Section 5. Case Study
Case title: Animal Transplants
Description: This case is about Jeff Getty who is suffering with the AIDS
virus. In order to help save or prolong his live he received a transfusion
fluid containing two types of baboon cells. This case describes another
controversial solution to the transplant organ shortage.
Pig Livers to the Rescue?
Vexing questions at the frontiers of
By Bryn Nelson
August 20, 2002
One scenario envisions doctors delivering a limitless supply of
livers, hearts and other organs to save the lives of countless
transplant patients. In another, doctors unwittingly release a
horrific plague upon unsuspecting millions.
In the controversial field of xenotransplantation, or the transfer of
cells, tissues and organs from one species to another, the wildly
divergent prophecies offer a glimpse of the potential glories and
perils attached to none other than the common pig. Proponents view the
quest for animal organs as one of the most realistic solutions to the
human organ donor shortage, a deficit they say cannot be overcome by
organs from living donors or cadavers alone.
"Xenotransplantation has appeared to me to be a potential solution to
an enormous number of people who would die otherwise without an
organ, says Dr. David Sachs, a surgeon at Harvard Medical School and
director of the Transplantation Biology Research Center at
Massachusetts General Hospital.
Dr. Marlon Levy, the surgical director for transplant surgery at
Baylor All Saints Medical Center in Fort Worth, Texas, calls a
limitless supply of organs or cells the "Holy Grail of
transplantation. "And at least on the organ side of things, he says,
"the answer is using animal organs.
Critics, on the other hand, joke that the future of transplantation is
xenotransplantation -- and always will be. Others declare more soberly
that the procedure poses the unacceptable risk of allowing potentially
deadly viruses to accompany the transplanted animal organs, first into
human patients and subsequently into the general public.
"In my opinion -- and I am not alone on this -- putting animal cells
and tissues or organs into humans is kind of like playing Russian
roulette, says Alan Berger, executive director of the Sacramento,
Calif.-based Animal Protection Institute and a member of the U.S.
Secretary of Health's Advisory Committee on Xenotransplantation.
No matter what their position, most doctors and researchers admit the
field faces other vexing questions, such as whether pig organs can
evade initial rejection by the human immune system, and whether they
will function properly afterward.
In 1963, in New Orleans, Tulane University surgeon Keith Reemtsma
performed the first xenotransplants of the modern medical era, using
chimpanzee kidneys. A pair of the transplanted organs worked for
nearly nine months in one patient.
Since then, doctors have tried transplanting hearts, kidneys and
livers from baboons, chimpanzees, pigs and sheep. All have ultimately
failed, including a baboon heart that ceased functioning 20 days after
it was transplanted into the famous California newborn known as "Baby
Fae, born with an underdeveloped heart in 1984.
Yet advocates aren't deterred.
"I think there's no other immediate solution to overcoming the human
organ shortage, says Dr. David Cooper, an associate professor of
surgery at Massachusetts General Hospital and Harvard Medical School
in Boston. Cooper says he has a "reasonable expectation that
xenotransplantation might solve the problem in the next 10 years.
Baylor's Levy is reluctant to adhere to any specific timeline but
nevertheless forecasts eventual success as well. "And I think the
challenge for us is to keep exploring any and all ways to eliminate
the waiting list for solid organs, he says.
Xenotransplantation isn't the sole avenue of research. Scientists are
pursuing stem cell therapy, tissue engineering and bioartificial
organs as other potential ways to assist faltering organs or grow new
ones from scratch.
Dr. Robert Lanza, for one, views animal organs as a temporary solution
until stem cell therapy and tissue engineering reach the bedside. The
vice president of medical and scientific development at Advanced Cell
Technology in Worcester, Mass., Lanza recently published a study with
colleagues in which they used a combination of the two approaches to
produce heart muscle, skeletal muscle and even miniature kidney-like
organs in cows.
Others are trying to develop artificial organs, and a half-dozen
companies are pursuing liver-assist devices to cleanse a patient's
blood of toxins in emergency situations in a process akin to kidney
dialysis. Some of the devices are technically considered
xenotransplant procedures because they contain pig cells. (Pig-derived
heart valves, on the other hand, have been used for decades to treat
heart patients but are chemically treated so they do not contain
living cells, and as a result can't be rejected.)
Although recent xenotransplantations have included injections of cow,
pig and mice cells to treat conditions ranging from chronic pain to
Parkinson's disease, the focus of the future has narrowed almost
exclusively on pigs as potential organ donors.
The ease and speed with which swine can be bred have given rise to the
notion of "organ farms, but advocates tout other amenities as well.
