Briefing on the U.S. Public Health Service STD Inoculation Study of 1946-1948 Via Teleconference

Special Briefing
Arturo Valenzuela
Assistant Secretary, Bureau of Western Hemisphere Affairs
Francis Collins, Director, National Institutes of Health
Washington, DC
October 1, 2010

OPERATOR: Welcome and thank you for standing by. At this time, all participants are in a listen-only mode until the question-and-answer session of today’s call, and at that time, you may press *1 to ask a question. I’d also like to inform all parties that today’s call is being recorded.

Now I’d like to turn the call over to Mr. Michael Ratney. Sir, you may begin.

MR. RATNEY: Okay. Good morning, folks. Thanks for joining us this morning. We have with us Assistant Secretary of State Arturo Valenzuela, Assistant Secretary for Western Hemisphere Affairs, and Dr. Francis Collins, the director of the National Institutes of Health. They’re going to be discussing the U.S. Public Health Service’s Sexually Transmitted Disease study from the 1940s. You should all have seen already the statement that Secretary Clinton and Secretary Sebelius put out on this, plus other fact sheets that are available on the HHS website.

Just to reiterate, this is the only topic these two gentlemen will be discussing this morning, no questions on any other public health or foreign policy issues. This is going to be on the record. Assistant Secretary Valenzuela and Dr. Collins will make brief opening statements and then will take your questions. We will go for about 45 minutes.

So with that, I’m going to turn it over to Dr. Collins to make a brief statement. Dr. Collins.

DR. COLLINS: Thank you. Today, I will share with you information that has come to light about deeply disturbing research that was conducted over 60 years ago. This case of unethical human subjects research represents an appalling example from a dark chapter in the history of medicine. I would like to briefly summarize what we know about the research project and then describe the protections that are in place today that prohibit such unethical conduct.

While conducting research on the Tuskegee Study, history professor Susan Reverby of Wellesley College discovered the archived papers of the late John Cutler. Dr. John Cutler was a U.S. Public Health Service medical officer. The archived papers include detailed records from a study that was never published conducted by Dr. Cutler in Guatemala from 1946 through 1948. The study appears to have been funded by a grant from NIH to the Pan-American Sanitary Bureau, now the Pan American Health Organization.

In the study, Dr. Cutler and his collaborators intentionally infected vulnerable populations, including prisoners and mentally ill patients, with sexually transmitted diseases, including syphilis, gonorrhea, and chancroid. The purpose of the study was to test the effectiveness of penicillin, which was relatively new at the time. Notably, the intention was to provide treatment, and the evidence supports that the vast majority were adequately treated.

But there were four primary ethical violations in this study. First, all of the study sections were members of one or more vulnerable populations. Second, there is no evidence they gave informed consent. In fact, third, the subjects were often deceived about what was being done to them. And fourth, without their understanding or consent, individuals were intentionally infected with pathogens that could cause serious illness.

When Dr. Cutler and his colleagues were conducting their studies in Guatemala in the 1940s, there were no formalized regulations regarding the protection of human subjects in research. I want to emphasize that today, the regulations that govern research funded by the United States Government, whether conducted domestically or internationally, would absolutely prohibit this type of study. Today, researchers must fully explain the risks associated with their study to all research participants, and participants must indicate their informed consent.

I want to conclude by saying the National Institutes of Health, the Department of Health and Human Services, the entire U.S. Government are committed to protecting and respecting participants in biomedical research. We are all deeply saddened that so many vulnerable individuals were unwitting subjects in this risky and unethical research study. Thank you.

MR. RATNEY: Okay. Thank you. And now, Assistant Secretary Valenzuela will make a brief statement.

ASSISTANT SECRETARY VALENZUELA: Yes, I want to say that Secretary Clinton called President Alvaro Colom of Guatemala last night to express her personal outrage and deep regret that such a reprehensible research could have occurred, making clear that this does not represent the values of the United States. She reaffirmed the importance of our relationship with Guatemala and her respect for the Guatemalan people.

The United States Ambassador to Guatemala Steve McFarland and I have also been in touch with President Colom and Ambassador Francisco Villagran, the Guatemalan Ambassador to the United States, also to express our regret. And as we move forward, we want to try to better understand what happened and how something like this could have transpired. And we’ve expressed, as the Secretary did also, our commitment to human dignity and to the respect for the people of Guatemala.

