The Guatemala syphilis experiment, human subjects research abuses, and CAM

If there’s one thing that burns me about so-called “complementary and alternative medicine” (CAM) clinical trials, it’s how unethical many of them are. This is particularly true for trials that test modalities that, on the basic science grounds alone, can be dismissed as so highly implausible and with such a low prior probability of success that it is unethical to subject patients to risk with close to zero potential for benefit. Perhaps the most egregious example of such a clinical trial is the Gonzalez protocol in pancreatic cancer, a cornucopia of woo and quackery including up to 150 supplements a day, various dietary interventions, and coffee enemas. When the results were finally reported over a year ago, four years after the trial ended, to no one’s surprise (at least no one with at least a modicum of scientific knowledge) the results not only showed that the Gonzalez protocol produced inferior results to those of science-based medicine (SBM), but it wasn’t even close. Patients in the conventional medicine arm lived three times longer, an astonishing result in light of the poor efficacy of existing treatments for unresectable pancreatic cancer, a result that Gonzalez couldn’t just wave away, although he did try. Other examples include clinical trials of homeopathy for infectious diarrhea in Honduras and a clinical trial of chelation therapy. I’ve also criticized the “autism biomed” movement, that amalgamation of parents who believe that vaccines cause autism and are willing to subject their children to all sorts of quackery to “cure” the “vaccine injury” of uncontrolled and unethical experimentation on autistic children, the worst examples of which are Andrew Wakefield and, even worse, Mark and David Geier.

These abuses of science and ethics notwithstanding, whenever a story describing a lapse in research ethics in clinical trials in SBM come around, you can count on the crazies to pounce all over it as “proof” that SBM is hopelessly corrupt and, by implication, that there must be something to their woo, be it anti-vaccine pseudoscience and quackery or quackery of any variety. That’s why it didn’t surprise me too much to see that neither the anti-vaccine crank blog Age of Autism nor über-quack Mike Adams wasted any time pouncing all over a news report about a horrifically unethical study that the U.S. Public Health Service (PHS) carried out in Guatemala in the 1940s. At AoA, Media Editor Anne Dachel layed on the stupid with a post entitled Valid Concern for 60 Year Old Medical Travesty: What About Today’s? while over at NaturalNews.com Mike Adams ramped the crazy up to 11–does he even have a lower setting?–in writing Guatemalan STD medical experiments were just one crime in a long history of medical-government collusion to use humans as guinea pigs. In each case, an advocate of pseudoscience and quackery starts out with a reasonable complaint, a terrible and disturbing story, even, and then completely misses the point. Instead of understanding that such incidents emphasize the need for guidelines to protect patients from unethical experiments, including those by their heroes, they use them as a weapon, as you will see. This particular incident was indeed a gross failure on the part of SBM to live up to ethical precepts, but, as shocking as this incident is, it does not validate Mike Adam’s quackery and conspiracy theories or Anne Dachel’s anti-vaccine pseudoscience any more than it invalidates science-based medicine.

The Guatemalan syphilis experiment

A couple of weeks ago, I wrote about the concept of clinical equipoise. Clinical equipoise is a critical concept in any clinical trial. Basically, a state of clinical equipoise exists when there is genuine scientific uncertainty over which of the options being tested in on living, breathing human beings is better, and any clinical trial in which a state of clinical equipoise does not exist is at the very least ethically dodgy and probably downright unethical. What all this boils down to is that science is only part of the basis of science-based medicine. Medical ethics must take precedence. After all, arguably the most efficacious way to test a new antibiotic would be to infect people with the bacteria the antibiotic treats and then dividing these people up into a placebo control group and a group receiving the antibiotics to see how each group does. In fact, this is the sort of thing that the Nazis and Japanese did during World War II and the same sort of dehumanization and abuse of research subjects that every ethical precept regarding human subjects research that has been developed since World War II, such as the Helsinki Declaration of 1964, has been designed to prevent.

