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DR. HAUSER: Thank you, Jim. Delighted to.
Fellow Commission Members and audience, my name is
Stephen Hauser from the University of California, San
I would like to just briefly describe the
details of the experiments that were carried out in
Guatemala during this two-year period between 1946 and
1948 and maybe as a prelude just very briefly discuss
the scientific environment and milieu at this time. I
think without that, it's harder to understand the
rationale for what happened in Guatemala.
As we all know, sexually-transmitted diseases
throughout the 20th Century have been a giant problem,
both in the military and civilian populations. In the
military, it was estimated that hundreds of thousands
of individuals would become infected if we could not
develop effective prophylactic therapy post-exposure.
In the civilian populations, these illnesses,
particularly syphilis and gonorrhea, were also very
Just as one example, it's been estimated that
at least 20 percent of people living in psychiatric
institutions at the time were there because of
neuro-syphilis. So these were enormous problems.
How was disease prevented in the mid 20th
Century? Well, the primary method was chemical
prophylaxis. I will say a few things here that are
graphic but I will keep these to a minimum, but I think
that without understanding a bit of the graphic detail,
it's very difficult to understand what was done.
Soldiers were advised after exposure to
urinate, to wash themselves with soap and water, and
then for gonorrhea to inject a silver solution directly
into their urethras in the penis, and for syphilis to
rub a calomel ointment on their genitals and pubic
region. I would say that the evidence that these
chemical measures were useful was very limited at the
There was a new very exciting advance for
treatment of established infection, of course, with the
development of antibiotics. Sulfanilamide first, a sulfa
drug for gonorrhea, in 1938, and for syphilis,
penicillin, which was extremely effective for
established infections, first reported in 1943,
replaced arsenic-based therapies and earlier very toxic
So there was an earlier attempt to study the
effectiveness of some of these prophylactic measures in
the Terre Haute Prison earlier in 1943 to 1944 that was
unsuccessful and these experiments included inoculation
of some prisoners with gonorrhea.
So it was with that as a background, as Dr.
Wagner said, the first question that I will summarize
is the following: what scientific questions were the
researchers trying to answer? Some of what we've
learned is retrospective, some of it is work based upon
the reports as long as a decade later of the principals
involved in the studies. So there is very little
information or proof in certain aspects of our
understanding of this question.
However, as stated later, in 1955, the overall
goal was to develop an effective prevention called
prophylaxis after exposure to syphilis as well as
gonorrhea and then, as a second goal, prolonged
observation of individuals exposed to early syphilis
and treated with penicillin.
According to Dr. Cutler, the original primary
aim was to test this local wash named orvus mapharsen
against syphilis in prisoners who had recently had
sexual activity with an infected commercial sex worker.
This primary goal never happened.
The experimental transmission of syphilis to
human volunteers aligned with the desire to find
improved methods of prophylaxis was another aim. The
primary purpose of the gonorrhea experiments was to
test the effectiveness of a variety of prophylactic
measures, including a number of chemical lotions as
well as oral penicillin.
In his later writings, Cutler wrote that other
aims included trying to understand the changes in the
blood and in the body that occurred following injection
of syphilis organisms and whether these changes were
different when the syphilis was taken from rabbits who
had been passaging the syphilis or from humans who were
infected with syphilis. So were the organisms
different when they were coming from the experimental
laboratory animal or directly from humans? Was
virulence lost when it was passaged in animals?
What was the effectiveness of a broader
penicillin therapy and intramuscular penicillin
prophylaxis, and could treated subjects with early or
late latent syphilis become re-infected?
So the second question involves what methods
were used to carry out these studies and they were
basically of two main types, serologic studies, looking
at blood and other fluids, and intentional exposure and
The serologic studies included blood draws,
preparation of smears, taking tissue from the local
areas and culturing these materials. They also
involved lumbar punctures or spinal taps to sample
fluid bathing the surface of the brain and spinal cord
and cisternal punctures which are punctures in the neck
rather than in the lower back as is the case for lumbar
puncture. So those were the serologic studies done.
The intentional exposure experiments that
consisted in total of about 50 different experiments
involved, first for gonorrhea, what was called normal
exposure which is exposure through sexual contact with
an infected carrier, a commercial sex worker.
