When it comes to biological materials, personal property does not get any more personal. Or, does it?
Recent court decisions could make it more difficult for scientists to individually secure usage rights for research involving the study of human biological materials, as patients and clinicians have begun to question exactly what is granted—and to whom it is granted—when a patient signs an informed consent agreement.
These court decisions deal largely with questions of ownership and commercial gain, and have not led to changes in existing federal guidelines for research involving human biological materials, which focus on ensuring ethical practices and protecting patient privacy rights. Indeed, there exists a delicate line between information that is scientifically valuable and information that potentially violates a patient’s right to privacy. There is a concern that the research use of genetic information could infringe upon an individual’s privacy and, if misused, could result in trauma or discrimination (e.g., paternity findings or diagnosis of incurable genetic disease). Researchers must be aware that patient concerns focus not only on privacy, but on questions of ownership, particularly as the commercial potential of donated biological materials is closer to being realized.
Where is the focus of any inquiry? The case law reveals that it involves a careful analysis of the substance and scope of informed consent. When must a specifically-defined, informed consent be obtained from subjects whose biological materials are to be donated to, or stored in, a biorepository? What parameters must be specified within that consent document?
In general, written informed consent should be obtained, without coercion, from each donor-subject whose data will be entered into the database, in accordance with the Department of Health and Human Services regulations at 45 C.F.R 46.116.
The applicable regulations mandate that the basic elements of informed consent should include "clear descriptions" of:
- the operation of the cell repository;
- the specific types of research to be conducted;
- the conditions under which data and specimens will be released to recipient-investigators; and
- procedures for protecting the privacy of subjects and maintaining the confidentiality of data.
Regulations also advise that informed consent documents not include any exculpatory language through which subjects are made to waive, or appear to waive, any legal rights, and that the written descriptions of the nature and purpose of the research be as specific as possible.
But the guiding provisions, however comprehensive, fail to take into account the human and potentially emotionally-complicated relationship between a donor and his or her donated cells or tissues. In our age of biotechnology, of pharmacogenomics and “designer” embryos, patients are well aware that one’s biological materials are truly personal and uniquely one’s own. And for researchers to retain control of these unique materials and to preserve the integrity of their research, patients must understand the nature of their research participation and must be informed. Case-by-case judicial activity is now defining the standards of what constitutes and what is given by informed consent.
Washington University v. Catalona (2006)
Dr. William Catalona, developer of the prostate-specific antigen (PSA) test for prostate cancer, was employed by Washington University (WU), St. Louis, Mo., from July, 1976 through February, 2003. There, he was instrumental in developing a biorepository for the collection and storage of biological research materials—specimens of prostate tissue, blood, and DNA samples—for prostate cancer research.
When he left WU for a research position at Northwestern University, Dr. Catalona attempted to reclaim from WU those samples that had been collected from his own patients by mailing letters to his patients, asking them to request from WU that their tissues be transferred to another institution, for his use. Roughly 6,000 of the 10,000 patients whom Dr. Catalona solicited responded as he suggested. In response, WU filed suit for ownership of the samples, in August, 2003.
The 2006 decision from the US District Court in Missouri, ruled that the samples belong to WU and Dr. Catalona’s patients have no rights to relocate them. This decision was upheld by the Eighth Circuit Court of Appeals in 2007, and is consistent with laws governing property ownership and donation. The case of Washington University v. Catalona highlights the reality, that researchers themselves have limited rights over their own work, and provides a focal point by which to explore the question: How does informed consent grant a researcher the right to explore one’s biological materials in the name of science, and does it strip consenting patients of all interests in something that is uniquely their own?
The district court found that WU had alone assumed the burden of all legal, regulatory, and compliance risks with respect to all research done in connection with the biorepository that Dr. Catalona had helped to create. The court found thus that WU had, at all times, exercised undisputed and exclusive possession over the samples in question, demonstrating prima facie evidence of ownership. The court ruled that the samples were donated to WU as gifts and donors had no ownership interest in those samples. Dr. Catalona appealed the decision.
The Eighth Circuit recently upheld the lower court's decision and affirmed that patients who make an informed donation of their biological materials for the purposes of medical research have no ownership interests in those materials and no ability to direct their transfer to anyone or anyplace else. The court found material support for its decision in the text of the signed informed consent documents which bore the WU logo, characterized the patients’ participation as a voluntary donation and indicated that the research would be conducted by Dr. Catalona or one of his colleagues.
But many of Dr. Catalona’s patients believed they had granted their consent to him alone, and therefore the University could not control the samples they had donated. The eight patients who joined Dr. Catalona as co-defendants in the suit before the district court argued that:
- They had merely transferred ownership of their biological materials to WU and had not made an inter vivos gift;
- The biological specimens were not gifted, because of "exculpatory language" in the informed consent forms;
- They had “intended” for their samples to belong to Dr. Catalona and therefore the samples had not been gifted to WU;
- The "right to discontinue participation" as stated in the informed consent documents includes a "right to control the samples' use" and a "right to transfer" samples to a specific person or entity; and
- The informed consents are invalid as being violative of certain ethical documents regarding human-subject research.