Unfortunately, medical scientists in the U.S. have not always lived up to these precepts. The most famous example is arguably the Tuskegee syphilis experiment, in which poor black men with syphilis were studied and the control group denied effective therapy for syphilis even after it was known that penicillin was an effective treatment for syphilis. Unfortunately, it turns out that there was arguably an even worse atrocity against medical ethics perpetrated by U.S. investigators in Guatemala over 60 years ago that only now has come to light in stories in the New York Times, MSNBC, and elsewhere. So bad was the offense that Secretary of State Hillary Clinton and Secretary of Health and Human Services Kathleen Sebelius have issued a formal apology to the Guatemalan government for the experiments in which Guatemalan prisoners were intentionally infected with syphilis and then treated with antibiotics, an apology that President Obama reiterated in a personal telephone call to Guatemalan President President Alvaro Colom on Friday. This is the story that Adams and Dachel are using as a weapon to use against their foes for their own viewpoint. As despicable as the actions of U.S. researchers were, however, it is nothing of the sort.

A crime against humanity

The Guatemalan syphilis experiment might have remained lost in the depths of history, unknown, records of its having taken place buried in archives at the University of Pittsburgh, were it not for the efforts of Wellesley College Professor of Women’s Studies Susan Reverby and medical historian, who unearthed the notes of John C. Cutler, who, ironically enough, was later an important member of the team carrying out the Tuskegee experiment and continued to defend the study 20 years after it was closed. In fact, Cutler defended the Tuskegee experiment to his dying day in 2003.

What Professor Reberby found was horrifying, and she has recently published a manuscript describing her findings. Because I always like to go to the primary source wherever possible, I will refer you to the manuscript, available on Dr. Reverby’s faculty web page and entitled “Normal Exposure” and Inoculation Syphilis: A PHS “Tuskegee” Doctor in Guatemala, 1946-48 (synopsis here). The HHS response can be found here, including the statement issued on Friday by Clinton and Sebelius in both English and Spanish.

The Guatemalan syphilis experiment was arguably worse than the Tuskegee experiment because the men involved in the experiment were intentionally infected with syphilis. The fact that the Guatemalan experiment only lasted two years and every man infected who contracted syphilis was given penicillin does not mitigate the guilt of the researchers. As the full manuscript describes, although researchers did obtain permission for their studies from the prisons and other institutions with which they worked, they did not receive permission from the inmates or their families. Indeed, deception was part and parcel of the entire process. In return for cooperation, researchers offered supplies to the institution, such as anti-seizure medications like Dilantin, refrigerators to store medications, and a “motion picture projector that supplied the sole recreation for the inmates, metal cups, plates and forks to supplement the completely inadequate supply available.” Individual subjects were plied with cigarettes, “an entire packet for inoculation, blood draws or spinal taps and a single cigarette for ‘clinical observation.'”

Researchers also went to ludicrous extremes to infect the men with syphilis. First, they took advantage of legalized prostitution in Guatemala and the fact that Guatemala allowed prostitutes to pay regular visits to men in penal instituions by locating prostitutes with syphilis:

With the cooperation of officials at the Ministry of Justice and the warden of Guatemala City’s Central Penitentiary, which housed nearly 1500 inmates, prostitutes who tested positive for either syphilis or gonorrhea were allowed to offer their services to prison inmates, paid for by U.S. taxpayers through the funds of the PHS. In yet another set of experiments, uninfected prostitutes had inoculum of the diseases placed on their cervixes before the sexual visits began. Serological tests were done on the inmates before the prostitutes were invited to the prison and then afterwards to see if infection had occurred. The men were divided into groups and various chemical and biological prophylaxis techniques were tested after presumed infection. If positive, the men were then provided with enough penicillin to produce a cure.

