Bioethics Clinical trials History Holocaust Medicine World War II

Revisiting the issue of ethics in human experimentation

Progress in science-based medicine depends upon human experimentation. Scientists can do the most fantastic translational research in the world, starting with elegant hypotheses, tested through in vitro and biochemical experiments, after which they are tested in animals. They can understand disease mechanisms to the individual amino acid level in a protein or nucleotide in a DNA molecule. However, without human testing, they will never know if the end result of all that elegant science will actually do what it is intended to do and to make real human patients better. They will never know if the fruits of all that labor will actually cure disease. However, it is in human experimentation where the ethics of science tend to clash with the mechanisms of science. I refer to “science-based medicine” (SBM) as “based” in science, but not science, largely because medicine can never be pure science. There are too many other factors that affect choice of therapies, including patient preferences as well as what is available and feasible. Science has resulted in amazing medical advances over the last century, but if there is one thing that we have learned it’s that, because clinical trials involve living, breathing, fellow human beings, what is the most scientifically rigorous trial design might not be the most ethical.

About two weeks ago, the AP reported that experiments and clinical trials that resemble the infamous Tuskegee syphilis study and the less well known, but recently revealed Guatemala syphilis experiment were far more common than we might like to admit. As I sat through talks about clinical trial results at the Society of Surgical Oncology meeting in San Antonio a week ago, the revelations in this AP story reminded me that the intersection between science and ethics in medicine can frequently be a very tough question indeed. In fact, in many of the discussions, questions of what could or could not be done based on ethics were frequently mentioned, such as whether it is ethically acceptable or possible to do certain followup trials to famous breast cancer clinical trials. Unfortunately, it was not so long ago that such questions were answered in ways that bring shame on the medical profession.

More than Tuskegee and Guatemala

The most notorious of highly unethical human experiments outside of Nazi Germany and the Japanese empire during World War II is the infamous Tuskegee syphilis study. This study, conducted by our very own Public Health Service (PHS) was conducted between 1932 and 1972 and examined the natural progression of untreated syphilis in poor black men who received free health care from the government. In 1932, when this study was conceived it was not totally unethical. At the time there were precious few treatments for syphilis, and none of them worked very well. Consequently, observing the progression of syphilis, using the treatments available at the time, and following the subjects prospectively constituted a reasonable trial design. What did not constitute a reasonable trial design was not telling subjects’ wives. Worse, in the late 1930s and early 1940s, penicillin became available. By 1947 was the standard of care for treating syphilis. When campaigns to eradicate syphilis came to the county in which most of the subjects, study researchers prevented their subjects from participating. In essence, even after an effective treatment for syphilis had become widely available, study still researchers denied it to their subjects. By the end of the study in 1972, of the original 399 men in the study, 28 had died of syphilis; 100 were dead of related complications; 40 wives had been infected with syphilis; and 19 children had been born with congenital syphilis. The rationale for not providing effective treatment for these men and even discouraging them from undergoing such treatment? This:

Such individuals seemed to offer an unusual opportunity to study the untreated syphilitic patients from the beginning of the disease to the death of the infected person. An opportunity was also offered to compare the syphilitc process uninfluenced by modern treatment, with the results attained when treatment had been given.

Worse, there was no informed consent, and considerable inducements were offered to the men to join the study.

The Tuskegee syphilis study, unfortunately, is not the only abuse committed by the PHS. About six months ago, it was revealed that these sorts of experiments had been more widespread than commonly believed. Indeed, in the 1940s in Guatemala, the PHS had gone one better in that they had deliberately infected prison inmates in Guatemala with syphilis. As I described in a lot more detail when the revelations first hit the press, prostitutes who had tested positive for syphilis were recruited to visit the men in prison. The hypothesis to be tested was whether prophylactic penicillin treatment could prevent infection, and the other purpose was to define the response of syphilis to penicillin treatment. Again, there was no real informed consent. Worse, subjects were intentionally infected with a potentially fatal disease. True, they were treated, but treatment is not 100% effective, and one has to wonder if the prisoners, a vulnerable population completely under the control of prison personnel, understood the nature of the risks they were being induced to take.

Two weeks ago AP medical writer Michael Stobbe published a long article detailing the sordid history of medical research in the U.S. before the 1970s. His timing was not coincidental, because on the that followed there was a meeting of a presidential bioethics committee, the Commission for the Study of Bioethical Issues, triggered by the revelations last fall about the Guatemala syphilis experiment 65 years ago. Those revelations led the AP to do an exhaustive review of reports from medical journals and press clippings, and the AP found at least 40 studies similar to the Guatemala syphilis study in that patients were put at risk for serious disease or, even worse, healthy people were intentionally made ill to study disease. Some of these abuses are well known, others much less so.

Here are some examples from the AP article:

The AP review of past research found:

  • A federally funded study begun in 1942 injected experimental flu vaccine in male patients at a state insane asylum in Ypsilanti, Mich., then exposed them to flu several months later. It was co-authored by Dr. Jonas Salk, who a decade later would become famous as inventor of the polio vaccine.

Some of the men weren’t able to describe their symptoms, raising serious questions about how well they understood what was being done to them. One newspaper account mentioned the test subjects were “senile and debilitated.” Then it quickly moved on to the promising results.

