When I was in undergrad, I had a medical ethics professor that liked to give seemingly simple examples. It’s wrong to kick a kid, he would say, and the class would nod in agreement.
Then he would expand upon the situation. It’s wrong to kick a kid to find out what kicking a kid does, he would say, and most of the class would still be nodding. It’s easy to infer that kicking a kid will probably just result in a crying kid.
Eventually, the situation would become so complicated that what used to be unanimous agreement would become this shattered, spiraling conversation on just what would make it okay to attack a child. Would it be okay to kick a kid if you got $1000? Probably not. Would it be okay to kick a kid if there was a 5% chance of preventing other kids from being kicked in the future? That seems like low odds. But is it okay at 25%? 50%?
I wanted to start this show off with an example of unethical human experimentation that, honestly, doesn’t have much information available about it. What we do know is that in the early 1940s, Dr. William C Black studied 23 very young children with herpesvirus and infected at least two of them with herpes virus on purpose to see if the virus caused herpes.
Viruses were not 100% understood in the 1940s. Tobacco mosaic virus was first discovered in 1892, and by the 1920s, a multitude of viruses had been written about in academic literature. However, the prevention and treatment of viral diseases was still pretty nebulous. While bacteria seemed to be defeated by the Golden Age of Antibiotics, the treatment of viral infections relied greatly on the body’s ability to just take care of itself. If you just wait long enough, many viral infections will just go away.
You’ve probably heard of herpes before, whether as a cause of genital lesions or cold sores around the mouth.
Today an inflammation of the gums and surrounding areas that is specifically caused by herpes simplex is referred to as herpetic gingivostomatitis. The main symptoms of this disease include anorexia, fever, headache, ulcers, and severe mouth pain that prevents one from eating or drinking. It causes these painful, whitish-gray sores on the gums, just beneath the teeth. It almost looks like a new set of teeth coming in. The disease usually happens to very young children and young adults.
In the 40s, the connection between the herpes simplex virus and what we know now to be herpetic gingivostomatitis symptoms was not completely understood. It was known from research done in 1932 that herpes simplex in adults can cause oral inflammation. There was some previous research done that showed that the herpes simplex virus was often found in the lesions of Vincent’s stomatitis patients. Dr. Black wrote that “these observations, the only ones of their kind in literature, may be accepted as proof that the herpes simplex virus is present with a high degree of regularity in the lesions of acute infectious gingivostomatitis. This important finding certainly provides a promising etiologic hypothesis but is scarcely sufficient evidence to establish proof that the virus of herpes simplex is the cause of this disease.”
In children, the collection of symptoms was referred to as acute infectious gingiovostomatitis, or Vincent’s stomatitis, or--in young adults--trench mouth. Soldiers in the trenches during WWI, lacking dental care, would have similar instances of painful gum decay. Multiple causes, both bacterial and viral, can result in trench mouth or a collection of trench mouth-like symptoms.
So, Vincent’s stomatitis had a clear set of symptoms, but the cause of the disease was unknown. It can be hard to tell what the exact agent behind a disease is, especially because a place as unsanitary as the mouth can be filled with thousands of different kinds of bacteria and viruses.
The predominant theory at the time about the cause of Vincent’s stomatitis was that it was caused by a fusospirochetal infection, or a specific type of bacterial infection. Fusobacteria and spirochete species were well documented as present in cases of trench mouth. Other well known species of spirochete include syphilis, which Dr. Black was very familiar with and had published papers on it in the past. Dr. Black did not believe that fusospirochetal infection was the cause of Vincent’s stomatitis. Instead, he believed that the herpes simplex virus present in the infected tissue was the cause of the disease.
Dr. William C. Black, seeing an opportunity to prove cause-and-effect, selected 23 children at random from his patients, at least one only 12 months old, and exposed at least two of them to herpesvirus infected tissues in order to prove that the multiple symptoms of Vincent’s stomatitis were caused by the single type of herpesvirus.
The children had been “volunteered”. There’s no real explanation as to what “volunteered” truly means, or if the children or their parents knew that “volunteering” would give them herpes.
So the study worked as follows:
“There were 23 consecutive personally observed cases of acute infectious gingivostomatitis and 22 control cases, 13 of which manifested oral inflammations not characteristic of acute infectious gingivostomatitis, whereas 9 were normal healthy children. One of the latter group was a healthy volunteer for oral inoculation with the virus of herpes simplex.”
And here is a description of that volunteer:
“SD, a white girl 12 months old, was offered as a volunteer for inoculation with material from a typical “cold sore” of the lip of an otherwise healthy adult...The gum above SD’s upper left central incisor was scarified with a sterile needle and directly inoculated with material from two of the intact herpes simplex vesicles...On the third day her rectal temperature rose to 101.6 F. The following morning she would not eat...All the gums were red and slightly swollen...She vomited twice during the night...There was pain on eating. The breath had become very foul. Solitary small white ulcers had appeared on the upper and lower lip...The gums were swollen, intensely inflamed, tender and loose, and bled easily. Small white ulcers studded the insides of the lips, the tongue, and the anterior pillars.”
She recovered from this condition after 15 days.