Your tax dollars at work in 1946. This method soon ran into problems. Ultimately, Cutler and his team went beyond using prostitutes and isolated syphilis to directly inoculate inmates with. Their sources were the gumma (syphilitic growths) on the testicles of infected rabbits or scraping the penile chancres of infected men, from which they had to isolate the spirochete that causes syphilis. This was difficult, because the spirochete could not survive more than 45 to 90 minutes outside the body, during which time it had to be isolated, centrifuged with fresh home made beef heart broth, and then delivered to the subjects:

With the men, the inoculation was often much more direct after what soldiers for generations had called the “short arm” inspection. They chose men with “at least moderately long foreskins [to keep the mucus membranes moist]” and who could “sit or stand calmly in one spot for several hours.” In the experiments, a doctor held the subject’s penis, pulled back the foreskin, abraded the penis slightly just short of drawing blood by scraping the skin with a hypodermic needle, introduced a cotton pledget (or small dressing) and dripped drops of the syphilitic emulsion onto the pad and through it to the roughed skin on the man’s penis for at least an hour, sometimes two.

This was also compared with other methods of introducing the spirochete, including scraping of the forearm, ingestion of syphilitic tissue mixed with distilled water, introduction into the spinal fluid, and direct injection into the bloodstream.

It turns out that even back in 1946 many of the officials who knew of or participated in the experiment knew it was unethical. Even Cutler was reported to have said, “As you can imagine, we are holding our breaths, and we are explaining to the patients and others concerned with but a few key exceptions, that the treatment is a new one utilizing serum followed by penicillin. This double talk keeps me hopping at time.” Even more disturbing is the general attitude among several researchers seemed to view law breaking as sometimes necessary for the advancement of medical science, as Thomas Rivers, who led the Rockefeller Institute for Medical Research Hospital in New York, made clear in his memoir in 1967:

Well, all I can say is, it’s against the law to do many things, but the law winks when a reputable man wants to do a scientific experiment. For example, the criminal code of the City of New York holds that is a felony to inject a person with infectious material. Well, I tested out live yellow fever vaccine right on my ward in the Rockefeller Hospital. It was no secret, and I assure you that the people in the New York City Department of Health knew it was being done….Unless the law winks occasionally, you have no progress in medicine.

The mind boggles at this attitude, in which the physician, the scientist views himself as somehow above the law, above “conventional” morality. Once a scientist goes down this path, he can justify almost anything. It is against this attitude that ethical standards and laws have evolved. It is also as a result of these abuses that many minorities and underprivileged groups of people are mistrustful of physicians and science. Supporters of SBM can’t deny that there have been serious ethical violations committed by overzealous scientists who came to value the study of their scientific question more than they did for the rights and dignity of their human subjects, because the evidence of such violations of human rights are incontrovertable. The questions remain: What to do about them and how to prevent them?

The Belmont Report, The Common Rule, and CAM

After the horrors of Nazi medical experimentation and the abuses during the Tuskegee syphilis study (remember, the Guatemalan syphilis experiment was not widely known about until now), it was clear that rules were needed to protect human research subjects from such abuses. First came the Nuremberg Code in 1947. This code, drafted in the wake of the infamous Doctors’ Trial at Nuremberg set forth ten principles to govern human subjects experimentation. Examples include the requirement for informed consent; that unnecessary pain and suffering be avoided; that the experiment should be designed based on the results of animal experimentation and knowledge of the natural history of the disease that justifies the performance of the experiment (prior plausibility, anyone?); the requirement that subjects can refuse to continue at any time; and that no experiment should be conducted where injury, disability, or death can reasonably be expected (clinical equipoise). The Declaration of Helsinki, introduced in 1964 by the World Medical Assembly, is based on the same principles as the Nuremberg Code but takes them even further, for example, stating that “the interest of science and society should never take precedence over considerations related to the well-being of the subject.” The Helsinki Declaration was last updated in 2008. For once something other than a quack destroyed my irony meter; at the time the Nuremberg Code was being written and approved that the U.S. government was engaging in the same sort of abuse of human research subjects that the Nuremberg Code was designed to combat.

