Dr. David White’s goal: saving lives with pig organs – Cover Story
Genetically customizing a pig organ before transplantation could trick the body’s immune system into thinking that the new organ is its own. Injecting the future donor pig’s embryonic egg with the human recipient’s DNA could eliminate the dreaded post-transplant rejection.
Edward Jenner ran into resistance when he first tried to popularize smallpox inoculaton because the vaccine he used was derived from cows. Opponents to the lifesaving inoculation published derisive cartoons of children with cows’ horns growing from their heads. Today, researchers are running into a similar problem trying to expedite the use of pig organs for human transplantation.
At this moment, over 50,000 people are on the national waiting list for an organ transplant, yet most won’t receive one. Nearly 10 people die each day waiting and hoping for a lifesaving organ. And the need for organ transplants will only grow as the baby boom population ages. But advances in genetic engineering are offering a solution. Dr. David White of the biotechnology company Imutran in Cambridge, England, has been trying to reduce this critical shortage of organs using organs of genetically engineered pigs, suitable for transplantation into humans. The science of transplanting organs across species is called xenotransplantation. In the future, Dr. White’s “transgenic” pigs will be produced by injecting the future pig’s embryonic egg with the human recipient’s DNA. The dreaded organ rejection will thus be avoided because the host’s immune system would not recognize the customized pig organ as foreign material. The immune system would recognize the organ not just as a human heart, but as the patient’s own heart. Surgery can be scheduled as soon as the pig is ready.
“The nice thing about the pig is you know who the donor is going to be weeks or months before the transplant,” Dr. White said. “It’s not like you’re waiting for someone to fall off his motorcycle.”
For decades, medicine has been relying on animals in saving human lives. Insulin from the pancreas of pigs has kept diabetics alive; pig valves have been successfully used to fluids with pigs for millennia, if you think about pig farmers or slaughtermen who cut their fingers while butchering pigs. So we don’t believe that there’s anything out there that is not known. Furthermore, we think the fact that man and pig have been associated closely for so many millennia is good evidence that there are no unknown antigens in pigs to affect man.
Q. What, then, is preventing you from transplanting pig organs into people?
A. Well, the problem that we currently face is that we have these pigs, and people will say, “Yes, you can transplant them into your patients if you know it’s safe.”
But how do we know it’s safe if we can’t transplant them into our patients? In order to get around that, we’ve been doing studies transplanting these hearts and kidneys into monkeys. We can now demonstrate it is safe for the monkeys. Of course, our opponents will say, “Yes, but even though it’s safe for the monkeys, how do you know it’s safe for human beings? We can’t let you transplant into humans until you’ve made it safe for human beings.”
So what we are trying to do is move sideways, as it were. Our first clinical trials will be using livers of pigs, not as a transplant but as a bridge to liver transplantation in which we can pump the patients’ blood through the pig liver and keep them alive until a human liver becomes available, or possibly until their own liver recovers.
Q. Your company has joined with the pharmaceutical giant Novartis. How will this help your research efforts?
A. In the development of new technologies such as genetically engineering pigs: first of all, clearly, it’s a very high-risk business. Secondly, it’s a very expensive business, so that you need to have a very wealthy backup who is prepared to take the long-term view. It’s really only the large pharmaceutical companies such as Novartis who are able to support what potentially could revolutionize medical care. So the Novartis support for our research program is absolutely critical.
Q. How soon do you think you could be transplanting pig organs ?
A. I would be very disappointed if we don’t start our transplantation program before the end of the millennium. [Here he exudes confidence!]
Q. If a baby receives a pig heart, do you believe the pig heart will grow as the baby grows, or might you have to transplant a larger heart later?
A. It’s almost certainly the case that these organs will grow as demand is put upon them. In the monkeys, the kidneys of pigs grow to about twice the size that you would expect. But of course, that’s because the monkey would normally have two kidneys. So we believe that growth is demand-driven, that organs grow to support the level that you want.
Q. What do people on the transplant waiting list think about this alternative
A. Well, you know, you can be as replace damaged valves in cardiac patients, and pig skin has helped save bum victims. (We consume some 90 million pigs each year.)
Dr. White’s research has brought us to the threshold at which pig organs–such as lungs, livers, and hearts–can be used to save the lives of people dying for lack of a human donor transplant.
We invited Dr. White to dinner and attended his seminars at the Indiana University School of Medicine.
Q. When did you begin researching the use of pig organs for transplants?
A. We have been very concerned over the lack of organs for transplantation for 10 or 12 years. To combat the problem, we’ve been genetically engineering pigs so that they now can provide hearts and kidneys for transplantation into patients. We’ve been able to demonstrate that we can transplant pig hearts and pig kidneys into monkeys without the rejection process that is normally associated with that kind of transplantation.
We’re excited that we now have developed a new lifesaving therapy that can be applied to hundreds and thousands of people across the world. But we do have the duty to make sure that this process is safe.
Q. What about the fear of some new viral infection?
A. There is a concern that there may be some unknown virus in pigs that will get into the human population and cause a new epidemic as a result of the transplant. We’ve spent the past year–and intend to spend a lot more time–to show people that there is absolutely no worry at all as far as the possibility of a pig virus is concerned. We’ve developed protocols that allow us to breed pigs in an environment where we can eliminate any known pathogens. But, to be quite frank, people have been exchanging bodily philosophical as you like about death. The fact of the matter is, most people would rather be alive than dead, and if you say that you can be dead in three months or you can have a pigheart transplant with a risk that in 20 years you might get leukemia, there are no choices. It’s an option other than death.
Q. In the United States, nine out of ten people die waiting for organ transplants.
A. It’s the same everywhere. Transplantation currently for the treatment of heart failure is an entirely peripheral activity. The numbers of heart transplants we do don’t even begin to reflect the number of deaths from coronary disease.
Transplantation is a direct reflection on the number of donors. If you look at the United Kingdom, we will produce about 13 donors per million of population per annum. In the U.S., you produce about 21 donors per million of population per annum. Actually, the best country in the world is Spain, with 29 donors per million per annum. The problem is, for the transplantation to be a successful therapy, it’s not 29 donors per million we need, it’s 290, maybe 2,900. If you just look at the figures in the United States, it’s been conservatively estimated that you need to do about 100,000 transplants a year. Last year you had just under 6,000 donors. For 100,000 transplants you have 6,000 donors. The equation doesn’t add up.
Q. What can our readers do to help?
A. There are several important things that they could do. Xenotransplantation is in a very early stage. We hope to start clinical trials, perhaps at the end of this year, perhaps early next year. So, the first thing I’d ask them to do is to continue supporting current organ-donation processes. The second thing I would ask is that they think very carefully about the way organ donation is now and the way it could be if xenotransplantation becomes a reality–how many more lives we could save–and that they support us as we introduce this kind of model technology (which is perhaps a little bit frightening) in a calm, sensible, safe, stepwise approach.
Q. Pigs are the answer?
A. I think pigs will be the obvious solution.
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