Over the past 30 years, Harvard's Sachs has bred a line of miniature
swine that possess human-sized organs. And many pigs have been purged
of common pathogens, a vital step in developing herds for
Conversely, several factors have kept nonhuman primates from emerging
as likely candidates. The kidneys of baboons, for example, are smaller
than those of humans. And because most primates used in studies are
caught in the wild, they may harbor a broader range of pathogens than
animals bred in captivity. Some scientists also believe viruses from
primates may cross over to humans more readily than pathogens from
pigs, a contributing factor in the FDA's 1999 call to halt the use of
nonhuman primates in clinical xenotransplant studies. HIV, now thought
to have arisen in chimpanzees, provides a stark example.
Critics counter that the influenza pandemic of 1918 killed 20 million
humans worldwide and featured a viral strain that originated and then
mutated in pigs.
"There isn't any question that we have a higher degree of known
viruses from primates, Berger says. "But since pig haven't been
studied as well, who knows?
The focus on pigs also raises the question of whether its organs will
function properly in humans, especially the multitasking liver. "We
know that it [a pig liver] does a lot of good things, Sachs says.
"The question is, does it do everything?
Many researchers say the medical use of nonhuman primates tends to
raise more ethical qualms with the public than the use of pigs, which
already have a long history as a human commodity. "Most people would
agree that if you use a pig for bacon, then you should be able to use
a pig's heart to save someone's life, Sachs says.
This rationale is anathema to many animal rights advocates, who oppose
both uses. "They think the public is less sensitive to pigs, so let's
use pigs, Berger says. "They're just trying to find the easy way to
Animal rights activists say continued efforts to improve
xenotransplant survival times in nonhuman primates could require the
sacrifice of countless more monkeys, chimpanzees and baboons. And
eventually, such research could pave the way for the slaughter of
thousands of pigs bred as human organ factories. The outcry has been
particularly harsh in the United Kingdom, where observers say the
public is more aligned against animal research.
Significant obstacles remain on the scientific front as well,
especially the human body's rejection of anything perceived as
foreign. Pig cells are studded with sugar molecules that provoke a
particularly vigorous response from human antibodies. If an organ
containing these sugar molecules were introduced into the human body,
Lanza says, "it would turn black and reject within a matter of a few
minutes and certainly within a few hours.
With immunosuppressive drugs and other strategies, researchers have
reached an average survival length of one month among primates that
have received pig organs, and three months in some cases. "When we get
to months to years, then it will be the time to start treating
patients, Sachs says, though he refuses to speculate when that might
Researchers have found at least one major cause for optimism. In
January, the biotech companies PPL Therapeutics (associated with the
company that cloned Dolly the sheep) and Immerge BioTherapeutics
independently announced the creation of pigs that lack one copy of the
gene whose protein product correctly positions the sugar molecule that
causes the human immune system to react so violently. Breeding
programs could eliminate both gene copies in the pigs' progeny and
entirely remove the sugar molecule from the cell surface.
"If these pigs come to fruition, then we will have a pig that I
strongly suspect we'll be able to get over these immunological
problems , Cooper says. "That will be a big step forward. The feat,
experts say, is akin to removing a major roadblock to see what lies
beyond it. No one yet knows whether its absence alone will
substantially increase the survival time of xenotransplant recipients
or whether other immune obstacles will remain.
Sachs says his group is pursuing another line of anti-rejection
therapy called tolerance in which researchers try to fool a patient's
immune system into recognizing a foreign organ as self and thus
leaving it alone. Sachs says he's already found success with the
approach in human-to-human transplants.
The concern over unleashing a lethal pig pathogen onto the public
hangs over such recent successes like a storm cloud, however.
"To me, it's just a really scary Pandora's box, says Betsy Todd, an
infection control nurse in Manhattan. "This is not some sort of
fantasy that these things can happen. We know that viruses can jump
from one species to another.
Simian herpes B, for example, is nonpathogenic in monkeys but can
cause fatal brain swelling in humans. In 1998, the Nipah virus killed
more than 100 Malaysian farmers who were apparently infected from
handling pigs. Even more worrisome, experts say, is the possibility
that pig retroviruses may recombine with other viruses or appear in
unfamiliar forms and lie dormant for years.
"It's not a Chicken Little thing but you're only as good as the
technology at the moment, says Jonathan Allan, a virologist at the
Southwest Foundation for Biomedical Research in San Antonio.
"All technology is not all knowing.
Furthermore, Allan says a full organ transplant may provide a ready
conduit for a virus that wouldn't normally have access to humans.
