Prime Time Replay:
Dr. Denise Faustman
on
Xenotransplantation
MsgId: *breakthrough(1)
Date: Wed Aug 27 20:57:25 EDT 1997
From: moderator At: 152.163.206.88
Hi, this is your moderator, Madeleine Lebwohl, and tonight I'll be speaking with Dr. Denise Faustman. Welcome, Dr. Faustman!This is an in-studio interview with Dr. Faustman.
MsgId: *breakthrough(3)
Date: Wed Aug 27 20:58:55 EDT 1997
From: moderator At: 152.163.206.88
Dr. Faustman: Hi.
MsgId: *breakthrough(4)
Date: Wed Aug 27 21:01:14 EDT 1997
From: moderator At: 152.163.206.88
In an age of limited organ donations, xenotransplantation seems to offer an extra chance for many sick people. How do you see the field developing? What is xenotransplantation?
MsgId: *breakthrough(6)
Date: Wed Aug 27 21:03:55 EDT 1997
From: moderator At: 152.163.206.88
Dr. Faustman: I see it developing along two lines. One is that potentially in the future, providing organs for the current diseases' retreat, with allotransplantation or human to human, transplants, but probably more importantly, xenotransplantation may offer the hope of treating a broader range of diseases.An example would be that certain tissues for transplantation need to be harvested from a specific type of donor, or a specific age of donor, and this is not feasible for a large scale range of diseases. An example would be neurological diseases, where the neurons to be transplanted need to be of a precise age, usually of fetal origin. So, using xenogeneic timed pregnancies, you avoid of using human untimed pregnancies from multiple donors, thus making xenotransplantation safer, and possibly more efficacious at having desired outcomes.
MsgId: *breakthrough(9)
Date: Wed Aug 27 21:08:08 EDT 1997
From: moderator At: 152.163.206.88
What is a xenogeneic timed pregnancy?
MsgId: *breakthrough(10)
Date: Wed Aug 27 21:10:07 EDT 1997
From: moderator At: 152.163.206.88
Dr. Faustman: Example: Let's say you want fetal pig neurons that are in a specific stage of development that might integrate into the human brain, and send out neurons, into the brain. And you would have to know the precise donor age, and using human fetal tissue you would never know that. So effectively, xenographs offer a greater degree of quality control that you could ever hope for from adult allographs or fetal human allographs.And then the second potential benefit of xenographs is that they might offer the recipient the advantage of being resistant to the original disease process, in contrast to an allograph. An example would be that a pig liver transplanted into someone that had liver failure from hepatitis would be naturally resistant to the hepatitis virus that destroyed the original liver.
And I think the third major advantage of xenographs could potentially be the fact that they can be more carefully quality controlled for infection and monitored for infection weeks, and months and years prior to harvesting, and this is in contrast to human donor, which is someone usually in an accident situation, where you have hours to determine if the donor organs are clean enough for transplantation.
MsgId: *breakthrough(13)
Date: Wed Aug 27 21:16:08 EDT 1997
From: moderator At: 152.163.206.88
Does that happen frequently -- that someone who has indicated that they want to donate their organs turns out to be infectious in some way and not a suitable donor?
MsgId: *breakthrough(14)
Date: Wed Aug 27 21:18:37 EDT 1997
From: moderator At: 152.163.206.88
Dr. Faustman: Sure, and worse yet, the testing for the human viruses has to be done at such a rapid pace for the organs to be useful, and complete testing can result in the transmission of a recognized virus to the new transplant recipient. This can happen in two ways, the rapid test can be a false negative, or sometimes, because of the desperate shortage of organs, the test is positive but you still transmit the virus with the organ because the host has no other option.An example of that is something called Cytomegalo virus (CMV). This is a virus found in approximately 20% of the population. The problem is that alot of people can fight it off, but when you do the transplant and add on the traditional immunosuppressive drugs, the virus causes complications.
MsgId: *breakthrough(17)
Date: Wed Aug 27 21:25:59 EDT 1997
From: moderator At: 152.163.206.88
When you were preparing the xenotransplantation guidelines for the Institute of Medicine/National Academy of Sciences what were some of the issues you had to address?
MsgId: *breakthrough(18)
Date: Wed Aug 27 21:27:39 EDT 1997
From: moderator At: 152.163.206.88
Dr. Faustman: One concern was how close was the technology to actually perform these sorts of experiments with actual success? Two, was is there any risk to the population at large that there's some unknown, mysterious virus that is not yet identified that could be passed from pigs or baboons to humans, and then subsequently passed from human to human. And then third was, are there enough animals for the number of people who have diseases to make this feasible, in other words, it would be terrible to say yes, we have this great technology, but only five people can benefit from it because there's only five donor animals of the correct type to treat those five people. In other words, if there is technology that could allow this to proceed, was it something that the insurance companies would support, or would it only be the wealthy that could afford access to these innovations.
MsgId: *breakthrough(21)
Date: Wed Aug 27 21:31:46 EDT 1997
From: moderator At: 152.163.206.88
Are vast quantities of animals being made available now?
MsgId: *breakthrough(22)
Date: Wed Aug 27 21:34:38 EDT 1997
From: moderator At: 152.163.206.88
Dr. Faustman: Yes. An example would be, the committee and most of the scientists believe that if this procedure would only work baboon to human, then there's going to be major stumbling blocks. First, if baboons were going to be the source, the cost would be prohibitive, and there would be ethical costs of raising herds of baboons just to harvest hearts for victims of cardiac disease. In contrast, if there are thirty to sixty million pigs each year killed in the U.S., and animals that are traditionally part of the food chain, and animals that are traditionally part of the food chain could be additionally used to benefit people with diseases not amenable to medical treatment, then most people would believe that could be a significant benefit economically, as well as morally, as well as ethically, to people dying.I think the opposite was more of an issue, its kind of a shame to raise primates for human use, people wanted to avoid that if they could. And the other scientific reason is that there's more of a concern of a baboon transferring a virus that might be compatible with a human, than there is with a pig. So pigs potentially could be safer than a baboon or human donor for human transplantation.
