(Picture taken by Thomas Tu)
On this blog, you’ve read a lot about awesome science things like diseases, placebo effect, rockets made out of lasers, etc. However, beneath the awesomeness, there are a huge number of ethical issues in science. Science, biology in particular, has formed vast areas of ethics philosophy. Today I’ll focus on one case, which involves the Willowbrook State School Hepatitis studies.
The year is 1956. Elvis would enter the music charts for the first time, the Olympic games would start in Melbourne, Werner Forssmann would share a Nobel Prize for threading a tube up his own an arm vein, into his heart then taking an X-ray of himself (a story in itself). Meanwhile, virology (the study of viruses) is just getting off the ground. Dr. Krugmann and his team see a need for characterising and controlling the spread of infectious hepatitis.
Meanwhile at Willowbrook State school, a New York-based institution set up for mentally-handicapped children, excess demand for their services and severe overcrowding has become a huge problem. Originally built for a capacity of 3 000 children, Willowbrook now houses >6 000 and more families are lining up to drop off their high-maintenance, mentally-retarded children. To quote the director of Willowbrook, Dr. Jack Hammond: “The overcrowded conditions in the buildings make care, treatment, supervision and possible training of the patients difficult, if not impossible. When patients are up and in the day rooms, they are crowded together, soiling attacking each other, abusing themselves and destroying clothing. At night in many dormitories the beds must be placed together in order to provide sufficient space for all patients. Therefore, except for one narrow aisle, it is virtually necessary to climb over beds in order to reach children”.
Both adults and children alike are being infected continually with respiratory diseases, gastrointestinal infections and hepatitis. 2.5% and 4% of all children and adults respectively in Willowbrook show symptoms of hepatitis. Dr. Krugman and his team start investigating the infectious hepatitis aspect with the approval of the school, government bodies and the Armed Forces.
After looking closer at the blood of students and teachers, Krugman et al. found that almost all of them had contracted hepatitis before. They had both the mild liver damage and the antibodies that were associated with infectious hepatitis. It was almost inevitable that these people would get it once starting their term at Willowbrook. But how was it being transmitted between these people?
The case
To answer that, Krugman et al. designed what would become one of the most controversial studies in biological history. They took filtered blood and faeces from infected patients and either injected or fed them to new arrivals to the school not yet exposed to the conditions of Willowbrook. Through these studies, it became obvious that there were actually 2 agents responsible for the hepatitis; agents we now know as hepatitis A and hepatitis B viruses.
As an added result from this work, they developed two ways of preventing the infection of hepatitis. They found that if you purified the blood of patients who had overcome hepatitis and injected it into new arrivals, that you could prevent infection. This is because the antibodies in the cured patient would neutralise the virus that infected the new arrival. Hepatitis B antibodies (although not manufactured in this way anymore) are still used today in people who have recently been exposed to the virus.
Also, they showed that if you boiled a tube of diluted purified blood of patients with the virus, you can inject it into new arrivals and prevent infection. This works because the boiling breaks up the virus so much that it can’t infect the patient effectively, but the body still produces antibodies against it. These antibodies can neutralise any virus that the patient is exposed to. This mechanism is how the current day hepatitis B vaccine works.
Back to the ethical aspects of the work, when the findings were published and the media caught whiff of it, there was a huge outcry (understandably). Death threats towards scientist and staff were not uncommon. Was this vitriol justified?
There are several points that Krugman later brings up and emphasises in a defence for the ethics of the work:
- The disease was rampant in Willowbrook and the children would no doubt have been infected anyway. This was clear in the initial results where >90% of tests were positive for infectious hepatitis antibodies.
- The disease was generally benign in children. They rarely felt any ill-effects from having the infection. However, I must say that it is known now that most of these children would have life-long chronic infections of hepatitis B, which dramatically increases their risk of cirrhosis and liver cancer (~25% of patients with chronic hepatitis B infections die because of it).
- They only accepted into the study children whose parents had given informed consent. No children who were wards of the state or were orphans were part of the study. The main purpose of conducting the studies here were because the disease was bound to happen anyway, not because they were easy to get consent from.
- Children who were infected were isolated in a special unit to prevent contamination of results. This also had the effect of protecting those children from other endemic diseases in the facility, such as respiratory infections, shigellosis and indeed other hepatitis.
I think personally I am convinced by his defence. Though a study like this would most likely never be approved by today’s ethics boards, with the available knowledge that they had then justification for the study stands fairly strongly. I am informed that this case is still a major talking point in bioethics classes. Maybe some of you guys disagree and think he’s a monster. I would like to get a discussion going on here in the comments.
Some potential talking points:
- Were Krugman and his team ethically justified in carrying out this study?
- What is the difference between letting someone into a situation where they will eventually be infected with hepatitis and intentionally infecting them, if any?
