Crossing Species: The Politics of Desperation
From Mainstream, Volume 27, Number 1, Spring 1996
Judith Reitman's article, from which with her permission Mainstream has excerpted portions, was written for a leading national magazine in the Fall of 1995, before Jeff Getty received his transplant of bone marrow cells from a baboon. As of press time, that operation -- successful only in that the procedure did not kill the patient, although the "donor" died regardless -- seems to have had no success in delaying the progression of Jeff Getty's AIDS. In fact, preliminary tests indicate that the baboon cells failed to join with Getty's bone marrow cells, as had been hoped.
Judith Reitman's argument remains valid, however. There is no hope that the medical community will stop xenotransplantation just because Jeff Getty's operation did not succeed. The prevailing attitude is to continue with more xenotransplants, more animals sacrificed on cul-de-sac procedures, and the terrifying prospect that a virulent virus living undetected in an animal host may leap the species and infect humans with catastrophic results. -- Editor
Crossing Species: The Politics of Desperation
By Judith Reitman
The history of scientific experimentation using non-human primates has been a roll-call of near misses and direct hits of human slate-wipers: bizarre, transmissible diseases for which there are often no cures. None at all. By the time a primate-borne virus has been identified in a human, the victim may have already been reduced to the consistency of tapioca pudding, and the mutated pathogen well on its way to annihilating chunks of the human race.
Over 60,000 viral time bombs sit in the nation's university, commercial, and military primate laboratories. The pathogens these chimps and monkeys harbor can, given the opportunity, explode into the human population, with dire consequences. In many cases their effect can make AIDS look like nothing more than the common cold. These lab animals may be asymptomatic, their viruses latent. But given human negligence and disease mutability, it doesn't take much for primate viruses to jump species. Just how they will behave in their new human hosts is not predictable. But to epidemiologists and virologists one thing is certain: a major source of sudden disease outbreak in the human population is viral traffic between species.
A significant barrier between cross-species viral trafficking was recently lifted by the FDA. On July 14, 1995, the agency recommended that an AIDS patient in San Francisco be allowed to receive an experimental bone-marrow transplant from a baboon. This xenotransplant, cross-species transplant, or XT, will test a new treatment devised by University of Pittsburgh researcher, Dr. Suzanne Ildstad. This approach has, according to Ildstad, eliminated the risk of a fatal adverse reaction to "graft-versus-host disease" in rodent transplants; that is, organ swapping between mice and rats did not cause the recipients to reject the foreign tissue. She and colleague Dr. David Deeks, an AIDS specialist with the University of California in San Francisco, hope that this "facilitator" cell approach will enable the AIDS patient, Jeff Getty, to engraft the uninfected, implanted baboon cells. Getty's HIV-ridden marrow thus replaced by baboon marrow, his damaged immune system would ostensibly be restored. Baboons have been shown to be naturally resistant to HIV-1, at least 'in vitro' (test tube).
Taking the plunge from rodent grafts to baboon-to-human transplants and from test tubes to living organisms may be presumptive. Ildstad has not made available enough supporting data to demonstrate the existence of her "facilitator" cell, which makes some of her peers rather suspicious. The National Institutes of Health (NIH) declined to fund this project because of significant scientific questions. It's the wild card, though, which raised FDA's own hackles. In the unlikely event organ rejection were satisfactorily addressed, there still remains no fix on the imponderable: cross-species viral contagion.
Earlier in 1995, FDA had temporarily halted Ildstad's experiments. At issue was the threat of introducing into the human population dangerous agents that are known to be endemic to the XT process. Even more worrisome were lethal, unknown diseases for which there are, as yet, no names, let alone assay tests. The Journal of the National Institutes of Health Research delivered a sobering prediction: "The fear that the baboon harbors a virus that is capable of triggering a deadly new human epidemic is not an hysterical fantasy." Dr. Sy Kalter, president of the Virus Reference Lab in San Antonio, also sees a big problem in cross-species transplants, the high probability of "transplanting strange viruses." Even the Journal of the American Medical Association recognizes the impracticality of this sort of procedure since "baboons will not solve the organ shortage problem." As for Ildstad's plan, retrovirologist Jonathan Allan, a member of the FDA's Biological Response Modifier Committee, told me: "This is not science fiction. This is exactly the perfect scenario for dumping a baboon virus or retrovirus into the human population. The minute a recipient of a baboon organ leaves the hospital you are looking at a public health catastrophe waiting to happen. The only science fiction is her hypothesis."
Nonetheless, FDA stepped aside and waved the experiment on. Behind this acquiescence are two intransigents: the politics of science and politics of desperation.
More Than 150 Diseases
The survival of human recipients of animal organs has generally been measured only in hours or days. The patient's depressed immuno-defense system, specifically the complement protein system, invariably rejects the non-human grafted organ. The recipient becomes susceptible to latent or ordinarily harmless viruses. Medical complications arise, followed by death. In 1984, a 14-day-old girl named Baby Fae, who was born with a defective heart, received a baboon's heart at the Loma Linda University Medical Center. She died 20 days later of progressive graft necrosis characteristic of organ rejection. In June 1992, a University of Pittsburgh team implanted a liver from a 15-year-old baboon into a 35-year-old man suffering from end stages liver disease. The patient died 71 days later of a brain hemorrhage stemming from peritonitis. In January 1993, the recipient of another University of Pittsburgh baboon liver transplant died 26 days later of renal failure and sepsis precipitated by an overdose of anti-rejection drugs.
