21

I think it is important to emphasize that

our end objective in this matter is to clarify

our responsibility as a supporting agency and to

identify the courses of action that our responsibility
42
imposes upon us.

Livingston, with assistance from NIH's Office of Program

Planning, completed the study and submitted his report on November 4,

Concerning the background of the problem, the report made

the following points:

Historically progressive changes in the kinds of clinical research possible to undertake are changing the nature of risks and values relating to clinical research.

There is no generally accepted professional code
relating to the conduct of clinical research.

The legal status of clinical research is ambiguous.
The NIH supports clinical research in a wide

There

variety of research institutions and hospitals.
exist conspicuous differences in institutional attitudes
toward acceptable professional conduct of clinical research.
As the number of investigators, subjects and
institutions engaged in clinical research increases and
as the nature of the risks ventured changes according to
the extension of research into new areas, a mounting
concern is expressed over the possible repercussions of
untoward events which are increasingly likely to occur
and which may occur in an unfavorable pattern of context.
Highly consequential risks are being taken by individuals
and institutions as well as the NIH as a direct result
of the complexity and ambiguity associated with research
44

on man.

The report also referred to the wide publicity then being given

42 James A. Shannon, Memorandum to Dr. Robert B. Livingston, "Review of the Ethical Aspects of Clinical Investigation," March 5, 1964 (Hereinafter referred to as "Memorandum to Livingston").

43, 3Robert B. Livingston, Memorandum to Director, NIH, "Progress Report on Survey of Moral and Ethical Aspects of Clinical Investigation," November 4, 1964 (Hereinafter referred to as "Livingston Report").

Ibid., pp. 2-3.

22

to earlier experiments at the Jewish Chronic Disease Hospital in Brooklyn, New York, which had resulted in charges of unethical conduct against Dr. Chester M. Southam and Dr. Emanuel E. Mandel. This research project had been funded by grants from the PHS and the American Cancer Society. It is important to examine some of the details of the incident because it probably "stimulated a greater attention to the problems"45 associated with research in humans.

Dr. Southam was a physician acting as an employee of the Sloan-Kettering Institute in New York and was conducting cancer research. Dr. Mandel was the Director of Medicine and Director of Medical Education at the Jewish Chronic Disease Hospital. Both doctors were found guilty, censured, and placed on probation for their "conduct in the planning

and execution of a research project at the Jewish Chronic Disease Hospital

prior to and on or about and after July 16, 1963."46

The two doctors were found "guilty of fraud or deceit and unprofessional conduct for injecting cancer cells into patients."47 The doctors informed the patients that they were going to do something to them of an experimental nature, but they "did not tell the patients that they

were receiving cancer cell injections, and

[the patients] were not

This episode focused attention upon the

45Interview with Edward J. Rourke.

46 Regents Committee on Discipline, University of the State of New York, Report on the Matter of Southam and Mandel, Nos. 158, 159 (undated).

15,

47"Two Physicians Put on Year's Probation," New York Times, December 1965, p. 58.

48Elinor Langer, "Human Experimentation: Cancer Studies at SloanKettering Stir Public Debate on Medical Ethics," Science, vol. 143, February 7, 1964, p. 552.

23

actual and potential risk that humans could carelessly be used to achieve the objectives of clinical investigators whose ultimate goals may have been very commendable, but who were exercising unacceptable judgment in achieving those goals. Since NIH officials had been concerned with such problems prior to this incident, its impact upon them is not surprising.

It made all of us aware of the inadequacy of our
guidelines and procedures and it clearly brought to
the fore the basic issue that in the setting in
which the patient is involved in an experimental
effort, the judgment of the investigator is not
sufficient as a basis for reaching a conclusion
concerning the ethical and moral set of questions
in that relationship.49

The case also brought into focus the legal issues in which the PHS could become involved and dramatized the PHS responsibilities as a public agency. One participant at the National Advisory Health Council (NAHC) meeting on September 28, 1965, clearly expressed this concern when he stated that "if the Southam-Mandel case were to come to court, I think we [the PHS] would look pretty bad by not having any system or any procedure whereby we could be even aware of whether there was a problem of this 150

kind being created by the use of our funds." A related case, Fink

v. Jewish Chronic Disease Hospital, did eventually reach a state court in New York. The defendant hospital demanded that the PHS, as one of the sponsors of the research, hold the hospital innocent and take over the defense of the action. The PHS rejected this demand and denied legal

49 Interview with Joseph S. Murtaugh.

50Stenographic Transcript, National Advisory Health Council meeting in Washington, D.C., September 28, 1965 (Hereinafter referred to as "Transcript, NAHC meeting").

24

responsibility. The case was settled out of court; the plaintiff reportedly received a large sum of money. While no precedent was established in the area of a grantor's legal responsibility, government official were clearly aware of the possible implications. One legal advisor, Edward J. Rourke, suggested at the time that "the greater need for the PHS is to define to what extent it has responsibility" 51 with respect to its status as a granting agency.

In his report, Livingston also directed his attention to the

problem of NIH control.

NIH is not in a position to shape the educational
foundations of medical ethics
More than that,
whatever the NIH might do by way of designing a code
or stipulating standards for acceptable clinical
research would be likely to inhibit, delay, or distort
the carrying out of clinical research . . .
.. it would
be advantageous to the national health research
program if any general guidelines or code of clinical
research behavior were developed by a nonfederal body
In our view, it would add to existing insecurities
if the NIH were to assume an exclusive or authoritarian
position concerning the definition of ethical boundaries
or conditions mandatory for clinical research.52

One of the participants in the Livingston group recalls the reluctance on the part of the group to suggest any action by the NIH. "It was

very difficult to get that small group that was convened to agree on the necessity for any action on the part of the NIH. There was strong resistance on attempting to set forth any guidelines or restraints or 153 policies in this area. It was this particular part of the report,

51 Edward J. Rourke, Memorandum to the Surgeon General, "Clinical Research," October 26, 1965, p. 3.

52Livingston Report, pp. 7-8.

53 Interview with Joseph S. Murtaugh.

25

regarding the responsibility of the NIH, that Shannon found "wholly unsatisfactory, because what it said basically was that what a

scientist does within his own institution is of no concern to the

PHS and therefore there is no reason for you as Director of the NIH 1154 to be concerned with what was going on. For Shannon this was an

unsatisfactory resolution of a significant problem; it was his

conviction that "we did have as an institutional responsibility the decision to assure that an institution had a mechanism that would have

to be used to review the experimental work for suitability."55

In July 1964, as part of the process of developing its

report, the Livingston group held an informal, ad hoc meeting with a small number of NIH advisors knowledgeable about problems relating to clinical research and experienced in a variety of research institutions and professional societies. This ad hoc committee made four recommendations; they were included in Livingston's report. These recommendations may be summarized as follows:

56

1. That an appropriate professional group be encouraged to formulate a statement of principles relating to the moral and ethical aspects of clinical investigation.

2. That there was a need for more factual information
regarding actual research practices.

3. That the NIH should consider providing advice, at
the request of grantees, concerning the ethical problems
and risk-reducing practices appropriate for the development
of clinical research.

54 Interview with James A. Shannon.

551dem.

56 Livingston Report, pp. 9-11.