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Nov/Dec 2000
Vol. 3, No. 9, pp. 23-24,

insight and analysis
BY KATHLEEN WONG

Tissue debates

Research using tissue taken from patients sparks new debates on privacy and property.Opening Art

When a patient goes to the hospital these days to have a biopsy or operation, chances are good they’ll be asked to sign more than the waiver and the bill. They might be given a form asking for permission to use tissue removed during the procedure for medical research.

On the surface, that request sounds pleasingly benign: a chance to further medical science, maybe even find a cure for your own ailment, with no extra effort beyond attending to your own health. What’s an altruistic individual not to like?

Possibly plenty. Depending on the fine print and the success of the research, giving up your cells for scientific scrutiny could open the door to a terrifying invasion of privacy and cause considerable financial and social risks to donors.

Need for permission
Offering up tissue to scientific inspection hasn’t always been this risky, mostly because there wasn’t much researchers could glean from a few scrapings of cells. Pathologists might be able to tell why an individual had sickened and how illness had ravaged their cells, but not much more. Correspondingly, there were few protections for patients. Pathologists routinely helped themselves to samples taken during operations and autopsies, along with the juicy details of medical records, without patients ever knowing. This laissez-faire system resulted in groundbreaking discoveries such as the links between smoking and lung cancer and between the drug diethylstilbestrol and vaginal cancer, but it would not be tolerated today.

The power of biotechnology to unveil the secrets of the genetic code is what has changed this arena. Today’s researchers are finding genes that cause a predisposition to disease and are using DNA to connect the dots between living people and their long-dead ancestors. They are also discovering treatments for illnesses at an astonishing rate. Each step forward, however, brings with it a whole new set of ethical questions that aren’t always immediately apparent.

A minefield of questions surrounds the unwitting tissue donor, according to Richard Lynch, professor of pathology at the University of Iowa College of Medicine. He brings up the case of researchers who find that a certain gene in a patient’s tissue puts them at risk for disease. As the tissue donor, “you could say you don’t want to know about it because you would worry. You might want to know so you could plan for it. Or you don’t want anyone else to learn about it, because if the insurance company finds out, you could be discriminated against.”

The danger of one’s medical information falling into the wrong hands is frighteningly real. As vice president for consumers at the Alliance of Genetic Support Groups, Sharon Terry has heard numerous horror stories of people denied health insurance, life insurance, and even employment—just because the wrong people learned of their medical history. “I know of someone who actually lost her job before their employer even understood the ramifications of their disease and how it wouldn’t affect her ability to work,” Terry says. And in the 1970s, several insurance companies and employers discriminated against sickle cell gene carriers even though their health would not be affected by the allele.

Tissue ethics
Bioethicists generally agree that the best way to avoid the quandaries of tissue donation is to ask the right questions before research ever starts. “It’s important to ask, what is the risk to the provider of the tissue? And second, what kinds of consent are needed from the source of the tissue?” according to James Childress, professor of religious studies and medical education at the University of Virginia and a member of the National Bioethics Advisory Commission (NBAC). But meeting even these basic standards can be tricky. How much do patients need or want to know about each study? Can they be adequately informed of the risks they face for their participation, given the uncertainty of what scientists might uncover about genetics or disease in the future?

“Over the long run, this type of research is clearly worth pursuing. We want to provide researchers with a steady supply of tissue, but we want to ensure the appropriate moral limits are respected,” Childress says. The two are linked because people will only contribute their tissues if they are satisfied that human subject research policies offer donors adequate protection. “If you really want to go forward in this kind of research, you need the public trust,” says Childress.

Federal policy already provides some safeguards for tissue donors. Scientists conducting federally funded research on tissue that can be linked to living persons must obtain specific consent for the research from subjects or the investigation must impose minimal risks to subjects. Institutional Review Boards (IRBs) made up of scientists and community representatives decide whether studies meet these criteria. Yet this system of checks and balances can be flawed. Various IRBs interpret the law differently, and members might be swayed by a personal stake in the research, such as desiring to promote the status of a colleague.