  • In federally funded studies in the 1940s, noted researcher Dr. W. Paul Havens Jr. exposed men to hepatitis in a series of experiments, including one using patients from mental institutions in Middletown and Norwich, Conn. Havens, a World Health Organization expert on viral diseases, was one of the first scientists to differentiate types of hepatitis and their causes.

A search of various news archives found no mention of the mental patients study, which made eight healthy men ill but broke no new ground in understanding the disease.

  • Researchers in the mid-1940s studied the transmission of a deadly stomach bug by having young men swallow unfiltered stool suspension. The study was conducted at the New York State Vocational Institution, a reformatory prison in West Coxsackie. The point was to see how well the disease spread that way as compared to spraying the germs and having test subjects breathe it. Swallowing it was a more effective way to spread the disease, the researchers concluded. The study doesn’t explain if the men were rewarded for this awful task.
  • A University of Minnesota study in the late 1940s injected 11 public service employee volunteers with malaria, then starved them for five days. Some were also subjected to hard labor, and those men lost an average of 14 pounds. They were treated for malarial fevers with quinine sulfate. One of the authors was Ancel Keys, a noted dietary scientist who developed K-rations for the military and the Mediterranean diet for the public. But a search of various news archives found no mention of the study.
  • For a study in 1957, when the Asian flu pandemic was spreading, federal researchers sprayed the virus in the noses of 23 inmates at Patuxent prison in Jessup, Md., to compare their reactions to those of 32 virus-exposed inmates who had been given a new vaccine.
  • Government researchers in the 1950s tried to infect about two dozen volunteering prison inmates with gonorrhea using two different methods in an experiment at a federal penitentiary in Atlanta. The bacteria was pumped directly into the urinary tract through the penis, according to their paper.

The men quickly developed the disease, but the researchers noted this method wasn’t comparable to how men normally got infected — by having sex with an infected partner. The men were later treated with antibiotics. The study was published in the Journal of the American Medical Association, but there was no mention of it in various news archives.

Stobbe goes on to point out the “Holy Trinity” of news stories in the 1960s and early 1970s that brought to light the sorts of activities that we now consider abuses in medical research. The last of these was, of course, the Tuskegee syphilis study. The first of these occurred in 1963, when it came to light that researchers had injected cancer cells into elderly debilitated patients at the Jewish Chronic Disease Hospital in Brooklyn to discover whether their bodies would reject them. With our knowledge of tumor immunology now, we can look back on this experiment and know that the odds of any harm were quite small because tumors, with very, very rare exceptions, are not transplantable in humans. Our bodies recognize cells from another person to be foreign, whether they are cancer or not, and quickly destroy them. However, at the time, based on what was known, undoubtedly the scientists thought that there was at least a chance that these tumor cells would form cancers in the patients into whom they were injected, the denial of the hospital director who deemed the cells “harmless,” notwithstanding. (Indeed, the hospital director strikes me as either lying or deluded.) Otherwise, why seek to answer the question? Just as bad, there was no informed consent, the justification being that the cells were thought to be “harmless.” More details can be found here. The outcome was that the Board of Regents censured the researchers and suspended the licenses of two of the doctors involved. Later, however, they stayed the suspensions and instead put the doctors on probation for one year. There were no repercussions for the hospital or for Memorial Sloan-Kettering Cancer Center, where one of the investigators was on faculty.

The third of the “Holy Trinity” was an infamous experiment in Staten Island at the Willowbrook State School, which was a school for children with mental retardation. During the mid-1960s, children there were intentionally infected with hepatitis in order to determine whether gamma globulin could cure it. Besides the targeting of a vulnerable population (children and teens with profound mental retardation), this study demonstrated a number of problematic issues as well. First, the investigators rationalized infecting these children by rationalizing that hepatitis was so endemic in the facility due to the fact that most of the children there were incapable of being toilet trained that over 70% of new residents became infected within a year. This, of course, leads to the obvious question, namely: If that were the case then why not study the effect of gamma globulin on children who were infected normally? More disturbing, again investigators played fast and loose with informed consent, the form being worded in a vague and ambiguous manner that played down the fact that the children were going to be intentionally infected with hepatitis and implying that the serum they would be given would be an experimental vaccine. Finally, as is the case in many such studies, there was an element of coercion. Willowbrook at the time was very crowded, with long waiting lists for children to be admitted. At times, there was only room in the experimental wing. For parents who could not afford to take care of their children, this situation could bring considerable pressure to bear to “persuade” them to “do the right thing.”

Changing ethics

In studying the history of medicine and clinical trials, what never ceases to amaze me is the different attitudes that physicians and scientists had towards their human subjects not all that long ago. Remember, it was primarily in the 1960s and 1970s when attitudes began to change. Before the 1970s, for instance, researchers thought almost nothing of using prisoners for experiments, even though prisoners are correctly considered a population for whom true informed consent without coercion is difficult to obtain without special effort. Indeed, in his news story Stobbe recounts an anecdote of a man at Holmesburg Prison in Philadelphia who agreed in exchange for cigarette money to have the skin peeled off of his back and searing chemicals painted on the open wounds in order to test a drug. Similarly, as the Willowbrook story shows us, it was not really all that long ago when scientists apparently felt justified in infecting profoundly mentally retarded children with hepatitis on the basis of at best dubious ethical justification.

