Although we are famous for our beaches and mild climate, San Diego has the third largest concentration of biotechnology companies among U.S. metropolitan areas, with hundreds of companies employing tens of thousands of people (city-data.com, 2004).
In addition, academic research conducted at UCSD, The Salk Institute, The Scripps Research Institute and more make San Diego a focal point of discovery and innovation in science and medicine. Accordingly, ethical and social concerns associated with new technologies and medical advances may have a greater impact in San Diego than other communities in California. Tissue ownership has emerged as one such issue. The Center for Ethics in Science and Technology is hosting a talk on this topic next month as part of a series exploring the ethical themes in The Immortal Life of Henrietta Lacks by Rebecca Skloot.
Fundamental to scientific and medical research is the availability of human tissue samples for use in experimentation. From these samples, scientists have learned about both normal and abnormal processes in the cell, identified genes that cause and fight disease and developed methods for disease diagnosis and treatment. The tissue used for biomedical research is varied and comes from many sources, such as biopsies and blood samples. Also commonly used are human cell lines, which are created when a tissue sample is removed from an individual and then cultured outside the body for an extended period of time. Certain cell lines have the ability to grow indefinitely because they are derived from a cancerous tumor or have been purposefully altered. These cell lines are known as “immortal” and are significant because an unlimited number of laboratories can conduct ongoing research with the same cells. The first, and perhaps most famous, immortal cells are the HeLa cell line, named for the patient (Henrietta Lacks) they were originally removed from. The story of Henrietta and her cells is told in the book The Immortal Life of Henrietta Lacks.
Ms. Skloot’s book has spent over 55 weeks on the New York Times best sellers list and was mentioned on many 2010 notable book lists. One of the most compelling aspects of Henrietta’s story is that neither she nor her family were aware the cells derived from her cervical cancer completely revolutionized science and medicine. Henrietta’s doctors never asked to take her cells for research. It is reasonable to expect that in the 50 years since Henrietta Lacks died, the scientific and medical community has made improvements to ensure that patients are aware of what happens to the tissue they leave at a doctor’s office. Surprisingly, this is not the case. Legislation exists to protect people participating in medical research (The Federal Policy for the Protection of Human Subjects). Legislation also exists to protect patient privacy (The Health Insurance Portability and Accountability Act of 1996). However, these laws do not cover what happens to tissue once it is removed from the human body, particularly if the sample has been stored for some time and the researcher has no contact with the original patient.
Thus, a substantial amount of research involving the use of human tissues remains outside the realm of statutory regulation. While many research organizations and institutions have strict ethical guidelines requiring informed consent for all research involving human tissue samples, ethical guidelines are not laws. This ambiguity can create a situation in which a patient and his doctor are at odds, particularly when financial gain is involved. Several such instances have resulted in litigation. In John Moore v. The Regents of the University of California et al. (1990), Moore, a leukemia patient, had his spleen removed as part of his cancer treatment. The treating physician retained and used Moore’s cells, without Moore’s knowledge, to develop an immortal cell line for which a patent was obtained, resulting in significant financial gain for Moore’s physician and the Regents. Similarly, in Greenberg v. Miami Children’s Hospital Research Institute (2003), biological samples were used to conduct research that eventually led to a patent and financial gain for the researcher and his research institute. Although the plaintiffs voluntarily provided biological samples for research into the genetic basis of Canavan disease, a disease afflicting the plaintiffs’ children, the plaintiffs alleged they were unaware of the defendants’ intention to seek patent protection for the gene. In each of these cases, the court held that the plaintiffs did not have property interests in their biological material once the tissue was removed from their bodies and donated to research. In making this finding, the courts relied on the plaintiffs’ lack of possession of or ownership interest in the tissues following removal.
Leaving tissue donor rights to the determination of the courts on a case by case basis is unacceptable, and uniform regulations should be established. However, the questions associated with the issue are complex and competing interests must be balanced. First, should a donor retain any rights to their tissue once it is removed from the body? If so, do these rights extend to controlling how the tissue is used in the future or sharing in any profits earned from their tissues?
