Afternoon panel:

What is the responsibility of the researcher to the patient or subject in cases in which human organs, tissues, cells, or body fluids (henceforth called "human materials") are used in research that might lead to the development of products that might have market value? Before I respond

to this question I wish to consider briefly the point at which persons lose their "interests" in materials that once were part of their bodies. In this discussion I shall make frequent reference to my book, Ethics and Regulation of Clinical Research, Urban & Schwarzenberg, Baltimore, 1981. After a person abandons human material in order to serve his or her personal good, he or she loses all but one interest in it; that interest is privacy. Common ways in which this is accomplished range from urination to surgical removal of a diseased organ (e.g., the gallbladder). These materials should be seen as passing into the public domain after the urine has been flushed or after the gallbladder has been examined by a surgical pathologist and is destined for its usual disposition cineration. After the surgical pathologist has completed his or her examination of the gallbladder, we permit researchers to use this organ for their own purposes as long as the patient's privacy interests are protected properly. Usually this is accomplished by not letting the researcher know whose gallbladder it was. Thus, in the development of something like the HeLa cell line, which, of course, has considerable commercial value, the modern researcher usually does not know who "Helen Lane" is. Helen Lane is the fictitious name of the woman from whom the original cervical cancer cells were taken to establish the HeLa cell line.

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in

We do not use informed consent in such cases.

a "right of notice" (Levine, pp.111-113).

Rather, we recognize

The customary practices of the

hospital are made explicit on the forms used to authorize surgery or autopsy. The surgical permission form, for example, states that it is customary to deliver the removed part to the surgical pathologist for diagnostic examination and that in some cases it might be retained for research or teaching purposes before it is destroyed.

In the event the researcher must know the name of the patient in order to accomplish the purposes of the research, additional procedural protections are involved. In some cases, in order to protect privacy interests, it is necessary to negotiate full informed consent with the patient (Levine, pp.112-113). Such procedures are also used for "leftover" blood, urine, spinal fluid, and so on, collected for diagnostic

purposes.

If the researcher wishes to remove human material primarily to serve research interests, the situation is different. In this case, full informed consent is required ethically as well as by the regulations of DHHS and FDA.

Among the elements of informed consent defined in federal regulations are: "... an explanation of the purposes of the research..." and "A description of any benefits to the subjects or to others which may reasonably be expected from the research." In order to illustrate how such requirements are made operational in the practical arena, let us consider the consent form we might have prepared for Dr. Hagiwara's mother (Royston, I.: Cell Lines From Human Patients: Who Owns Them? A Case Report. Clinical Research 33:442-443, 1985). In order to make this discussion less compli

cated let us disregard the fact that Dr. Hagiwara is a molecular biologist In passing

whose father has the capacity to produce the antibody in Japan.

I wish to note that the entire incident could have been avoided by following the Task Force recommendations I discussed this morning.

The IRB at Yale University School of Medicine would have approved a consent form which included the following statements of purpose and benefits:

"The purpose of this research is to learn more than we now know about cancer of the cervix. In particular, we wish to learn whether cells like yours can be used to make antibodies to cancer cells.... This research is not designed to bring any direct benefit to you. Rather, we hope that the knowledge developed in the course of this research will form the basis for developing improved treatments for future patients with cancer of the cervix." In general, we ask researchers to tone down their usual overly exuberant statements of anticipated benefit. We do this in order to avoid creating the appearance of what the Nuremberg Code refers to as ".. ... deceit, duress, overreaching, or other ulterior form of constraint or coercion...." Should we also go on to discuss the commercial implications of this research? For the sake of this discussion, let us tentatively say "yes." The statement of benefits may be expanded to read: "If we are successful we may be able to develop a cure for cancer which, of course, would have enormous market value."

If we are to make such statements, to whom should they be proferred? As we consider answering this question it is worth keeping in mind that most such efforts fail. Researchers may take cells from hundreds of people

before they achieve success.

Should such statements be made to all of these

people? Are they all entitled to negotiate for a share of the proceeds?

Or, instead, is it more like a lottery in which there will be but one winner? It is a commonplace that all scientists stand on the shoulders of their predecessors. They all draw on the work of those who have earlier discovered, validated, and published. Such is also the case for these research subjects. Should we have discussed potential market value with all of the many men and women who donated their cells so that researchers could learn how to make hybridomas and monoclonal antibodies in the first place? The number begins to loom large.

Much is made of our current capacity to make synthetic human hormones using recombinant techniques. This capacity is totally contingent upon knowing the molecular structure of the hormone. In order to learn the structure of ACTH, Dr. Aaron Lerner and his colleagues had to first purify the hormone. This required taking the pituitary glands from approximately 7,000 dead human beings. Are their estates entitled to a share in the proceeds? The field of drug development provides us with another example to ponder. The average number of patients participating in phase I-III drug studies is about 3,000. They all give their blood, their urine, and much more in order to participate in such development. Are they entitled to an opportunity to negotiate for their share of the market?

If researchers have a duty to disclose their economic interests, should we also require disclosure of what I referred to this morning as the other traditional coins of the academic realm? Should they disclose the relevance of the subject's cooperation to their opportunities for promotion, recognition, and so on? Are the subjects entitled to a share in the Nobel Prize? Should Aaron Lerner offer to divide the Lita Annenberg Hazen Award with 7000 estates? I think not.

I think that if the market value is to be disclosed, it should be at the "stage of inevitability," the stage in applied research at which the development of a product that could have market value becomes inevitable. At that point, this fact could be disclosed to prospective subjects in order to give them an opportunity to accept or reject cooperating in the development of the product. Thus, while some persons might be delighted to contribute to the development of an improved oral contraceptive, some others might not.

I agree with the intent of Congress expressed in the Organ Procurement and Transplantation Act in which it proscribes "...sale for valuable consideration of human organs.... People should not be encouraged to sell

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either themselves or parts of themselves. I recognize that the Act explicitly excludes replenishable tissues such as blood or sperm."

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It may be somewhat hypo

However, for various good reasons, I do not think that persons should be encouraged to sell any parts of themselves. critical or evasive but when we give people money in exchange for "replenishable tissues" we usually call it a payment for services rather than a purchase of tissue. Moreover, the amounts of money that change hands in such transactions tend to be rather trivial when compared with the amounts we are considering today.

With regard to research subjects, I think we should continue the prevailing practice of paying them for their time and inconvenience as suggested by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (Levine, pp.59-61).

If we disclose potential market value at the stage of inevitability, no doubt some prospective subjects will wish to negotiate for a share of