A sheep who keeps ethicists awake

From ANIMAL PEOPLE, April 1997:

EDINBURGH––Embryologist Ian
Wilmut of the Roslin Institute in Edinburgh,
Scotland, on February 23 announced the birth
of a lamb cloned from a mammary gland cell
taken from one adult ewe, fused with an egg
cell of another adult ewe, and implanted into a
surrogate mother last July.
The first known successful cloning of
a mammal from fully developed adult cells, the
experiment was done by a team of 12, of
whom only Wilmut and three others knew the
details––and the announcement was delayed
until the team patented the lamb, named Dolly.

The Roslin Institute team achieved
the cloning on their 277th try. Of 29 eggs that
became embryos, only 13 impregnated the
ewes into whom they were transplanted, and
just one ewe carried the pregnancy to term.
Within two weeks, however, the
accomplishment itself seemed cloned, as others
announced similar results.
The most dramatic announcement
came from the Oregon Regional Primate
Research Center in Beaverton, where director
M. Susan Smith and senior scientist Donald
Wolf revealed on March 1 that they had used
embryonic cloning, a simpler method, to produce
male and female rhesus macacques, born
last August––the first cloned primates. The
object was to breed genetically identical
research animals, who would presumably
respond the same way to experiments. In theory,
researchers would then need fewer animals
to validate results––but using fewer animals to
get more accurate information could also stimulate
more primate experiments.
“What we want to do is establish an
immortal cell line, something like an embryonic
stem cell line,” Wolf told media, “where
you can produce literally unlimited numbers of
these things.”
The first pair were not genetically
identical, because they were cloned from different
embryos, but in theory multiple identical
animals could be made from each embryo.
Observed Associated Press writer
Bob Baum, “As they hugged each other in the
corner of a small room, they seemed only to be
two frightened baby monkeys.”
The method that produced them could
presumably produce cloned people.
On March 4, Tim Cessano, 13, of
Honeoye Falls, New York, won top prize at a
school science fair for cloning African frogs he
got for Christmas. Of three frogs hatched, two
survived. Scientists have cloned frogs, who
have a very simple reproductive system, for
approximately 100 years, and Cessano borrowed
his technique from a 60-year-old textbook,
but he was nonetheless the youngest person
known to have cloned successfully.
In Taipei, Taiwan Livestock
Research Institute research fellow Ming-je Wu
reminded the world that his team had cloned the
endangered native Lanyu miniature pig,
announcing the results at the 1994 World
Congress on Genetics Applied to Livestock
Production. The Taiwanese technique involved
transplanting Lanyu pig nuclei into 30 four-cell
embryos, which were then transferred to the womb of
a Landrace pig. Of eight piglets born in March 1991,
five survived, and bred conventionally at maturity.
The Taiwanese experiment may have been
the first use of cloning in species conservation. In
theory, cloning could both prevent extinctions and
erase the need to protect habitat, since the genetic
survival of species could be guaranteed. Endangered
species law does not now address conserving environment-linked
wild behavior.
Zhu Yuding of the China Academy of
Agricultural Sciences’ Institute of Animal Sciences
said on March 11 that a secret project in Beijing had
cloned “rabbits, pigs, goats, and bulls using embryonic
cells,” but added that the research was likely to
be dropped due the high cost and limited opportunity
for genetic manipulation of the embryonic method.
But in Melbourne, Australia, a team led by
Alan Trounson announced March 13 that they had
cloned 470 cattle embryos identical to the first, a significant
advance toward mass clone production. The
previous record was fewer than 100.
Cloning for dollars
While media discussion centered on the
possibilities and ethical implications of human
cloning, present prospects for profit mostly involve
animals bred for medical and agricultural use.
Explained New York Times reporter Youssef M.
Ibrahim, “Through genetic engineering and cloning,
animals could be created to produce pharmacological
proteins like the clotting factor that hemophiliacs
need. Cloning might also permit widespread transplantation
of animal organs into humans. For example,
pig clones could be engineered to make their surface
proteins identical to proteins that coat human
cells. The researchers would then make cloned pigs
whose organs would look to a human immune system
like human organs, and not be rejected.”
Marketing rights to milk from sheep conceived
by the Roslin cloning process belong to PPL
Therapeutics PLC, whose managing director, Ron
James, told Lawrence M. Fisher of The New York
Times that the firm could produce transgenic cloned
animals capable of secreting pharmacologically useful
proteins in their milk within two years.
“Also,” James said, “instead of producing
just one, we could produce half a dozen females at a
time, making sure we could produce enough proteins
to go into clinical trials.”
Public sale of new drugs from the process
remains a decade away, James indicated, allowing
for delays in testing and winning approval from the
Crown, the European Union, the U.S. Food and Drug
Administration, and agencies of other nations.
One firm, Genzyme, has already completed
first-phase human trials of a blood-clotting drug
made in the milk of genetically altered goats. The
estimated market for this drug alone is circa $200 million
a year.
“Transgenically derived proteins should be
safer than [conventional] blood-derived proteins
because they will not be subject to the theoretical risk
of transmission of viruses,” Fisher explained, “They
should also be less costly than biotechnology drugs
produced by fermentation, because one large mammal
can produce far more protein in her milk than the
vast colonies of cells needed for current processes.
Biotechnology industry analysts say these could substantially
increase the market for therapeutic proteins,
currently about $7.6 billion dollars a year and expected
