In Our Time - Immunisation

Episode Date: April 20, 2006

Melvyn Bragg and guests discuss the search for immunisation. In 1717, Lady Mary Wortley Montagu, the wife of the British Ambassador to the Ottoman Empire, wrote a letter to her friend describing how she had witnessed the practice of smallpox inoculation in Constantinople. This involved the transfer of material from a smallpox postule into multiple cuts made in a vein. Lady Montagu had lost her brother to smallpox and was amazed that the Middle Eastern practice of inoculation rendered the fatal disease harmless. In Britain, the practice was unknown. Inoculation was an early attempt at creating immunity to disease, but was later dismissed when Edward Jenner pioneered immunisation through vaccination in 1796. Vaccination was hailed a huge success. Napoleon described it as the greatest gift to mankind, but when the British government introduced the compulsory Vaccination Act in 1853, targeted at the poor and the working class, it sparked a mass opposition movement.How did a Gloucestershire country surgeon become known as the father of vaccination? Why did the British government introduce compulsory smallpox vaccination in 1853? What were the consequences of those who opposed it? And how was the disease finally eradicated? With Nadja Durbach, Associate Professor of History at the University of Utah, Chris Dye, Co-ordinator of the World Health Organisation's work on tuberculosis epidemiology, Sanjoy Bhattacharya, Lecturer in the Wellcome Trust Centre for the History of Medicine at UCL

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or wherever you get your pods. Thanks for downloading the In Our Time podcast. For more details about In Our Time and for our terms of use, please go to BBC.co.com.uk, I hope you enjoy the program. Hello, in 1717, Lady Mary Montague, the wife of the British ambassador to the Ottoman Empire, wrote a letter to her friend

describing how she'd witnessed the practice of smallpox inoculation in Constantinople. This involved the transfer of material from a smallpox postule into multiple cuts made in a vein. Lady Montague had lost her brother to smallpox and was amazed that the Middle Eastern practice of inoculation rendered the fatal disease harmless. In Britain, the practice was unknown. Inoculation was an early attempt at creating immunity to disease,

but was later dismissed when Edward Jenner pioneered immunization through vaccination in 1796. Vaccination was hailed as a huge success. Napoleon described it as the greatest gift to mankind, but it met unexpected opposition after it was made compost. in Britain in the middle of the 19th century. How did a Gloucester country surgeon become known as the father of vaccination? Why did the British government introduce compulsory smallpox vaccination in 1853?

And what were the consequences of those who opposed it? And how was the disease finally eradicated? With me, to discuss the search for immunisation, a Sanjoy Batacharya, lecturer in the Welcome Trust Centre for the History of Medicine at UCL, Chris Dye, coordinator of the World Health Organisation's work on tuberculosis epidemiology, and Nadia Dürbach, Associate Professor of History at the University of Utah. Nadia Dürbach, can you tell us what inoculation is? Sure. Inoculation is the direct insertion of disease straight into the body

in order to produce a very mild, controllable and essentially curable case of that disease, which will then protect you, will make you immune from a more virulent and dangerous and potentially fatal case of that same disease. later. Have you an idea where the practice originated or when? The practice is quite old and we know that it took place in many different countries, not in the Western world, for quite some time, before it was then imported into Britain in the beginning of the 18th century. So can you give us some idea of what those countries are and about when it was being practiced? In Turkey, in the Ottoman Empire, it was being practiced in India as well, in a variety of places, but I'm not in Britain until the

beginning of the 18th century. It's also called variolation. Can you tell us how it's performed this inoculation or variolation? Why is the word variolation introduced? Varyolation specifically means inoculation with smallpox matter. So inoculation can be done on any number of diseases, but the term variolation means inoculation specifically with smallpox matter. And the way it's performed, or the way it would have been performed in the 18th century in particular, would have been to take a small surgical knife called a lancet and to make a series of cuts into the flesh, usually in a scarified pattern, a crosshatch pattern on the flesh. In a number of places, could have been on the arm. For more vain women, it could be on the so it wouldn't be visible. And then what you would do is you would

take matter from the pustule on somebody else's arm who had smallpox. You'd scoop out matter and you would smear that into the cuts and then you would wait seven to ten, maybe even 14 days. for that to take on the arm. And so this was a process of transferring smallpox directly from one person's body to another person's body. And the term variolation refers to variola, which is the Latin term for smallpox. Christa, let's take that one off.