In the U.S., the Nuremberg Code and the Helsinki Declaration notwithstanding, he Tuskegee debacle was the impetus that led to the Belmont Report on Ethical Principles and Guidelines for the Protection of Human Subjects of Research finalized on April 18, 1979, which remains to this day essential reading for anyone doing human subject research in this country. Later these regulations were finally codified into what is now known as The Common Rule. All institutions doing federally funded research are required to adhere to The Common Rule.

A key aspect of The Common Rule is the Institutional Review Board (IRB). The IRB is in essence a committee that oversees all human subject research for an institution and makes sure that the studies are ethical in design and that they conform to all federal regulations. I’ve written extensively about The Common Rule before in the context of how certain CAM trials violate the Common Rule and how, for example, Mark and David Geier created a sham IRB packed with their cronies (as so ably documented by Kathleen Seidel) to rubberstamp their unethical studies of using Lupron to treat the “vaccine injury” they believe to be the cause of autism. What is important (and embarrassing for proponents of SBM) to note is that The Common Rule only first went into effect in 1981 and only reached its current form in the 1991 revision to the U.S. Department of Health and Human Services Title 45 CFR 46 (Public Welfare) Subparts A, B, C and D. Subpart A. What that means is that, in the United States at least, the current government regulations mandating a baseline standard of ethics have only been in effect less than 30 years and only in their current form for less than 20 years.

The CAMsters attack

Not surprisingly, CAM proponents have jumped all over these revelations. For example, even quackery promoter Mike Adams has a grain of a valid point when he writes hysterical headlines like Guatemalan STD medical experiments were just one crime in a long history of medical-government collusion to use humans as guinea pigs. This post by Adams is yet another in a line of examples showing that there are no depths to which Adams won’t sink in order to attack SBM and that, if there’s one thing he excels at, it’s taking a legitimate criticism of SBM, such as a trial like this one in which a gross violation of research ethics, and hopping on the crazy train with it, only to go off the rails. For example, most of the examples Adams cites date back at least 50 years and are now commonly known. Few of them are more recent than the 1970s. More deceptively, most of these more recent ones are either problems that couldn’t reasonably been foreseen (for instance, the observation that 30%% of the participants of a trial for a vaccine against hepatitis B were found to be HIV-positive in 1983) or that are questionable pseudoscience at best, such as ranting against the clinical trials of Gardasil or labeling vaccine mandates as being the equivalent to the Tuskegee or Guatemalan syphilis experiments. If you want to know how vile Adams can be, check out this passage:

If you really want to be freaked out by the true, documented history of how people have been tortured, abused, injected, maimed and otherwise had their lives destroyed by the medical industry, check out the Psychiatry An Industry of Death Museum created by CCHR (www.CCHR.org).

Watch the video here: http://www.cchr.org/museum.html%23/…

You can actually walk through this museum yourself. It’s in Los Angeles, and it’s one of the most disturbing things you’ll ever see about the true history of medicine. The STD experiments in Guatemala, by the way, were carried out in a psychiatric hospital. (No surprise.) I walked through this museum and practically found myself in tears before it was over. The things that psychiatrists and doctors will do to other human beings in the name of “medicine” will rock you to the core.

The psychiatric industry has done unspeakable things to women, children, prisoners, senior citizens, African Americans and racial minorities — all in the name of “science” and “medicine.” In fact, these experiments continue to this day in the form of the psychiatric drugging of children who are diagnosed with fictitious health conditions such as “ADHD.” See my disease mongering engine to invent your own psychiatric disorders, if you want a bit of satire on this subject: http://www.naturalnews.com/disease-…

Nobody has documented the real history of medicine’s criminal abuse of human beings as well as CCHR – the Citizens’ Commission on Human Rights. Check out their amazing, shocking and eye-opening videos such as The Marketing of Madness (http://www.cchr.org/videos/marketin…) and Making A Killing (http://www.cchr.org/videos/making-a…).