Jonathan Allan's affiliation, the Southwestern Foundation for Biomedical Research in San Antonio, Texas, supplies the University of Pittsburgh with its xenotransplant baboons. Nonetheless, baboon tissue and organ swapping worry Allan, a primate virologist who has been studying AIDS for over a decade. Despite pathogen screening tests to ferret out monkey diseases, truth is there are no "clean" baboons. Virtually all primates carry foamy viruses, an AIDS-like retrovirus that is highly pathogenic and transmissible to humans. Ninety-seven percent of baboons are infected with Herpes simplex, cytomegalovirus (CMV), and Epstein Barr. All lead to severe immunosuppression in XT recipients. Simian-transmitted herpes results in a particularly agonizing death by encephalitis. One donor baboon supplied by Southwest Foundation for a prior liver XT at the Pittsburgh carried all these viruses. The baboons initially selected by Ildstad were as infected. When FDA balked, she found another; this one harbors a baboon Endogenous Virus, a common retrovirus that can attack human cells, and Herpes Papio which can cause cancers in humans.
These viruses are among more than 150 diseases that can be transmitted from non-human primates to humans. The once farfetched notion that human HIV was an adaptation of monkey SIV (Simian AIDS) is now the prevailing medical opinion recognized by even the more conservative NIH. Recently, American Cyanamid has been placed on court order to participate in tests to determine whether SIV-infected monkey cells used to prepare oral polio vaccine caused human AIDS. Non-human primates can transmit the neurological disorder Creutzfeld Jacob; monkey pox; elephantiasis; leukemia; yellow fever; TB. Jumping species, monkey herpes causes genital lesions, a liquefying of bones and, finally, a burn-out of the victim's internal organs. The more exotic hemorrhagic fevers like Ebola and Marburg pulverize their victim's immune system. The internal organs become jammed with blood clots. The skin becomes pulpy, speckled with purple hemorrhages. The eyeballs bleed. The victim vomits black fluid. Paralysis sets in, then a mask-like expression, shock and death.
Of Ildstad's XT, Jonathan Allan predicts: "In trying to cure AIDS we may be starting the next epidemic."
But to the patient and his AIDS activist supporters, Act Up and Project Inform, this operation is a potential cure. At the FDA hearing, Martin Delaney, founder of San Francisco's Project Inform, fought to keep the experiment.
This was good news for one of Delaney's principal medical advisors, Suzanne Ildstad, a researcher who had suddenly found herself adrift with a patent-pending facilitator cell, and no way to prove it works.
A Rashomon-like Scenario
Ildstad's financial portfolio did look a bit grim. NIH chose not to fund her XT proposal which was submitted as part of a larger funding request. Why not? NIH says that's proprietary information. Geneic Sciences, her biotech sponsor and co-patenter, is in the process of terminating its $1 million support. Why? Geneic demurred from answering. As for support from the University of Pittsburgh, Jeffrey Romoff, president of the University of Pittsburgh Medical Center, told me, definitively, that no formal review or vote was ever conducted on Ildstad's project.
But this Rashomon-like scenario doesn't seem to bother the AIDS community, many members of which are willing to try just about anything to stay alive.
Several years ago, Ildstad had met Delaney at a Project Inform-sponsored "Think Tank" where selected scientists and FDA officials brainstormed AIDS therapy ideas. A major player among the San Francisco AIDS elite, Delaney had an easy rapport with decision-makers at the city's principal AIDS research hospital. Singling out HIV patients to demonstrate her facilitator cell had not been Ildstad's initial intent, but with doors closed at her university, a light bulb must have gone off in her head. Stretching her theory, the facilitator cell might offer immunological respite to Martin Delaney's constituents who had the kind of clout she needed.
Martin Delaney appeared to be Suzanne Ildstad's political lifeline.
The scientific legitimacy of her protocol was swiftly obfuscated by hope, however dim. "What you have in a panicky environment like this is not the science of patients but the science of desperation and opportunism," says Dr. Sheldon Krimsky, Tuft's longtime science industry watcher. "This has enabled scientists with very poor data to engage in human experiments, to use opportunities for their own advancement, perhaps."
The Prospect of a Quick Fix
The July 14, 1995 FDA public hearing marked Jeff Getty's 38th birthday; he had been fighting AIDS for fourteen years. The purpose of the meeting was to give the public, AIDS patients, and medical personnel a forum to present their views to the agency on the proposed xenotransplant. Taking into account those varied perspectives, FDA would decide whether to approve Ildstad's baboon protocol, or stop it. The agency had that power. FDA's decision was, some observers say, a foregone conclusion.