How did early inoculation develop then? And Nadia's mentioned it or alluded to it. What were the advantage of inoculation, particularly for young women in the earlier days? Well, as Nadia has said, some of these infections like smallpox, various other diseases, cause nasty skin lesions, and those skin lesions can appear on prominent places. The face of young women, for example, would disfigure them and could ruin their marriage prospects under some circumstances. So the observation that infection could lead to acquired and a permanent immunity encouraged people to try to intrad. try to introduce these diseases artificially to create a small incident of disease which would

self-heal. And that individual would then be protected from disease thereafter. So if you could cause the disease on an inconspicuous part of the body, then you would protect the more conspicuous parts of the body from later infection. I'm interested in how it was developing in the 16th and 17th century, some notion of how it was regulated, some notion of how it was accepted. Can you feel us any bit more on that? If you go back for several hundred years when these practices began in the Middle East, practices

to prevent diseases like Leishmania which caused nasty skin lesions on people and were given local names like Oriental Saw and Aleppo Boyle and so forth, I think the practice was done spontaneously, it was done in an unregulated environment.

It was a folk remedy before it became part of hardcore medicine. Folk remedies usually apply among people in the past who were illiterate country folk and so on. Was it restricted there or was it accepted in other parts of society? Sandroi. There were different techniques of variolation.

I think we have to be careful about assuming that there was one technique, one predominant technique. There are references to variolation being conducted in medieval China. We know that the Mughal armies would variolate their soldiers. and therefore in the early 18th century when the British army was involved in battles with the Mughal armies, they realized that the Mughal armies had an advantage, so to speak,

in that their armies were more prepared to tackle the outbreak of smallpox. So in certain contexts, I think their relation was regulated, like within the Mughal armies in India. And again, there were techniques dependent on the use of fresh smallpox matter from someone's arm or body to virulate people. But other techniques would involve actually keeping dry scabs, smallpox scabs, and then using them after a time lag precisely to ensure that the resultant infection was mild,

because that was always a concern. You could use fresh material and then have a very acute outbreak of smallpox, which could then become the focus of an epidemic. It was quite easy to let us say overdose or over and, Absolutely. Absolutely. And this would happen in so many. So that's why I think as historians, we need to be very careful about assuming the existence of one kind of air relation.

What we know of a violation shows that the technique was very heavily dependent on creating a mild infection of smallpox. And therefore, dosage, sort of smallpox matter you used was all very important. Nadia Durbach, can you just give us in detail, describe the nature of the smallpox disease? Well, it's an eruptive disease. It obviously causes a great deal of pocking and scarring on the body, and one could actually be one giant scab. I mean, for us today, because it's been eradicated, we have no idea what it might look like,

but you couldn't have your entire body covered with a scab. And it could be fatal in a third of a case as it was fatal, and you could be blinded by it as well. So it's extremely disfiguring. And if one were covered, it would not be uncommon to be quite pockmarked. And that goes back to Chris's point about vanity, that it would be quite obvious to anybody that you had had smallpox because of the pock marks.

Sanjoy. Again, there are two types of the disease, Varyola Major and Varyola Minor. Europe generally housed Varyola Minor, also known as Alastrian. Now, the death rate from Varyola Minor was 1 to 3 percent, so it was significantly less dangerous than Varyola Major.

Varyola Major, on the other hand, could kill from 13. 50% of the people it affected. But even amongst the survivors, it could cause blindless, infertility, and severe scarring of the face. But it's interesting that variola minor cases when they occurred in Asia,

or indeed in Britain, were seen as very valuable sources of smallpox matter for variolation. Because it was assumed that if you took variolous matter from someone who was suffering from a mild dose of smallpox, that material would then bring about a controlled mild infection of smallpox. In my introduction, I spoke about the wife of the British ambassador, Lady Mary Wirtley Montague, and her famous, as it now, is letter back to a friend, which was the letter was later taken up by Voltaire,

and so describing in a fair amount of detail what was going on in Consented, with wonder, and she was extremely impressed by it and wanted to come back to England and introduce it there. The event she described, did she describe it accurately in your view? It is certainly one of the techniques that we know of in that time, in that cuts were made in someone's forearm, and then various material was taken from someone supposedly not suffering from an acute case, a smallpox, and then it was given to the patient.