Arguably, this willingness to experiment on children who were not normal and who were never going to be able to contribute to society was a holdover from the eugenics movement earlier in the 20th century. It’s important to remember that, however much eugenics was discredited by the Nazis, prior to the Holocaust Hitler was actually quite the admirer of American eugenics policies, drawing inspiration from them. Another factor that is frequently invoked as an explanation for the willingness of American scientists to flout ethical considerations is war, particularly World War II and then the Cold War, the resulting idea that it was “us against them,” and that for us to win would require shared sacrifice in the name of the nation. After all, the scientific primacy of the U.S. was correctly viewed as one of the most critical sources of our economic and military strength. Unfortunately, the lesson derived from that observation was that this primacy needed to be maintained at all costs. Moreover, the concept of the Cold War could be generalized to other “wars,” such as the “war on disease” or the current “war on cancer” that I’ve written about twice in the last month. As Stobbe put it:

Attitudes about medical research were different then. Infectious diseases killed many more people years ago, and doctors worked urgently to invent and test cures. Many prominent researchers felt it was legitimate to experiment on people who did not have full rights in society — people like prisoners, mental patients, poor blacks. It was an attitude in some ways similar to that of Nazi doctors experimenting on Jews.

“There was definitely a sense — that we don’t have today — that sacrifice for the nation was important,” said Laura Stark, a Wesleyan University assistant professor of science in society, who is writing a book about past federal medical experiments.

There was clearly also more than a little hubris at play as well:

It was at about this time that prosecution of Nazi doctors in 1947 led to the “Nuremberg Code,” a set of international rules to protect human test subjects. Many U.S. doctors essentially ignored them, arguing that they applied to Nazi atrocities — not to American medicine.

Finally, with the rise of large pharmaceutical companies in the 1940s and 1950s, increasingly there was more of a profit motive than a purely scientific one. Drugs needed to be tested, and prisoners provided a convenient source of young, healthy men upon which to test new products. Hubris, profit, and a wartime attitude that sacrificing for the good of the nation all swirled together into a mixture toxic to medical ethics during World War II and well into the postwar period. In having defeated the Nazis, we failed to learn a lesson from what had happened in Germany, where one of the most technologically and medically advanced societies then on the face of the earth did horrible things in the name of its ideology.

Yes, it is true that American scientists did not intentionally expose prisoners to freezing water in experiments designed to find better ways of rewarming pilots shot down over frigid waters or sailors who survived the sinking of their ship, as Nazi doctors did. It is also true that American scientists did not intentionally irradiate men’s testicles and women’s ovaries in order to develop a means of rapid sterilization, causing horrific bowel and bladder complications, especially in women, as Nazi scientists did, although American scientists did subject many to various radioactive substances in the name of research. Nor did American scientists inject dyes into the eyes of children in order to try to turn them blue, as Dr. Mengele did. On the other hand, American scientists did, as we have seen, intentionally infect prisoners and mentally retarded children (the same sort of children that the Nazis would have called Lebensunwertes Leben, or “life unworthy of life”) with diseases and then treat them, just as Nazi physicians intentionally infected concentration camp inmates with various diseases in order to determine the efficacy of different treatments or as Japanese physicians did when they intentionally broke the limbs of prisoners and contaminated them with bacteria-laden dirt. American offenses were different in scale and horror, but not significantly different in kind. Unfortunately, it was not until the 1970s, years after the international Helsinki Declaration was first published, until the Belmont Report was adopted and then not until the 1990s when The Common Rule became the basis of all federal regulations protecting human research subjects.

Could it happen again?

Fortunately, as one who now participates in clinical trials and clinical trial development, given the current level of regulation on human subjects research by the federal government, I have a hard time imagining how abuses such as the one’s I’ve described could happen again now. The amount of paperwork, regulation, and oversight of clinical trials has become so burdensome and complex that sometimes I wonder why I or anyone else would want to continue doing clinical research. Unfortunately, Stobbe doesn’t sound too optimistic. Actually, it’s not so much Stobbe, but rather the presidential Commission for the Study of Bioethical Issues, as Stobbe documents in a followup story:

Speakers noted that over the last several decades, as many as 1,000 rules, regulations and guidelines have been enacted worldwide to ensure the ethical conduct of medical research. In the United States, there are rules to protect people in every study done by federal scientists, funded by federal agencies or those testing a product requiring federal approval to be sold.

But that oversight is inconsistent — ethical rules can vary among federal agencies. What’s more, if federal funding or review is not involved, an unethical study could be done and no one in authority would ever know about it.
“We have a leaky system,” said Eric Meslin, director of the Indiana University Center for Bioethics.

Dr. Robert Califf, Duke University’s vice chancellor for clinical research, agreed there are weaknesses.

“It’s night and day and what you could do in the ‘good old days’ with no one knowing about it. But there’s no 100 percent guarantee. There still will be bad things that will happen,” he said.