- There was a >90% chance that these patients would have gotten infected anyway, but what if it was only 75%? 50%? Where do you draw the line?
Study results at http://pediatrics.aappublications.org/cgi/reprint/22/5/1016
Krugman discussing the ethics 30 years afterwards at http://www.jstor.org/stable/4453816
TT
I think the real ethical problem in this situation is the fact that the institution kept on accepting new people despite the overcrowding. Was it was ethical of the Krugman team to take advantage of this situation? Assuming he couldn’t do anything about it, I suppose you could say it was an ethically viable act.
@Jillian: The Willowbrook institution was the biggest one of its kind in the country at the time. Demand for support far exceeded supply. And most probably in at least some cases, they were better taken care of at Willowbrook than they otherwise would if they were not accepted.
According to Krugman, the staff were under pressure from parents and their legislators to accept more children than capacity. Krugman remarks that “it was “society” that was responsiblel for the overcrowded, unhygenic conditions in Willowbrook, not the dedicated people who worked there under stressful conditions”.
I tend to agree with you Thomas. Personally I feel that for the era and the situation he was relatively justified in carrying out the study- if it was indeed true that most children would get Hepatitis anyway. I would be interested to know what was known about anitbodies at the time- as it seems fairly groundbreaking to develop a vaccine without any idea what they were doing. The fact that their work lead to a viable and positive outcome works in their defence; that is the cost appears to be out-weighed by the benefit.
A hypothetical situation though: I wonder if we would still see it as ethical if a large group of the children came forward in a civil suit, now older and as you suggest suffering chronic diseases, and the study hadn’t actually found any benefit- ie the study hadn’t found a vaccine. We would likely sympathise with the ‘children’ as they did not give consent- only their parents. Perhaps it would change our view on whether the study was ethical- even though the actual situation and reasons behind the study were exactly the same.
@Michelle: I mean, yes, it’s good that there was a positive conclusion to the study, but I don’t think that’s really a sturdy ethical defence. If you go the “ends justify the means” route, you start to justify horrible things like Dr. Mengele’s experimentation on concentration camp prisoners and the human experiments of Unit 731 (both fascinating and depressing subjects that I may write future articles about). In both of these instances, highly valuable medical data was produced (Ever wonder where the information of what pressures are needed to kill a person or all the human toxicity data associated with some chemicals comes from? Partly from these kinds of studies). But ask any reasonable person and they would be immediately seen as unethical.
I’m actually not sure how advanced the knowledge about antibodies was at that stage, but I’m quite sure they were known about. Other vaccines had been developed and used for quite a while (rabies and smallpox, just off the top of my head).
I think it was totally unethical to inject the “patients” with untreated blood and faeces (or their extracts). It was well known that viruses and bacteria are carried in blood and some in faeces. It wasn’t LIVE smallpox virus that Jenner used; he used a “weaker” cowpox virus. I think they were viewing these experimental participants as laboratory animals, not as humans. Whatever happened to the old US ideal of equal rights? To my way of thinking the ends did not justify the means- they thought of denaturing the virus through boiling, so they could have done that in the first place.
Yes, it was known that virus and bacteria were present in bodily fluids in general. However, in this particular case it wasn’t known whether the agent behind the infectious hepatitis was in the blood or the faeces. Without knowing that, the group could not even start to treat or prevent the hepatitis.
The group filtered the extracts with very fine filters, so they were sure they were only letting through viruses and no bacteria.
Regarding the boiling, if they did boil the solution beforehand and given it to the kids, the results would not have been very strong. If no antibodies were found after injection with the filtered blood, was it be because the virus wasn’t in the blood, or was it because the boiling completely tore the virus apart so that the immune system could not recognise it? There are some viruses that aren’t able to be inactivated by heating, so there’s still risk of infection. If the data wasn’t strong, even more patients would have been put through these experiments and put at risk to increase the reliability of the results.
Re: Jenner. I beleive he did infect the child with live small pox after the initial cowpox virus. In fact, during Jenner’s time, it was standard practice to infect people with very small amounts of smallpox in an effort to induce protecting. In ancient China, this was done by snorting the dried scabs from smallpox patients!
Re: equal rights. They required consent from the parents before carrying out the experiments. This also was standard practice at the time for children as experimental subjects, disabled or not. It is the same now in fact, although ethics boards are much more stringent in what you can and can’t do these days.
TT
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Although I believe that the Hep vaccines have saved many lives. It was morally and socially wrong to submit these CHILDREN to such atrocities! How anyone can believe that these test subjects should have been fed Feces, injected in their bodies against their wills and let me tell you I work with previous Willowbrook “students” they certainly do not remember it as a good thing! When speaking about ethics there is not a chance that any of his testing was appropriate. would any of you submit your children to such testing? do you think that informed consent was really and truly informed??