It describes as almost a social event with women gathering for these events, And that makes it seem that people had accepted it, that they were pleased to have it, that it was something of benefit to them. They knew that and engaged in it willingly. This is important for what happens later to this system. Well, we know that it is accepted by certain sections of society in the Middle East and certainly in India. What surprises me is that although the practice was introduced into Britain in the early 18th century, it took such a long time to become established practice. Usually when you read the history of the subject, the next step is Edward Jenner,

and that's not until the 18th century when he carried out his experiments, and then the practice didn't become frequent in Britain until the 19th century. And compared with the pace of science today, that is a tremendously long period of time, 100, 150 years before it became established practice. Although one important thing to keep in mind is even though this was imported by Lady Mary, and it seemed to be quite an aristocratic practice in Britain. The poor thought they invented it. They took this up quite readily

and it was practiced by midwives. It was practiced by itinerant clergymen by tax collectors and blacksmiths. And so... I've always been, always, I've just said the last few since I've been reading about this, intrigued where tax collectors and blacksmiths came into this. How do they get involved in this?

Well, tax collectors because they're itinerant. They travel quite a bit. And this is something that if you can take, Sunjoy has said you can actually dry it, take it as scabs around with you. You travel around quite a bit, and this is why a tenorant clergyman come into the question as well. You can then do this as you go around your tax-collecting business. Blacksmiths is an interesting question. It probably has to do with access to metal products.

The making of knives and these kinds of things would make when ideally suited to do this. Sanjoy, when the British arrived in India, they found this practice. Can you tell us about the interface there, please? When the British first arrived in India, they admire the system, they try to copy some of the systems that existed in India. That is where I think they note the fact that the Maratha armies, the Mughal armies, had the practice of violation which seemed to protect people from smallpox,

which was everyone agreed quite a dangerous disease in India. Was it affecting the British, though, the smallpox? It was. And that, and that. us why smallpox was one of these diseases that was recognized from very early on as capable of going across racial boundaries and geographical borders. And class boundaries as well. Absolutely. And therefore.

If you had certain, there was no defense at all. Absolutely. But the realization was that it wasn't just enough to protect yourself. So you could virulate or vaccinate yourself. But that wasn't guaranteed protection as long as there were a wide variety of people who were not immunized. So vaccination, that brings us an idea, to Edward Jenner, an 18th century country surgeon in Gloucester. Now, can you tell us a story of how he arrived at vaccination? Well, he was a country surgeon, not a physician, but a surgeon, which is a little bit lower on the scale of ranking at this time.

And he lived in Gloucestershire, which was a dairy district. And it was very well-known sort of common lore in the region at the time that dairy maids tended not to come down with the smallpox, that they generally had quite clear and lovely skin, that they were not pockmarked, but that they often had contact with infected cows who had cowpox, which meant that often on their hands they had quite large postules from the cowpox. So people in the region knew about this connection. And what Jenner decided to do was do an experiment to actually see if he could prove the connection.

Can you give us some sort of date, mid-18 century? No, late. This is the 1790s. It's actually 1796. So quite late, indeed, when he performs this experiment. And what he does is he takes the son of a local laborer. He knows quite well, a little boy, eight-year-old boy called James Phipps, and he decides to do an inoculation on him.

But instead of using smallpox matter, he uses cowpox. He takes matter out of the hand of a woman by the name of Sarah Nelms, who is the daughter of a local farmer, so she's had a lot of contact with milking cows, and she has these telltale cowpox pustules on her hands, he takes matter out of her, and he inoculates it into the arms of James Phipps. And he waits, I think at seven, ten days,

to see if this is going to take, which it does, it takes quite nicely. And then he then introduces smallpox into his body. And the result is that James does not come down with any signs of smallpox. He appears not to be suffering at all from the disease. And so he concludes that cowpox, actually protects one quite well against smallpox,

even better than a variolation. And he calls this vaccination. And it comes from the Latin word for the cow and for the cow pox. And so he then, vaca, right, exactly. And so he then publishes a treatise in 1798, an inquiry into the effects of the cowpox inoculation. And this starts the practice of what we now call vaccination. Before we move on to that,

I'm going to ask Christaim about that in a moment, but did he think he was taking risks with this boy? Were there any laws? Had he got it wrong, would he have been jailed, for instance? Certainly not. And I don't want to say that Jenner was at all callous. I think he actually would have been quite happy to do this on his own children, but his children had already been inoculated with smallpox.

