With Five-Year Ban On Fetal Tissue Studies Lifted, Scientists Are Striving To Make Up For Lost Time

With Five-Year Ban On Fetal Tissue Studies Lifted, Scientists Are Striving To Make Up For Lost Time Author: MYRNA E. WATANABE, pp.1 delayed by the moratorium, that may relieve human suffering Sometime this month, the National Institutes of Health will announce the recipients of the first federal grants since 1988 for research on human fetal tissue transplants using material derived from elective abortions--the main source of live and healthy fetal tissue that can be maintained in culture and used for therapeutic transplants. Proposals for the projects were submitted in early 1993, only a few days after newly inaugurated President Bill Clinton lifted a five-year- old moratorium on federal funding for such research. Throughout the ban's duration, it was vociferously challenged by scientists who regarded it as a serious roadblock in the pursuit of cures for many human diseases; the ire of these scientists was heightened by the widespread assumption that the moratorium resulted from pressure applied on the White House by anti- abortion groups. The moratorium prevailed until this year, however, despite the recommendations by a blue-ribbon panel of scientists that human fetal tissue research continue, with strict controls to ensure that women would not be encouraged to abort in order to donate or sell their fetuses. When the ban was reversed on January 22, scientists who had had to abandon or cut back on their fetal-tissue-related studies naturally breathed a collective sigh of relief and went about completing grant proposals they had begun after last November's election in the hope that Clinton would indeed lift the ban. FETAL TISSUE RESEARCH AREAS Fetal tissue is used extensively in research, from basic studies of cellular processes and development to investigations of abnormal development of cells, such as occurs in cancer and as a result of genetic and infectious diseases and environmental insult. Numerous cancer treatments and diagnostics for cancer and infectious diseases have resulted from studies using human fetal tissue. Human fetal tissue transplants, which are in the experimental stage now, have been used successfully in individuals with Parkinson's disease; diabetes; severe combined immunodeficiency disease (SCID); thalassemia (a hereditary hemoglobin abnormality); and complete DiGeorge's syndrome, a congenital lack of the thymus, an organ necessary for the integrity and function of the immune system. Animal studies indicate that fetal tissue transplantation may be useful in patients with Huntington's disease, various forms of blindness, skin diseases, and trauma, such as spinal cord injury and burns. The five-year moratorium on federally funded research using fetal tissue from elective abortions prevented the government from financing all of this work, forcing researchers to revamp their studies and use only animal models or tissue from spontaneously aborted fetuses or ectopic pregnancies--a limited source of healthy, viable tissue--or look for funding here. --M.E.W. In doing so, however, many of them wondered how they could possibly make up for what they considered five lost years of work--work that, they note, might have made a contribution toward easing the suffering caused by such devastating afflictions as Parkinson's and Alzheimer's, conditions that are among a host of targets for fetal tissue research (see story on page 14). "As soon as Clinton was elected in November, on the assumption that the ban would be lifted, we began writing a grant," explains Curt Freed, a clinical pharmacologist at the University of Colorado Health Sciences Center in Denver. Freed, who specializes in movement disorders, is the author or coauthor of numerous papers on the use of human fetal tissue transplants for Parkinson's disease. On February 1--a mere 10 days after Clinton's lifting of the moratorium--he, his colleagues, and others submitted proposals to NIH. The successful proposals that are to be announced this month are from the batch submitted immediately after the ban was lifted. Freed describes the ban as "very peculiar" and "narrowly cut politically." Another vocal opponent of the moratorium is researcher Leonard Hayflick, who, 30 years ago, isolated and cultured human fetal tissue lines that are still used today for the production of human virus vaccines. Hayflick, a cell biologist and gerontologist at the University of California, San Francisco, School of Medicine, doesn't mince words. "It's just the height of hypocrisy," he asserts, pointing out that throughout the time of the ban, NIH continued to take advantage of human fetal tissue cultures. During the period of the moratorium, NIH--except for studies involving fetal material obtained from elective abortions-- continued to support human fetal tissue research. In 1992, this support totaled some $12.4 million, more than 90 percent of which went toward extramural projects. And the agency apparently wants to make its position on the matter very clear. The introduction to an April 1993 report on its funding efforts in this area