"You're basically producing the most ideal setting for getting one
pathogen from one species to another, he says, perhaps allowing a
brand new disease to emerge.
Eventually, if such a virus came into contact with other humans, he
says, "you don't have to be a science fiction writer to imagine dire
Pig viruses known as PERV, or porcine endogenous retroviruses, have
created the biggest stir so far. Like humans, pigs have apparently
harmless retroviruses incorporated into the DNA of their cell nuclei.
The unanswered question is whether such pig viruses could become
harmful in a human cell. In 1997, a British medical researcher
reported that these pig retroviruses could infect adjacent human cells
grown in culture. The discovery led the FDA to hold public hearings
and put a hold on xenotransplantation trials until researchers could
document improved safety precautions. "We're not too worried about the
patient, Cooper says, pointing out that the patient would succumb
without an organ transplant. "We're only worried about if the patient
will become a public health hazard to those around him.
Although the risk may never be eliminated entirely, researchers say
they are taking three main approaches to make it as small as possible:
diagnostic tests to establish a pathogen's presence, effective
antibiotic or antiviral agents, and outright elimination of the
pathogens through breeding.
"It's unlikely that we're going to find the perfect pig as transplant
donor, says Dr. Jay Fishman, head of infectious disease for the
transplant unit at Harvard. "On the other hand, if we get all our
pieces in order, we may be able to prevent the transmission of a
particular virus from a particular herd.
Sometimes luck helps. Immerge has discovered a subset of its inbred
miniature swine that apparently doesn't transfer PERV to human cells.
"If it's in the pig organ but can't get into human cells, then the
problem is solved, Cooper says.
No so fast, others say.
"If you put PERV in a whole human and let it sit for 30 years, who
knows what's going to come out? Allan says. "If you unleash a virus
in the population, you may not know you've done it. But Cooper is
"If you always waited for the unknowns to become known, you'd never
advance in anything, he says. "As long as we've solved all of the
known problems, I think we should push ahead.
Norman Daniels, a professor of medical ethics at Tufts Medical School,
joined colleagues four years ago in calling for just the opposite: a
moratorium on xenotransplantation.
"This is not a Luddite effort to eliminate technology or progress, he
says. "It's an attempt to manage the risks for an unprecedented
medical issue: receiving informed consent from those at risk of
contracting any pathogen emerging from a patient's xenotransplant.
"So in this sense there's a public health issue that there isn't in
other medical treatments, and that's what's at stake here -- a public
health-public risk issue, Daniels says. And even if researchers can
obtain the informed consent of sexual partners, family members and
friends of xenotransplant recipients, "how do you enforce it? he
"Once the genie is out of the bottle, it's flying around and no one
can put it back it, and so my position is still to support a
moratorium, Daniels says.
Despite the risks, the lucrative potential of xenotransplantation has
attracted the notice of analysts and biotech firms alike, with one
1996 estimate predicting worldwide revenues of $6 billion per year by
2010. But disappointing research results, mainly in the survival
lengths for nonhuman primate recipients of whole organs, may be
forcing a re-evaluation.
"You've seen a bit of a retrenchment in this field, Levy says, with
biotech companies re-examining where they want to go. "I suspect they
wanted to be farther along than where they are now.
Between 1992 and 2001, the FDA received 40 new applications for
xenotransplantation clinical trials in humans, about one-fourth to
treat liver failure. Half were withdrawn or on hold in 2001, with only
13 in effect. In one of the approved trials, conducted in 1997 and
1998, Levy and other Baylor researchers successfully used transgenic
pig livers to cleanse the blood of two patients who later received
livers from human donors. Both patients are still living, Levy says,
with no evidence of PERV.
The apparent success of the clinical trials notwithstanding, "the
sponsor, Nextran, hasn't wanted to throw more resources into this
effort, Levy says, with obvious disappointment.
"I guess I've had a glimpse at what could be and my natural
inclination is to learn more, he says, "and you couple that with the
frustration from the number of patients dying on our waiting list and
that's very frustrating.
In the absence of more funding, Levy has switched his main focus to
questions of safety. "And I think once those are answered, the field
will feel more comfortable with moving forward, he says. Levy's
testing the 40 to 50 health care workers who were voluntarily involved
in the two clinical procedures and came in contact with the patients
to see if any have developed signs of a pig viral infection.
"I think vigilance is absolutely required but what we applied so far
hasn't turned up anything, he says.
Not yet, anyway.
Copyright © 2002,
Now 22, Robert Pennington of Dallas says he owes his
life to doctors use of a pigs liver in 1997.
(Photo by John David Emmett)
August 20, 2002
Alive: With Help From a Pigs Liver
By Bryn Nelson
August 19, 2002, 2:06 PM EDT
During the summer of 1997, 17-year-old Robert Pennington had little
reason to expect a life- threatening illness. "I've been healthy most
of my life, says the soft-spoken Texan. "I've always had a good
But during the course of three weeks that summer, Pennington developed
flu-like symptoms and became progressively weaker and more dehydrated.
One day, he looked in the mirror and noticed that the whites of his
eyes had turned yellow. By the time doctors diagnosed him with
fulminate hepatic failure, or sudden liver death, his urine had turned
the color of coffee. He slipped into a coma soon afterward.
In desperate need of a liver transplant, Pennington was moved to the
top of the transplant list at Baylor University Medical Center in
Dallas while doctors debated their options. Finally, Baylor surgeon
Marlon Levy approached Pennington's grandparents, his legal guardians,
and discussed a novel experiment designed to buy their grandson more
time -- one that involved using a pig liver to cleanse his blood of
On Oct. 3, 1997, Pennington became the first patient in the world to
successfully undergo an experimental xenotransplantation procedure in
which doctors cycled his blood through a genetically altered pig's
liver placed in a saline bath beside him.
"It was the main thing that was keeping me alive, Pennington says
with conviction. His doctors halted the procedure, known as
extracorporeal perfusion, less than seven hours later when they found
him a suitable human liver from a cadaver. A few weeks after the
transplant, the U.S. Food and Drug Administration placed a temporary
hold on all xenotransplant trials over concerns that pig retroviruses
could jump to humans. One year later, Baylor doctors found similar
success with a second patient, a woman.
Now 22 and living in Dallas, Pennington owns his own business selling
watches, jewelry and car accessories. His doctors never found out why
his liver failed, he says, but he hasn't had any major problems since
the transplant, save a bout of dehydration a few months ago.
"I pretty much live a normal life, he says, with daily doses of
anti-rejection medication, vitamins and iron supplements some of his
few concessions. His doctors have kept a close eye on him, first
taking blood samples daily, then weekly. He now goes once a month for
routine tests and undergoes more extensive tests every four to six
months. "And they've never found anything abnormal yet, he says.
Although Pennington believes xenotransplantation granted him a new
life, he has become an advocate for human organ donation and is
developing a Web site to encourage such donations after death. "I
think the main thing is that if more people donated organs, then
wouldn't have to resort to research with animals, he says. Until that
time comes, however, "they're going to have to do this to save lives.
I'm all for it. It saved my life, so what else can I say?
Copyright © 2002,
Pigs Have 'Knockout' Promise for Transplant
THE ASSOCIATED PRESS
August 23, 2002
London - Scientists have cloned piglets lacking both copies of the gene
that prompts the human immune system to reject transplanted pig tissue - an
advance toward producing herds that could supply lifesaving replacement
organs for humans, a Scottish company said yesterday.
PPL Therapeutics plc., the company that in 1997 helped make Dolly the
sheep, the first mammal cloned from adult sheep cells, said four healthy
piglets with both copies of the gene "knocked out" were born July 25 at the
company's U.S. subsidiary in Blacksburg, Va.
"The advance brings us closer to the promise of a potential solution to
the worldwide shortage of organs and cells for transplantation," said David
Ayares, vice president of research at PPL Therapeutics Inc., the U.S.
A fifth piglet died of unknown causes shortly after birth, the company
In January, PPL Therapeutics and competitor Immerge BioTherapeutics both
said they created pigs lacking one of the two copies of the critical gene,
known as GGTA1. That step proved the science was possible.
The GGTA1 protein product transfers a sugar called alpha-1-galactose onto
the outer surfaces of pig cells. Because it is nearly identical to a
bacterial sugar, the human immune system attacks it. As a result, pig organs
transplanted into people are destroyed almost instantly.
Scientists have predicted that transplanting genetically modified hearts
and other organs from pigs to people - a practice called xenotransplantation
- could be possible in five to seven years but many scientific and ethical
No one knows for sure whether pigs can survive without alpha-1-galactose.
But if they can, the animals could be raised to supply hearts and kidneys
for human transplants.
Dr. Jeffrey Platt, head of transplantation biology at the Mayo Clinic in
Rochester, Minn., said the "knockout" piglets were an important advance and
will help scientists determine what is necessary to make transplants from
pigs work in humans.
Scientists will have to test the process first by transplanting the pig
organs into other primates, such as baboons.
Another worry is whether the organs will carry pig viruses that could be
harmful to people, especially if they spread from the organ recipient to
Copyright © 2002, Newsday, Inc.