In terms of pharmaceutical companies, there are clearly loopholes when it comes to overseas studies. Indeed, pharmaceutical companies have been doing more and more studies overseas. Although federal law states that such studies, if they are funded by the federal government or if they are to be used as part of an application for FDA approval of a drug, that is not always enough of a guarantee of oversight:

Last year, the U.S. Department of Health and Human Services’ inspector general reported that between 40 and 65 percent of clinical studies of federally regulated medical products were done in other countries in 2008, and that proportion probably has grown. The report also noted that U.S. regulators inspected fewer than 1 percent of foreign clinical trial sites.

Clearly, this is an unacceptable level of oversight, particularly outside of developed countries, such as those in Europe, where clinical trial oversight is comparable to that in the U.S.

Ironically, two examples come to mind of clinical trials that show the holes in our regulatory system for human subjects protection, both of which I have written about right here on SBM before. The first trial was a trial of homeopathic remedies for infants with infectious diarrhea in Honduras, as I wrote about here. At the time I couldn’t figure out how the investigators at the University of Washington managed to get this study through their IRB, but somehow they did, demonstrating that an IRB is not a guarantee against the approval of totally unethical and scientifically worthless experiments. Fortunately, as far as I can tell, no infant was injured, but the potential was definitely there. Then, let’s not forget the Gonzalez trial, a trial of a regimen of what can best be described as pure quackery consisting of up to 150 supplement pills a day, various nutritional pseudoscience, and daily (or more) coffee enemas. The results were devastating, in that subjects on the standard-of-care chemotherapy arm lived three times longer than those on the Gonzalez protocol arm. Such is the effect of the National Center for Complementary and Alternative Medicine (NCCAM) on research ethics.

The more disturbing example is Mark and David Geier, the father-son tag team of anti-vaccine activists who fervently believe that mercury in vaccines causes autism and somehow came up with an idea that can only be described as dangerously wacky, namely that by suppressing testosterone with a powerful drug (Lupron) they could make the quackery known as chelation therapy “work better” at chelating mercury from the brains of autistic children. The reason? Because “testosterone sheets” bind mercury and keep it from being chelated! In pursuing this research, the Geiers have created an IRB stocked with their cronies and fellow anti-vaccinationists to “oversee” the research, as Kathleen Seidel has so thoroughly documented. In the process, autistic children were subjected to a powerful drug that depresses their sex hormone levels, which is why its use is often referred to as “chemical castration.”

Predictably, Anne Dachel, Media Editor over at the anti-vaccine crank blog Age of Autism, has leapt all over this story as “evidence” that vaccines must be dangerous and that unethical scientists have been lying all along about the science showing tthat there is no evidence that vaccines cause autism:

Either Stobbe is a naïve and trusting soul and can’t consider that the same government that allowed horrific medical experiments in the past also allowed our children to become vaccine guinea pigs, or he’s afraid of an issue that’s just too controversial to talk about here and now. It’s much safer to attack what went on in the last century.

Maybe 70 years from now, some enterprising reporter will bring up the ethics of injecting known neurotoxins in pregnant women, babies, and small children.

Maybe around 2080, they’ll ask why no one ever demanded independent studies on the cumulative effect of so many vaccines, so soon, on the health of a baby. Or why there was never a simple vax-nonvax comparison study looking at autism rates.

Or maybe in 2050, Dachel will cease laying down such burning stupid on a regular basis and realize that this is the sort of work that’s been replicated so many times and done in so many different countries that even if you were to throw out all the U.S. data it wouldn’t change the scientific conclusion that there is no good evidence to support the claim that vaccines cause autism. She also overlooks the fact that the vast majority of the studies that have failed to find a link between vaccines and autism were performed after the adoption of the Common Rule and much-increased federal oversight over clinical trials. Of course, stories like Stobbe’s make it easier for cranks to attack the entire U.S. clinical research enterprise as corrupt and unethical. However, that is not the reason why we need to close the loopholes in our current clinical trial regulations. We need to do it because it is the right thing to do.

When I write about SBM, I argue that medicine should be based on science, rather than be a science, because I realize that medicine can never be completely scientific. There are too many human variables, not the least of which are patient values, individual patient situations, and resources. Another reason is the clinical trial process itself. Sometimes the most scientifically rigorous clinical trial design is not the most ethical design; indeed, sometimes it might be downright unethical. One example is, as I have pointed out, the aforementioned study of vaccinated versus unvaccinated children that seems to be every anti-vaccine activist’s most fervent dream. The most scientifically rigorous design for such a study would be a randomized, double-blind, placebo-controlled trial. However, such a trial would leave half of its participants completely unprotected against potentially deadly childhood infectious diseases, making it totally unethical to perform, even if it could be scientifically and fiscally justified based on existing preliminary data, which it really cannot. This leaves population-based studies as the only alternative, despite their difficulties and shortcomings.