And here is a description of the second person inoculated:
“On the same day as the primary inoculation of SD, RM, a white boy 6 years old, was inoculated into the scarified gum with fluid with one of the WB herpes simplex lesion vesicles.” He quickly recovered and didn’t show such extreme symptoms as the younger volunteer.
Dr. Black also wanted to see if being infected with herpes simplex once would prevent it from reinfecting you in the future. He did the following experiment:
“Four cases were inoculated with the CP strain one, one and one half, two, and seven months, respectively, after the onset of the disease. In no case did any symptoms or lesions develop. The inoculations were made by scarifying the upper anterior gum with a sterile needle and rubbing the virus (mashed rabbit brain) thoroughly into the abrasion”. These presented no herpes symptoms.
So, basically, whenever herpes virus was collected from a lesion sample or a lip sample, they could either expose rabbit corneas to it, and if it formed a lesion on the rabbit cornea that meant that the herpes virus was present. They also injected it directly into the brains of the rabbits, and if it was present it would kill the rabbit, and then they could recollect it, which is what they used in this experiment. They also did the same thing with mice to check the same different strains of herpes virus that they were isolating, where they would inject it into the brains of the mice. If the mice died, then the herpes virus was present, and if they didn’t die, then it wasn’t present.
The children quickly displayed the known set of symptoms, giving strong evidence that the herpesvirus was what caused the Vincent’s stomatitis. Dr. Black sent the results of this work to the Journal of Experimental Medicine, where it was quickly rejected by Dr. Payton Rous. Dr. Rous wrote an editorial in response that has themes that will echo through most all cases of unethical human experimentation.
“I cannot let this occasion pass without saying that in my personal view, the inoculation of a twelve month old infant with herpes virus obtained from an adult was an abuse of power, an infringement of the rights of an individual, and not excusable because the illness which followed had implications for science. The statement that the child was ‘offered as a volunteer’--whatever that may mean--does not palliate the action.” (AHRP.org)
Dr. Black bounced back from this rejection and instead sent the manuscript to the Journal of Pediatrics, where it was published in 1942.
So what, exactly, was Dr. Black trying to achieve? He did want to prove that the herpes simplex virus led to Vincent’s stomatitis. He did have a thorough understanding of the important link between diagnosis and treatment. In a previous study he did on syphilis, he wrote:
“It is of great importance that the diagnosis of syphilis, whether congenital or acquired, be certain before treatment is started because of the prolonged, expensive, and heroic specific therapy which is essential for its cure.”
However, proving that a virus was the causal agent of Vincent’s stomatitis would not lead to more effective treatment. Antivirals for herpes viruses didn’t start development until the 1960s. Even today, most viral infections, including herpes, are only managed by antivirals, not cured by them.
Dr. Black even seemed to be aware of this. In the conclusion of the paper he wrote:
“No specific treatment for the disease is known. General supportive and local hygienic procedures may be relied upon to be followed by complete recovery.”
Without antivirals, or any proper form of treatment, what is the significance of proving that herpes is the cause of Vincent’s stomatitis? Yes, he was able to quickly prove that herpesvirus caused herpes, which is a valid scientific discovery, but there are other methods of gathering evidence that are not infecting 12 month olds. For example, you could compare the presence of herpesvirus in diseased individuals to the presence of herpesvirus in those without the disease.
He also could have disproved the fusospirochetal hypothesis by using antibiotics. If you have the flu, which is caused by the influenza virus, and you take antibiotics, it will not get rid of your flu, because antibiotics target bacteria, not viruses.
If antibiotics removed the possibility of bacterial infection, but the disease persisted, then that was evidence for a viral cause. Dr. Black probably performed the experiments before penicillin was available for pharmaceutical use--while it was discovered in 1928 by Alexander Fleming, the first patient treated with penicillin was not until March of 1942. However, Dr. Black could have used one of several sulfur-based antibiotics or Salvarsan, which was known to be an effective treatment for syphilis.
Of course, there is the possibility that you could mistake the natural course of the viral infection for the antibiotics being effective. If the herpes infection sort of goes away on its own after 15 days, and an antibiotic treatment course lasts for two weeks, it would seem like the antibiotics cleared up the infection.
So this is a case where the difference between right and wrong seems very clear. It’s wrong to kick a kid just to prove that kicking a kid causes crying. It’s wrong to infect a kid with herpes simplex just to prove that it causes a specific disease. Due to what was known at the time, proving that herpes simplex was the culprit would not have improved their health outcomes. So that means that kicking this particular kid would not even prevent kids in the future from getting kicked.
Not every case of unethical human experimentation is so clear cut. There are many cases where “this is good” and “this is bad” is not so clear. But it is common that in the search of a valid scientific discovery, doctors and researchers will basically cut ethical corners. And in the case of Dr. William C. Black, where so little is known about how the parents were informed, how any of the older children were informed, if any of the publishers he was sending to really knew what was going on, if there really was any form of informed consent in this study at all--in this case there were a lot of ethical corners that were cut. And it is from these sorts of blatant cases of unethical human experimentation that we can learn to apply ethical principles to cases that are more complex.
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