Number range CHAPTER

Oral History of the

Belmont Report and the

National Commission for the Protection of Human Subjects

of Biomedical and Behavioral Research

Interview with

Robert J. Levine, M.D.

Professor of Medicine and

Co-chair, Yale Interdisciplinary Program in Bioethics

Yale University

New Haven, CT

May 14, 2004

Belmont Oral History Project

The Tower Building • 1101 Wootton Parkway • Suite 200 • Rockville,
Maryland 20852 • (301) 496-7005

**INTERVIEW**

*Interviewer: Dr. Bernard A. Schwetz, D.V.M., Ph.D., Director, Office
for Human Research Protections.*

DR. LEVINE: I\'m Robert Levine. I have an M.D. degree and an honorary
master\'s degree from Yale. And that\'s my degrees. I am now a professor
of medicine and lecturer in pharmacology at Yale University, and also
o-chair of the Yale University Interdisciplinary Program on Bioethics.
And that\'s about it.

*INTERVIEWER: Thank you very much. The focus of our discussion is going
to be primarily on the Belmont Report, and the things that surrounded
making the Belmont Report at that time; and kind of how it has survived
so well in these 25 years. So, to start out, maybe a question of what it
was about your background, at that time\--more than 25 years ago\--that
brought you into being part of writing the Belmont Report?*

DR. LEVINE: In 1974\--which is the year I was asked to join the staff of
the Commission\--I was chief of clinical pharmacology at Yale University
School of Medicine. I had begun to write about the regulations that the
federal government\--in those days, the Department of Health, Education
and Welfare\--were proposing as regulations for the protection of human
research subjects. I thought they were, in general, very bad proposals,
and started writing editorials, polemics, position papers, and so on.
And then when they finally decided to have a commission, I was asked to
join the staff, I refused, because in those days\--and perhaps to this
day\--if you agreed to accept your salary from the federal government
you could not criticize the government. And so they made an arrangement
with me through which they called me a \"special consultant,\" and gave
me 90\--I think, 90 or 95 percent of my salary, which meant that I was
still free to criticize things if I saw fit. Fortunately, I didn\'t have
to exercise that very much.

I had no education, or took no courses, in ethics except some related
courses as an undergraduate in college. But during my time with the
Commission I had a marvelous experience. It was kind of like being a
post-doctoral student in bioethics, with the best and the brightest of
the country serving as your dissertation committee, because all the
papers I wrote\--what the Commission called their \"background
theoretical essays\"\--were sent out to philosophers, lawyers, surgeons,
nurses\--people all over the country who then criticized my work. And
then I got to work again with it, and these all--most of the very large
appendix to the Belmont Report-- is the papers I wrote in those
circumstances.

*INTERVIEWER: The National Commission wrote many reports, but the one
that probably has more prominence today than some of the others is the
Belmont Report. Did you anticipate at that time that the Belmont Report,
decades later, people would be saying that this is probably one of the
best reports that\'s ever been written by a committee or a commission
for the government?*

DR. LEVINE: I did not anticipate that. The Belmont Report, after all, is
just a very slim volume. Thanks, in good part, to me, its appendices are
longer than those of any other report. \[Laughs.\] That\'s because I
tended to write very long papers in those days.

But all it does is simply name and flesh out a little bit the meaning of
the basic three ethical principles, and then provide some advice on
distinguishing research from practice.

*INTERVIEWER: Did you anticipate that the Belmont Report would, in
effect, become the basis for the regulations that we now have from the
FDA and HHS?*

DR. LEVINE: Well, yes and no. I mean, the Belmont Report consists of
formal principles. And as is typical of ethical principles\--and,
particularly, the way ethical principles were considered in the
mid-1970s\--they\'re written at a level of formality and abstraction so
that they don\'t direct any particular action. And then part of the
bioethics project of the \'70s was that you would write ethical norms or
rules\--what the Congress called \"recommend guidelines.\" And the
purpose of these guidelines was to show how these abstract principles
could be made applicable to the actual activity that they were being
interpreted for; in this case, research involving human subjects.

