Jenner tests smallpox vaccine - HISTORY
Humankind has benefited from vaccines for more than two centuries, but Using material from her lesions, Jenner inoculated James Phipps. Edward Jenner was an English country doctor who introduced the vaccine with cowpox, into a cut made in the arm of a local boy, James Phipps. The full results of his study were published in , but his apparent discovery was met with. Edward Jenner inoculated 8-year-old James Phipps with matter from a cowpox sore on the hand of milkmaid Sarah Nelmes. Later, Jenner exposed the boy to smallpox through variolation—a process in which pus was Did you know? VACCINE HEROES · EDUCATION · MEET THE GERMS · Order Trading Cards · Claim.
Jenner's understanding of the cuckoo's behaviour was not entirely believed until the artist Jemima Blackburna keen observer of bird life, saw a blind nestling pushing out a host's egg. Her description and illustration of this were enough to convince Charles Darwin to revise a later edition of On the Origin of Species.
He attended many lectures on chemistry, medicine and physics. Jenner married Catherine Kingscote died from tuberculosis in March He might have met her while he and other fellows were experimenting with balloons.
Jenner's trial balloon descended into Kingscote Park, Gloucestershireowned by Anthony Kingscote, one of whose daughters was Catherine. Oil painting by an English painter, c. Jenner did this by inoculating James Phipps with cowpox, a virus similar to smallpox, to create immunity, unlike variolation, which used smallpox to create an immunity to itself.
ByEnglish physician John Fewster had realised that prior infection with cowpox rendered a person immune to smallpox. Jenner may have been aware of Jesty's procedures and success.
The initial source of infection was a disease of horses, called "the grease", which was transferred to cattle by farm workers, transformed, and then manifested as cowpox.
Dr Jenner performing his first vaccination on James Phippsa boy of age 8. He scraped pus from cowpox blisters on the hands of Sarah Nelmes, a milkmaid who had caught cowpox from a cow called Blossom,  whose hide now hangs on the wall of the St George's medical school library now in Tooting.
Phipps was the 17th case described in Jenner's first paper on vaccination. Later, he injected Phipps with variolous materialthe routine method of immunization at that time.
The boy was later challenged with variolous material and again showed no sign of infection. Smallpox is more dangerous than variolation and cowpox less dangerous than variolation. If target is infected with cowpox, then target is immune to smallpox.
If variolation after infection with cowpox fails to produce a smallpox infection, immunity to smallpox has been achieved. Immunity to smallpox can be induced much more safely than by variolation.
Donald Hopkins has written, "Jenner's unique contribution was not that he inoculated a few persons with cowpox, but that he then proved [by subsequent challenges] that they were immune to smallpox. Moreover, he demonstrated that the protective cowpox pus could be effectively inoculated from person to person, not just directly from cattle.
James Gillray 's caricature of Jenner vaccinating patients who feared it would make them sprout cowlike appendages. After revisions and further investigations, he published his findings on the 23 cases, including his 11 months old son Robert. They would also ask whether subjects will be paid for their trouble or given any free medical care, and if they will be, is the amount to be given to them so much that it could compromise their ability to make an authentically free choice without undue inducement?
Will the individual volunteers be adequately protected? Will their well-being take ultimate precedence over any social or scientific benefit that the investigator might want to achieve? Will the researcher be able to protect subjects against the kinds of hazards that might result from a failure of the experiment? Let us now examine each of these four categories of ethical concern. In Jenner's time, of course, there was as yet no notion of double-blind, placebo controlled studies, so a committee in his time would not have required anything in the nature of a control group.
But they might have been concerned whether there was anything at all even resembling a control group in his study with which he might compare his test results. Of course, having a strictly defined control group would have required having an equal number of subjects who received some kind of "placebo vaccination," who would then have waited the same length of time that the test subjects waited, and who would then also have been deliberately challenged with a dose of virulent smallpox pus, as were the test subjects.
This control procedure is exactly what the Nazi doctors did in their typhus vaccine experiments in Buchenwald and Natzweiler concentration camps during World War II. This practice was strongly condemned at the Nuremberg Trials as highly unethical, since the control subjects were put at maximally high risk for lethal typhus infection.
In Jenner's case, however, the practice of attempting such infection with smallpox i. Thus, perhaps Jenner did have something resembling a control group after all, viz. If these "controls" were to be challenged with smallpox infection by the method of variolation, they would theoretically have an acute reaction to the procedure, just as did all other variolated persons.