The district court rejected these arguments, holding that the consent forms clearly indicated that the donated samples were the intended property of the university. The Eighth Circuit affirmed.
Dr. Catalona has indicated that he may appeal to the Supreme Court.
While patients do have a right to “discontinue participation” in research, the right to discontinue is not the right to retake control and ownership of donated samples. Rather, the right to discontinue is interpreted as the right to cease any active participation in research. The research institution is still allowed to retain ownership of samples already collected, but must meet a responsibility to destroy, retire, or "anonymize" the sample.
But the removal of identifying markers, to thus "anonymize" a sample, does not change the core biological material itself—and it has been argued that, one’s cells and genetic material represent an individual’s uniqueness more profoundly than a name and identifying number. Thus, even an anonymous sample contains a unique identity of value to the person whose DNA matches that of the sample.
Depending on one’s perspective, it may be either logical or disturbing, that laws of property and ownership are applied to such a profoundly personal material. Regardless of their personal perspective, it is of great importance for clinicians and researchers to be aware that ownership is of concern to patients. Patient consent must thus be well-informed.
Precedent: The question of ownership, and the value of consent
In deciding Catalona, the district court relied on two other well-publicized cases: Moore v. Regents of the University of California (1990) and Greenberg et al. v. Miami Children's Hospital Research Institute, Inc., et al. (2003). In both cases, patients sued researchers for patenting a cell line or gene isolated from samples without the donors' knowledge, and the challenges similarly revolved around the scope of informed consent.
Moore v. Regents
John Moore, a hairy-cell leukemia patient, sought treatment at the University of California Los Angeles (UCLA) Medical Center under the care of Dr. David Golde. In the course of Moore’s clinical treatment, Dr. Golde extracted samples of blood, bone marrow and other tissues; Moore also underwent a splenectomy. Dr. Golde then utilized portions of Moore’s removed spleen, blood, blood serum, skin, bone marrow aspirate and sperm for medical research—without Moore’s express consent—and eventually derived and patented a cell line derived from Moore’s tissues.
Moore sued Dr. Golde, the Regents of the University of California (to whom the patent was assigned) and the patent licensees alleging among other things that his extracted cells had been used in commercially valuable research without his permission and that Golde had breached his disclosure obligations as a physician.
The California Supreme Court agreed that Moore did have a claim for breach of fiduciary duty and lack of informed consent because Dr. Golde had failed to disclose the extent of his research and his economic interest in Moore’s cells. The court stated in its decision, that an adult of sound mind has the right to exercise control over his own body and, within that right, should have the power of deciding whether or not to submit to lawful medical treatment. For that power to be effective, the court stated, a patient’s consent must be informed consent.
Greenberg, et al. v. Miami Children's
In Greenberg, et al., the "Greenberg" group of individuals and nonprofit institutions entered into collaboration with Dr. Reuben Matalon to identify the gene responsible for Canavan disease. The individual members of the Greenberg group were parents of children afflicted with Canavan disease, who had collected blood and tissue samples from other Canavan families for the purposes of Dr. Matalon’s research. Using these samples—and the information contained in a clinical and medical information database, also created by the Greenberg group—Dr. Matalon and his research team successfully isolated and patented the sequence of the Canavan gene.
The Greenberg group, believing that the commercial patent limited the public’s access to potential therapies, sued Dr. Matalon and his institution. The plaintiffs claimed, among other things, breached duty of informed consent and unjust enrichment. Plantiffs believed that they had a property interest in their excised body tissues, in the genetic information extracted from such tissues and in the registry which contained the donors' personal and genetic information.
The Florida district court did find that Matalon and his group had unjustly benefited from the licensing fees negotiated under the commercial patent. However, the Florida court also ruled that the case involved no patient-physician relationship—because Dr. Matalon was not a treating physician to the Canavan patients or their families—and thus found no breach of duty of informed consent.
Implications and regulations
To researchers, particularly clinicians, case law might be interpreted to stress the importance of explicit informed consent. Patients must be made to understand that their donations are just that: donations, over which they will exercise no future control, even if they discontinue research participation. Hence, the realities of the right to withdrawal from research participation, and the use of anonymized samples, should be explicitly explained to patients. The possibilities of commercialization and restrictive patents should be discussed broadly—to make patients aware that, ultimately, profits might be realized, but not shared.
The importance of informed consent should not be minimized. A careful review of the informed consent document and an extended conversation with a potential donor might prevent legal trouble and negative press for both researcher and institution.
About the Author
J. Mark Waxman is a partner in the Boston office of Foley & Lardner LLP. He is the leader of the firm's health care industry team and a member of the white-collar defense and corporate compliance practice group.
This article was published in Drug Discovery & Development magazine: Vol. 10, No. 12, December, 2007, pp. 30-31.