states: "The use of human fetal tissue in basic biomedical research has been well-established and important since the 1950s, and [NIH] has supported this area of research for many years." The report goes on to point out that human fetal tissue transplantation therapy has been used successfully in certain diseases, including Parkinsonism. But, according to the report, in the past five years, this research had to be funded privately or was done abroad. Despite the NIH record, in 1988, the Reagan administration dismissed recommendations by the Human Fetal Tissue Transplantation Research Panel--an ad hoc scientific advisory group assembled by NIH--and rejected guidelines that the panel had devised for the conduct of therapeutic human fetal tissue transplantation research, guidelines that, with strict constraints, allowed for the use of tissue from induced abortions. Indeed, the experts' recommendations were "just thrown out the window," according to Nancy Wexler, a professor of clinical neuropsychology at the Columbia University College of Physicians and Surgeons in New York, a strong advocate of continuing fetal tissue transplant research who is working with researchers to devise protocols for treatment of Huntington's disease using these transplants. Ironically, one member of the panel who voted with the majority in favor of the guidelines and of lifting the ban was Bernadine Healy, who went on to become director of NIH and the enforcer of the ban. Search For Funds A researcher whose efforts have been hampered for the past several years by the scarcity of human fetal tissue is neuropathologist William D. Lyman of Albert Einstein College of Medicine in the Bronx, N.Y. In 1992, Lyman received nearly $1.5 million from NIH--the largest NIH grant for human fetal tissue studies that year--for work on fetal tissue and HIV-1 exposure relating to neurological damage seen in children withAIDS. To make sure he and other scientists had sufficient material of good quality to work with, however, Lyman obtained private funding to establish a tissue bank for transplantation purposes containing material originally obtained from induced abortions. Previously, he had begun cooperating with scientists in Tel Aviv--where tissue from elective abortions is available--and was contemplating the prospect of continuing his work with his Israeli colleagues if the ban was not lifted. C.R. Freed, et al., Advances in Neurology, 60:721-8, 1992 C.R. Freed, et al., Neurochemistry International, 20:S321-7, 1992 C.R. Freed, et al., New England Journal of Medicine, 327:1549-55, 1992 W.C. Hatch, et al., FASEB Journal, 6:1328, 1992 (Abstract) L. Hayflick, Bio/Technology, 10:824, 1992 J.R. Sladek, Jr., et al., Experimental Neurology, 122:16-27, 1993 D.D. Spencer, et al., New England Journal of Medicine, 327:1541-8, 1992 Following implementation of the ban, scientists such as Yale University School of Medicine's D. Eugene Redmond, one of the pivotal investigators in the transplantation of human fetal tissue into the brains of Parkinson's disease patients, had to rely on foundation and other private funding for continuation of their research (M. Clemmitt, The Scientist, July 20, 1992, page 1). To make matters worse, in Redmond's case, Yale's development office--typical of policies at most universities--not only refrains from raising money for individual faculty members' research, but also discourages university researchers from contacting foundations that, according to Redmond, the school has been pursuing for major donations, scientific or otherwise, or that had received proposals from other departments in the university. While Redmond does not specify the foundations he could not approach, he does say that his research group obtained funding from Hammond, Conn.-based Axion Research Foundation, the Communities Foundation of Texas in Dallas, an unnamed Texas foundation, and private individuals, many with family members suffering from Parkinsonism. With the ban, therefore, the task of scrambling for financial support became a worrisome, burdensome, and distracting challenge for many individual investigators. "Besides doing the research," Redmond says, "we had to work on funding." While previously he would be funded on a three-year NIH grant, he instead found himself relying on private backing, he explains, which generally means relatively short-term funding. Thus, he and his colleagues found themselves in the position of constantly scrounging for dollars to support very expensive work. Worries included not only how to pay for the research itself, but also a host of mundane administrative problems, such as meeting payrolls and dealing with human resource concerns involved with hiring and firing. "It's a very unsettling way to fund research activities," Redmond says. Animals No Substitute Compounding the funding problem for Redmond and others were the impediments to rogress in their research caused by the lack of human fetal tissue. For example, during the period of the ban, Redmond still received NIH funds for experimental transplantation of monkey fetal tissue into the brains of nonhuman primates. But furthering his work clearly