According to the NBAC, there should be a continuum of permissibility that depends on the level of risk to the donor. “Part of what would make it less risky is confidentiality,” Childress says. At the permissive end of the continuum are “unlinked” samples for which personal information cannot be obtained. At the other end are samples that can be connected directly to an individual or family and for which identifying information such as medical records can be obtained. An NBAC report suggests that researchers who wish to use identified or linked tissue must provide a high level of disclosure, whereas researchers who wish to use unlinked tissue that has been stored for decades might not need to notify patients at all.

The Web site of the National Action Plan on Breast Cancer in Washington, DC (www.napbc.org), offers a sample consent form for donating tissue excised during biopsy for research. The form discusses how tissue donation may assist research. Patients are given the option to consent to the use of their tissues for cancer or other disease research, and are asked whether researchers may contact them in the future to take part in further research. The latter option was controversial among NBAC members, including Alexander Capron, professor of law and medicine and codirector of the Pacific Center for Health Policy and Ethics at the University of Southern California. “I don’t think people should be able to ask others for open-ended permission to use identifiable records. I don’t think people can make those choices without knowing more,” Capron says.

Profiting from tissue
In the high-stakes world of modern biomedical research, the issue of profit cannot be avoided. What, if anything, are people entitled to if something of commercial value is developed from their cells? This question has gained importance as more biomedical research is conducted by private, for-profit companies rather than by university researchers supported by federal grants, and as genes have literally become their stock-in-trade.

At the forefront of this kind of research is GeneLogic of Gaithersburg, MD, for which 18 hospitals in the United States and the United Kingdom have agreed to procure a steady stream of human tissue samples. The agreements “require them to provide us with X number of samples on a regular basis,” says Robert Burrows, spokesman for GeneLogic. In exchange for the tissue, which is generally donated by patients for free, GeneLogic pays the hospitals a collection fee or gives its researchers access to some of the massive genetic databases it builds with the samples. Burrows says GeneLogic takes in hundreds of tissue samples a month and eventually hopes to build gene expression profiles for a football stadium full of people.

The company’s hospital contractors use a standard consent form and medical record-taking process that includes diagnosis, treatment, medical history, and other patient information. Burrows says the distance between GeneLogic and the patient helps the company avoid potentially thorny patient privacy issues. “It’s all anonymous. We don’t know any of them, and we never can.” It also allows the company to avoid the issue of whether to pay the original tissue donors.

Researchers take all
Existing legislation and court precedent are inconsistent regarding the issue of profit from human body products. It’s perfectly aboveboard to sell human eggs, sperm, and blood, but since the National Organ Transplant Act was passed in 1983, it has been illegal to buy and sell organs in the United States. And thanks to the precedent-setting case of Moore v. Regents of California, you cannot sell your cells, either. Even though John Moore established that David Golde, a researcher at the University of California–Los Angeles, not only failed to obtain consent to use Moore’s spleen cells but also tricked him into providing additional samples of blood and other cells under the guise of further treatment, the court found that Moore did not have sufficient property rights to claim ownership of the valuable cell line and other products Golde had developed from Moore’s spleen. (See Modern Drug Discovery, June 2000, p 63.)

Not everyone is comfortable with the “researcher take all” rule. Says Capron, “If it’s something from which you derive great value, paying something back is not a bad idea. If it’s from the entire city of New York, maybe not, but what about an undeveloped society without the ability to do the research themselves? That’s like strip mining their land.” Lynch suggests establishing a system by which companies might pay a percentage of donor-derived profits into Social Security or another fund for public development.

The NBAC’s recommendations are being considered by the federal government, but it is unclear at this point how they will affect federal research policy. And only the future will tell how the nation as a whole will tackle the blessing and curse of genetic knowledge. Says Childress, “It’s an ongoing societal conversation that has not been settled yet.”