The CCHR, which stands for the Citizens’ Commission on Human Rights, is a well-known Scientology front organization. I’ve written about its Psychiatry: An Industry of Death Museum before. It’s so vile an abuse that even the Hitler Zombie wouldn’t touch it. Indeed, the last time I was in Los Angeles, I seriously thought about going into the museum just for yucks (it happens to be located less than a half a mile from a place to which I consider a visit to be absolutely mandatory any time I’m in LA, Amoeba Music and I’ve even walked by it). Fortunately for my blood pressure I didn’t go in. It was a wise decision, too, given the reputation of Scientology for using any and all means to silence criticism. Also, the sheer paranoia, conspiracy theory mongering, and blatant idiocy of the exhibits would have sent waves of neuron-apoptosing burning stupid at my brain, and I have enough problems to deal with as it is.

That’s right, Mike Adams is using the Guatemalan syphilis study to side with the Church of Scientology and attack all psychiatry as pure evil. In fact, as Andrew Gumbel noted nearly five years ago, to Scientology, it’s not enough just to say that psychiatry has been guilty of abuses in the past, it has to be completely demonized. Mike Adams agrees. In fact, this is the sort of thing he says about all SBM, not just psychiatry.

The anti-vaccine propagandists at AoA were also more than happy to use this story for their own purpose, namely to attack vaccines. Anne Dachel, Media Editor for the anti-vaccine propaganda blog Age of Autism, predictably parroted yesterday tried to equate the Guatemalan study to how supposedly medicine is harming children with those evil vaccines in a post entitled Valid Concern for 60 Year Old Medical Travesty: What About Today’s? Here, Dachel attacks bioethicist Art Caplan for alleged hypocrisy in his refutations of anti-vaccine misinformation in “contrast” to his justifiable outrage over the revelation of the Guatemalan syphilis experiment, even going so far as to write:

Caplan’s harsh words over the syphilis experiments should extend to the government’s actions covering up the evidence linking vaccines to autism. His words, “Nonetheless, officials knew it was wrong,” also apply to the issue of using mercury in vaccines. The mercury-based vaccine preservative thimerosal has a history that should call any safety claims into question.

And:

Increasing exposure to mercury is having a dramatic impact on our lives. “Nonetheless, officials knew it was wrong” also means that there’s a great incentive to cover up the damage at all costs. There is a real lesson from the Guatemala and Tuskegee experiments. Let’s hope it doesn’t take 60 years before officials admit what mercury exposure in vaccine has done to our children.

Meanwhile, the commenters on AoA, as is usual, chime in with even more napalm grade flaming stupid. The usual suspects are there. There’s Jake Crosby parroting his new favorite phrase of “tobacco science,” apparently having learned it from Dr. Jay Gordon and having zero clue exactly what he is talking about. He even uses the tired old quack tropes about Semmelweis and Galileo, apparently unaware that the Galileo gambit is every bit as lame as he views appeals to prestige. Here’s a hint, Jake: To wear the mantle of Galileo it is not enough to be persecuted for your scientific views. You also have to be right. Neither Jake nor any of his heroes at AoA can in any way be considered “right. In the case of vaccines science is on the side of those defending the clinical trials studying vaccines and their efficacy, not on the side of anti-vaccine activists like Anne Dachel. Odd, too, that neither she nor any of the commenters mentioned Mark and David Geier’s and Andrew Wakefield’s completely unethical experiments. Yes, charges of hypocrisy go both ways.