Artificial direct inoculation, for sex workers
inoculation by swabbing the cervix, for males
inoculation inside the penis, sometimes following
sexual exposure, and also inoculation in other body
parts, including the rectum and the eyes.
For syphilis experiments, there were
experiments performed in which there was sexual contact
with known infected commercial sex workers, direct
injections into the cervix. There were also
experiments, called scarification and abrasion, where
the penis would be scarred or abraded to make the
epidermis possibly more accepting of the subsequently
For chancroid, another sexually-transmitted
disease, there was a single experiment involving
abrasion of the penis, the arms, and the back.
So let's speak about who was involved, what
populations of individuals were involved in this series
of experiments. Commercial sex workers, prisoners,
soldiers from the military Honor Guard which provided
personal protection to the president of Guatemala, and
psychiatric patients in a state-run mental institution,
so those were the exposure populations.
For the diagnostic testing, the serology,
lumbar punctures, cisternal puncture population, most
of the subjects consisted of children from an orphanage
or school, leprosarium patients, U.S. Air Force
personnel, and all of the other populations discussed
previously in the inoculation studies, and again the
serology experiments did not involve intentional
We believe that more than 5,000 individuals
were involved in diagnostic testing, serology or lumbar
or cisternal taps, and somewhat more than 1,300
individuals were exposed by contact or inoculation to
one of those sexually-transmitted diseases.
Of the 1,300, under 700 received some form of
treatment as best as could be documented. So this
involved in total approximately 5,500 individuals in
both groups which overlap.
Of these groups, we believe that there were 83
deaths. We do not know to what degree the deaths were
directly or indirectly related to these experiments but
there are a number of ways to try to get at this that
staff and the Commission are exploring.
We do know that with some of the cisternal
punctures, there was inoculation of infectious material
and that several patients developed symptoms suggestive
of bacterial meningitis and one person became paralyzed
for a two-month period, almost certainly related to
damage to the spinal cord from the needle insertion in
So one last question. Was the methodology
sound for the standards of the day? The Commission
identified numerous problems with both methodology and
recordkeeping. Multiple experiments were conducted that
were excluded from Cutler's summary reports. The
note-taking was, at best, haphazard. The experiments
at times lacked a logical progression. Baseline
experiments for background infection rates, for
example, were conducted after treatment prophylaxis
experiments began. So the timing of the experiments
More experiments were started before the
results of the previous experiment was known. There
was a clear deliberate effort to deceive experimental
subjects and also the wider community, both the
scientific and lay community, that might have objected
to the work.
I would say, in conclusion, that there were
also differences in the Guatemala experiments from the
Tuskegee experiments. The events occurred over a
shorter period of time, ended at an earlier date,
subjects in Guatemala but not Tuskegee were subjected
to deliberate inoculation, and also in Guatemala,
subjects were citizens of a foreign country.
DR. WAGNER: Thanks, Steve. Thank you, Steve.
Appreciate that review.
One of the conversations I know that
we've -- a couple of us had offline and, Nelson, I
might go to you on this, aside from the ethics
questions that just scream from the raw facts, talk to
us a little bit about experimental design. Was this
even good science beyond that?
DR. MICHAEL: Thanks, Jim. Thanks, Stephen.
That was a great summary of the dark period.
So I'm an experimental researcher myself. I
direct the U.S. Military HIV Research Program at the
Walter Reed Army Institute of Research. I've been
doing science almost my entire professional life and
when you look into what happened here, again taking off
the ethical imprimatur which is difficult to do, when one
does that and looks at in a cold objective way, it's actually
difficult to perceive why these kinds of experiments
would even pass preliminary muster for asking basic
scientific questions in a clinical environment and
deriving meaningful information from those kinds of
experiments, as heinous as one would view them and one
should view them.
If we look at them from an objective
standpoint, it is difficult to understand the specific
aims. Looking at the methodology, the absence of
alternative strategies, the haphazard note-taking, as
Stephen mentioned, if you look at that body of work in
its entirety, my conclusion, and I think I said this
pretty clearly in London, it just was bad science. It
was bad science.
So regardless of what you think about the
ethical issues and I think that it's difficult to find
any sanction or any succor in the ethical issues which
we'll describe and we'll talk about later, from a
purely scientific standpoint, I found this body of work
really bereft of merit.