So the Belmont Report, as a report, does not\--none of it is in the
regulations. What\'s in the regulations is exactly what Congress
requested or required, and that is guidelines that the Commission
recommended, which were converted by the Secretary of HEW\--Health,
Education and Welfare\--into regulations.

In almost every case, the regulations came out almost exactly the same
as the Commission\'s recommendation, the exceptions being primarily in
the field of what the National Commission called \"those
institutionalized as mentally infirm,\" which, unfortunately, ended up
with no regulations, I think because the Commission disbanded before the
time came to promulgate those final regulations.

The Department Health, Education and Welfare also tried to introduce
drastic changes into the children\'s special regulations for research
involving children, but the Commission was still in office then, and
they said, \"No, that\'s not what we recommended,\" and they
straightened them out and then did go ahead and promulgate regulations
that were based on the Commission\'s recommendations.

If I may say so, I think the full expression of the Commission\'s
contribution to the field of research ethics is best realized in that
report \"Research Involving Children,\" because there they had fully
come to terms with the meaning of their new definitions of research and
practice; where, in the Report on Research Involving the Fetus, they
still were using that grotesque dichotomy between therapeutic and
non-therapeutic research. I say \"grotesque\" because it inevitably
generates regulations that make no sense.

*INTERVIEWER: But there are people who feel that some parts of the
regulation need to be rewritten today; the one in particular about
prisoners. How would you think it would be best if someone chose to
rewrite a subpart of the Common Rule? How would we involve the people
who had the background in ethics and philosophy as we tried to rewrite
regulations today?*

DR. LEVINE: I think a model for this was set when the regulations\--the
so-called Subpart D regulations for the fetus, the *in vitro*
fertilization, pregnant women\--they were rewritten, and they needed
rewriting because, as I said just a few minutes ago, the Commission\'s
recommendations were based upon the old dichotomy between therapeutic
and non-therapeutic research. Everybody knew the regulations made no
sense. But it took years for them to get around to rewriting them.

The people who rewrote the Subpart D were based primarily in what was
then called the Office for Protection from Research Risks, with
consultations with various offices in Health and Human Services. And
they\--as I understand it, they were not permitted to formally engage
outside consultants in this rewrite process. But I can tell you that
they informally engaged them, and some of the outside consultants that
they informally engaged were very much involved in the development of
the Commission\'s recommendations on children, and the revision of the
definitions of research and practice. I can tell you that because I was
one such informal consultant. And it came out quite satisfactorily.

I think that the federal government has got to find a way to include
outside experts in these rewrite processes. Whatever the rules might be
for\--I mean, they can have some sort of role in this, whatever role
would be permitted by the way the regulations are now written. I
honestly don\'t know what the regulations are for where you can get
consultants to do what sort of thing.

But I think if they go through a process that was more open, and
therefore less tediously cumbersome than going through this end-run of
informal consultations that they should be able to come up with a good
job.

Now, the prisoner recommendations are--I think they\--I said a little
while ago that the fetus\--I mean the children\'s regulations, or the
children\'s report was the Commission\'s finest hour. The prisoner
report was perhaps its worst hour. And that\'s because\--and I did use a
bit of my 5 percent free time to criticize things at the time.

The big mistake the National Commission made is that it confused the
agendas of prison reform and protection of human subjects. Their report
was contrary to the evidence it received by having hearings at places
like Jackson State Prison, and site visits to Vacaville and Walla Walla,
Washington. And what they did is they set a bunch of criteria up for
justification of doing certain types of research in prison, and they
thought that the drug companies\--the pharmaceutical firms\--had such a
powerful vested interest in keeping their prisoner research going that
they would accomplish the agenda of prison reform in order to do so.

We had expert consultants who were themselves sociologists who had been
prisoners, who said, \"No. The only thing you will accomplish by this is
to get the only people out of the\--the only people who ever showed any
concern for the well-being of the prisoner are the drug company
researchers. You\'re going to force them out.\" And it came to pass.

