Somewhere in a medical laboratory, there may be a scientist who knows far more about you than you do yourself.
Labs in hospitals, medical schools, and biotechnology and drug companies across the U.S. hold more than 300 million samples of human blood, tumors, skin, hearts, kidneys, livers, placenta, embryos, sperm, ova, hair, urine, and even sweat, which can contain skin cells. The samples might come from potentially cancerous tumors, organs removed during surgery, or cells taken from inside your mouth to check for infections. Because the tissues are crucial for studying the workings of human genes, hospitals, biotech companies, and pharmaceutical houses are racing to collect them. Every year, 20 million samples are being added to the nation's tissue banks.
Many samples carry codes that can be used to identify the person they came from. And even though federal guidelines require researchers to get patients' consent before studying tissues, rules do not necessarily apply to hospital laboratories that are testing for diseases. Thus, people whose samples are being studied often don't know that a little bit of themselves is sitting in a laboratory freezer. "It's typically done by hospital pathology labs without consent," says Thomas H. Murray, president of Hastings Center, a bioethics think tank in Garrison, N.Y. "If you've had a biopsy, your tissue is in a lab."
All this tissue is at the center of a new market that is spawning a host of ticklish ethical questions. Laboratories are buying and selling tissue and recruiting patients to establish new collections. This frenzied activity reflects the changing world of research in biotechnology. With the human genome project now completed, researchers are left with the gargantuan task of figuring out what each of the 30,000 or so human genes does, a field of study known as functional genomics. To do that, the researchers need to examine how the genes function in human tissue. "Everyone who is doing biomedical research does experiments in tissue," says Steven H. Holtzman, chief executive officer of Infinity Pharmaceuticals Inc. in Boston.
While the research will probably have a huge payoff in new treatments and diagnostic tests, it could also lead to an erosion of privacy. Virtually all of the tissue samples are accompanied by codes identifying the donors, and information on their medical history. The information can get back to a patient's medical record and fall into the hands of employers or insurance companies--or even law enforcement officials--without the consent of the person the tissue came from. That, in turn, could lead to loss of insurance coverage or loss of employment.
The most thorough study to date on the ethics of tissue handling and research raised a number of troubling questions. Current federal regulations on human research "are inadequate to ensure the ethical use of human biological materials in research," said the 1999 study by President Clinton's National Bioethics Advisory Commission. And the regulations apply only to federally financed research. They do not cover privately financed research at biotech or pharmaceutical companies. The demand for the tissue is so great that its use in research has grown enormously, even though the ethical and privacy issues remain unresolved. The commission estimated the nation's tissue collections held 282 million samples and that the total was growing by 20 million per year. Nobody knows exactly how big the market is, but many tissue banks report they are making tens of thousands of samples available to research every year, so the total number of samples used is likely to be in the millions.
Tissue hasn't always been the valuable commodity it is today. For a hundred years or so, doctors and researchers have been casually tossing discarded human tissue into beakers of preservative or freezers--often without any clear idea of what to do with it. Such samples have become a "library of the human experience with disease," says Dr. David Korn, senior vice-president for research at the Association of American Medical Colleges. And that library has led to stunning breakthroughs. The first solid evidence linking smoking to cancer came from studies of thousands of samples of lung tissue collected over decades at a Veterans Administration Hospital in East Orange, N.J. Research on arterial tissue removed from young soldiers who died during the Korean War showed for the first time that atherosclerosis begins early in life, and that it is more common in Americans than in Koreans or Japanese. Such discoveries radically changed thinking about lung cancer and heart disease, Korn says.
Tissue collected over time has become even more valuable in recent years as researchers have developed new tools to study its genetic characteristics. "We can really use tissues to understand the genetic difference between tumors that may look identical under the microscope," says Korn. "The more precise subclassification you get, the more you can tailor pharmacological or other therapies to the disease." Researchers hope these tailored treatments will be more effective and have fewer side effects than existing therapies.
Sequenom Inc., a San Diego biotech, is among the many companies working on such customized treatments. One of the company's strengths, it says, is a technology for rapidly scanning genetic samples. That can be used with DNA samples from patients to identify several hundred genetic characteristics, or "markers," that might be linked to a certain illness. That's too many to study in detail, so the company screens those markers against hundreds or thousands of tissue samples to shrink the number to 10 or 20 genes likely to be major contributors to the disease, says Dr. Andi Braun, Sequenom's chief medical officer.
This research requires that its practitioners know as much as possible about the symptoms and the medical condition of the patients from whom the tissue came. Most samples are given a code so researchers don't know which patient an individual sample came from. But it's often important to discern, for example, who among a population of lung cancer victims died quickly and who survived longer, Braun says. That can require breaking the code and going back to the patients or their records to get more information on the patients' medical histories.
Yet the genes in the samples carry secrets the tissue's original owners might not want revealed. The research can uncover a susceptibility to cancer, heart disease, or diabetes. It can reveal evidence of past illnesses or exposure to AIDS or other infectious diseases. The danger is that such personal information could prove devastating if it fell into the hands of insurers, employers, or police. One study found that as many as 400 people may see the medical records of someone in the hospital.
Police and other law enforcement officials might also come calling for access to tissue samples to help solve crimes, or to try to track the movements of suspected terrorists. At present, the law does not make clear whether police can get access to the samples--or whether tissue banks have a right to refuse it, says R. Alta Charo, professor of law and medical ethics at the University of Wisconsin Law School.
It's not only the patients whose privacy is compromised. If an inherited disorder or a susceptibility to a disease is found in a tissue sample, other family members may be similarly afflicted--meaning their privacy has been violated, too. Even tissue from someone who is no longer alive can say much about the health of that person's children and grandchildren.
Federal guidelines for the protection of human research subjects generally apply to research on human tissue samples as well as individuals, says Michael Carome of the Health & Human Services Dept.'s Office for Human Research Protection. But the guidelines apply only to federally funded research, not to research funded by industry. And the guidelines do not require that names be taken off tissue samples--only that efforts be made to protect patients' privacy.
Tissue studies raise unusual questions that are not triggered by other kinds of human research, however. For one thing, getting proper informed consent is complicated. Sheri Alpert, a bioethicist at the University of Notre Dame, has suggested that many of the samples obtained after surgery may have come from patients who signed a form saying their tissue is to be "disposed"--without realizing that such tissue could be used in research.
Hospitals and companies collecting tissue samples generally make a serious effort to educate patients before seeking their consent, but it is difficult for the collectors to say exactly how the tissue sample will be used. "The dilemma is you don't know all the kinds of research you might want to do," says the University of Wisconsin's Charo. "How can you ask people to give consent for a limitless, unknowable amount of research?"
A further problem for researchers is what to do when studies of a particular sample reveal that the patient it came from is at high risk for breast cancer or a heart attack. Do researchers have an obligation to send word back that the code should be broken and the patient notified? This issue is still unresolved, says Charo, who served on Clinton's bioethics commission. Such information can be devastating, particularly in cases, such as those involving Alzheimer's disease, in which nothing can be done to treat the patient.
Researchers and ethicists agree that excessive restrictions on such research would delay the many biomedical advances promised with the completion of the Human Genome Project. Yet many experts concur with the Clinton commission that patients are not adequately protected. Without such protection, patients may refuse to make their tissue available. That could cripple the biotechnology industry and delay many promising, potentially life-saving treatments.
By Paul Raeburn in New York