DR. WAGNER: Barbara, yes.
DR. ATKINSON: I'd just like to comment the
same way. I absolutely agree that one of the main
things that struck me was the work was never published
in scientific journals by the people that did the work.
They did -- Dr. Cutler did submit a report in 1952 for
some of the studies and even later, I believe, for some
of the other ones, the syphilis one wasn't reported
till 1955, and you can wonder why it never was
submitted or they were submitted as secret reports to
the people that had funded it but not to scientific
And in my mind, it was either because the
scientific conclusions didn't match or couldn't really
be concluded from the way the studies were done. The
records were so poor and the way the studies were set
up was so poor that you couldn't really believe the
scientific outcome but also I think there was -- again,
you can't separate the ethics.
I think there was a recognition that these
were -- had real ethical issues that would have
horrified the public if they'd actually seen them in
scientific journals. So I think there were both
aspects to the fact that this was never published.
DR. WAGNER: Amy, sure.
DR. GUTMANN: I think we are beginning with
the science, first of all, because you can't even
understand why these experiments were done if you don't
know what the people who were doing them thought they
were doing and they thought they were doing science and
presumably they thought they were doing good science,
but I think it's important that the Commission states
clearly, and we will do this in our report, that there
is no dichotomy between good science and ethics, that
you cannot have an ethical experiment on human subjects
that exposes human subjects to any risk, no matter how
small, if you don't have good science.
So good science is the precondition, it is the
groundwork upon which any experiment with human
subjects that's ethical can be done, and so it's very
important if you think, well, why even ask about the
science because there's some obvious ethical problems
with these experiments. The most obvious first ethical
problem with these experiments were that they were not,
even by the standards of the time, good science.
DR. WAGNER: May I ask a little conversation
here then? What corrupts then, Amy? I think everybody
agrees that there is -- you really can't divorce the
two. It can't be good science if it has this sort of
violations of safety for human subjects. But maybe we
should have a little conversation on what were the pressures
corrupting this. I think one could imagine anything
from mad science, which I don't think is entirely the
case with Dr. Cutler, but we've spoken only about him,
but also some of the national pressures, pressures in
the national interests being brought to bear at that
DR. MICHAEL: I'll be brief. I am a military
officer and a scientist, as well as a soldier and a
physician So I can tell you that at the time, World War
II was just winding down. The United States was a much
smaller population, had almost 11 million people in
uniform, had just fought a war that raged across the
entire world, and there was significant issues in terms
of military readiness to find ways to keep troops
healthy and doing their job and not sick and in
hospitals. That includes the entirety of medical
practice, includes sexually-transmitted infections.
So, clearly, there was that kind of pressure
that would have provided at least some rationale for
asking those kinds of questions, if they were asked in
a meaningful and scientifically-rigorous way, and done
in an ethical fashion, they would have had value.
So I think that I've tried to ask myself
whether or not that was really the driver for why the
science was just so atrocious because there was just
pressure to do that kind of work, but I must say that I
can't find that evidence for that being a major driver.
What I do find is a relatively junior scientist who was
existing far away from the home laboratories that he
reported to without much local mentorship in terms of a
scientific mentorship and lack of periodic review.
I think those are -- you know, I'm dealing
with hypotheticals, but I tried to put myself in that
individual's shoes back in 1946 and he was pretty far
away from effective mentorship and I think his work was
desultory and described a meandering pathway.
I'm not sure he really knew what he was doing
scientifically from a standpoint of rigor, but I would
say that I think the pressures of the time of the
military issues that were at that time had -- frankly,
the United States was demobilizing. We
demobilized very, very quickly at that time. So I don't
think that can be a reasonable justification.
DR. WAGNER: Christine and then John, Nita.
DR. GUTMANN: Introduce yourselves, actually.
DR. GRADY: I'm Christine Grady. I work
currently at the National Institutes of Health,
Clinical Center, Department of Bioethics.
What struck me about this question of what
happened, the scientific questions that Steve read that
were articulated after the fact in the reports were not
unreasonable questions. They were actually good
questions. What can prevent syphilis? You know, does
penicillin prevent it if it's given post-exposure?
Those are reasonable scientific questions.
The problem is it wasn't clear from the
history whether or not those questions preexisted the
studies or came up later, Number 1, and, Number 2, even
if they did preexist what the conduct of the studies,
it doesn't justify how they tried to answer them.
