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鈥檛 disappoint. No sooner had little Noel, Angel, Star, Joy and
Mary鈥攂orn on Christmas day鈥攕quealed 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.
鈥淲e are looking at four to five years for clinical trials to begin in humans,鈥�
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鈥攁nd sufficiently free of pig viruses鈥攖o 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.
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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鈥攁 technical advance, but hardly proof that pigs can be
turned into organ donors.
We鈥檝e 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鈥檛 happen. In 1998, we were again told about an imminent clinical
trial involving pig kidneys. That didn鈥檛 happen either.
In fact, so far the only recipients of organs from Astrid鈥檚
offspring鈥攐r from other 鈥渉umanised鈥� pigs created in her wake鈥攈ave
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鈥檛
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鈥檛 bargained for was 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鈥攁 surge of
blood clotting factors and an oxygen-starved organ.
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 artficial
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 鈥渆vidence
of efficacy has not advanced at the rate predicted鈥� and that the 鈥渓ikelihood of
whole-organ xenotransplantation being available within a worthwhile time frame
may be starting to recede鈥�. 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鈥檚 willingness to tolerate the
continued loss of primate life.