In fact, when the FDA was on the eve of finalizing, or promulgating its
final regulations, the prisoners at the Jackson State Prison filed a
class action suit saying that the proposed FDA regulations were an
unconstitutional deprivation of their liberty to serve as research
subjects. And it was on the eve of putting out those regulations in
final form that FDA backed off and withdrew the proposal.

But that expressed exactly the sentiments of the prisoners as we heard
them during our visits to the prisons. I will never forget, when we met
in Jackson State Prison, with the group called the trustees, and the
chair of the trustees committee\--these were all mandatory lifers. He
welcomed us with these words: \"Ladies and gentlemen, you are in a place
where death at random is a way of life. We have noticed that the only
place around here that people don\'t die is in the research unit. Now,
just what is it you\'re here to protect us from?\"

Wow, what an opener! That\'s the lead-in of the prisoner chapter in my
book on ethics and regulation of clinical research. That\'s why I
remember it so well. I wrote it down at the time. \[Laughs.\] It\'s very
interesting.

*INTERVIEWER: In general, how was the Belmont Report received at that
time?*

DR. LEVINE: In 1978? I think it was widely heralded\--widely celebrated.
It didn\'t say anything that anybody could experience as a threat. It
said, \"Respect persons.\" It said \"Do good, don\'t do harm.\" It said,
\"Be fair.\" That\'s wonderful.

You don\'t begin to see where your problems might be\--or what some
people might call the \"obstacles,\" until you begin to see the
regulations that interpret what does it mean\"to respect persons?\" What
does it mean, \"to be fair?\" Then, after they see that, they say,
\"Uh-oh, that\'s a little different than we would have hoped for.\"

*INTERVIEWER: How much of the thinking of the team of you who wrote the
Belmont Report was dominated, or impacted at least, by the Tuskegee
experiments?*

DR. LEVINE: I would say, in those days\--well, first: there can be no
doubt that in the past decade\--give or take five years\--that the
Tuskegee experience has become the number one metaphor for evil in the
name of research. When somebody wants to point at a project and say,
\"That is the worst thing I can imagine,\" they say, \"That reminds me
of Tuskegee.\"

That position was held in the 1970s by the Nazi experiments. And so
almost everything else paled in comparison with the Nazi experience. I
mean, all you have to do is spend a half-hour at the Holocaust Museum in
Washington\--I mean, it\'s one thing to deprive people of treatment, to
tell them lies instead of informed consent, and to do that sort of
thing. It\'s quite another thing to cut them up into four quarters and
drop them in vats of the sort that\'s on display on the top floor\--you
know, to throw people in freezing water. So, the freshness of the Nazi
experience meant that it was going to dominate any thoughts of what\'s
evil in research.

I think now it has yielded to Tuskegee, because, one, Tuskegee is a very
American experience. I mean, it happened right here. And, two, I think
the people who lived with and through the time of the Nazi experiments
are moving on; they\'re retired, they\'ve passed away. But there can be
no doubt that Tuskegee now holds the place that the Nazis once did.

*INTERVIEWER: Do you think we could see another Tuskegee type of
situation emerge today?*

DR. LEVINE: Ahh\--there are respectable authors who claim that they have
seen it. Isn\'t that what Marcia Angell said when she reviewed the
research, trying to validate the use of the short-duration AZT to
prevent perinatal transmission of AIDS?

I disagree with her\--but, yes, there are going to be people\--that was,
what, 1997 or 1998 when she wrote that?\--it\'s going to happen again.
Next year somebody will see something that looks as bad as Tuskegee. I
think the odds that they actually will see such a thing are small.

Today we\'re not talking about no informed consent. We\'re not talking
about endangering people on a grand scale. We\'re talking about\--let\'s
say\--an individual like Jesse Gelsinger, a tragic situation, but
mismanagement of a single case, rather than recruitment of 600
illiterate men in conditions of extreme prejudice. I mean, the Black man
in Alabama in 1932 didn\'t have much by way of rights or concern for his
welfare.

*INTERVIEWER: Are there issues of human subject protection today that
you wish the Commission had been able to anticipate?*

DR. LEVINE: I wish they had anticipated all of the concern there is
today about just what is the distinction between research and practice.