Perhaps a better example is how placebo-controlled trials have almost gone the way of the dodo in cancer chemotherapy trials. Most oncology trials are now designed to test a new drug against the current standard of care or the new drug plus the standard of care versus standard of care alone. This is because our ethical considerations have evolved such that we now no longer consider giving placebos to cancer patients to be ethical unless there truly is no existing effective treatment for their cancer or if we truly do not know if the proposed treatment is better than observation alone and observation alone is currently the standard of care. As I have described before, in clinical trials, there must be clinical equipoise; i.e., based on the scientific evidence as it is known at the time the trial begins, a reasonable scientific assessment of the risks and benefits must conclude that the risks to the experimental group are either minimal or outweighed by the potential benefits. Here’s another thought to chew on. Experiments in which people were intentionally exposed to infectious agents and then subjected to various treatments to cure the disease thus caused are potentially the most scientifically rigorous way of all to test such treatments in humans because they allow control of the start of the infection, the amount of bacteria injected, and many other variables that can’t be so easily controlled in “wild” cases of infectious disease. However, because such experiments violate the precept of, “First, do no harm,” they are utterly unethical and now properly condemned by any physician with a shred of ethics. That we should require laws, rules, and regulations to prevent such unethical experiments by scientists is unfortunately, but scientists are no different than any other person. Not all of them are ethical; some are completely unethical. Some can be corrupted.

There will always be unethical scientists, at least as long as there are unethical people. That’s why we need laws to protect human subjects. However, we must also remember that the protection of human subjects is a balancing act. Go too far in the direction of lax regulation, and incidents such as those described in Stobbe’s article will start to happen again. Go too far in the other direction, and the pace of discovery will grind to a halt. The key to finding the balance is to respect patient autonomy and to provide true informed consent that accurately balances risks versus benefits and to protect patients from any form of coercion. Doing so without making the clinical trial process so onerous that researchers flee the field while at the same time protecting patients from foreseeable harms will be the challenge.

By Orac

Orac is the nom de blog of a humble surgeon/scientist who has an ego just big enough to delude himself that someone, somewhere might actually give a rodent's posterior about his copious verbal meanderings, but just barely small enough to admit to himself that few probably will. That surgeon is otherwise known as David Gorski.

That this particular surgeon has chosen his nom de blog based on a rather cranky and arrogant computer shaped like a clear box of blinking lights that he originally encountered when he became a fan of a 35 year old British SF television show whose special effects were renowned for their BBC/Doctor Who-style low budget look, but whose stories nonetheless resulted in some of the best, most innovative science fiction ever televised, should tell you nearly all that you need to know about Orac. (That, and the length of the preceding sentence.)

DISCLAIMER:: The various written meanderings here are the opinions of Orac and Orac alone, written on his own time. They should never be construed as representing the opinions of any other person or entity, especially Orac's cancer center, department of surgery, medical school, or university. Also note that Orac is nonpartisan; he is more than willing to criticize the statements of anyone, regardless of of political leanings, if that anyone advocates pseudoscience or quackery. Finally, medical commentary is not to be construed in any way as medical advice.

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31 replies on “Revisiting the issue of ethics in human experimentation”

The anti-vax crowd is so convinced that vaccines are a) ineffective b) dangerous or c) don’t care about vaccine-preventable diseases that they’d be more than happy to ignore the ethical implications & volunteer their children for such a study.

Fortunately, despite their relative lack of ethics, the rest of us can’t ignore the fact that purposely not giving vaccines (though saying that we are – since this would be a double-blind placebo study) is exactly a Tuskegee situation.

That’s also ignored by the anti-vax crowd – if you truly wanted to do it right, none of the parents in the study would know if their children were given vaccines or not (meaning that some of the anti-vaxers’ children would receive the full vaccine schedule, on time – oh, the horror for them).

At the end of the day – regardless of how much money is spent & how many studies are done, to the detriment of real science, as long as the studies continue to show no link between autism & vaccines, show that vaccines are still the best protection against childhood disease, and are effective (and not dangerous), they will be ignored by the anti-vaccine mob. They will never agree with anything that disproves their own pre-conceived notions.

We don’t need another layer of laws or deeper regulation; that system has already failed economically.

Our medical systems are becoming intrinsically coercive. If you spend your formerly discretionary income on “insurance” or “tax”, and the third party payer balks, defaults, loots, disagrees with, or outlaws your treatment plan, where does that leave John Q Public? Something between “Nothing” and “Do and/or die”?

Restricting access to long existent drugs or materials of commerce is a common form of medical coercion and market control, some cases with spectacularly disastrous results.

Notice a common theme in the examples above are the governments’ failures, either funding the damned things, granting access to vulnerable groups, or both.

Adding another layer of legal failure probably won’t fix the problems with human nature.

In you list of ethical lapses, don’t forget the willingness of all winning parties to overlook the ethical problems with the Nazi and Japanese experiments and grab the results, in the case of the Japanese with a promise of full immunity from prosecution.

Von Braum & his rocket buddies were instrumental in helping the US put a man on the moon, but they were also guilty of using slave labor during their days in the Reich – so it wasn’t just the Japanese that go away fairly lightly as well.

If the situation had been different at the end of WWII, then more justice would have prevailed, but unfortunately, both sides were looking at the next conflict & wanted to take advantage of what they could from the spoils of war.