They'd been very elated, so they wouldn't have been very good subjects. But he had actually been wanting to do this for quite some time, and I think had his children been available, he would have taken this risk himself. He knew this family quite well, and so he was not just sort of grabbing a local boy off the street. And I think he truly believed that this was going to work, and he had some evidence for that, given the region that he lived in, given the common knowledge at the time. But this was a risk, certainly. This was certainly not ethical practices today, where we believe in informed consent. But I don't think that he was callous about doing it. I think he had very good reasons to believe that this was going to work.

Chris, I, can you explain further then why Edward Jenner's vaccines were successful and how vaccination differs from inoculation? Well, Jenna's experiments were successful following on his observations on cowpox because he was working with a group of viruses which are very closely related to each other, a group of viruses called pox viruses. And because they are so closely related, they generate a very similar kind of immune response. So the cowpox, which doesn't cause serious disease in humans, after all it's really a disease of cows, not of humans, is sufficiently closely related to generate an immunological response, which is like the one that is generated by smallpox in people. So by using cowpox to cause a mild form of the disease in people, he was protecting those people against other related viruses, such as smallpox, which of course was his principal target. And of course you couldn't catch cowpox from each other. Persons couldn't catch cowpox one to the other, couldn't they? I know of no examples where cowpox are being transmitted from person to person

that the milkmaids that are talked about in this story were inquiring their infections from working with cows continuously. They were continuously exposed to pox acquired from cows, not from each other. Can we talk about Louis Pasteur then, who he adopted the term vaccination, but he made another contribution to this development. developing story of immunisation, didn't he? Yes, his researchers proved that particular infectious diseases were caused by specific germs. And then again, his researchers also showed that you could use a weakened form of that particular germ and introduce it to a human body or an animal body and therefore protect humans and animals

from a more virulent attack of that disease. So by identifying causative organisms and then showing, how they could be weakened and then inserted into human animal bodies. He took our understanding of vaccinology a step further. When we get to Pasteur, we're really moving into the age of microbiology proper. People were beginning to understand much more about the organisms that caused these diseases. And they were also developing experimental techniques so that they could work with these organisms. Pasteur is celebrated for developing the first rabies vaccine at the

end of the 19th century. And one of the reasons he was able to do that is that he understood how to passage viruses through animals, that is, repeat infections with rabbits. You infect one generation of rabbits, you take the virus out, you put it back in more rabbits, and you do that many, many times. And then the disease becomes weakened or attenuated. And when you have that weakened or attenuated form of the virus, you can then safely inject that back into susceptible animals or people. And that's how he discovered how to make a rabies vaccine, which he then tested on people in the same way that Jenna had done a hundred years previously with smallpox. But between Jenna and Pasteur, the idea of vaccination did, and Nadiobach did catch on,

and governments became interested. Let's start with this country. In 1840, the government of the country in which we find ourselves at the moment, offered free smallpox vaccination and banned the practice of inoculation the following year. So they had obviously taken generous seriously. It is almost half a century afterwards, but they were now trying to put it in practice for their whole society. And then in 1853, they brought in the Vaccination Act.

So can you talk about the government's decision to move forward in this area? Well, the government makes it free to the poor only in the 1840s. And they're very concerned that it's the poor and working classes who are spreading the disease to their social betters. So they make it free and available

and nobody takes it up. And at the same time, they ban the practice of variolation because they're concerned that it has become unsafe. Now that we have cowpox inoculation, vaccination, they believe that to be a safer practice. And so they introduce that. But because nobody is actually taking them up on this free offer, they make it compulsory in 1853.

And again, the government is concerned on the one hand that it's being practiced by a variety of different people. again, vaccination then gets taken up as a practice by the midwife, by the tax collector, again. They just use cowpox instead of smallpox now. But they're concerned about who's actually doing this. And they're responding in many respects to lobbying from doctors who decide that they actually want to be the ones doing this as a medical practice that should be practiced by the proper authorities. So on the one hand, the government's concerned about who's doing this. And they feel that if they make it compulsory, they can then control who's doing this.

