Variolation, Vaccination and Edward Jenner’s “experiment”

In 1798 Dr Edward Jenner published an account of “vaccination” (1), arguing that this gave safer protection against smallpox than the existing treatment, variolation. Proponents of immunization, a technique that developed from Jenner’s work, often claim currently that a Research Ethics Committee, had it existed in the 1790s, might have rejected his work. Is it therefore possible, more than 200 years later, to assess this claim and the ethical standard of Jenner’s work in its historical context? This paper looks at a (hypothetical) review of Jenner’s experiment and discusses its ethical dimensions.



  • Chairman of the Berkeley REC
  • The rector of Berkeley
  • Zebediah Cowstock, a local farmer
  • Mr John Moore,
  • Archibald Turner, the town apothecary
  • Dr. Reginald Arbuthnot, a local doctor
  • Lady Sarah Wright
  • Dr Edward Jenner

CHAIRMAN “Members, thank you for attending. Dr Jenner has kindly agreed to attend and discuss his application.”


EDWARD JENNER “Mr. Chairman, my work is designed to explore how we might prevent people contracting smallpox and I believe cowpox, a disease in our countryside, may hold the answer. What I have suggested in my application may seem dangerous but I would propose it is no more than an improvement of current preventive measures based on our modern experimental methods. Let me place my work in context. Smallpox is a serious threat to our community and our current methods for prevention carry significant risk of death and disfigurement. This technique is called “variolation” and uses fluid from smallpox vesicles. I believe that fluid from cowpox vesicles could protect more safely and that there are persuasive theoretical reasons to believe inoculation for the cowpox will be of greater benefit than current variolation. My modification to this technique is based on a long history of country folklore, supported by my own observations.

Much effort has been spent in trying to prevent smallpox, starting in this country when Lady Mary Montague, wife of our ambassador in Constantinople, brought the technique of inoculation for the smallpox (variolation) to England. Variolation is achieved by placing a small amount of the fluid from a smallpox blister into a small cut on the recipient’s skin. It suffered setbacks, the deaths of the Earl of Sunderland’s 2 yr old son the Hon William Spencer and a 19 yr old son of footman of Lord Bathurst but subsequently

Dr James Jurin, secretary of the Royal Society established annual reports. He reported a death rate for smallpox of 1 in 5 or 6 and a corresponding lower fatality rate for variolation of 1 in 48 or 60. Dr Nettleton added further evidence in 1722. He reported 3405 cases of smallpox, of which 636 died. At the same time he reported 61 variolations with no fatalities. In 1752 Mr Brown, apothecary in Salisbury, reported his experience of variolation. He inoculated 422 persons of whom 4 died. Dr  Maty FRS reported his experience from Geneva, vaccinating foundlings.  All recovered. In 1754 Monsieur  Bonnet (FRS) of Geneva wrote to John Clephane reporting his experience in Geneva. This author reported good results in 70 people but wrote “But I presume that the French will be a long time in adopting the practice of inoculation. The clergy there throw a terrible obstacle in its way”

Thus, while variolation can provide protection against the smallpox, it carries a significant risk. In 1767 Josiah Wedgwood decided to variolate his two children Sukey and John. Both had convulsions as the rash developed and he wrote

“they have had a pretty smart pox as our Doctor terms it, but both have been so very ill that I confess I repented what we had done, and I much question whether we should have courage to repeat the experiment”.

There is an illness to which the horse is subject that is called the “grease” which seems to generate disease in the human after it has gone through modification in the cow. This human disease is called the cowpox. Any person so affected seems to be secure from smallpox. I also have cases that support this commonly held belief. In fourteen cases under my supervision, variolation failed to take, and all had previously contracted the cowpox. I now wish to collect fluid from a human cowpox vesicle and inject it into the skin of a suitable child subject. I have found two references to a similar process in my researches.”

RECTOR OF BERKELEY “Dr Jenner I must express disquiet. I believe that your project interferes with the natural order.  You will know, and have mentioned that many religious men raised objections. You refer to only a few of many condemnations.”

EDWARD JENNER “Current experiments don’t question the divinity, rather they try to explain His workings. The great Sir Isaac Newton, the greatest scientist our country has produced, sought to explain our world as God has created it. Our motive is to undertake this work for the benefit of mankind.”

ZEBEDIAH COWSTOCK “I myself am most concerned. I lose several of my farm hands a week at a time when they go down with this contagion cowpox, and we know that they can contract it again and again.”

EDWARD JENNER “I thank you for your comments, but I ask you to think of the benefit you will accrue from the eradication of the smallpox. I believe that any reduction in illness will help your farms”

JOHN MOORE “I’m very concerned about injecting material, particularly when it has come from an animal such as a horse or a cow. It is unnatural and might it not introduce animal spirits?”

EDWARD JENNER “None in my practice of variolation have thus suffered. We now have 80 years of experience. Furthermore I see enormous benefit coming from my work, and a small risk is justified.”

ARCHIBALD TURNER“Dr Jenner, after injecting the cowpox fluid, I understand you intend to challenge your patient with smallpox?  How could you possibly justify this deliberate exposure to a disease you have just admitted carries such a terrible possibility of death or disfigurement?”

EDWARD JENNER “I would be offering my patients variolation anyway. The design of my project allows me to use this not only as therapy and also the end point of my experiment.