entailed the use of human material. Pointing out this requirement is John R. Sladek, Jr., a professor and chairman of the department of neuroscience at Chicago Medical School in North Chicago, Ill., who has been working with Redmond's group transplanting primate fetal neuronal tissue into brains of primates with Parkinsonism induced by MPTP (N-methyl-4 phenyl-1,2,3,6 tetrahydropy- ridine). MPTP, according to Sladek, is a protoxin that can cause neuronal degenerationclosely resembling that which occurs in Parkinson's. The work has been very promising, he says, but ongoing progress depends to a great extent on the use of human fetal tissue transplants into the primates. "With fetal cell transplants, those animals improve," states Sladek. "In many cases, they improve greatly." The studies have shown that brain dopamine levels are significantly elevated after the implant and that numbers of synapses increase. But the research moratorium prevented Sladek and colleagues from "studying the human cell." And, as Sladek explains, what one sees in a rat brain or monkey brain is likely to be different from what occurs when human fetal tissue is transplanted into a human brain. The scarcity of human fetal tissue has several profoundly negative effects, says Colorado's Freed. One is pressure put on the pocketbooks of patients, and the other is that research subjects are limited to those patients who can afford the transplant procedure, thus greatly skewing the experimental group. During the ban, Freed was able to continue his work on human neural fetal tissue transplants to ameliorate the effects of Parkinson's disease. But an average transplant procedure costs $30,000-$40,000, he says, and nine of his first 13 patients "paid cash." Only four of the procedures were covered by the laboratory's grants and, after publications began coming out on the success of the technique, three patients reportedly were reimbursed by their insurance companies. Nevertheless, Freed complains that because of the high cost and the likelihood that the cost had to be borne by the patient, "only people with a lot of money could afford to participate, and that distorts the research base." Immediate Impact According to Sladek and Redmond, the lifting of the moratorium has served to remove the moral stigma on their research that the presence of the ban produced. Sladek says that the ban "gave an impression that the work was so unimportant, or unacceptable, or controversial that it shouldn't have been done." But, he adds, "when the moratorium got lifted, that general stigma and a skewing of scientific perception was lifted." However, although individual researchers once again are submitting their proposals to NIH, scientists remain concerned that money will not be available in the NIH budget to support human clinical work. According to an NIH spokesperson, this is, indeed, possible. Colorado's Freed points out that even with federal funding available, the surgery is so expensive that only a relatively small number of procedures could be carried out. And Redmond cautions that the lifting of the moratorium without sufficient money to fund all of the research that scientists have been waiting to launch during the past five years is a double- edged sword. Although researchers are happy for the opportunity to apply for the funding, he reasons, the private sector may be under the misapprehension that federal money is available and that it no longer needs to fund the research. This, he points out, could put a further squeeze on proj-ects that have yielded promising results but have been hindered by the unavailability of federal funding. An Interim Stage Although Colorado's Freed has "concluded that only transplants are likely to cure Parkinson's disease ...or make a difference," Columbia's Wexler sees the use of fetal tissue as an interim stage in development of disease treatment. Wexler is president of the Santa Monica, Calif.-based Hereditary Disease Foundation, which currently is developing protocols for fetal tissue implants in patients with Huntington's disease, a genetic disorder that leads to long-term neurological degeneration. By using fetal tissue, Wexler explains, researchers will learn exactly what factors are involved in these diseases, and, eventually, gene transplants or pharmaceuticals will be developed to counter the diseases'effects. Meanwhile, Wexler sees an "opportunity to provide therapy" for patients suffering from what she calls "horribly devastating diseases." Chicago Medical School's Sladek notes that for now, as long as abortion is legal, "we'll see the opportunity to help truly sick people." Einstein's Lyman, however, wonders whether the current legality of abortion and the availability of human fetal tissue will prevail. "I think the political winds can always shift," he says. Myrna E. Watanabe is a biotechnology consultant based in Yonkers, N.Y.

With Five-Year Ban On Fetal Tissue Studies Lifted, Scientists Are Striving To Make Up For Lost Time

With Five-Year Ban On Fetal Tissue Studies Lifted, Scientists Are Striving To Make Up For Lost Time

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