Waiting for a miracle:
Time is running out for organ transplants from animals
Extract from the New
Scientist, 12 January 2002.
It has become an unwritten rule of the biotech business that all
newly cloned animals must have PR-friendly names. On this score,
at least, the latest cloned piglets didn't disappoint. No sooner
had little Noel, Angel, Star, Joy and Mary - born on Christmas day
- squealed their way onto the front pages than a rival team of cloners
was unveiling an equally cutely named litter of four.
Suddenly, the race to turn pigs into organ donors seemed to be
hotting up."We are looking at four to five years for clinical
trials to begin in humans," announced Alan Colman of PPL Therapeutics,
the company that created the quintuplet. At this point readers averse
to a little cold water being thrown should turn the page. It would
be wonderful if biotechnologists could make the kidneys, lungs,
hearts and livers of pigs compatible enough with the human immune
system - and sufficiently free of pig viruses - to make good the
desperate shortfall of transplant organs. But the commercial hype
surrounding xenotransplantation often obscures the fact that the
obstacles to success are still colossal.
Despite the blanket publicity these animals achieved, they are
not the first cloned pigs nor even the first pigs to be genetically
redesigned to make their organs more human-like. What they are is
the first GM pigs created via the cloning process - a technical
advance, but hardly proof that pigs can be turned into organ donors.
We've been somewhere like this before. Remember Astrid, the first
genetically modified pig created for research into organ donation?
A couple of years after her birth in 1992 her creators predicted
human trials within three years. The trials didn't happen. In 1998,
we were again told about an imminent clinical trial involving pig
kidneys. That didn't happen either.
In fact, so far the only recipients of organs from Astrid's offspring
- or from other "humanised" pigs created in her wake -
have been a string of previously healthy laboratory monkeys and
baboons. Their dismal fate suggests that xenotransplanters have
made no real progress for about five years. In the early 1990s,
the big obstacle to transplanting pig organs into primates like
ourselves appeared to be the violent immune response known as hyperacute
rejection, in which grafted tissues are starved of blood. So naturally
enough, the genetic changes in the first generation of humanised
pigs were designed to overcome this reponse.
And mostly they do overcome it. The problem is, the organs still
don't survive. True, most of the monkeys and baboons given these
organs are able to live for days or weeks, instead of the hours
they might survive with ordinary pig organs. But no matter how many
immunosuppressive drugs the monkeys have pumped into them, none
of the modified pig organs has lasted much more than a couple of
months. What scientists hadn't bargained for as a second powerful
immune response, known as acute vascular rejection. It gets going
more slowly than hyperacute rejection, but the end result is just
as ugly - a surge of blood clotting factors and an oxygen-starved
Whether the new genetic change made to the latest batches of cloned
piglets will make much of a difference is unclear. But even if it
does help, few experts think it will be sufficient to completely
halt this form of rejection. The immune system is like a well-drilled
army. Penetrate one line of defence and a second line quickly moves
in. In all likelihood far more genetic tinkering will be required
to stop the army in its tracks. And by then advances in artificial
organs and stem cell research aimed at patching up natural organs
may have made donor pigs redundant.
Whatever happens, expect the latest cloning triumphs to trigger
a new phase of xenograft research, coupled with renewed concern
about the ethics of using pigs this way. Such worries miss the point.
When it comes to animal welfare, the bigger problem is the large
number of primates that have to die in what even animal experimenters
concede are grisly circumstances.
In its last major report, UKXIRA, the panel of experts set up by
the British government to monitor xenotransplantation research,
concluded that the "evidence of efficacy has not advanced at
the rate predicted" and that the "likelihood of whole-organ
xenotransplantation being available within a worthwhile time frame
may be starting to recede". It was a diplomatic way of saying
the technology was dying on its feet. The question now is whether
Noel and her siblings can help scientists create the big advance
in organ survival necessary to resuscitate it. They need a breakthrough
fast. The patience of those bankrolling the research will not last
forever. Nor will the public's willingness to tolerate the continued
loss of primate life.
For more science news see www.newscientist.com.