MsgId: *breakthrough(26)
Date: Wed Aug 27 21:40:41 EDT 1997
From: moderator At: 152.163.206.88
How often are xenographs actually happening?
MsgId: *breakthrough(27)
Date: Wed Aug 27 21:42:37 EDT 1997
From: moderator At: 152.163.206.88
Dr. Faustman: Over the last twenty years scattered reports of people attempting xenographs, usually in the setting of whole organs, can be found in the literature. But these transplants did not have much success for long term survival. And then in Sweden over the last 8 years significant numbers of humans were transplanted with pig fetal islets for the treatment of diabetes. Again, not much long term transplant survival, but with no complications.But then in the U.S., over the past two years, significant progress has been achieved in cross-species transplants on the cellular level, and these transplant results, which were initially human tissue transplanted into mice, were gradually moved up into pig tissue into humans using the same technology. They have shown that in these sorts of cellular transplants, potentially longterm graft survival is possible, even for periods beyond a year, without treatment of the recipient with the traditional nasty immunosuppressive drugs.
The new approach was not the traditional pharmaceutical approach of developing new drugs to treat the recipient, but were based on the idea that you could perhaps produce designer donor organs because of the advantage of being able to have the organs themselves and the animals available for months and years prior to harvesting.
MsgId: *breakthrough(31)
Date: Wed Aug 27 21:47:30 EDT 1997
From: moderator At: 152.163.206.88
How does the designer approach work?
MsgId: *breakthrough(32)
Date: Wed Aug 27 21:48:55 EDT 1997
From: moderator At: 152.163.206.88
Dr. Faustman: This concept was the idea that perhaps only the modification of only the surface antigens or proteins would perhaps disguise them sufficiently to make them 'invisible' to the immune system, and allow long term survival without drug treatment of the host.
MsgId: *breakthrough(33)
Date: Wed Aug 27 21:50:27 EDT 1997
From: moderator At: 152.163.206.88
Did your lab find that diabetes was a good place to start working with xenographs?
MsgId: *breakthrough(34)
Date: Wed Aug 27 21:53:34 EDT 1997
From: moderator At: 152.163.206.88
Dr. Faustman: Diabetes was a great place to test the efficacy of these inventions, but as we got to human clinical trials, diabetes was not the best place, i.e. the optimal clinical setting, to test these inventions. It had been the hope of the diabetes community that if you could ever get a xenograph to work, then the original disease process would not reoccur in a xenograph. But in the case of diabetes, would could prevent graph rejection beautifully, but not recurrent disease. So now the clinical trials are now in disease settings such as Parkinsons disease and Huntingtons disease, where there's no known immune component, i.e. autoimmunity, as to why the original tissue was destroyed.
MsgId: *breakthrough(36)
Date: Wed Aug 27 21:55:55 EDT 1997
From: moderator At: 152.163.206.88
How long have the trials been going on?
MsgId: *breakthrough(37)
Date: Wed Aug 27 21:57:35 EDT 1997
From: moderator At: 152.163.206.88
Dr. Faustman: I should mention to the readership that you certainly wouldn't want me to be injecting these neurons into your brain, so the efforts at this point represent diverse talent to take this basic science technology from our animal studies into humans, and you wouldn't want me as a non-neurosurgeons doing the microinjections into your brain even if you did have Parkinsons.The reported results, so far, from the FDA, demonstrate at least 12 patients have been transplanted with fetal pig neurons for Parkinsons disease. Six of those patients had fetal pig neurons with donor antigen modifications. And all had clinical improvements, with the suggestion of continuing survival beyond a year. In one patient who was randomized to the immunosuppressive group, at six to eight months, died for unrelated reasons, and surviving pig neurons could be found with long neurons innervating the target nuclei long distances away. Therefore, suggesting, by pathology documentation, that longterm xenograft survival might really be feasible in humans, and those results were supported in Nature Medicine this spring.
MsgId: *breakthrough(40)
Date: Wed Aug 27 22:04:23 EDT 1997
From: moderator At: 152.163.206.88
What is the outlook for xenotransplants?
MsgId: *breakthrough(41)
Date: Wed Aug 27 22:06:45 EDT 1997
From: moderator At: 152.163.206.88
Dr. Faustman: I think the data supports the concepts that at least for cellular transplants, in contrast to whole organ transplant, that these new scientific methods may be feasible to create a new technology for a diversity of terrible, poorly treated diseases. We still have a ways to go for whole organs.
MsgId: *breakthrough(42)
Date: Wed Aug 27 22:09:26 EDT 1997
From: moderator At: 152.163.206.88
Thank you, Dr. Faustman, for an introduction to the concerns and progress in xenotransplantation. Goodnight.
MsgId: *breakthrough(43)
Date: Wed Aug 27 22:10:13 EDT 1997
From: moderator At: 152.163.206.88
Dr. Faustman: Goodnight, and I hope I've been helpful.
MsgId: *breakthrough(44)
Date: Wed Aug 27 22:11:25 EDT 1997
From: moderator At: 152.163.206.88
Please join me next week for Breakthrough Medicine. I'll be speaking with Peter Snell, Ph.D., Director of the Human Performance Lab at UT Southwestern Medical Center.
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