What the Commission was asked to do by the Congress was to consider the
boundaries between research\--biomedical and behavioral research\--on
the one hand, and on the other hand, the routine and accepted practice
of medicine or behavioral therapy. I think the Commission responded to
that charge very well. It said, \"There is no boundary.\" You know?
It\'s like being asked to consider the boundary between North Dakota and
Nebraska\--you see.

The boundary is that when you do research on practices, you start
confusing what is the overall goal of this project? And their definition
said, \"Now you\'ve got research here, you\'ve got practices here. And
with some new practices, which we\'re going to call \'non-validated
practices,\' or \'innovative practices,\' you\'ve got research on the
practices.\" That\'s where the confusion is. But it gave us a way to
sort it out.

By doing this, it sort of passively defined research as it applied to
social and behavioral science as it was understood in the mid-1970s. But
now the question is being asked, \"What about in the field of public
health? Outbreak investigations? Surveillance? These use the same
methodologies as research, and yet they\'re are routine and accepted
practices for a place like CDC. Should they be submitting to IRB
review?\"

And so\--you\'ve got in the field of quality improvement\--you see? We
are manipulating everything every day, hoping that each day we\'re going
to do a little better. And we want to throw in some evaluation so that
we can make a statement about whether we\'re doing better or worse. Can
we even\--if you review that, can we even put together a protocol that
tells you what we\'re doing, because we\'re responsive, day by day, to
what did we see yesterday. It tells us what we\'re going to do tomorrow.
It\'s almost like anthropology on a grand scale, which is another place
we have a problem. Anthropologists are saying they\'re not being
evaluated properly because, you know, very often they walk into a
situation\--they have no hypothesis. They evaluate a good project as one
that generates a good hypothesis.

Now, what I have seen\--and let me issue a little disclaimer here\--it
was my job to write the definitions of research and practice. So when I
say I think we did a good job in \'78, that can be construed as
self-congratulation\--a little. But I had the help\--a lot of what I
wrote was formed in debate with the members of the Commission, so I
can\'t claim that I did it all alone. In fact, if Joe Brady hadn\'t been
on the Commission it would have based the whole definition on intent.
But radical behaviorists don\'t concede that there is such a thing as
intent. So there we were. I said, \"It depends upon what you\'re
intending to do.\"

Now, I think what we have to do is to concede that the distinction
between research and practice\--and therefore the definition of
research\--was not intended to cover some of the activities we\'re
discussing today. And so what I\'ve been advising people who are
relentlessly trying to redefine \"research,\" so that what will be
reviewed is only what they want to have reviewed\--I\'ve been telling
them, one, you\'re not the only people who want to redefine
\"research.\" All the other people want to redefine it in a different
way that would be bad for your cause. So you\'re all fighting with each
other, even though you don\'t even\--you\'re not even aware of each
others\' existence.

My recommendation is to go the exemption route; the same way we have for
all six of the exemptions, but particularly the public benefits
exemption, to say that there\'s something so important about what we
want to do that we should not have to go through the full panoply of
regulation by the Common Rule and all of its implications. And I think
that would be a much better approach to doing things. Of course, that
will depend upon Health and Human Services and, to no small extent, your
own office in agreeing that that\'s a good way to go with this problem.

But that may not be the best way to go with the problem. But the way the
process of redefining research will certainly cause more confusion than
anything else.

That\'s why we continue to have so many discussions about reaching
conclusions of what to do with it.

*INTERVIEWER: During the discussions that brought about the principles,
how much of that was based on social and behavioral research, as opposed
to biomedical?*

DR. LEVINE: All of my writings, right from day one, included social and
behavioral. But the mainstream of the Commission\'s deliberations were
biomedical. The main stories that created the need for the Commission
were biomedical stories. They were impressed with the ethical problems
of the randomized clinical trial. They were impressed with Phase I drug
studies. They did not spend a lot of time looking at the problems
peculiar to social and behavioral science.