Unfortunately, the paranoia is so thick on AoA that no reason or science can overcome it and a a commenter there can say without irony:

I have a sneaking suspicion that Kathleen Sebelius’s apology to Guatamala and the engineered-seeming press “outrage” over the 60 year old atrocity is a bomb disposal operation to preempt and defuse certain revelations in Olmsted and Blaxill’s The Age of Autism. Because of the way the authors present the history of syphilis and unethical experimentation in the US in relation to the vast human trial of deliberately injecting infants and pregnant women with mercury, it was only a matter of time before light was shed on other hideous human trials by other journalists and activists. And when those issues come to light, certain parties wouldn’t want The Age of Autism to be cited as a chief resource.

Somehow, I highly doubt that either Hillary Clinton or Kathleen Sebelius are even aware that Blaxill and Olmsted’s book exists, much less that they would time their apology to the Guatemalan government in order to distract attention from the “revelations” within that misbegotten book. That anti-vaccine activists would think that they would go so far just illustrates their paranoia and undeserved sense of self-importance.

The real lesson of the Guatemalan syphilis experiment

The craziness provoked by revelations of the research misconduct of the Guatemalan syphilis experiment aside and my desire to express my disgust at not just the abuses committed by U.S. researchers but the disgusting eagerness of advocates of pseudoscience to draw entirely the wrong lesson from them, the primary reason I wanted to write about the Guatemalan syphilis experiment is that it is a new and stark reminder to proponents of SBM (like myself) that practitioners of SBM do have a history of not always being as ethically pure as it should be. Indeed, the U.S. Government was right, albeit late, to apologize to the Guatemalan government, and reparations to survivors and families would be entirely appropriate in a case like this, as is the investigation ordered by the U.S. government into what happened. It is also entirely appropriate to point out, as Robert Herriman does, that at the time Dr. Cutler’s experiments were being carried out, the U.S. government was passing judgment on the Nazi doctors who carried out the same sorts of experiments, such as purposely infecting prisoners with tetanus and other agents to test the effectiveness of the antibiotic, sulfonamide? What was done in Guatemala in the name of public health was, at its core, different only in that the U.S. didn’t actually round up prisoners and throw them in concentration camps to do its experiments. In other words, there was little difference.

There is one difference in how we as proponents of SBM react to news of abuses like this and the ethical questions they bring, however, and that difference is critical. The difference is that proponents of SBM must be (and, for the most part, are) advocates for ethics in all medical experimentation, be it animal or human research. SBM depends upon science and rigorous clinical trials, but never at the expense of violating clinical equipoise, subjecting subjects to risks without true informed consent, or violating patient autonomy. All too many CAM advocates and anti-vaccine advocates use ethical misadventures and abuses as nothing more than a tu quoque argument; they delight in pointing out the gross ethical violations that are committed from time to time by science-based investigators while ignoring those committed by “their side,” such as Nicholas Gonzalez and the investigators performing the Gonzalez trial, Mark and David Geier, Andrew Wakefield, and the investigators performing the TACT trial. (Ironically, except for the Geiers’ trial, all of these trials were funded by our tax dollars–every bit as much as the Guatemalan or Tuskegee syphilis trials.)

I have long argued that there should be no such thing as “alternative” medicine. Rather, there should be one scientific standard for medicine regardless of where it comes from, and that includes all of what is commonly referred to as “CAM.” Similarly, there should be one ethical standard for all research involving human subjects. Unlike Adams and Dachel, who gleefully leap upon any scientific misconduct by medical investigators, whether real, exaggerated, or imagined, when I condemn gross ethical violations in CAM trials I condemn them because they are unethical, not because they are CAM trials. My condemnation of the ethics of various CAM trials does not mean that I will turn a blind eye when such lapses occur in trials of ostensibly science-based medicine. I will admit to using the Guatemalan syphilis study to illustrate a point, but that point is to argue for a single, unified, unequivocal set of ethical standards for human subjects research, not to try to justify “my side.” Whether we’re discussing CAM trials, trials of a new psychiatric drug, trials of surgery, or trials of Tai Chi or acupuncture does not matter; all that matters are treating patients according to the highest ethical values and doing the most rigorous science.