So it's a really complicated issue in terms of
what made them do it. I don't know that we'll ever
really know the answer to that question, but it is
absolutely true, also, that at that period of time,
Nelson spoke about military readiness, but a major
focus of research was STDs. I mean that was one of the
major problems in the United States for sure, maybe
around the world, and so a lot of research was focused
on trying to find ways to treat and prevent STDs.
DR. WAGNER: John.
DR. ARRAS: Yeah. Thanks for that historical
background. It was very well done, really appreciate
DR. GUTMANN: Introduce yourself.
DR. ARRAS: Oh, I'm sorry. John Arras. I
teach Philosophy at the University of Virginia.
When we think about the moral dimensions of
this study, we make a distinction in our report between
contemporary standards, what we think today about the
principles and practices in research and what people
thought at that time, and I want to raise a similar
question here with regard to scientific methodology,
right, because, I mean, if you read any study published
in a medical journal, there are always going to be
people who are going to quibble with the methodology.
There are always going to be people who say, well, the
methodology isn't quite right. It subtracts from the
scientific value of the study.
I'd like to get your opinions on, you know,
the extent to which you think this set of studies
really deviated from a contemporaneous conception of
good enough science at the time and what was it
precisely about the defects in their methodology that
undercut the research.
In other words, were the defects things that
cast some measure of suspicion on the results or was it
more serious than that? Did they just completely
subvert any kind of scientific validity that we could
DR. WAGNER: Is that to us generally or are
you asking Steve in particular because I have my own
view on that.
DR. ARRAS: Well, you know, I don't even
pretend to be a doctor on TV, you know. So I'm
primarily interested in the opinions of people with
scientific background but, you know, whoever wants to
take a shot at it, sure.
DR. WAGNER: Well, it's not unusual even in
modern science to pose a hypothesis that assumes that
one can build an experiment around that hypothesis.
In this case, if part of the hypothesis was what
might be an appropriate prophylaxis for these sorts of
diseases and the experimental design requires a pool of
people infected and it turns out that that's the bad
assumption, that it turns out that I can't actually
build that experiment, and then to get stuck in that
and run out of control because you have deviated from
good scientific practice happens sadly all the time, I
hope with not these sorts of tragic results, but it's
not unusual for, particularly as you say, an unseasoned
scientist to find that they are spending all of their
time redefining, pursuing, reshuffling the cards of the
experiment and almost forgetting the hypothesis that
they had originally and losing discipline as a result
I'm sorry. Steve, were you going to comment?
DR. HAUSER: Yes. I would, I think, agree
completely with Dr. Wagner's position and with what
some of the others have said.
The decision that one needs an experimental
group who are infected under certain conditions so that
you can then judge the effectiveness of therapy was
solved by actually infecting a group experimentally.
Second, there was a published literature at
the time indicating that in this specific situation,
this was unethical and not achievable.
Third, the data was kept private and records
not kept to standards of the time and, fourth, the data
was not published.
DR. WAGNER: I think Anita was next and then
DR. ALLEN: There seemed to be a mixing of
research scientific goals with therapeutic goals in
some of these experiments and the one that stands out
that I'd love to have you comment on, Stephen, is the
experiment in which there was cisternal puncture of
epileptics and their rationale was, well, maybe this would
shock the epileptics into not having seizures anymore
which strikes me as being something that a contemporary
neurologist might, you know, find baffling or at least
What do you think about that? I mean, was
there in this case an inappropriate, from a sort of
scientific point of view, inappropriate mingling of
research agenda and possible therapeutic medical
DR. HAUSER: We have treated epilepsy over
time in numerous inappropriate non-evidence-based ways,
but I thought that for this particular situation,
Anita, that this was part of a post-hoc description of
the variety of benefits that might accrue from these very
Others included the goal to establish a
competent infrastructure for STD treatment in Guatemala
to better understand the natural history of STDs and to
understand ethnic differences in the clinical
manifestations of these disorders.
So post-hoc, there were numerous
rationalizations given for this work but clearly the
primary goal was to establish models of infection in
human beings to test the effectiveness of treatment.
DR. WAGNER: Barbara.
DR. ATKINSON: I just would like to go back to
John's question a little bit and talk about the
methodology using the syphilis as an example.