@Mu (#3):

I don’t know that using the results of an unethical experiment is itself unethical. Is it really ethical to let people die of hypothermia rather than use the techniques developed by the Nazis in their (horrific) re-warming experiments? Should we just pretend that useful data doesn’t exist if it was obtained unethically?

On the other hand, protecting the researchers from war crimes trials in exchange for their data, as was done with the scientists of Japan’s infamous Unit 731, is awful, and, in that case, didn’t even yield any particularly useful information.

@Mu (#3):

I don’t know that using the results of an unethical experiment is itself unethical. Is it really ethical to let people die of hypothermia rather than use the techniques developed by the Nazis in their (horrific) re-warming experiments? Should we just pretend that useful data doesn’t exist if it was obtained unethically?

On the other hand, protecting the researchers from war crimes trials in exchange for their data, as was done with the scientists of Japan’s infamous Unit 731, is awful, and, in that case, didn’t even yield any particularly useful information.

By the late ’70’s/1980, studying abuses was part of the curriculum. I find it odd that many alt med stories are being told now( e.g @ NaturalNews, by LKH) as though no one else were aware of this very common knowledge. Tuskegee and Guatemala fit in nicely with the “cigarette science”/”corporate sicence” memes. Sometimes they throw back to Jenner.

I had this prof who talked about Cyril Burt in every class he taught: what Burt did, the tell-tale signs, and how his “results” affected social/ educational policy and fit in with long-held prejudices. His punch line was, ” And he was *knighted* for his work!”


Thanks for blogging about this. Times nicely with the start of my series on a vax vs. unvax study over at Harpocrates Speaks.

As I read, I was wondering if you’d bring up the IRB issues. Having sat on a committee for a while now, I can say that there is potential for IRBs to let things through that shouldn’t. An IRB is only as good as the individuals on board, as evidenced by the Geiers.

I’m also glad you touched on the issue of loopholes and how if a study is not funded by or under the jurisdiction of a Federal agency, the Common Rule doesn’t apply.

prn: No, we precisely need the regulations we’ve gotten in the last few years. The abuses detailed here are partly the results of lack of oversight, and partly the results of a society that didn’t recognize that disabled children, the institutionalized elderly, or poor black men are human beings with rights.

Neither law nor your precious market is an effective way of preventing things that are approved by huge portions of the population, including lawmakers and the rich. The market, in fact, was part of the problem in the Guatemala study: poor women were paid to infect men with syphilis. Where is the market fix for that?

A common thread in all the experiments is the dehumanizing of the subjects used in these experiments.

German scientists were a product of the government’s “official” view toward others who didn’t meet the criteria for the “master race”, such as the mentally retarded/mentally disabled, physically impaired and Jews. Only the young and healthy, who might be used as “workers” for the German war effort, were kept alive. Others such as children were used as lab rats for cruel experimentation, before they were exterminated or died as a result of the barbaric “experiments.”

I have seen the “informed consent” form signed by parents whose children were admitted to the “special” Willowbrook medical unit. Dr. Krugman and NY State officials who agreed to the human experimentation played “fast and loose” with parents. Willowbrook’s capacity was originally designed to provide care to 3,000 developmentally disabled individuals, when the actual population reached 6,000, the “school” was closed to new admissions. Conditions at Willowbrook were deplorable at double the original capacity, with transmission of hepatitis and other highly infectious diseases being rampant. Children and adults with the severest of impairments were partially clothed or totally unclothed, lying in their own feces in large cage-like apparatus called “crib cages.” Dangerous understaffing in these warehouse-like wards was abominable and those who didn’t die from neglect were left more impaired, because their basic needs for appropriate care were not met. The “campus” in Staten Island was isolated from public view and it became the dumping ground for children and adults, who were born less-than-perfect.

With the opening of the special medical unit, that was clean, where the “inmates” would be clothed and cared for with enriched staffing ratios, Dr. Krugman and NYS officials now had the perfect unit to “entice” parents to bring their kids. To speed up the results, children were fed and innoculated with live viruses…because they stood a good chance anyway (upwards of 50 %) of acquiring the diseases. I wonder if Krugman and NYS officials who approved this human experimentation ever “held their noses” or put blinders on if and when they ever visited the other parts of the Willowbrook warehouse.

Sheila and David Rothman, professors at Columbia University-School of Public Health published a book (“The Willowbrook Wars”) in 1984 and reissued in 2005, that is a compilation of the conditions at Willowbrook, the “informed consent” that enabled the human experimentation that were conducted and the Federal Class Action Lawsuit/Consent Decree that lead to NYS finally de-institutionalizing those at Willowbrook.

Some would say that regulation of group homes, hospitals and nursing homes is not needed…or that over regulation bogs down the system. Maybe so, when you consider the adding of new regulations without consolidating existing regulations. Efforts have been made in the past to come to consensus about basic human rights…for appropriate care, minimum staffing levels, medical care on site and for meeting the social needs of the mentally retarded and mentally disabled, the frail elderly and others who are receiving out-of-home care, funded by tax dollars. But first and foremost is the pervasive mind-set that dehumanizes sections of our society.

Just another quick insight or two re: IRBs. When a study comes up for review, there is a lot of trust that what the PI submits is actually being followed and that the materials are complete. Usually, missing documents can be discovered because mention was made somewhere in the protocol or consent form. In large part, though, it is a matter of trust.

