Attack of the gene splicers wins hearts and minds

From ANIMAL PEOPLE, November 1996:

CAMBRIDGE, U.K.––With 80
Britons a day dying from lack of human hearts,
lungs, livers, and kidneys suitable for transplant,
Imutran Ltd. had no trouble finding 25
seriously ill volunteers in September to participate
in the first trial of organs grown in genetically
engineered pigs specifically for transplant
into humans. Subject to approval by
seven different governmental bureaus, the
experimental xenographs will be conducted at
the earliest opportunity.
Immunologist David White and
transplant surgeon John Wallwork told media
that the Imutran approach is, as London
Sunday Times medical correspondent Lois
Rogers put it, “to trick the human immune
system into tolerating animal organs. The system
is naturally programmed to mount a massive
attack to kill implanted foreign tissue
within minutes. Organs from the pigs specially
bred by the company have the same protective
proteins on their surfaces as tissue within
the human body––a mechanism designed to
stop the body from attacking itself.”

Imutran is 18 months ahead of formidable
competition, claimed White and
Wallwork, including Alexion Pharmaceuticals,
which last year sold exclusive marketing
rights to organs grown in genetically engineered
pigs to U.S. Surgical Corporation. On
June 4, Alexion won a patent on genetically
engineered embryonic stem cells. According
to Alexion president Leonard Bell, M.D.,
“Embryonic stem cell technology offers the
potential not only for adding genes, but also
for deleting or knocking out genes.” The
patent, Bell predicted, gave Alexion such “an
important competitive advantage” that trials in
humans could begin in one to two years.
Biotransplant Inc., of Boston, is
another leading contender, working to develop
pig organs for transplant in partnership with
the University of Missouri. The Missouri
researchers in June were awarded $500,000 by
the National Institutes of Health.
Clearing way
A U.S. Institute of Medicine committee
headed by Norman Levinsky, M.D., of
Boston University Medical Center, helped
clear the way for rapid expansion of xenotransplanting
with a July 17 finding that the potential
of xenotransplants for treating disease and
resolving the shortage of transplantable human
organs is so great that although federal guidelines
should be established to preclude the possibility
of bringing new diseases across species
boundaries, work should advance without
delay. The FDA and Centers for Disease
Control and Prevention are drafting guidelines,
but trail the Canadian Council on Animal Care,
which published preliminary guidelines in
1995, followed by revised guidelines in
February 1996.
The Levinsky report followed similar
pronouncements in March from the independent
Nuffield Council on Bioethics,
formed by leading biomedical research funders,
and in May by the British Medical
Association. The BMA recommended, however,
that human-to-human transplants remain
the preferred alternative until the success of
xenographs is established.
The BMA position, declared on
May 4, rebutted that of Doctors and Lawyers
for Responsible Medicine, a 122-member
coalition formed by Doctors in Britain Against
Animal Experiments, whose spokesperson,
Andre Menache M.D. of Israel, on May 1 proclaimed
“an urgent need to put transgenic
transplants on hold until valid scientific
research establishes the truth about xenotransplantation,”
a view that the BMA implied was
a contradiction in terms.
Blood and brains
Also racing to engineer animalgrown
organs for human use are blood product
producers. One U.S. firm, BioPure Inc., is
reportedly already testing a synthetic blood
replacer based on cattle hemoglobins. A rival,
Baxter Healthcare, of Britain, is developing a
similar product based on recycled human
blood which has passed the expiration date for
use in direct transfusion. Altogether, at least
eight companies are known to be working on
blood replacements. The profit potential for
the company that first gets a successful synthetic
blood replacement into surgical suites is
immense––and the stakes have some company
publicists sounding like antivivisectionists.
Warned Baxter Healthcare, at the
height of public panic over the discovery that
“mad cow disease” may have leaped from cattle
to consumers of beef and cattle byproducts,
“Viruses present in animal blood are not as
well characterized and are therefore more difficult
to detect than those in human blood.
Animal-sourced products also must be subject
to rigorous purification procedures, since contamination
with animal-derived proteins can
cause allergic reactions.”
Returned BioPure, “We are very
aware of the BSE issue, and we have a very
significant herd management program that
really prevents that from being a problem. We
also have a proprietary process that we believe
would take it out even if it was in there,” an
eyebrow-raiser, since the prion proteins
believed to transmit BSE have proved virtually
indestructible by conventional sterilization.