In my mind, it goes even back further than in
some of the mistakes they made. In syphilis, you can't
always tell if a person has it or not if you miss it at
the first primary stage and so that's why they wanted
to do the serologies to find out if there was a
background level in the population that had it or not
because their studies wouldn't be meaningful if there
was and they actually found a high background level but
they didn't do those studies until after they'd done
the original ones infecting people. So they did it in
the wrong order. They didn't look at that first.
Then when they infected people, they tried the
commercial sexual workers but they found almost no
transmission that way, very low levels, five percent
maybe transmission that way. So they had to readjust
right in the beginning and they just kept readjusting,
readjusting all out of order, all out of synchrony,
without any kind of a plan, and that really was in my
mind what was the matter with the methodology of the
So you can't prevent something if the people
who already have it and you can't know if the results
are accurate in the end when you've had so many
different changes to the protocol as you went along and
so much variation in everything you try.
DR. WAGNER: I'm sorry. Yes, Nita.
DR. FARAHANY: I want to build on that just to
be crystal clear. So as we talk about the methodology
being flawed and the fact that the reports weren't
published, are we clear that there was no -- nothing
that we've learned from these experiments -- I mean,
for example, given that at the time this was such a
priority for the military, that it was such a priority
for understanding STDs and the effect of penicillin for
having models, were these studies in fact -- did they
yield valuable science nevertheless or, Barbara, as you
put it, is it such that because the methodology was so
tainted the accuracy of any of the studies, whether
they are models or the treatment of penicillin for
syphilis or for any other studies, that simply there
was no value to the studies whatsoever?
DR. MICHAEL: There was no value, Nita. I
mean, it was -- I think Stephen laid it out pretty
nicely when he went down the list that included, you
know, poor note-keeping, but a meandering research
series of questions.
I think what stings the most for them in terms
of it being bad science is that the work never passed
peer review, it was never published, and in my world,
if it's not published, it's as good as not done and
therefore it doesn't influence medical practice or
advance the field.
DR. WAGNER: You can't build on it. Yes, Amy.
DR. GUTMANN: When we talk about bad science,
when it is science involving human subjects, one of the
things that comes most glaringly in focus is how bad
science abuses human subjects when there's any risk
In this case, as I read through the historical
documents and reread them and read them again, I kept
asking the question of what -- how could they do this?
These were people who had a certain pedigree. I mean,
they were as young and inexperienced as Dr. Cutler was,
Dr. Mahoney was not inexperienced, and people all the
way up the chain who knew about the experiments. There
were other people kept in the dark but the people who
knew about them approved of them, and this is a segue
to the discussion of the ethical aspects of it, but the
conclusion that I come to in this is the only way such
bad science could be done, so serology studies done
after the evidence was needed that they would yield on
Now mind you, the serology studies didn't
impose the worst risks on some of the human subjects,
except the ones that included lumbar and cisternal
punctures which did, how could that happen?
My conclusion is, and it has to be a reluctant
conclusion when you're judging other human beings, that
the people who were doing these, people in positions of
authority and responsibility and privilege, doctors did
not treat those human beings as if they were human
beings worthy of respect, worthy of consideration as
human beings, that the only way you could continue
doing this is to think of what you were acting on as
material as opposed to other human subjects, and that
I'm not saying that's the way they thought but that's
the way you could only act like that if you think,
Number 1, you're doing good science which I think no
doubt they must have believed, and, secondly, the
people you were doing it on don't matter as much as the
people you would normally be associating with in your
daily life, your family, your friends, and other
people, because as we will get into the next section,
the people weren't asked to consent to these
experiments, they weren't told what the risks were, and
the experiments were not done according to the
standards of science at the time, the good standards of
science at the time.
DR. WAGNER: I'd love to take your segue but I
do have one other --
DR. GUTMANN: No, I didn't mean it to be, but
it's the way in which you can't separate science and
the fact that it's operating on human beings.
DR. WAGNER: I think Nelson would suggest that
if it were even dealing on things, it was still bad
The point there --
DR. GUTMANN: But not as bad.