Also, while most studies are pretty easy to determine whether or not they’re okay to move forward, sometimes the question is not so clear-cut, especially when the research involves cutting edge science. The risk-benefit analysis can be rather difficult at times, and the majority of a committee meeting could focus on one question on a single study. Ultimately, the study may be deferred pending additional info from either the PI or some other expert in the field.

Vicki, I presume the individuals and corporations involved already violated laws that need to be prosecuted somewhere. More unenforceable, broken laws aren’t an effective answer, and have long term detrimental social effects themselves.

For individuals, even more such laws may be threat to choosing and implementing the best technologies as they might see fit from the doctors and countries’ research, of their choice. The corporations actually feed off exploitation of the arbitrage of legal differences between countries. More laws = more food.

I not promoting potential experiments on other people, I am considering treatment options available, or not, to intelligent people trying to choose the best medicine they can(not) find. I’ve already been down that road, and I am voting for “not one more”.

There is a lot of legal ledgermain and interference going around the US, then being exported as copycat regulations overseas. A lot of people are fed up and sick to death of US corporate games.

Could it happen again?

“Fortunately, as one who now participates in clinical trials and clinical trial development, given the current level of regulation on human subjects research by the federal government, I have a hard time imagining how abuses such as the one’s I’ve described could happen again now.”

Russian prosecutors probe vaccine trials

More than 100 children between the ages of one and two were given the vaccines during the trails, which have since been halted, the statement said.

Prosecutors said the deputy director of the hospital had been paid $50,000 to participate in the trials and that such tests on minors were illegal in Russia. They also said parents had been told the vaccines were humanitarian aid.

Homeless people die after bird flu vaccine trial in Poland

Three Polish doctors and six nurses are facing criminal prosecution after a number of homeless people died following medical trials for a vaccine to the H5N1 bird-flu virus.

Human Guinea Pigs

Unusual as it is, the Oklahoma case isn’t an isolated incident—and in many ways, it isn’t even the worst.

At one extreme are those who believe that most trials are tainted because they play on the fears of desperately ill patients, involve some sort of subtle coercion like money or free medicine or fail to warn patients of the very real dangers they face.

One issue that can come up with informed consent forms, especially for minimal risk protocols is that they can be too complete. For example, for a protocol in which the patient is asked for a single 5 ml blood sample, which will be analyzed for a single RNA product, the consent form is 8 pages long. The consent is actually far more intimidating to a lot of patients, especially those not terribly at home with reading, than the experiment itself. I’d like to see some level of streamlining this process so that patients don’t end up feeling traumatized by the very informed consent intended to protect them.

prn – you seem to think that US corporations (really a misnomer – since most corporations are based overseas in nice tax safe havens) have cornered the market in “suspicious” behavior, why is that?

It seems that the lack of any or enforceable regulations have seen much larger problems develop overseas, particularly in China & India. These corporations (mostly government sponsored or controlled) export counterfeit drugs, chemical-laced drywall & toys, etc, etc, etc.

At least in the US, there is some teeth to our regulatory agencies (and if they are flawed, we at least hear about it).


Yeah. Not only that, but imagine being faced with a 15-20 page consent form as you’re being prepped for surgery. Due to the nature of some research, it may not be possible to give potential subjects much time to read and consider whether or not they wish to participate (e.g., emergency situations).

The main IRB office here has seminars on how to write ICFs to help make them simpler to understand. When they come up for review, we also take a look to see if it is too complex or not complete enough. That’s where laypeople like myself come in handy.

“I refer to “science-based medicine” (SBM) as “based” in science, but not science, largely because medicine can never be pure science.”

Interesting. Does that apply to causation as well as to cure?

Todd, I typically have my partner, who is not in the medical field at all, look at my consent forms before submitting them to the IRB. If he bursts out laughing or looks chronically puzzled, I know they need work…

Part of the problem is that there is standard information and language that must be included in every consent form regardless of what it’s for. This can obscure the important parts of the consent, especially in situations like the one you mentioned where time is short and the patient and/or surrogate may be distressed and distracted.

I’m not sure what the best way to solve this problem is, but I’m really not happy with the current situation either from the point of view of a researcher or of a doctor trying to help the patients make a good decision about their care. Or as a potential research subject for that matter.


In situations where the length of the CF can get in the way of the consent process (like in emergency situations), for us there is the possibility of using a short form that hits the important parts, but leaves the lengthier explanations and legal bits to the long form. There are also provisions for using a patient advocate to enhance protection during the consent process.

It’s a very tough situation sometimes, straddling a very fine line between inadequate information for informed consent vs. too much info that bogs everything down.

prn — It isn’t just attitudes that have changed, it’s laws. Yes, there are abuses that go on despite being illegal (go over to Ed Brayton’s blog for examples of police abuses being forgiven or normalized). But the laws have also changed. IRBs are relatively recent, for example.

The other thing is that your rant has nothing to do with this issue. Protecting retarded children from being used as guinea pigs won’t reduce your ability to buy whatever drugs you like. It’s a red herring here. So either you’re threadjacking because you hate single-payer enough that you’d drop it into a discussion of the All Star Game if you could make people listen, or you actually think children, prisoners, and the disabled have too many protections. Or, and I really hope this is the case, you’re making a logical error, and seeing connections that aren’t there.