When Jenner's subjects who had been "vaccinated" as Jenner's cowpox immunization came to be called were challenged by the method of variolation, however, Jenner expected them to have no negative results from it at all.
Therefore, although Jenner did not have a strictly defined control group of subjects who were like his test subjects in every variable except one, he did nevertheless have a theoretical group of controls in the general population of non-"vaccinated" persons who had been successfully variolated.
Preliminary evidence Was there sufficient preliminary scientific evidence gathered prior to the experiment to suggest a good likelihood that the trials would be effective? On the application form, Jenner details six kinds of supporting evidence: The accepted notion that persons who have contracted smallpox once, whether by the practice of variolation or by a naturally acquired infection, did not seem to contract smallpox ever again. This evidence supported the notion that immunization against smallpox was at least possible.
Jenner On Trial: chapter 5
Substantial anecdotal evidence and local folk wisdom among dairymen and their families to the effect that anyone who had once contracted cowpox would not ever contract smallpox.
This anecdotal evidence supported the notion that naturally acquired cowpox infection could immunize a person against naturally acquired smallpox infection. Jenner's attempts to variolate i. These attempts at variolation led, as we saw earlier, to no acute reaction to the smallpox. This evidence supported the notion that naturally acquired cowpox infection could immunize a person against artificially induced smallpox infection.
Jenner's experiment with his ten-month old son Edward, Jr inin which he inoculated the child with swinepox pus to see if an artificially induced swinepox infection would protect him against infection with smallpox. Several weeks later, after young Edward had healed from the mild swinepox disease, Jenner challenged him with smallpox pus by means of variolationand this attempt led to no reaction whatsoever.
This evidence supported the notion that an artificially induced pox infection even though it was swinepox rather than cowpox could immunize a person against artificially induced smallpox infection.
The Newgate jail experiment with six variolated prisoners, which experiment was designed to prove the safety of the practice of variolation. Jenner used this evidence to argue for the safety of deliberately inoculating challenging with smallpox, and thus for the ethical propriety of deliberately infecting, or trying to infect, a person with a lethal disease.
The longstanding practice of variolation throughout England for the previous sixty or seventy years. Jenner also used this evidence, as he used the Newgate jail evidence, to argue for the safety and the ethical propriety of deliberately challenging subjects with smallpox.
Whether the experiment with his son would itself have passed an ethical review seems to me rather questionable, particularly due to its serious lack of prior evidence that swinepox protected anyone against anything, let alone against smallpox. In light of the lack of any such evidence anecdotal or otherwisefor Jenner to deliberately attempt infecting young Edward, Jr with smallpox - seven separate times - on the belief that he was protected against it by his prior infection with swinepox, seemed like a great leap of faith at best.
It would seem that an application for scientific or ethical review of this experiment would have found serious fault with Jenner for attempting it. This distinct possibility now raises the question of whether it is ever ethically permissible to use data discovered in an ethically improper experiment. Should data from unethical experiments be considered as inadmissible evidence, and therefore never to be used?
Should such data perhaps even be completely destroyed? The concerns raised by these questions may apply as well to the Newgate jail experiment inan experiment which Jenner uses as evidence for the safety of the practice of variolation. He could also have used it as evidence in support of the claim that artificial inoculations can produce efficacious immunity against smallpox, though with only one subject the nineteen year old woman involved in the efficacy portion of the experiment, it would be very weak evidence indeed.
The Newgate jail experiment would also likely not have passed ethical review with an ERC for three reasons: For these reasons, the Newgate jail experiment concerning the safety and efficacy of variolation may also not have passed ethical review in a modern ERC. But of course Jenner was not advocating variolation.
He was advocating a much safer i. However, the ERC would certainly have had to struggle with the question of whether it would allow Jenner to use results from experiments that violated ethical norms as support for his own proposed experiment. If the committee chose to not allow any data from these two ethically questionable experiments because of the principle that using data gathered from unethical experiments is itself ethically untenable, then the committee would have to face another question, viz.
I think he does, for the following reasons: The experiment of inoculating his ten-month-old son with swinepox was of questionable relevance in any case.
Swinepox and cowpox would seem to be two entirely different diseases. Inclusion of the swinepox experiment in the application materials may not have been necessary or even important.
- VARIOLATION AND EARLY ATTEMPTS OF TREATMENT
- Edward Jenner (1749-1823)
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As for the Newgate jail experiment, it was probably also not necessary to Jenner's argument, since the subsequent 50 years of variolation throughout England was even stronger evidence for the relative safety with the emphasis on "relative" of smallpox inoculation. Therefore, in my opinion, the committee may well have disallowed Jenner's inclusion of those two experiments in his research proposal. They would probably at least have admonished him to never again do experiments similar to the swinepox experiment on his son.
