Tag: Xenotransplantation

Genetically Modified, Cloned Pigs Could Provide Organs for Humans

PPL Therapeutics announced this week that on Christmas Day five genetically modified and cloned Pigs were born that bring the possibility of Xenotransplantation — transplanting organs from animals to human beings — one step closer.

The pigs are genetically modified to make it more likely that an organ transplanted to human beings would not be rejected by the human immune system. Researchers knocked out a gene in the pigs that produces an enzyme that adds a sugar to the surface of the cells. This sugar would be identified immediately by the human immune system which result in an attack and the rejection of the organ.

Which does not mean that organs from these genetically modified pigs are ready to be transplanted into humans. In fact, another gene that performs a similar function would have to be knocked out as well as several human genes added in order for there to be a reasonable chance at transplanted organs not being rejected.

Still, PPL Therapeutics vice-president David Ayares told New Scientist that he hopes human trials could begin within five years. Pigs, by the way, would be ideal for heart transplants since the heart in this particular species of pig is roughly the same size as the human heart.

Since the pigs were cloned, PPL Therapeutics would have the ability to quickly ramp up production of replacement organs should their technology eventually succeed in human trials.

Of course, the animal rights community is opposed to this, with the Campaign for Responsible Transplantation once again raising the red flag about possible pig viruses being passed on to human beings. CRT has spent the last couple of years arguing that the possibility of cross-infection of porcine endogenous retrovirus should lead to an outright ban of xenotransplantation with pigs.

In 1997, researchers proved that, at least in laboratory conditions, PERV could jump from pig cells to human cells. PPL Therapeutics and other companies hoping to market this technology will likely have to create pigs that are free from PERV. The PERV virus has been completely sequenced and patented, however. Another company, Immerge, has bred pigs which it says are genetically modified so they cannot pass along PERV to human beings.

Which is largely irrelevant to the animal rights activists, for whom the argument is largely a smokescreen. Wired, for example, cites an earlier interview with CRT’s Alix Fano in which Fano said,

Every animal has hundreds of retroviruses, and there’s no way you can breed them out. And there could be other viruses lurking in these pigs, not to mention parasites, bacteria, fungi and latent infections of all kind.

Of course if medical technologies are required to meet a criteria of eliminating unknown fears and possibilities, then a lot more has to go out the window than just xenotransplantation. For example, pig heart valves are currently used in valve replacement surgery — and with no reports of cross contamination of pig viruses, parasites, etc. to my knowledge.

Ironically, Dr. Jay Fishman, who sequenced the PERV disease, presented a paper in May 2000 noting that organs transplanted from animals to humans might actually turn out to be safer because common human diseases that cause organ failure would likely not grow in organs transplanted from another species. Wired quotes Fishman as writing in that paper,

Due to the species differences between the host (human) and donor (non-human species), the risk of infection of the transplanted organ … may actually be decreased. This incudes common pathogens such a cytomegalovirus, Epstein-Barr virus, … herpes, hepatitis B and C, and possibly human immunodeficiency viruses.

Sources:

Cloned pigs as organ donors?. Kristen Philipkoski, Wired, January 3, 2002.

Knock-out pig clones advance transplant hopes. Emma Young, New Scientist, January 3, 2002.

Animal transplants: a step closer?. The BBC, January 3, 2002.

New pig clones born. The BBC, January 2, 2002.

Moving Forward with Xenotransplantation

There has been a lot of debate back and forth in recent years over the safety and efficacy of Xenotransplantation. Massachusetts-based BioTransplant says its time to move on to actually doing such transplants and hopes that within three years it will gain FDA approval to begin clinical trials in human beings.

The main safety concern with xenotransplants is the risk of viruses passing from animals to human beings through such transplantations. The risk was confirmed in 1997 when researchers demonstrated that porcine endogenous retrovirus (PERV) could jump from pig cells to human cells.

BioTransplant hopes to meet this risk head on with a two-pronged strategy. First, it recently licensed the genetic map for PERV. Dr. Jay Fishman, an associate professor of medicine at Harvard Medical School, managed to sequence and patent the genetic map of PERV. BioTransplant licensed the sequences so they can keep the virus out of any pig transplant organs. BioTransplant’s Elliot Lebowitz told Wired,

What’s important is once you know the code in terms of the alphabet that makes up this virus, you could detect the virus if it were in a pig or human patient, and also you could develop the ability to delete the virus.

BioTransplant has also been working on breeding a subspecies of pigs that cannot pass along PERV to human beings. It has developed an inbred strain of miniature swine that is larger than pigs, making their organs more suitable for human-sized bodies, and according to BioTransplant the swine are PERV-free.

BioTransplant will, of course, have to back up its optimism with solid animal data before the FDA will allow it to go forward with human testing.

Still, if everything works out, it might turn out that animal to human transplants could be far safer than human to human organ transplants. Fishman presented a paper at last year’s meeting of the American Society for Microbiology that made just this argument. If the PERV problem can be eliminated, Fishman wrote,

Due to the species differences between the host (human) and donor (non-human species), the risk of infection of the transplanted organ … may actually be decreased. This includes common pathogens such as cytomegalovirus, Epstein-Barr virus, human herpes virus 6, 7 and 8, hepatitis B and C, and possibly human immunodeficiency viruses, and even HIV 1 and 2.

Source:

Organ transplant: men are pigs? Kristen Philipkoski, Wired, February 27, 2001.

Using Cow Veins to Improve Human Health

Although Xenotransplantation may seem like an exotic new turn in medical research, but in fact researchers have been doing it for years. When infants are born with defective heart valves, for example, transplants from cows are routinely used to reinforce the heart.

Now researchers at the Toledo Hospital’s Jobst Vascular Center successfully transplanted the jugular van of a cow to replace the weakened femoral vein of a man.

The femoral vein is a major vein in the upper leg that regulates blood flow to the heart. When it is weakened, it results in a condition called chronic venous insufficiency (CVI). The weakened valve makes it difficult for blood to continue up to the heart, causing it to pool in the lower leg leading to extremely painful ulcers.

Why the jugular vein of a cow? “The neck vein of a cow is very similar in size to the femoral vein,” Dr. Hugh Beebe, director of the Vascular Center, told CNN. The bovine vein is treated with drugs before the transplant operation to prevent the body from rejecting it.

Several other hospitals are also experimenting with such transplants to assess the efficacy and safety of the procedure. Assuming the initial positive results hold up, it will still be several years before this sort of operation is widespread, but it does point to a very near future where xenotransplanation will be common.

Source:

Cow vein used in transplant. Jonathan Aiken, CNN, February 23, 2001.

Infant Received Pig Heart Valve

The BBC reports that 16-month old Amy Davies, who lives in Great Britain, received a heart valve transplant from a piglet when she was just seven month olds. The infant had a large hole in her heart as well as severe blockage of one of her heart valves. Surgeons said she was too small for an artificial valve and they doubted she could cope with the immunosuppressive drugs that are needed to prevent the body from rejecting artificial valves.

Many animal rights activists argue in favor of a ban on such xenotransplants arguing that the animal, in this case the piglet, have rights that supercede the human infants, and/or that the risk of diseases crossing from swine to human is simply to great to offset the medical benefits of such transplants.

Source:

Baby given piglet’s heart valve. The BBC, December 4, 2000.

Medical Advances Thanks to Animals

In April, Alexion Pharmaceuticals
and Harvard Medical School’s McLean Hospital announced they transplanted
genetically altered pig nerve cells into an animal model of Alzheimer’s
disease (in this case, mice). The mice regained cognitive abilities once
the pig cells were implanted.

“The current test model represents
the most rigorous animal model of Alzheimer’s disease, in which wholesale
loss of cholinergic neurons is associated with highly advanced stages
of the disease,” said Dr. Ole Isacson, associate professor in the Neuroregeneration
Laboratories at McLean Hospital. “Today’s reported findings represent
the first demonstration of functional restoration using transgenic pig
neurons in an animal model of Alzheimer’s.”

Meanwhile, researchers at Genzyme
Transgenic Corp., Tufts University and Louisiana State University announced
in April that they had genetically engineered goats to produce a human
protein used to affect the clotting of blood. The goats were the result
of a cloning experiment, suggesting that someday large numbers of genetically
engineered animals, carrying important drugs for treating human diseases
and medical conditions, may be produced relatively rapidly.

More Xenotransplantation Advances

Even if they don’t lead
immediately to treatments in human beings, the announcement of two recent
advances in genetic engineering of organs provides more evidence of the
sort of technologies likely to hit the mainstream of medical technology
before the end of the next decade.

In mid-February researchers
announced in Science News that they had successfully transplanted
bladders grown in the lab into six beagles. The scientists grew the bladder
cells around a plastic form to make it take the shape of the bladder and
then implanted the artificial bladders in the dogs. Within three months
the artificial bladders were completely active and some of the dogs have
had the bladders for almost a year with no problems.

Obviously getting the technology
to work in human beings is a whole other problem, but these experiments
are doing for this technology what the early animal experiments on organ
transplantations did – they suggest solutions and help scientists better
understand the problems they will encounter when seeking to grow human
organs in the lab.

In a related story, Canadian
researchers are hoping to take that step of translating animal experiments
into a treatment for human beings sometime this year. Researchers there
expect for the first time to use a genetically engineered pig liver to
keep a human being alive while waiting for a liver transplant from a human
being.

Pharmaceutical company Novartis,
which has been harshly criticized by animal rights activists for its efforts
in genetic engineering, is reportedly ready to spend up to $1 billion
to develop a viable pig liver. To avoid the risk of spreading disease
from pigs to human beings, the pigs will be raised under special conditions
to assure they are disease free. The pigs are isolated from other animals
and housed in a sterile environment. The pigs are fed by hand to avoid
microbes that might pass from pig to pig while suckling.

The impetus to move forward
with this technology is especially strong in Canada which has a rather
low rate of human organ donation – only 12.1 donors per million people
compared to the U.S. with 17.7 donors per million people.

As I noted two weeks ago,
the Campaign for Responsible Transplantation attacked Americans for Medical Progress for highlighting former Chicago Bear running back Walter Payton’s
recent announcement that he has a rare fatal liver disease. The CRT attack
on AMP, however, seemed like an act of desperation. They tried to throw
everything but the kitchen sink at AMP – xenotransplantation might not
work, it poses a risk of transmitting disease across species, it could
be avoided by increasing the donor pool, etc.

There are many responses to
these claims (CRT doesn’t seem to keep up with recent scientific advancements
in genetic engineering) but as far as I can tell the bottom line is this:
animal rights activism in the medical experimentation field has been successful
largely to the extent that it has engaged people’s sympathies against
hurting animals, especially unnecessarily. But that play on emotionalism
is a double-edged sword, since most people are openly “speciesist”
who, when it comes down to it, will find the suffering and pain of Walter
Payton far more compelling and worthy of alleviation than that of a pig
whose death could save Payton’s life.

What seems to anger CRT to
no end is that AMP gave them a taste of their own medicine with their
focus on Payton. I say more power to them.