DR. REGINALD ARBUTHNOT” Dr. Jenner, how will you know it is the treatment that has effected the protection? Recent studies have talked about the need for patients that “have been treated exactly the like in every respect besides (the experimental process)”. Shouldn’t your study be similar?”

EDWARD JENNER“Such work requires the doctor to be in doubt as to which treatment is better, to be in  “equipoise”.  I am not in this position. I would be offering some of my patients inferior treatment. Not only would this be unethical but also my practice would suffer. My arguments convince me that vaccination will be safer than variolation, I therefore can’t justify a control group.?”

THE CHAIRMAN “How will you seek consent?”

EDWARD JENNER “As a doctor I offer my professional skills to any who attend and I assume consent. I have no monopoly. I do, however, recognise that my method is experimental and I have followed the example of Doctors Warrick and Cowper who discussed their experiments with colleagues first and obtained their agreement before offering it to their patients (15,16). They clearly felt that patients might not be in a position to balance the value and risk of what they were being offered.”

CHAIRMAN “Dr. Jenner, might I ask how whether you would identify your patient?”

EDWARD JENNER“At the moment, I propose to follow current practice and use full names but I would appreciate the committee’s advice as there seems to be no consensus. I have found some that don’t divulge subjects names  although others do. Some do both.”

LADY SARAH WRIGHT “Dr Jenner, I’m really very unhappy about your proposal to experiment on children. Don’t you think your early work should be on adults?”

 EDWARD JENNER “I understand your concerns Lady Sarah, but I can be more certain whether children  have or have not had either the smallpox or the cowpox, factors which would obviously affect my results. The results of my experiment will therefore be easier to interpret. Secondly children are more vulnerable to the smallpox than adults. Remember I do not start from any position of equipoise.”

CHAIRMAN “If Lady Sarah is happy with that answer, I don’t think there are any more questions. Dr Jenner, perhaps you could withdraw, we will finish our deliberations. Our secretary will let you know our decision.”

Dr Jenner leaves


It is clear that Jenner’s study had purpose, justification and a base in the practice of the day. It addressed an major risk to the health of the community, given the devastating nature of smallpox and the significant risk of variolation. Contrary to much popular belief today, it was a logical development of the practice of the day. Jenner, himself, had case based evidence that cowpox infection prevented variolation taking (and by extension the patient would not contract smallpox). Cowpox seemed to be a milder illness and vaccination was, theoretically at least, a vast improvement on variolation. Jenner argued that he, and by extension the medics of his day, were not in equipoise. We might therefore conclude that utilitarian or consequentialist analysis at the time, even when we recognise that there was no knowledge of the subsequent enormous benefit, would have supported Jenner’s proposal. Deontological analysis, 200 years later, is more difficult.

Beneficence / Non-maleficence

Society’s ethos has changed and the duties of a doctor then are different to those today. Jenner argued he was not in equipoise and could therefore contend that he was meeting his duty of beneficence. Adverse consequences however were unknown although Jenner argued that cowpox was a trivial condition of little long term consequence.

Respect for the patient’s autonomy

This would require that James and his family should have known what was proposed, its risks and benefits, so they could reach their own decision. There is obviously little information as to what was explained to James and his family, and we can reach no conclusion as to whether James or his family were fully informed of the nature of the treatment. At the end of the 18th century respect for autonomy had not achieved the moral standing it assumes today, and to our ethics committee would have been of less importance.  Those in authority expected to exercise it and those beneath submit! Informed consent can also be consequentially justified as a means of protecting the research subject. In Jenner’s day, the gap between the medical understanding of the population and doctors was probably greater than today, an d it could therefore be argued that informed consent would not have been the protection it is assumed to be today. The practice of consulting colleagues rather than patients might have afforded the subject greater protection.

Conduct of the study

The study design would obviously raise questions today. As it involed only one subject, it could be argued that it would not have answered the question posed (Could cowpox render the individual resistant to smallpox?). The design included a very clear and elegant end point – whether variolation would take or not and would have been the foundation for further work. It could be justified as a “test of concept”;  Jenner would have undertaken further experiments and extended the study had the epidemic not subsided.

Method(s) of recruitment

At the end of the 18th century, medical provision was vastly different to our modern model. It was a free market and doctors took their place amongst the many “healers”. Many disparate groups offered their services, doctors had no monopoly and they could argue that those who visited and paid their fees, had consented to recruitment and the proposed treatment.

The use of a child

This might seem to run counter to modern ethos. Jenner had methodological and moral reasons to experiment on a child. His method required a clear past medical history and if he performed the experiment on a child, he would be better able to ascertain this. Morally, as was not in equipoise, he would have proposed that the subject would probably benefit from vaccination. However the current hesitance to embark upon experiment on children is now being challenged. In the UK, the Royal College of Paediatrics and Child Health supports and promotes research involving children, feeling that they have, too long, been therapeutic orphans.

“Research involving children is important for the benefit of all children and should be supported, encouraged and conducted in an ethical manner” 

Does Jenner’s work meet this modern stipulation? I don’t think it is possible to reach a definite conclusion but Jenner proposed it would benefit children. It was a logical development of variolation and clearly based on the science of his time and supported by Jenner’s own clinical  observations. It can be argued furthermore that he met his duties as a doctor, as far as we can understand them 200 years on.