Let me just say that our countries partner on a range of issues. I met with President Colom just about a week ago in New York to discuss a broad range, as I say, of matters that we’re working on together, both Guatemala and United States. We’re bound by shared values, we’re bound by commerce, we’re bound by the many Guatemalans who live in the United States and enrich our country. And we consider Guatemala to be one of our close friends and neighbors in the Americas.

So I’ll leave that statement there and open it up for questions.

MR. RATNEY: Okay. Thanks. We’ll go to the first question.

OPERATOR: Thank you. At this time, *1 to ask a question.

MR. RATNEY: And if I could just reiterate, we’re going to do question at a time without follow-ups until we’ve satisfied everybody.

OPERATOR: First question comes from Betsy McKay. Your line is open.

QUESTION: Hi, I have a couple questions, if possible. One is: Has compensation been offered to Guatemala for this? And secondly, Dr. Collins, I’m wondering if you could talk about how revelations of this research might inform discussions that go on today about whether to conduct experiments – scientific or medical experiments among prison communities.

MR. RATNEY: Could you identify your outlet, please?

QUESTION: Oh, I’m sorry. Wall Street Journal.

DR. COLLINS: Well, I can answer the second question, if you’d like. Basically, as a result of this revelation, the United States Government is asking the Institute of Medicine, which is part of the National Academy of Sciences, to convene a committee of independent experts to conduct a fact-finding investigation by reviewing the conduct of the Guatemala experiments. And they will issue a report establishing all the facts of the study. We need to be sure we have all the details.

But separately, and particularly relevant to your question, the Presidential Commission for the Study of Bioethical Issues of the U.S. Government will convene an international group of experts to review and report on the most effective methods to ensure that all human medical research conducted around the globe today meets rigorous ethical standards, and how training of researchers will ensure such abuses do not occur.

With regard to your question about vulnerable subjects, that is an explicit component of the human subjects regulations in the United States and has been so for a couple of decades, that those kinds of experiments deserve a special scrutiny and a special attention to informed consent and whether or not it’s even possible in the circumstance of individuals who are incarcerated.

ASSISTANT SECRETARY VALENZUELA: All I would add to what Dr. Collins said is that we will wait for the findings and recommendations of these two efforts before any additional steps might be taken.

MR. RATNEY: Okay. Can we go to the next question, please?

OPERATOR: The next question comes from Kim Ghattas with BBC. Your line is open.

QUESTION: Yes. Hi, good morning. Thank you for the call. Reading the synopsis of the study by Susan Reverby, it looks as though the Guatemalan authorities gave their permission for this experiment. I was wondering whether this was your understanding as well, whether you believe that the Guatemalan Government was aware of all the aspects of the study. Or were they in some way deceived as well by what exactly was going on?

MR. RATNEY: Dr. Collins.

DR. COLLINS: So it remains, I think, for the investigation to clarify exactly what – the nature of the collaborative effort with the Guatemalan Government. It’s clear that some components of the government were aware of the study. But beyond that, it’s not entirely clear what the arrangements were.

MR. RATNEY: Okay. We can go to the next question, please.

OPERATOR: And our next question comes from Stephen Smith with the Boston Globe. Your line is open.

QUESTION: Hi. Good morning. Thank you for conducting the briefing. I had several questions. First, I was wondering if you could discuss whether efforts have been made or are going to be made to contact any potential survivors. Obviously, the individuals, many of them I’m surmising are deceased, but are there efforts going to be made to potentially contact any survivors or their family members?

And secondly, could you discuss a little bit further Professor Reverby’s role, how she came to contact the various health agencies, and whether there is any indication that anyone in the United States Government before this was cognizant – obviously, U.S. Government officials were participants in the 1940s – but is there evidence that there was knowledge of this at high levels of government either in the 1940s or subsequently?

MR. RATNEY: Dr. Collins, could you answer the first one? The second question, I’d refer any journalist to Dr. Reverby’s own study, which is available on the Wellesley College website for all of the information about the modalities of her study at that time.