The exchange came shortly after the
FDA warned on August 30 that 54 people had
contracted serious bacterial infections from
injections of an unapproved drug called
“adrenal cortex extract,” sold by Phyne
Pharmaceuticals of Scottsdale, Arizona,
under the label Hallmark Labs.
Controversy over animal-based
blood products was already in the headlines in
California, where neighbors of Santa Cruz
County goat ranchers John and Brenda
Stephenson, including nature photographer
Frans Lanting, persuaded the county to begin
drafting special regulations to govern farms
producing biotech products.
Reported Maria Alicia Gaura of the
San Francisco Chronicle, “The goats are not
milked, and will never end up on the barbeque
or in a stew poet. Instead, once or twice a
year they trot up a ramp, poke their heads
through a rubber flap, and donate their antibody-rich
blood to science.”
John Stephenson, a former National
Cancer Institute researcher, cofounded
Oncogene Science Inc., of New York, then
relocated to the west coast. The Stephensons
started Santa Cruz Biotechnology in 1991, to
cultivate more than 1,700 kinds of antibodies
used by biomedical researchers. Initially, the
antibody production was subcontracted out to
independent goat ranches, but in February the
Stephensons bought their own 200-acre ranch
to better control the operations. Rumors that
their goats might transmit deadly viruses erupted
within days, to the dismay of the local agricultural
community: many farmers whose pastures
are too small, too steep, and too surrounded
by expensive development to permit
continued profitable use in conventional agriculture
see bio tech as their potential salvation.
“Taking this kind of hysteria seriously
could set back California agriculture for
years,” former Santa Cruz County Farm
Bureau president Kirk Schmidt warned.
Despite the Santa Cruz County fracas,
the future of transgenic goat ranching got
a big boost on April 8 when Genzyme
Transgenics, of Framingham, Massachusetts,
announced the birth of a goat who may
become the prototype producer of a genetically
engineered antibody called BR96, used by
Bristol-Myers Squibb in an experimental anticancer
treatment. The birth could also have
been billed as a breakthrough in the reduction,
refinement, and replacement strategy for
reducing laboratory animal use: BR96 was
formerly obtained only by milking transgenic
mice, and hordes of mice had to be milked to
collect the output of a single goat.
Knots and stomachs
Such situations pose knotty problems
for animal advocates: should nonlethal transgenic
animal husbandry for biomedical
research be welcomed, for potential in reducing
lab animal use and in helping farmers to
keep green space open without sending animals
to slaughter, or should it be opposed as
“exploitation” and an adjunct to “vivisection,”
even if no animal suffering is evident?
Says BMA chair Sandy Macara,
M.D., “If we are prepared to eat animals,
there can be no ethical objection to using their
organs to save human life.”
For people who don’t eat animals,
the matter is more complicated. Most antivivisection
societies have been quick to denounce
biotechnology, as have some animal rights
groups, but others, along with most mainstream
humane organizations, keep discreet
silence––just as they long have about meat.
The American Anti-Vivisection Society said
little about meat before 1990; the New
England Anti-Vivisection Society has opposed
meat-eating only since it was taken over by
PETA and the Fund for Animals in 1988; and
the National Anti-Vivisection Society position
on meat-eating is still ambiguous.
Antivivisectionism was among the
original components of the humane movement,
more than 200 years ago, yet Carolyn Earle
White, founder of both the Women’s Humane
Society in 1869 and American AV in 1883,
saw reason to separate the causes, even
though she remained active in both until her
death in 1916. The donor base, she perceived,
substantially overlapped, yet many supporters
of animal protection would withhold their dollars
if they thought animal protection inhibited
the improvement of human health, while
many supporters of antivivisection were less
concerned about animals than convinced that
treatments based on animal research were
detrimental to their own health.
Essentially, White recognized the
dichotomy persisting to this day between the
PETA creed that “Animals are not ours to eat,
wear, or experiment on,” and the Hans
Reusch contention that “Vivisection is scientific
fraud.” Both positions are advanced by
antivivisection and animal rights groups,
including PETA, but as Andrew Rowan of the
Tufts Center for Animals and Public Policy
points out, the view that animals are so like us
as to have a moral claim prohibiting their use
in experiments at least potentially contradicts
the view that animals are so unlike us that their
use cannot yield valid information about
human health. Reusch, the most prominent
exponent of the latter view, has not opposed
either hunting or meat-eating, while Javier
Burgos of SUPRESS a.k.a. The Nature of
Wellness has long held that vivisection is not
essentially an animal rights issue.