and they appoint a series of public vaccinators to do that, who are medically trained. On the other hand, they're also very concerned that this is a disease, smallpox is a disease that's breeding in the urban slums. Britain is becoming very urban by the 1850s. The slums of the cities are becoming very overcrowded. And since they are concerned that the poor are the ones who are actually spreading it up the line, they want to make sure that the working class in particular is well vaccinated. since they haven't done this voluntarily, they decide to make it compulsory. And so this compulsory vaccination act is theoretically applied to the entire population of

Britain. However, it is only enforced upon the working classes. And it's quite strongly enforced. One is fined 20 shillings if one doesn't vaccinate one's child. You can have all your goods seized and auctioned off. At the time, working man, we're getting 15 shillings a week. 15 shillings a week. So 20 shillings is a heck of a fine. It's an enormous amount of money, and obviously most people didn't have the money to pay this.

Now, why was that there was resistance against vaccination quite strong? There's some estimate that about 25% of people would not accept it. There were riots. The people stood for, they made speeches pro-vaccination. They were cheered. They were arrested. The crowds wouldn't let them be taken to jail. There was serious social unrest about vaccination.

Can you just kick us off as to why there was such a force of reaction? because we're talking about serious riots, serious police forces, serious disturbances of the police, especially in the big northern cities. Yes, so we're actually talking about elections hanging in the balance on this issue as well. So it's a very serious issue. And there are a number of reasons why people objected. On the one hand, they felt that it was not the government's business, what they did with their children.

They felt this was a real imposition to their civil liberties to be told they must vaccinate their children. And the working classes in particular felt that this was class legislation. that they were the ones being sent to jail, they were the ones being fined, while middle class people were being let off the hook here. So on the one hand, it was an issue of civil liberties, let's say. On the other hand, it was an issue of very real fears

about the practices of vaccination. Partly this was about fears of having an animal product put into the bodies of babies, but partly this was because the practices were very unsanitary. As I've described it, you had a knife going back and forth from arm to arm between one child to another, and this is important to remember in Britain that this was practiced from arm to arm.

So live matter was scooped out of one baby and put into another. And this was not a sterilized instrument, and people firmly believe that other diseases such as syphilis could be passed from arm to arm. And of course, this left large wounds on the arms of babies who were then taken back to these dirty urban environments where the wounds would fester, become infected,

and it was not uncommon for a child to become severely injured or to die as a result of this. We're halfway through the trek to get the only major human disease ever so far to be eradicated. The state is moving in in this country to try to knock the whole thing out right over the place. Sanjoy, we have a sort of, not a mirror example, but a very useful parallel, let's use that word, or parallel universe in India, with the British army there, with the Indian, being way ahead of the British when they got there. Now the British of this idea of vaccination with all the possibilities of help, hindrance and upro.

Can you tell us how it, as it were, played the vaccination? The efforts to introduce vaccination in India came pretty early in the 19th century. But the problem was transferring vaccine stocks from Britain to India. They would often, the vaccine stocks that were being transported would often lose their potency and not work. Now, this was a problem where the vaccination operation was actually a very painful one. We have to remember that the primary target of vaccination services

from very early on were very young babies. So how did it differ from inoculation? Can you just explain to our listeners why it was more painful than inoculation, or variolation, as it's also known? Well, early vaccination was again done in a variety of ways, but generally speaking, it involved multiple kinds. on each arm. When I lecture on the subject,

the closest parallel that I can give is like stuffing the Christmas goose. You have this pulpy vaccinal matter, which you then insert into two or three cuts made on both arms

and then wait for the vaccine to take after such a painful operation on a baby. A month to six months. There were moves to. increase the age of vaccination, but again, a lot of power rested in the hands of the people on the ground, in the field, actually doing vaccination work. So, you know, the state could pass any number of rules or laws, but ultimately the people in the field held on to a lot

of power, which also explains why older ideas remains resilient and why it took time for new government strictures to take hold, both in India but also in Britain. Was there the same a ferocious reaction to vaccination in India that we'd seen in England? In some parts of India, yes, because what we have very well documented is attacks on vaccinators and vaccinating teams. Vaccinators and vaccinating teams would often be chased out of Indian villages by irate parents, especially when a vaccinator tried to come back to a village and say, can I vaccinate your child again?

