November 6, 2019

6: Dawn of the Vaccine Era

Why was the measles vaccine created, even while doctors then questioned its necessity?

6: Dawn of the Vaccine Era

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Transcript

And now we come to the era of measles vaccination. What I want to do is help you understand the events that led to universal measles vaccination. The background is against the declining mortality and serious morbidity from measles in industrialized nations. Was there universal support for measles vaccination, what reasons were advanced in its favor and if there was not universal support, why not, what were the terms and reassurances upon which that universal vaccination was adopted, because clearly it was.

Now, haunting this whole thing was the ghost of the great Louis Pasteur, the father of modern microbiology. He himself developed vaccines for diptheria, for cholera, rabies, anthrax, yellow fever, plague and tuberculosis. Some of these were more or less successful, but he wrote, "If it is a terrifying thought that life is at the mercy of the multiplication of these minute bodies, it is a consoling hope that science will not always remain powerless before such enemies." In other words, it was man versus microbe. The microbe was perceived to be an enemy and science was going to deal with this.

A number of events took place that led to the introduction to a vaccine. In 1954, working at Harvard, Drs. Enders and Peebles isolated measles virus for the first time from an 11-year-old boy, David Edmonston. Enders then began the development of the first measles vaccine, called Edmonston B. The second event was the perceived success of the polio vaccine program that gave man the ability, at least he thought, to conquer other infectious diseases in the same way.

The third event was more of a political event, and that is that there was competition with Russia in 1961, they had started trials on the Leningrad 4 strain of measles with the help of the French, and this clearly motivated America to compete. There was, in fact, considerable resistance from doctors and scientists. You may not believe that now, but there was. The official view from 10,000 feet even now is that in developed countries, measles is considered a trivial disease of childhood. We have this discordance because in developing countries in the absence of vaccination, the death rate was very high, as high as 30%, a situation that reflected 19th century London.

A clinical practitioner writing in the British Medical Journal in 1959, before measles vaccination, gave the practitioner's view. "In this practice, measles is considered as a relatively mild and inevitable childhood ailment that is best encountered any time from three to seven years of age. Over the past 10 years there have been very few serious complications at any age and all children have made complete recoveries. As a result of this reasoning, no special attempts have been made at prevention, even in young children, in whom the disease has not been found to be especially serious."

So what we have here is that what might be good for one country, that is a country like Africa, might not be so good for an industrialized nation like the US or the UK. And this is reiterated in 1983, from experts from the London School of Hygiene and Tropical Medicine. Measles is a mild disease where it exists in industrialized countries and among the elite in developing countries, but for every child who dies from measles in Europe, some 400 children will die in an epidemic of a similar size in an African country south of the Sahara.

Why is it so severe in Africa? There are a number of factors. Most children, it is most interesting of all, suffer measles early on under the age of three, much younger than children in industrialized nations, so more of them are in that high-risk bracket. And again, this is a function of family structure, family size, living accommodation and malnutrition. Vitamin A deficiency prolongs the disease and allows the virus to be excreted for a prolonged period, leading to high risk of intensive exposure in infants. Also, in insanitary living conditions, there is a much higher risk of secondary bacterial complications such as pneumonia or infective diarrhea.

Is there another factor? And I suspect there is, and we will come to that later. Nonetheless, let's go back to the United States of America at the beginning of the '60s. A key event was a meeting held at the National Institutes of Health in 1961, and this was a meeting to discuss the potential for a national measles vaccine program and, in fact, John F. Kennedy wrote a letter of encouragement prompted by the apparent success of the polio vaccine and the threat of Russian competition with trials of the Leningrad 4 vaccine, and he described measles as a formidable and widespread threat.

Sir Graham Wilson, who was in fact one of the world's experts in microbiology, had written the definitive textbook and he issued some warnings to those at the meeting. He said that measles is one of the inevitable, but relatively unimportant maladies of childhood, and he added that in England, and dare say the US, 1 in 100,000 children dies. And in Scandinavia at that time, this was one in 1 million. And his concern, his interest, was what is peculiar about that child? Did they have an immunodeficiency? What was it about the child that made them susceptible? Would it not be better to understand that, than perhaps introduce something that was unknown, such as universal vaccination. He asked, "What is the real burden of measles and what it is about the child who dies that merits further study?" To introduce the vaccine without this further study would be in his words, "unethical."

At the NIH, Alexander Langer, who was John F. Kennedy's envoy, and at that time, the CDC's Chief Epidemiologist, put it another way. He quoted the mountaineer Sir Edmund Hillary, when he asked why he claimed Everest, he said, "Because it was there," and he sought to justify his position by adding, "In the US, measles is a disease, the importance of which is not measured by disability or death, but by human values and the fact that the tools which promise effective control and early eradication are becoming available. In other words, we can and because we can, we should." That was his justification, not death, not disability, but because we had the tools to do it, we should. And he was sincere in the belief and assurance that eradication, that is, getting rid of measles completely was achievable, not only in fact, but within a short space of time.

Even Dr. Enders, who had originally isolated the measles virus, offered a word of caution. He said, "A measles vaccine is desirable only if it conferred immunity comparable to that afforded by the natural disease," and as we know, the natural disease equals lifelong protection, while the transient protection from an imperfect vaccine, an inherent risk of vaccination producing a weaker or attenuated form of the disease produced a more dangerous condition when measles was then experienced beyond childhood. In other words, if the vaccine only worked for a limited period and then rendered you susceptible again later in life, what you have done is displace the disease to a time when it is potentially much more dangerous.

But here's the question. Could we, and should we? Should we because we can? In the face of a declining mortality and morbidity from measles, natural herd immunity conferring protection on populations, could we and should we? Now, in the US, the vaccinologists won the day with the assurances, the certainties of protection from a single shot of the attenuated vaccine, that vaccine immunity would be lifelong, that there would be no permanent injury, brain damage or death, that measles would be quickly eradicated using this vaccine and the vaccine virus could not be shed and transmitted to susceptible individuals, albeit that it was a live virus.

Louis Pasteur was to haunt that meeting even more. "The greatest derangement of the mind is to believe in something, because one wishes it to be so." So here's the exercise: What factors distinguished measles outcome in industrialized and non-industrialized countries? And how did these relate to the known risk factors for severe disease, for severe measles and death, and how might these factors be addressed in place of or in addition to vaccination?