There\'s one piece in the regulations that\'s directly responsive to
concerns raised by social scientists. And when I present it that way to
many people\--even experienced people\--they can\'t guess what it is.
But it\'s the one that restricts the IRB\'s deliberations so that they
are not to take into account the long-range implications of doing this
research. That was particularly in response to social scientists saying,
\"That can be a very political problem. IRB members can say, \'We don\'t
like the long-range policy implications of this research, and therefore,
cut it out.\'\" But, as a matter of fact, almost everything that the IRB
does in reviewing, let\'s say, research in the field of therapeutic
development, has definitely in mind the long-range implications, and no
one is troubled by that\--I mean, the long-range implication is that
it\'s going to make it easier to treat-- tuberculosis or something.

*INTERVIEWER: One of the issues that we\'re focusing on a lot these days
is at least financial conflict of interest, if not institutional and
professional conflicts of interest.* *To what extent was that discussed
in the deliberations\--because the Belmont Report is relatively silent
in mentioning them by name.*

DR. LEVINE: I think it\'s absolutely silent. It\'s generous of you to
try to say we thought of it.

Conflict of interest was something we were all aware of, and yet we
considered that outside of our scope. That was\--not that we ever stood
up one day and said, \"Should we include conflict of interest?\" \"No,
we consider that outside our scope.\" We passively left it out. And yet
everyone was aware of conflict of interest and in the hearings that led
to the writing and passage of the Harris-Kefauver amendments to the
Food, Drug and Cosmetic Act\--the hearings that were held in the
aftermath of thalidomide\--conflict of interest was a big story, even
Kefauver himself, after he died, they showed the conflicts he had with
owing stock in several corporations who were being subjected to the
hearings, and that was\--oh, people wrung their hands, \"Isn\'t that
terrible!\" But they said, \"That\'s another thing. That\'s not the
same. We\'re concerned with protecting human subjects at the point of
what might you do to an individual to injure that individual\'s welfare
or to disregard his or her rights.\"

And we also left out plagiarism. We left out everything that\'s in the
Office of Research Integrity.

But, you know, the year I went to NIH as a clinical associate, I got a
big lesson about how do we deal with data figures. I went to hear a
paper that was to be presented by a young man from Yale. And he didn\'t
show up, his professor showed up and said, \"We found that he faked his
data.\" And we never heard that name again. Gone.

That\'s what the scene looked like in those days; grievance committees.

*INTERVIEWER: Research involving humans today is much more international
than it was in the \'70s--*

DR. LEVINE: Yes and no. We\'re getting more and more aware of it,
primarily through HIV-AIDS. But, you know, 1975 is when a group called
the CIOMS\--the Council for International Organizations of Medical
Sciences\--first convened its task force to develop guidelines for
international research. And it was primarily, in those days\--it started
as a project in the field of what they called \"biologicals,\" which in
Geneva meant vaccines. And they actually put out their first batch of
guidelines in 1982. So, there was an awareness that there were special
problems crossing national boundaries.

The National Commission did not pay attention to that aspect of its
work. I don\'t think the National Commission at any part of any report
makes reference to what are the special problems when an American goes
to Malawi or Cote d\'Ivoire or somewhere. So that\'s definitely one
thing it left out.

Much is made of the fact that the international documents have all
copied the Belmont principles, and many people have said, \"You see,
that shows how universal they are.\"

That\'s wrong. I can tell you how the Belmont principles first got into
international documents. It was in 1986 or '87, I was invited to be part
of a group for world health, for U.N. AIDS and world health, to develop
criteria for guidelines for HIV prevention vaccine research. And I was
put in charge of the legal and ethical writing group. And at the end of
the first day, the proposal was made that I should include the Belmont
proposals in the report of the legal and ethical group. And I said, no,
these are really American principles.

And so that night the leader of our group\--the leader of the overall
project\--wrote the Belmont principles and presented them to us as a
draft. And I said, \"They really shouldn\'t be there.\" And the group
said, \"Oh, yes, we want them there.\" I said, \"Well, in that case, if
you want them there, let\'s get them right. Because what you\'ve written
is not what they are.\" So I corrected them, and ever since that time
I\'ve been given the credit\--or the blame\--whatever you will\--for
introducing the Belmont principles into the international documents.

