WASHINGTON _ Flanked by her three daughters and poster-sizeenlargements of her son, Kim Getty pleaded with FDA officials notto let "fear stop you" from clearing the way for a highly experimentaltransgenic baboon bone marrow transplant to save her son who issuffering from advanced AIDS.
Several AIDS activists raised the political threshold by promisingretribution if the transplant is not permitted. AIDS activists PeterThorpe promised to "take the issue to the streets" if the FDA failed topermit the transplant to go forward. "After all, isn't science all abouttaking risks," he argued.
These emotional appeals resonated throughout the second day of atwo-day public hearing called by the FDA to examine the possiblepublic health risks of xenotransplantation.
The hearing was held before the FDA's Biologic Response ModifiersAdvisory Committee and was attended by scores of federal healthofficials who made it clear they are attempting to "reach a nationalconsensus on an acceptable balance between risks to the public healthand the need to aid an individual," according to Louisa Chapman, amedical epidemiologist with the Centers for Disease Control andPrevention (CDC).
The public debate was scheduled after the CDC raised some red flagsabout possible dangers to the public health from a planned infusion ofbaboon marrow into San Francisco AIDS activist Jim Getty. TheFDA placed a clinical hold on the transplant, planned by Universityof Pittsburgh transplant surgeon Suzanne Ildstad and infectiousdisease expert Marian Michaels, affiliated with Childrens Hospital ofPittsburgh.
FDA officials made it clear from the start of the hearing that theywanted to respond to the perceived public health risk byrecommending a `novel' regulatory scheme that would preserve localautonomy of academic research but provide some structure toconsider issues of public health and accountability.
Philip Noguchi, director of the Center for Biologics Evaluation andResearch Division of Cells and Gene Therapy, told BioWorld that theFDA plans to issue a set of guidelines in January 1996. But hestressed that the agency is "evolving" its position and urgedinterested parties to "enter into a dialogue with the agency."
In an interview with BioWorld, Keith Reemtsma, a professor ofsurgery at Columbia University who pioneered the field ofxenotransplantation in 1963, said "that the role of the FDA and CDCwas to make sure nothing jeopardized the public health by ensuringthat the clinical investigators took the appropriate steps in terms ofscreening the donor animal, monitoring the patient and collectinginformation following the procedure."
"However, there is also a need for research to be nourished and thebest way to accomplish that is through a decentralized institutionalsurveillance," he said.
FDA Challenged To Establish Protocols
Both CDC and FDA staffers who made presentations at the advisorycommittee meeting made it clear they are contemplating a series ofwritten protocols that document a number of key steps includingscreening of animals, informed consent that commits the patient tointensive follow-up, post-surgical surveillance and a national registryof xenografts.
The FDA is expected to make a decision soon on whether to allowthe Getty transplant to go ahead. But it was apparent from strongobjections raised by many panel members that the agency faces atough decision.
Ildstad defended xenografting as an alternative to allogeneictransplants in an era when the number of patients waiting fortransplants exceeds 30,000 but the number of eligible donors has heldconstant in the past four years to about 4,000.
She also defended transgenic experimentation as best supervised onthe local level so that it remains "free from the blanket restrictions"that the FDA might impose.
Several members pressed Ildstad and Michaels about the lack ofdiagnostic tests to perform baboon serology tests that woulddefinitively screen for certain unquantified health risks includingfoamy virus which is latent in baboons but may or may not betransmitted to humans through the transplant.
Concerns also were raised about measures taken to protect theclinical investigation team, hospital workers and the patient's familyfrom transmission of unknown pathogens. Michaels was reluctant torecommend a total quarantine and said the transplant team would usestandard infection control techniques now used on all transplantrecipients.
Several panel members pressured Ildstad about the consequences ofleaving the patient bereft of an CD4 T cells after the transplant.Baboons do not have these immune defense mechanisms and mostAIDS patients lose their thymic functioning and cannot produce Tcells. David Sachs, former head of immunology at the NationalInstitutes of Health, told BioWorld that he doesn't expect T cellfunctioning after the transplant. "There's a chance but it's highlyunlikely," he said.
Primate Studies Are A Must Before Human Trials
Hugh Auchincloss, a professor of surgery at Massachusetts GeneralHospital, Boston, chided Ildstad for insisting on going directly fromrodent studies to human tests. "We in the scientific community andthe FDA believe that primate studies are necessary before humantrials," he said at the hearing.
The issues raised before the advisory committee were familiar toMicheal Egan, senior vice president for Diacrin Inc., a Charleston,Mass. cell therapy firm.
Last July Diacrin confronted many of the same regulatory problemswhen it presented its investigational new drug application to the FDAto transplant fetal porcine neural cells into patients with Parkinson'sdisease.
"We recommended a number of guidelines and FDA responded withtheir suggestions. The upshot is that we think we have the goldstandard for transgenic cell therapy," Egan told BioWorld.
But he stressed that "there is a world of difference between wholeorgan transplants and cell therapy and there are considerabledifferences in porcine, primate and bovine transplantation issues."
"I hope the FDA crafts regulatory plans that recognize thesedifferences," Egan said.
Egan saw the issue of xenotransplantation as giving the FDA theopportunity to make its reinvention effort a reality. "Inspecting everytransgenic clinical trial is not the best use of FDA's resources. Ratherit should delegate certain issues to Institutional Review Boards andmulti-disciplinary teams of experts in immunology, infectious diseaseand veterinary medicine." n