DR. COLLINS: In terms of an effort to contact survivors, obviously, many of the individuals involved in this study would no longer be alive since this is more than 60 years ago. And yet, there are in the records addresses, so it may be possible if there is a desire to do that to search for names and addresses. But that will have to be a component of the follow-up study, which is to be conducted by the taskforce. And let me correct myself. There are names. I’m not sure, in many instances, whether there are addresses. After all, some of these were patients in a mental hospital, about which there may not have been much information.

MR. RATNEY: Okay. Could we go to the next question, please?

OPERATOR: Our next question is from Juan Lopez with CNN Espanol. Your line is open.

QUESTION: Yes, hi. I wanted to follow up on the second question. When you look at Dr. Reverby’s study, it says that not only the Guatemalan Government, according to her report, co-sponsored, but it also mentions the National Institutes of Health, the now Pan American Health Organization. So the question is: Why are you apologizing? And was there – did this study result in the treatment – in any new treatment, in any developments? Are you aware of any significant developments on the treatment of STDs?

DR. COLLINS: This is Dr. Collins. The results of this work were never published, so it would be difficult to ascertain whether they had any effect on medical practice.

ASSISTANT SECRETARY VALENZUELA: Well, the reason why we’re taking this up is because this was funded by the U.S. Government at the time. And I think that we recognize that that was an egregious mistake and that’s why we’re bringing it to the attention of everyone. And this is why we are taking this as serious as we are and why we’re proposing further studies to, in fact, find out exactly what transpired beyond the research that we have available at this particular point.

MR. RATNEY: Okay. We can go to the next question, please.

OPERATOR: And our next question is from Mr. Jeff Custer with the Voice of America. Your line is open.

QUESTION: Hi. Thanks so much. I just wanted to clarify just a couple of quick things. Dr. John Cutler helped to carry out this study, as I understand it, and he also was an investigator in the Tuskegee STD study. Also, was it only Guatemalans that were involved in this research?

DR. COLLINS: You are correct that Dr. Cutler was a participant in the Tuskegee study and in a variety of other studies done in the United States. But what we’re talking about today are the experiments that were carried out by Dr. Cutler and other colleagues in 1946 to 1948 in Guatemala.

MR. RATNEY: Okay. Can we go to the next question, please?

OPERATOR: Lori Montenegro from the Telemundo network. Your line is open.

QUESTION: Yes. Thank you for taking the question. This is for Mr. Collins. I understand that you say that in the ‘40s there were really no regulations that would have prohibited what you call as unethical practices. But my question is: You being from the medical field, wasn’t – wouldn’t there have been a common sense knowledge that this was unethical? How would you do this to people without telling them and not knowing what the results could have been with – by later treating them with penicillin that, at that time, was not known? It was new. We didn’t know what the side effects could be, et cetera.

DR. COLLINS: I find it very difficult, as a physician-researcher today, to imagine how these studies could have been conducted in a way that individuals participating in them could have considered ethical. Clearly, though, there were at that time inadequate norms that governed this kind of research activity. Fortunately, over the course of the last 60 years, we have now in place very effective oversight mechanisms to keep this kind of research from happening today.

MR. RATNEY: Okay. Thank you. We’ll go to the next question.

OPERATOR: Mr. Arthur Brice from CNN, your line is open.

QUESTION: Thank you. Mr. Valenzuela, could you characterize the response from the Guatemalan Government, please?

ASSISTANT SECRETARY VALENZUELA: Well, yeah. They were obviously extremely concerned about this information. They were saddened by it. They agreed with our characterization that this is an extremely unfortunate incident in the past.

But both the president, the ambassador, and others that we’ve talked to expressed to us that this is something that happened 64 years ago and that – reiterated the strong relationship that Guatemala has with the United States and the strong cooperation they have with the United States. And they were, in that sense, appreciative that we expressed to them not only information about this matter, but also our deep regret at what happened.

MR. RATNEY: Can we go to the next question, please?

OPERATOR: And our next question comes from Karen Zeitvogel. Your line is open.

QUESTION: Hi. I’m Karen Zeitvogel from AFP, Agence France-Presse. I have two questions. Secretaries Clinton and Sebelius said that there’s going to be a thorough investigation. Is that the same or in addition to the two investigations that you just told us about by the IOM (Institute of Medicine) and the Presidential Bioethics Committee? And the other question is: Is there any evidence maybe in, like, NIH grant funding trails that this might not be a one-off?