If everyone will pardon a shameless plug, here’s a recent “fan fic” chapter that I think touches on these issues:

The most disturbing line I came up with was, “Doctors are used to thinking situationally, even when they aren’t in a war zone.” It also occurs to me that, having bounced the idea of the “Angels” off several people, I have yet to notice incredulity as a response.

Vicki, I presume the individuals and corporations involved already violated laws that need to be prosecuted somewhere.

Don’t presume. What laws were broken? Let’s start with Tuskegee, to be concrete.

DW: “I had this prof who talked about Cyril Burt in every class he taught: what Burt did, the tell-tale signs, and how his “results” affected social/ educational policy and fit in with long-held prejudices. His punch line was, And he was *knighted* for his work!'”

Aye, knighted for being a lying get.

I’d have knighted him. With a sodding frying pan!

I haven’t especially noticed lots of corporations from India and China filing NDAs for novel new drugs in the US. Yet, anyway.

The US already has a lot of laws, enough, including the IRBs and other protections. There is a nexus driving “subsidized” experiments with (recently, FDA made) unavailable materials. This really does threaten the health of many involved. We don’t need whole new CFRs added that will further restrict access to anything, which is what new laws do, and is implied by Orac’s text.

I’ve dealt with family members nearly being “protected to death” several times in the recent past on generic medical substances egregiously unavailable in the US. e.g. “everywhere but the US”, FDA: “Grandfather?? shoot the old coot”; DEA: “low toxicity HIF angiogenesis inhibitor with decades of safe dosing? schedule it” Things that have claims to superior uses. So horsepucks on more legislative “wealth creation”. Single payer, FDA-DEA, and the mutated EBM (different than the original advocate/defenders expressed) combined to “rationalize” medicine in the US are corporate gatekeepers’ wet dream for obsolescence-volume-price protection. I’m sure I disagree at various points with Orac and others, but some form of SBM that includes rational individuals, and experimentation, in its vision are more my requirement.

@Beamup -#21:
What laws were broken in the Tuskegee case? Let’s see. Syphilis has been a reportable disease in most of the US for many decades. There’s a law broken. The wives of the men were exposed to a serious, potentially fatal, disease without being informed by the physicians. Depending on local law, that could be reckless endangerment or could even be construed as assault. Promoting the spread of a communicable disease falls under a basket of laws. The knowing withholding of a remedy for a serious illness by a physician is certainly malpractice and again depending on local law can be a criminal act. I am not an attorney, but I am sure a good prosecutor could find a fair-sized array of charges without breaking a sweat.

Fascinating post Orac, as it happens I’m reading “The Immortal Life of Henrietta Lacks” which covers a lot of the same ground that you do.

The laws governing clinical research need to be overhauled to close the loopholes, but it would also be a good opportunity to streamline the process for obtaining approval for large multi-center trials, which can currently get bogged down in multiple IRBs.

By the way Dario Ringach has a great post on the Speaking of Research blog on the latest efforts by PeTA to compare animal research to past unethical human subject research.

Yes, Justin Goodman of PeTA really is comparing David Jentsch to the Tuskegee doctors. I guess it’s not only scientists engaged in clinical research who are affected by the unethical conduct of past clinical researchers.

Vaccination is an organised criminal enterprise dressed up as disease prevention and a gigantic medical experiment on the human race without informed consent and without a control, in direct violation of the Nuremberg Code set up to prevent such medical abuse.

As many articles continued to address the unethical conduct of past clinical researchers and current illegal human experimentation, you must address the illegal human experimentation by the U.S. government as well. In light of the Washington Post article entitled ‘A Top Secret America’ and ‘Monitoring America’ you will find trillions and trillions of dollars spent on the illegal testing or war weapons on U.S. civilians. Weapons such as biochemical sprays in the form of ‘chemical trails’ also known as chem-trails, the Defense Appropriations Budget detailing the deployment of direct energy weaponry testing across the United States and the testing of other biochemicals in the testing of ‘mass destruction’ technology. These illegal activities have been despised for decades with nearly 68 percent of U.S. citizens included in this unethical testing. In researching these acts you can such Defense Approapiations terms as ‘War Games’, Direct Energy Weapons testing, Biochemical Testing, and Asset Management. These are the acts of our government and the continued illegal experimentation, so let’s add these acts to the pill of illegal medical experimentation. What those physicians are not aware of is that they to, and their families are test subjects.

DM @ 29:

in the form of ‘chemical trails’ also known as chem-trails

oooOOOooooo…a real, live chemtrailer! Wait, wait, imma get my tinfoil hat first…OK, go on…

I can find evidence that the Washington Post did article series titles “A Top Secret America” and “Monitoring America”.

I have not yet found any evidence that any of those articles describes the subjects of ‘chem-trails’ or Direct Energy Weapons that Darlene Miles claims.

I would certainly re-examine the evidence if someone provided specifics, i.e., naming the actual article instead of simply the umbrella title under which it appeared.

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