to grow to $18.5 billion” within three years.
The Roslin Institute stands to make a bundle,
not least because the British Ministry of
Agriculture for reasons unclear axed the institute’s
governmental funding, effective March 1, after six
years of supporting the cloning research. Funding of
the institute as a whole had already been trimmed
repeatedly, a reduction of fulltime staff from 450 in
1987 to just 170 now. The Roslin Institute will get
BMA funds at half the 1996 level through fiscal 1997,
and will then be completely cut off.
As a free agent, the Roslin Institute will be
able to sell its knowhow to the highest bidder, but
Wilmut still expressed disappointment. “We will certainly
get industry collaboration to use our cloning
technique commercially,” he said on March 1, “but
we have to get funding to improve our effectiveness.”
Wilmut had hoped this might be funded by the BMA,
toward finding a way to eliminate the cattle disease
bovine spongiform encephalopathy, which has ravaged
British herds since 1986 and is suspected of
infecting humans as Creutzfeldt-Jakob disease.
Wilmut needn’t have worried. Offers
poured in from Britain even before investors elsewhere
heard about the chance to cut a deal.
The Roslin Institute research may be closer
to payoff than U.S. cloning work, experts said,
because it was directed at practical goals. In the U.S.,
Princeton biologist Lee Silver told Gina Kolata of The
New York Times, “No way can you write a grant proposal
saying you want to clone a sheep,” because
National Institutes of Health reviewers would
respond, “What questions are you asking?”
“If Wilmut had submitted a grant application
to the NIH, it would not have been supported,”
agreed University of Wisconsin professor of reproductive
biology Neal First. In the U.S., applied
research and development is expected to be supported
by private investors. Thus agricultural researchers
achieved the major breakthroughs in such areas as
artificial insemination, embryo transplants, genetic
modification of sperm, and––just last year––replicating
the sperm of one animal in the testes of another.
University of Pennsylvania professor of veterinary
medicine Ralph Brinster told Kolata that
sperm replication could theoretically keep the genetic
qualities of champion racehorses or prize bulls essentially
immortal––and the sperm could be reproduced
by a mouse. The catch to that is that many highly
inbred racehorses don’t produce much effective
sperm. The Triple Crown winner Secretariat was a
notoriously mediocre stud, while Cigar, the 1995-
1996 Horse of the Year, with 16 straight victories and
almost $10 million in winnings, has covered 36
mares, impregnating none of the first 20 tested.
Therefore, said former owner Allen
Paulson, who retains an option to repurchase Cigar,
“We are certainly looking into cloning.”
Presumably Cigar could be cloned––but to
prevent artificial genetic manipulation of racehorses,
say by inserting into a horse the speed genes of a
cheetah, the Jockey Club bars horses produced by
artificial insemination from sanctioned races. The
rule could be extended to clones.
Further, cautioned James Stewart of the
American Association of Equine Practitioners,
“When the clones start to breed, they’ll bring out
recessive traits. You’ll open up some problems you
don’t want to think about.”
Biological limit
Simon Elliott of the Center for Vaccine
Development at the University of Maryland School of
Medicine warned colleagues on March 5 via the
Federation of American Scientists’ PROMEDAHEAD
newsgroup that infectious disease could limit
the value of cloning. “A group of 1,000 genetically
identical individuals could all be killed by one disease,”
Elliott explained. “Such a group would experience
magnification of pathogenicity.” Thus influenza,
for instance, could “become hyper-virulent and
lethal. There is evidence of this in plant monocultures
and in highly inbred lab animals,” Elliott said.
Examples also exist in wildlife, and are
why the Species Survival Plans for endangered animals
administrated by the American Zoo Association
emphasize keeping separate and discreet populations
of species descended from a limited gene pool––such
as cheetahs, who are all nearly genetically identical
due to some prehistoric catastrophe that nearly wiped
them out, and blackfooted ferrets, who were nearly
annihilated when canine distemper killed the entire
captive breeding population in 1985. The current
blackfooted ferret population, both in captivity and in
the wild, was rebuilt from a handful of other individuals
who were elsewhere when the distemper hit.
Clifton A. Baile of the University of
Georgia told Richard Saltus of The Boston Globe that
cloning may have many agricultural uses, but expected
opposition. Formerly with Monsanto Inc., Baile
headed the team that developed bovine growth hormone,
now widely used to make cows produce more
milk. Baile recalled that lawsuits filed against BGH
approval by Jeremy Rifkin of the Foundation on
Economic Trends “really held us back.”
Gary Webber of the National Cattleman’s
and Beef Association added, “I see more and more
consumer pressure for natural approaches. I think we
are going to have people screaming, ‘stop this train
for a while,’ while society confronts the ethical and
health issues.”
An ABC Nightline telephone poll of 519
adults found on February 25 that 53% approved of
cloning animals, with 44% opposition. Eighty-seven
percent opposed cloning humans. President Bill
Clinton responded with an executive order banning
the use of federal funds in human cloning experiments,
and asked privately funded researchers to
respect a moratorium on such work at least until May,
when the National Bioethics Advisory Commission,
appointed last summer, is to report on the legal and
ethical implications of cloning humans.
“Each human life is unique,” Clinton said
on March 4, “born of a miracle that reaches beyond
laboratory sceince. I believe we must respect this profound
gift.” The words may haunt him after his veto
of a ban on federal funding of partial-birth abortion,
in which the brains are sucked out of a sentient fetus
––a procedure that critics describe as vivisection.