DR. WAGNER: One point I'd like to hear us say
to each other, and I hope we can say this, it is so
easy to look back on a whole history of failed science
of all different kinds, you know, and to bash it from
I want to make sure that we are not doing that
and I don't think we are. I just want to hear the
Commission say that, that we believe really at the
standards available at the time, with the
sophistication of scientific practice in that era, and
not just in our own hindsight, do we feel that this was
Raju, you haven't said anything. Let me turn
it to you and introduce yourself, please.
DR. KUCHERLAPATI: Raju Kucherlapati from
Harvard Medical School.
I think there are a couple different points
that have not been mentioned. I think that they're
One is that prior to the initiation of the
study, there was a proposal that was made and the
proposal was reviewed by a group of peers and there
were different points of view by that group. So the
original proposal to do the experiments, whatever they
were, were, indeed, reviewed by the peers and the
funding was based upon that review. So that's an
The second thing that I think that's also
important to recognize is that throughout the period of
the time that the experiments were conducted, there
were reports that were sent from Guatemala to
Washington, D.C., and there are individuals who had the
opportunity to actually see the reports and they're not
the people who are inexperienced people. These are
people who are tremendously experienced and
knowledgeable about what is going on and are at a
distance from the experiments.
So one cannot say that the principal, Dr.
Cutler, who was doing the experiments, whatever the
motivations and however he did the experiments, there
were, indeed, opportunities for other people to review
what was happening and that the other groups had the
opportunity to have those findings reviewed by the
appropriate people, if they didn't know by themselves,
or they would be able to say that, you know, these
experiments are not scientifically -- this is not the
way to go and that you should, you know, do
So those two are actually very important
points to mention.
DR. GUTMANN: That's why whatever we say, I
think it's very important that this is not the action
solely of a principal investigator. This principal
investigator reported up, Cutler to Mahoney and all the
way up. They did, the people who were in the know, did
want to keep it secret because they feared that if it
were to become more broadly known, it would be subject
to public criticism.
There were some doctors who dissented. There
was a doctor who wanted to be involved and they were
afraid to involve him because he might be critical. So
there were different views in the scientific community
at the time but what Raju is saying is absolutely
right. This is not the actions of one person and what
I've said is to suggest that it was not an accident
that this happened in Guatemala with a foreign
population that was seen as ethnically, racially,
nationally different because we do know that some of
the people who were involved in this experiment said,
explicitly said we could not do this in our own
DR. WAGNER: Christine had a comment, Lonnie,
and then I think we'll wrap this session.
DR. GRADY: I wanted to respond, Jim, to your
comment that we should not bash science without
understanding it and go back to Nita's question about
I think some of the serological work actually
probably did have some value. They were published.
They compared different serological tests, you know.
That was not useless science in some respects, and also
for the most part, although there were some exceptions,
as Steve pointed out, did not expose the people that
were involved in them to a great deal of risk. So
there is some value perhaps in those studies.
The second thing I think is important to put
on the table is I think Steve mentioned that one of the
scientifically wrong aspects of this set of experiments
was using human beings as a model, an infectious
disease model, and I think we need to be very cognizant
of the fact that this was certainly not the only study
that did that and that even today, we use those kinds
So that if that is not in my view anyway the
thing that makes these set of experiments wrong but
there are lots of things about how those kinds of
infection experiments are done that are very important
to make them acceptable.
DR. WAGNER: Lonnie.
MS. ALI: Hi. I'm Lonnie Ali, caregiver.
Coming from a lay point of view and not having the
medical background and just reading this and being
horrified by a lot of what I was reading, I just don't
want to belabor Dr. Gutmann's point, but I think it's
important to note that if -- that these being doctors
and medical scientists and doctors who are supposed to
do no harm, to do good, I think it's important to note
that even though during these course of experiments and
studies that were going on and there was actually a
prophylactic that was discovered, penicillin, that was
effective and they decided to change course and figure
out whether or not penicillin could prevent infection,
but what was important to me, too, is that the way they
viewed the Guatemalans is that they left so many people
untreated after they had infected them.
It was like they were disposed of, they didn't
care what happened to them, and, you know, what
happened to them after they had actually been infected
with something that they intentionally infected them
with. So I think that's important to note, that when
it goes to how these people were viewed, that when they
had the opportunity to treat them and cure them of this
STD, that they failed to do so. They left so many who
were actually involved in the study, not people outside
in the general population but people who were actually
involved in the study, left them untreated.