In short order, power and pathos cleared the deck of the handful of virologists who warned of a species-jumping holocaust. Jonathan Allan and his colleagues were far outnumbered and outranked by the medical czars of the $87 billion pharmaceutical industry which umbrellas biotechnologies. Among FDA's advisors who weighed-in heavily with dollars and clout: Dr. W. French Anderson, considered the father of gene therapy; xenograft pioneer Dr. Keith Reemtsma from Columbia University, which is planning baboon heart transplants into human children; and Dr. David Sachs, head of transplantation surgery at Massachusetts General Hospital and a faculty member at Harvard Medical School. Sachs was also Ildstad's mentor.
The message from this industry/advocacy consortium: FDA had better play ball. The agency positioned itself right on cue. As network tv cameras rolled, FDA's Bill Freas, Executive Secretary of the panel, opened the morning session by reading aloud from a letter ostensibly sent from a member of John Q. Public. The writer beseeched FDA to allow the transplant to "definitely take place." On that note, the proceedings began. One of Jeff Getty's sisters told the committee that "Jeff considers the FDA as much a threat to his life as the AIDS virus." His mother, flanked by Jeff's two sisters carrying posters ("Today's Jeff's birthday. Make sure he sees another. Call the FDA"), pleaded for his life. A member of the local Act Up chapter then showed a CBS Evening News clip which covered the previous day's meeting and told the audience that the world is watching.
The pressure in the room was palpable.
Project Inform's Delaney then zeroed in on the heart of the matter. Bolstered by what author Elinor Burkett (The Gravest Show on Earth) calls the "shock troop of deregulation" -- AIDS survivors and their genuinely heart-wrenching stories -- Delaney trashed FDA for "its ever growing tentacles in terms of what it controls in this country." FDA's job was, Delaney told the agency, not to say "nay or yeah," and "not to dicker around," but to "help Dr. Ildstad and her cohorts ... make AIDS a point of history rather than a daily reality and daily body count."
But there was more at stake than life or death. FDA's approval means big bucks to a cash-intensive industry dependent on venture capital and academic expertise. As the CEO of a leading pharmaceutical firm explained: "Your first client is the FDA. Then you can start paying back the shareholder." On July 28, for instance, when FDA approved a genetically altered pig liver for human transplant, shares of the two biotech companies which funded the university-affiliated surgeon soared 38 percent on NASDAQ and 37 percent on the NYSE. Biotech's reliance on scientists for product and prestige has made "collaborative" agreements routine. Some of the FDA panelists on this XT issue were as reliant on industry.
Midmorning, French Anderson, Daniel Salomon from Scripps Research, and David Sachs aggressively questioned Ildstad's scientific data and her evidence indicating her XT will succeed. Jonathan Allan remembers this discussion ending as quickly as it began. Ildstad's critics backed off, bowing to what Salomon called "the proud tradition in the transplantation sciences of moving ahead." They even managed to shunt aside Hugh Auchincloss's prediction that the procedure will "hasten (Getty's) death." The future of an industry was at stake. "You think anyone was about to shoot down a whole industry and tell guys like French Anderson they're out of a job?" observes a high level official at NIH who asked not to be named. FDA was certainly not going to go out on that limb. So in the end, the industry of science and the prospect of a quick fix, no matter how remote, won out.
The FDA would prefer that the whole affair go away and that Getty have a quiet death in an isolated environment. "That way," an FDA official told me, "we can look good to the AIDS activists and not feel guilty that we're putting the public at risk."
Ildstad herself dismisses doomsayers' viral plague predictions. "In the worst case scenario," she told me, "if it (viral contamination) happens it would be similar to AIDS or hepatitis, but that's down the line." Wasn't that a rather chilling prospect? No, she says, "AIDS is controllable by barrier precautions."
Getty may not live long enough to test out Ildstad's confidence in barrier precautions which have limited HIV to mere millions. But in setting aside its mandate to protect the public, FDA has opened the proverbial Pandora's Box. This one is filled with still-throbbing, non-human body parts; spare parts, if you will. Nonetheless, Philip Noguchi, the mild-mannered director of FDA's Division of Cellular and Gene Therapies, Office of Therapeutic Research and Review, seems relieved that the ordeal is over. He hopes to avoid such confrontational productions in the future, now that a precedence has been set. Proposers of other XTs "will not have to jump through so many hoops," he told me. No more case-by-case reviews. Whether or not to XT will, most probably, be the call of local institutions which have little, if any, public oversight. As for the guidelines developed by FDA and CDC, they are strictly voluntary and utterly non-enforceable.
The feds have thus guiltlessly shed their stewardship over the public's health, at least as far as cross-species plagues go.
Historically speaking, human beings seem to derive solace from the notion of progress. One can only wonder whether this compulsion to push onward will bring us redemption or deeper into the heart of darkness.
Judith Reitman is an award-winning journalist and author of Stolen for Profit (Kensington Books), the story of how millions of beloved companion animals are stolen to supply the research laboratories (for a review, see the Summer 1995 Mainstream). Her next issue-oriented book, Bad Blood, concerning the blood industry, will be published in October 1996.