One think you notice, though, as you look at all these documents\--U.N.
AIDS, WHO, CIOMS\--they all mention respect for persons, beneficence and
justice in the preamble, and they\'re never heard from again in the
entire rest of the document. There\'s no explicit appeal to any of
these.

Why do I say these are peculiarly American? I\'m not going to bore you
with the whole\--I can give an hour lecture on that. But respect for
persons, let\'s say\--as the principle was articulated by Emanuel
Kant--could be considered universal, particularly at that level of
formality and abstraction. But once you begin to say that the primary
attribute of the principle of respect for persons is autonomy, then
you\'ve become American. Autonomy is very much less a dominant value
even in the rest of Western civilization. And in much of the rest of the
world, communitarian concerns will compete on an even keel with
individual self determination.

So this is why I say there is not the universality that there appears to
be there. Our very, very different way of seeing self-determination
from, let\'s say, a citizen of\--well, most citizens in Asia\--accounts
for why we have such profound misunderstandings over whether or not
we\'re going to get informed consent, and what form informed consent
should take when we\'re trying to do research, let\'s say, in China or
in Malawi, or somewhere.

*INTERVIEWER: This is even more important today than it has been in the
past, at a time when some 30 percent of data to support new drugs\--for
the FDA\--are from studies done outside the U.S.A.* *Coming back to the
three principles, there\'s been a lot of discussion about whether or not
they are independent, as opposed to sequential, and the question of
whether or not respect for persons trumps the other two.* *How much
agreement was there within the Commissioners\--between the
Commissioners\--about whether or not they should be independent?*

DR. LEVINE: Well, first, the issue was never joined during a meeting of
the Commission. I have done my best to put together everything I can
find, and everything I can recall about the Commission\'s deliberations,
and I come out with the conclusion\--which I published in my [Ethics and
Regulation of Clinical Research]{.underline} book\--that the Commission
intended that, at least in the abstract, each of these principles had
equal moral force; no thought of \"trumping.\" I don\'t even know if the
Commission had any bridge-players. But I think \"trumping\" was
introduced by my friend Robert Veatch, who did not meet with the
Commission, and who introduced the notion of trumping only after 1978.
So it was not contemporaneous.

So, it\'s important to recognize this, because the requirements that
derive from the three principles are often inconsistent with each other.
Almost invariably there is going to be tension between respect for
persons and distributive justice. And the way I like to put it in my
teaching is that this virtually guarantees that we will have productive
discussions for as long as anyone remembers the Belmont Report.

It\'s not as if you can say, \"Well, first let\'s take care of autonomy,
and then we\'ll worry about \'doing good.\'\" I don\'t think that\'s
right.

Now, I don\'t know if you\'re interviewing Al Johnson\--you\'re
interviewing Steve Toulmin, I see. Johnson and Toulmin, I think, well,
we wrote principles, but we\'re not guided by that at all. It was all an
exercise in casuistry. I think casuistry\--I mean, it\'s natural for
human beings to do a little bit of amateurish casuistry\--\"Well, how
did we handle this one last time out\"\--you know? But I don\'t think we
ever appealed to casuistic principles\--you know, identify paradigm
cases and so on and so forth.

I think you can look through the\--you don\'t have to look at the
appendices, you look at the parts of each report called \"Deliberations
and Conclusions,\" and you\'ll see statements that make it very clear
that this is principle-based. One of the statements on justice has to do
with equitable distribution of burdens, however minor those burdens
might be. And I think that\'s verbatim. That\'s a very principled stand.
That has nothing to whatever to do with any other theoretical model of
ethics.

*INTERVIEWER: Do you think there\'s need to rewrite the Belmont Report,
in view of the situation today?*

DR. LEVINE: I think there\'s always the need to update our
understandings of ethics from time to time. I would not say it\'s time
to rewrite the Belmont Report. But I think it\'s time to write things
that are fresh and responsive to the needs of the year 2004, and perhaps
for the next five or 10 years.