Nevertheless, in spite of such admonishments or exclusionsthe committee would probably find that Jenner had presented enough preliminary evidence to render a favorable outcome of the cowpox experiment at least possible, and perhaps even probable. They would probably not disallow his proposed experiment on any of these grounds. Is the principal investigator competent? Was the principle investigator competent to undertake such efficacy trials?
Colleagues in the two medical clubs to which Jenner belonged may well have had questions about Jenner's competence, in light of his constant harping on the illogical notion that having contracted one disease cowpox could protect a person against infection with another disease smallpox. Members of the Royal Society may also have questioned Jenner's competence to undertake this sort of experiment. After all, he had been voted in as a Fellow of the Royal Society FRSnot on the basis of any medical work or researches, but purely on the basis of his observations of the nesting behaviors of cuckoo birds.
A distinguished career observing the natural history of birds and other animals would hardly qualify one as a researcher in the prevention of infectious diseases. However, Jenner was also a well trained, highly educated, and certified medical practitioner who, in addition to his nine years of medical apprenticeship, had spent two additional years studying under the tutelage of the most famous surgeon and teacher of his time, Dr John Hunter, in London.
Jenner had earned his master's high commendation and even his friendship. In fact it was from John Hunter that Jenner had learned the principle: His belief in "vaccination," of course, was considered quite unorthodox by the medical establishment, but belief in the efficacy of unorthodox protocols does not in itself make an investigator incompetent. Nor does the seeming rashness of Jenner's willingness to inoculate his son with swinepox and then attempt to intentionally infect him with smallpox pus, though that experiment may have led some people to question his good sense.
Still, Jenner had been fully and appropriately trained, according to the standards of his day, as a medical practitioner and medical investigator. Furthermore, he had done as much preliminary research on the notion of inoculation with cowpox as could have been expected of any investigator before undertaking studies using human beings.
There was at the time no concept of using animal models for the study of infectious diseases so there is no likelihood that an ERC would have asked for such evidence. However, even if it had been common practice to do preliminary research with animal models, no animals seemed to get sick with smallpox, so it would probably have been difficult as it is today with AIDS research to find or develop any adequate animal model.
Endpoints and criteria of success Were the endpoints and criteria of success for Jenner's experiments adequately defined? Even though this issue is not formally addressed in his application for ethical review, we do see evidence that he had considered the question.
One endpoint was clearly defined, viz. If that were to happen, Jenner said, that would have been the end an unsuccessful end of that series of experiments.
But what would have constituted a successful endpoint of the experiment? One successful endpoint, the one that Jenner accurately expected, is that after being vaccinated with cowpox matter, and upon being challenged with smallpox pus i.
The site of the challenge would not redden, swell, form a pustule, or show any sign of infection whatsoever.
Jenner would then see this as evidence that the cowpox vaccination had "taken," i. The assumption he made, and a seemingly logical assumption it was, was that if the subject showed no reaction to the smallpox challenge, then that subject was therefore protected against naturally acquired smallpox infection as well and therefore protected against naturally acquired smallpox disease.
That seemed like a perfectly logical assumption, so he did not question it. But he should have questioned it. Artificially induced smallpox and naturally acquired smallpox were, after all, acquired by two different routes of infection scarification and inhalationand it could not be certain that protection against one route of infection also conferred protection against another route of infection as we have seen with AIDS vaccine research in some animal models. Any of today's more practiced designers of biomedical research protocols - Jenner was, I believe, the first medical investigator to do scientifically designed medical research with human subjects - would doubtless have reminded Jenner that this was still an assumption, i.
So how could the hypothesis that cowpox inoculation protects subjects against naturally acquired smallpox infection be tested? The only way to adequately test whether subjects would contract naturally acquired smallpox disease would be to monitor and observe them for a number of years, at least through one or two local smallpox epidemics, and perhaps even for the rest of their lives, to see if they ever contracted smallpox after being naturally exposed to it.
If it indeed turned out that none of his vaccinated subjects ever had any adverse reactions to direct smallpox challenge, and it also turned out that none of them ever contracted a naturally occurring smallpox infection, in spite of having been exposed to persons with smallpox disease, then at that point Jenner could finally conclude that cowpox vaccination did indeed protect people against contracting smallpox disease.
He would also, at this point, know one other valuable piece of information: