to pinpoint the problem at
a genetic level. Schvler decided to look at the activity of the Oct4 gene as
a model for reprogramming, because it is such a sensitive barometer of early
embryonic development.
The gene is shut off in virtually all adult cells. It is switched on in the
inner cell mass (ICM), the part of the embryo that becomes the fetus and
from which embryonic stem cells or ESCs are harvested.
Work by other groups has shown that Oct4 mis-regulation can derail normal
embryonic development. The researchers expected to see the gene go awry
occasionally. But they found that two-thirds of the embryos did not switch
the Oct4 gene on at all or did not limit expression to the ICM. About
another quarter of the embryos produced excessive or inadequate amounts of
Oct4.

"Like cockroaches"
Schvler concludes that poor reprogramming of Oct4 is enough to sink 90 per
cent of mouse clones, close to the actual failure rate of about 98 per cent.
Lanza thinks the work raises the exciting prospect that fine-tuning the
cloning procedure to improve Oct4 reprogramming could give a dramatic boost
to cloning efficiency. "This will be a very valuable research tool to
optimize cloning," he says.
But Schvler is less optimistic. He sees proper Oct4 expression as only one
of the first barriers most cloned embryos must cross.
Davor Solter of the Max-Planck Institute of Immunobiology in Freiburg,
Germany agrees. "Misreprogrammed genes are like cockroaches," he writes in a
commentary on Scholer's article. "Where you see one there are likely to be
many more under the surface."

Journal reference: Genes and Development (vol 16)
Philip Cohen
This story is from NewScientist.com's news service - for more exclusive news
and expert analysis every week subscribe
<https://www.newscientist.com/subscribe/subs_home.jsp?source=news>  to New
Scientist print edition.

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