And we always have a need to do that. And this comes out in many, many
forms. For example, the American Society for Bone and Mineral Research
recently put out its document on placebo-controlled trials in evaluation
of new drugs for the treatment of osteoporosis. Without
reinterpreting\--without redoing\--the Belmont Report, they give us a
fresh vision that responds to how do things look today?

Now, you\'ve got a lot of very thoughtful, respectable, ethics people in
on the writing. You know, they weren\'t all a bunch of osteoporosis
doctors.

*INTERVIEWER: There\'s been a shift away from protecting human subjects
from risk, toward permitting access to potentially useful, helpful
innovations, whether they\'re drugs or devices or whatever else. Is that
shift something that is consistent with the principles?*

DR. LEVINE: Sure. I mean, what you\'re really talking about is
interpretations of the principle of justice\--what the Commission called
\"justice\"\--which most philosophers would call \"distributive
justice.\" It\'s all about distributing the burdens and benefits of an
enterprise fairly or equitably. And you use the same principle to
distribute burdens as you do to distribute benefits.

In 1970, as the Commission was writing, the prevailing view was that
participation in research was a great burden. The prevailing view was
that research participation was always potentially harmful, always
potentially exploitative. One of the major papers\--consult
papers\--that the Commission had written was by the Boston
philosopher-ethicist Mark Swartofsky. His paper was on \"doing it for
money.\" This is not a paper you write about a field where you\'re
focused on distribution of the benefits. This is not the title you would
choose for such a paper.

I think even in the \'70s there were a small number a people who called
attention to the benefits of participation. A paper I co-authored with
the Commissioner Karen Lebacqz, referred to the benefits. We were
examining the oft-repeated accusation of the Veterans Administration,
that they were exploiting VA patients as research subjects. And our
paper said, well, you know, for all we know these veterans might think
it\'s a benefit to get all this attention, and new anti-hypertensive
therapies. Why don\'t you get them together and ask them? That was \'77,
\'78.

I don\'t think, though, we really turned it around. We didn\'t really
take seriously the fact that there was a responsible voice calling
attention to the benefits of research participation until \'86. And
that\'s when we first heard from a group that came to be known as the
AIDS activists. And they said, \"We keep reading in the paper that
participation in this clinical trial\--this placebo-controlled trial of
AZT versus placebo for the treatment of AIDS\--is a burden. Well, from
our perspective, it\'s a benefit. It\'s the only way these people can
get even a 50 percent change of getting the only drug that anyone things
is addressed to the cause of this disease. Moreover,\" they said,
\"Participation in any randomized clinical trial is the only way many of
these people can even get a decent physical examination.\" You may
recall, in the mid-\'80s health insurance companies were desperately
trying to find ways to exclude people in the at-risk groups for AIDS.
They couldn\'t even get to see a doctor.

That\'s when it began to turn around. After that, then we said, \"Well,
now, last year we told you you had to keep women who could get pregnant
out. Now, if you don\'t recruit them, we\'re going to penalize you in
your scientific priority score at NIH, and we might reject your new drug
application.\" Very different way of looking.

*INTERVIEWER: There is that\--the prevailing thought at that time was to
protect the vulnerable groups.* *As you say, now there are more women in
trials than there are men. We have pushed for research in children, and
there\'s a fair amount of research going on--primarily of the social and
behavior nature--on prisoners. Does that make you nervous?*

DR. LEVINE: Nope. If you believe Kurt Minert\'s studies, there were more
women being studied than men even before the new policies were
promulgated. Kurt was part of the Institute of Medicine group.

And he came out with that astonishing conclusion, which I had written
years earlier based on no data whatever, but I said you look around my
metabolic research unit, and mostly what you see are middle-aged women,
because\--and it\'s got nothing to do with ethics, it\'s because\--I
might get struck down for saying this, years later, but men had to go to
work. That\'s before women had to go to work. Times do change.

*INTERVIEWER: Yes.*

DR. LEVINE: If you edit that piece, do it very carefully.

--END OF INTERVIEW--