MR. RATNEY: Dr. Collins?

DR. COLLINS: So, yeah – the first question, yes. The two (inaudible) follow-up studies in – by the U.S. Government, as mentioned in the statement from the secretaries, are the ones that I also mentioned. One of them being an Institute of Medicine taskforce committee to look at the details of what happened in the Guatemalan study; the other being asking the President’s commission to look more broadly across the world at the way in which human subjects research is overseen to ensure that the highest rigorous ethical standards are now being maintained and that researchers are being appropriately trained.

With regard to your second question, there is no evidence of grants being received by Dr. Cutler after Guatemala until the 1960s, and those studies do not involve intentional infection of patients.

MR. RATNEY: Okay. The next question, please.

OPERATOR: Comes from Andrew Jack, Financial Times. Your line is open.

QUESTION: Yes, thanks. Yes, I have two questions. First of all, just following up on that one, but whether or not Cutler himself received more funding, I’m just wondering how many other horrendous ethical abuses like this might be out there from the past few decades, whether you’ve got any sense from other research; and secondly on the international ethical review going forwards, what issues you think potentially could be of concern, which, at least in a few decades time, we might look on today’s medical practice and say how could we have allowed that to happen.

DR. COLLINS: Well, in fact, when one considers that the ethical standards back in the ‘40s and even earlier and a little after that were inadequately in place, one can identify, and this is in the published literature, more than 40 other studies where intentional infection was carried out with what we would now consider to be completely inadequate consent in the United States. So these were done domestically.

In terms of trying to guess what we might in the future look back on and say, well, how could we have done that now, that is obviously something that bioethicists worry about a lot, and I don’t have an easy answer for you. But I am sure that we should all be cautious about trying to argue that we have somehow arrived at the final end point of understanding what is completely ethical and what is not.

MR. RATNEY: The next question, please.

OPERATOR: The next question is from Kristen Minogue with the Science magazine. Your line is open.

QUESTION: Hello, thank you for talking to us this morning. I was wondering with the investigations, what is the timeline for them.

DR. COLLINS: Since this is just now coming to the fore, and certainly the IOM has been asked to look into this and the President’s bioethics commission has as well, I don’t think, as yet, a timeline has been set.

MR. RATNEY: Okay, thanks. Next question, please.

OPERATOR: Lauran Neergaard, your line is open, with Associated Press.

QUESTION: Hi, Dr. Collins. A couple quick questions for you. Do you know what exactly the NIH approved in that grant? Did it specifically say that there was going to be intentional infection?

And you said that it looked like there was generally adequate treatment afterwards, but I wonder, given the iffiness of the serology then, what in these papers leads you to believe that.

DR. COLLINS: Well, the grant support, because of the fact this is more than 60 years old, all that remains in terms of documentation is the name of the grant, which was Investigation of Venereal Diseases in Guatemala. It was actually the grant issued to a Dr. J.P. Mahoney[1]. So we are unaware of what the grant itself might have proposed.

In terms of the documentation of adequate treatment, again, that’s what the task force should be looking at. And Professor Reverby’s paper as well covers that. The documentation was largely based on whether the standard therapy of penicillin was given in the accepted dose.

MR. RATNEY: Okay, next question, please.

OPERATOR: Mike Stobbe, your line is open, with Associated Press.

QUESTION: Hi, sorry just wanted to shoot a question. Doctor, to your knowledge what’s the highest sign-off that took place on this? Did it go to the NIH director, the surgeon general, the FSA administrator? And also, you made a comment a minute ago about there have been 40 other studies where intentional infection was carried out in the United States. Was that all done under the purview of the Public Health Service?

DR. COLLINS: The Surgeon General of the United States, Dr. John Curran, was aware of the study in the 1940s. In terms of the 40 studies done that also involved intentional infection, I don’t know whether all of those were, in fact, supported by the Public Health Service, but certainly many of them were.

MR. RATNEY: Okay, next question, please.

OPERATOR: And our next question comes from Teo Rodrigues. Your line is open.