Property is a broad legal concept, and a person need not have physical possession of something in order to have property rights in it. For example, a landlord, although not in physical possession of rental property, retains rights in the property including the right to sell the property and the right lease the property for profit. Similarly, although a patient may no longer of have possession of their removed tissues, they may still retain interests in how those tissues are used.
Last year, a case highlighting this conflict was settled out of court. In the settlement, researchers at Arizona State University agreed to pay members of the Havasupai Indian tribe $700,000 as compensation for the use of their blood samples in research for which the tribe members do not believe they provided consent. The blood was originally collected in hopes of identifying a gene linked to Type 2 diabetes, a disease that afflicts around half of all Havasupai tribe members, which is the third highest rate in the world. While, many of the tribe members signed a consent form allowing the use of their blood to “study the causes of behavioral/medical disorders,” they maintain they believed the blood would be used only for diabetes research. After researchers were unable to identify any genes related to diabetes, they used the blood samples to study inbreeding in the tribe, the genetic causes of schizophrenia, as well as the ancestral origin of the Havasupai. The results were embarrassing to the tribe, and research results pinpointing their ancestral origin to Asia contradicted the tribe’s oral history.
If we accept that patients retain the right to control the use of their tissue following removal from their bodies, what is the scope of this right? Should a donor be able to stipulate, based on moral or religious beliefs or personal interests in curing a particular disease, that their tissue only be used for certain types of research and not others? While it seems that patients should have the right to opt in or opt out of the use of their tissues in research in general, allowing donors to limit the use of their tissues to particular types of research raises a number of ethical and practical difficulties.
Tissue samples may be stored for many years and used by numerous researchers subsequent to the original scientist who obtained the samples. Although laboratory records are kept, they are often incomplete and difficult to decipher. Ensuring that all subsequent research complies with the limitations a donor has placed on tissue use would be a logistical nightmare. Furthermore, how are we to deal with the emergence of new areas of research that did not exist and may have been unfathomable at the time tissue samples were donated? For example, just a decade ago few researchers understood the importance of epigenetics, the study of chemical modifications to DNA that affect gene expression. It is now clear that epigenetic regulation is critical for many normal processes, and dysregulation has been linked to diseases such as cancer. Scientific and medical research will continue to make new and exciting breakthroughs. Should we require scientists to locate tissue donors to obtain their consent for every new discovery? Such requirements would substantially hinder scientific research, as would potential legal liability for scientists who unwittingly use tissue samples for research not consented to by the donor.
Another controversial issue related to tissue research is the donor’s right to share in the profits derived from their tissues. The majority of tissue samples, while valuable to scientific research, do not lead to commercial profits. However, some tissue samples are used to develop commercially valuable products for which patents are obtained and substantial profits are made.
In determining that biological matter can be patented, courts have distinguished between products of nature, which are not patentable, and biological inventions, which are the fruits of the application of researchers inventive effort to products of nature. Similarly, tissue samples have been held to be “factually and legally distinct” from the patented cell lines and isolated genes derived from these samples. Thus, on the one hand, given this distinction, donors of unpatentable tissues should not be entitled to share in profits derived from the patented biological inventions. However, on the other hand, what if the development of the patented invention was dependent on the unique properties of the donor’s tissue? For example, an immortal cell line cannot be made from any cell, rather the special properties of Henrietta Lacks’ cervical cells were essential to the creation of the HeLa cell line. In such cases, the donor has made an essential contribution to the invention and arguably, this contribution should be recognized by a share in the profits.
The issues surrounding research involving human tissues are complex and it is often unclear how best to handle the competing interests. Given the importance of the interests involved, namely the protection of donor autonomy and the promotion of medical research, it would seem that legislative consideration of these issues and determination of the rights of the parties involved is long past due.
The Reuben H. Fleet Science Center and the San Diego Center for Ethics in Science and Technology will be hosting a free public forum on September 7 at 5:30 p.m. to further discuss the ethical issues surrounding tissue donor rights. This is the first of a nine program series that will focus on the book The Immortal Life of Henrietta Lacks. Come join the conversation and share your perspective with leaders in the field.
Laura Rivard, PhD is an Adjunct Assistant Professor in the Department of Biology at the University of San Diego. Margaret Ng Thow Hing is an intellectual property attorney and former scientist and writes as a member of the San Diego Center for Ethics in Science and Technology.