The antivivisection movement,
boosted by the Hearst newspaper chain, took
such a separate direction from that of the mainstream
humane movement after White that by
midcentury the American SPCA and American
Humane Association advocated the use of animals
from shelters in biomedical research,
albeit over strong internal dissent. Christine
Stevens founded the Animal Welfare Institute
to reintegrate concern for lab animals into the
humane cause in 1952; Cleveland Amory,
Fred Meyer, and Helen Jones cofounded the
National Humane Society, now known as the
Humane Society of the U.S., for the same reason
in 1954; and Jones broke away to found
the even more militantly antivivisection
National Catholic Humane Society in 1959,
now known as the International Society for
Animal Rights.
The rapid growth of rivals brought
first the AHA and then the ASPCA back
toward anti-pound seizure and anti-animal testing
positions by the late 1970s. For nearly 20
years now, animal protection groups have
rarely opposed each other on fundamental biomedical
research issues, despite sometimes
heated debate over tactics.
Advances in biotechnology could
soon change that, blurring traditional battle
lines and taking ethical debate beyond hypothetical
“your child or your dog” syllogies.
For instance, another pursuit attracting
substantial interest and investment is the
development of a way for people to grow
replacement heart valves. Globally, 200,000
people a year get heart valve replacements,
including about 60,000 Americans. But the
replacements, taken from pigs, human cadavers,
or made from plastic, require the recipients
to use anticoagulant drugs, which can
cause serious side effects, and the valves wear
out in 10 to 20 years, a serious problem for
younger recipients, especially children born
with congenitally heart disorders.
“Ultimately, we want to give a newborn
baby a replacement that not only won’t
require anticoagulant therapy and have to be
replaced in a few years, but will also grow
with the baby,” explains Gail Naughton of
Advanced Tissure Sciences. ATS is seeking to
cultivate replacement valves from cells
extracted from infants’ foreskins, normally
discarded after circumcision. The procedure
already works using lambs’ foreskins.
The leader in the field, however,
appears to be Dr. Richard Hopkins, of
Georgetown University, whose work is
financed by LifeNet, a nonprofit tissue bank,
and St. Jude Medical Inc., a leader in producing
current valve replacements. Already able
to grow replacement valves for sheep in their
own bodies, Hopkins is reportedly close to
beginning tests of his technique in transplant
applications. Tests in humans are expected to
start within three to four years.
All the work so far is opposed at
least in principle by the position statements of
all the national animal protection groups with
written policies on biomedical research. Yet if
either ATS or Hopkins succeeds, pigs will
rarely be used as a source of heart valves.
Sheep will no longer be used in related experimentation,
because human biological processes
will replace the routine use of animals
throughout the heart valve replacement
field––an essential antivivisection goal.
Behind the scenes, some animal
protection and antivivisection group fundraisers
are already scrambling to find a way to
claim a piece of the “victory” when and if it
comes. That it will come within five to 10
years is believed to be a virtual certainty.
Meanwhile, scientific demand for
genetically engineered mice grew 400% in
1995, according to Jackson Laboratory, of
Bar Harbor, Maine, the world leader in breeding
mice to spec. In January, Jackson Lab
announced a $7.5 million expansion of its
Induced Mutant Resource, a living archive of
engineered mouse strains.
Many of the mice ordered in 1995
were involved in the genetic technology breakthroughs
of 1996, which by October were
coming almost daily:
• On October 4, University of
Minnesota researcher Karen Hsiao and the
Alzheimer’s Association unveiled a genetically
engineered mouse who is susceptible to the
human strain of Alzheimer’s disease.
• On October 8, Utah State
University molecular biologists patented a
gene that increases resistance to the bacteria
that carry the cattle disease brucellosis.
Incurable with present methods, brucellosis is
endemic in the Yellowstone National Park
bison herd, and is the reason Montana insists
on shooting any bison who wander out of the
park into the cattle range just to the north.
• On October 10, Dr. Andreas
Zimmer of the National Institutes for Mental
Health published findings from mice genetically
engineered to prevent production of
enkaphalin, described by London Daily
T e l e g r a p h science editor Roger Highfield as
“an opium-like chemical found in mice and
humans, thought to help in preventing pain
and controlling behavior.” The work was
billed as indicating a new direction for the
development of pain-relieving drugs; it also
suggests that high irritability and aggression
coincide with a low pain threshhold.

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