QUESTION: I’m from Guatemala. I work at a Guatemalan newspaper. I just want to know, do you think that after the U.S. Government paying for this monstrosity and then eight years later overthrowing a democratically elected president in Guatemala, are we going to get some sort of compensation? I’m not talking about economic or something, but is “sorry” enough for this?

DR. COLLINS: Thanks. Sorry, what newspaper are you with?

QUESTION: Diario des America.

ASSISTANT SECRETARY VALENZUELA: Well, I would just reiterate what I said earlier, and that is that with these two studies that are being commissioned now, we will await the findings and recommendations of those studies before we move forward. And I would caution you not to link the two events that you’re talking about. The one that we’re discussing now occurred in ’46, ’48, and the other one that you just mentioned occurred in ’54, and they’re not linked.

MR. RATNEY: Okay, next question, please.

OPERATOR: Jeannie Baumann with the BNA Medical Research and Law Report, your line is open.

QUESTION: Hi, thanks for taking my question. Dr. Collins, with minority participation in clinical research already a concern, I was wondering if there’s a concern that this – that these findings will further – be a further detriment in terms of recruiting minorities into clinical studies or if you think that since it happened 60 years it might now have an impact.

DR. COLLINS: Well, of course, we’re concerned about the way in which this horrendous experiment, even though 60 years ago, may appear to people hearing about it today as indicative of research studies that are not conducted in ethical fashion. I think the track record in the last 20 or 30 years has been really quite remarkable in terms of providing the framework to assure people who are considering participation in clinical research that ethical standards of the highest sort are going to be maintained.

But we all recognize that the Tuskegee study, which involved the same Dr. Cutler, did great damage to the confidence and the trust that individuals, particularly from the African American community, had in medical research. So it can’t be a good thing that we have now unearthed by Professor Reverby’s study through these archives of an example again of medical research being conducted on vulnerable populations in a way that is reprehensible.

At the same time, I want to make my personal commitment that we are doing everything we can at NIH, and the government now will be extending that in terms of making sure across the world that these standards are being adhered to to reassure people that medical research is being conducted with the highest standards. That is our goal. We will not be satisfied with less.

QUESTION: Thank you.

MR. RATNEY: Next question, please.

OPERATOR: Cristina Fernandez with the El Pais newspaper, your line is open.

QUESTION: Hi, thank you so much. I wanted to ask if you know if there’s any data available regarding any victims because of the infections that any of the members that participated in the study actually died from the disease.

DR. COLLINS: I believe in Professor Reverby’s paper there is an indication that one person of the hundreds who were involved in this, who had an epileptic condition, died in the course of penicillin treatment from what’s called status epilepticus which is a seizure that simply can’t be stopped. There would be considerable question, of course, about whether that was related to the penicillin treatment or whether that was a consequence of that person’s underlying condition.

MR. RATNEY: Next question, please.

OPERATOR: Stephen Smith from the Boston Globe.

QUESTION: Thank you. A couple of further questions. One, I’m wondering if you could discuss your sentiments about Dr. Reverby and her discovery of this and reflect upon the importance of researchers such as herself who scour the historical record. And second, I’m wondering, as a result of these findings, whether it is vivifying any sort of effort or whether this might be part of the IOM work to see if globally during this period there were similar experiments being conducted.

DR. COLLINS: Personally, I think Professor Reverby, who is a very capable medical historian, has done a good thing here by uncovering aspects of a study that was previously unknown, not published, but hidden away in the archives at the University of Pittsburg. And by uncovering it and bringing it to the attention of officials in the Public Health Service, giving us all a chance to look at this, and even as we are appalled at what was done, to try to redouble our efforts to make sure that nothing of this sort could ever happen again. And that’s very much what’s happening now.

Professor Reverby’s paper, which I really encourage everybody to read closely, I think is very clearly written in a fashion that doesn't overstate or understate the nature of what was done here. In terms of the further investigation of the circumstances of the 1940s in this study, that will be up to the IOM panel to investigate.

MR. RATNEY: Thanks. Next question, please.

OPERATOR: And I’m showing no further questions.

MR. RATNEY: Okay, thank you, ladies and gentlemen, and thank you to our participants.


[1] Dr. J.F. Mahoney

PRN: 2010/1396