Having gone through a traumatic experience, seeing their child suffer so much. Are these the same reasons in this country? it's to do with interfere with one's child, it's a do with methods that are themselves infectious because of the unhygienic instruments involved. Sometimes, but when you had a smallpox epidemic raging, the nature of the disease, the ghastly nature of the disease,

actually increased a demand for vaccination, which is what always stumped British administrators in India. They would go in in non-epidemic years and be criticized and attacked. And in epidemic years, they would be criticized for not providing enough services. So it always seemed that they were on the defensive. But I think this is closely linked to the nature of the disease. The fact that there was a high death rate,

the fact that people suffered so obviously from a disfiguring disease meant that people were willing to weigh up risks at such a point of time. And so, okay, the vaccine operation is dangerous, it's risky, but perhaps it's less dangerous than the disease itself. So which perhaps explains why there was sort of shooting up of demand and then very dramatic fall in demand. Christa, can you tell us when the idea of herd immunity came in and give us some idea of what it is?

Herd immunity is a much more recent idea. It's an idea of the 20th century rather than the 19th century when many of these practices were first introduced. Surely when in 1853 the Compulsory Act was in effect an attempt, although he didn't go by that name to introduce herd immunity? No. No, because the concept wasn't understood. The compulsory act was more about increasing vaccine coverage

with the view of protecting as many individuals in the population as possible. But the concept of herd immunity is different. It used to be thought that if you wanted to eradicate a disease from a population, you had to vaccinate everybody, protect everybody. But it's now very clear that that is not the case. you may only have to immunise 60, 70 or 80% of a population depending on how contagious the disease is in order to ensure that the disease will not spread through the population.

The mathematics of it is quite simple when you work it out. Imagine that you have a contagious disease which is introduced into a community that individual first case generates two more cases and each of those generate another two more cases. So you have a series 1, 2, 4. 4, 8, 16 and so on. Now imagine that in a population like that, you can vaccinate half the population. Then that individual case will generate not two more cases, but less than half of two. In other words, less than one case. And as a result of that, the disease will inevitably disappear.

So that idea, that simple mathematical idea, was the basis of an understanding of herd immunity. The practical difficulty is that many of the diseases, which, trying to eradicate, like measles, for example, generate many more than two secondary cases. They may generate 10 secondary cases. And under those circumstances, you have to vaccinate more than 90% of the population in order to guarantee that the disease will be eliminated. And yet, we've been talking about vaccination, but as I understand it, nobody understood it until the early 20th century. So when did the understanding of the immune system change and how did people come to an understanding of it?

It was based on practical results rather than theoretical knowledge. Vaccination was entirely based on an empirical understanding that if you did this, it worked, so let's do this. And it really is not until the 1890s with the immunological studies of Eli Mechnikov that we start to get a real understanding of the immune system as we know it today. Can you tell us a little about him? He's the man who came up in, he published a paper in 1891. He was awarded actually.

a Nobel Prize in 1908 for these studies. And he came up with the concept of antibodies and the phagocytes and the leukocytes and how a body actually fights off a disease. And this was not something that was well understood in the 19th century at all. In fact, nobody understood how vaccination actually worked. And it's not until the beginnings of what we might call

the germ theory of disease in the 1880s and 90s that we get people theorizing exactly what smallpox is. and it's not until the 1930s that anyone can actually isolate it and identify it because it is a virus, which is very, very small. And you need the electron microscope to actually be able to see it. So it's all theoretical until you can actually see smallpox. And it's really not until the early 20th century with an understanding of what the immune system is and does

that we can explain why vaccination works. Chris Dyke, can you tell us how the knowledge of the immune system change? Yes, a great deal after the germ theory came online, people recognised that it was particular organisms that were responsible for diseases. Then we were in a position to ask the question, what are the characteristics of these organisms that lead to an immune response? And then with the development of microbiological techniques, it began to be understood how the immune system works, that it consists, for example, broadly of two kinds of cells, B cells and T cells. and the B cells are the ones that generate antibodies, and these antibodies float around in your bloodstream and tag foreign invading infectious particles

and mark them out for destruction. And the T cells perform a variety of different roles. They kill invading organisms directly. Some of them play a command role. They're called T-helper cells. But what's very important in the concept of vaccination is that there are memory cells as well. So once your body has seen a foreign invading organism of virus or a bacteria

and has identified what kind of invading organism that is, there are cells that retain memory of that organism in your body. And they retain that memory for many, many years. And this is really the point of vaccination. Once you've stimulated this kind of immune response, your body remembers what it has been exposed to. And when you are next exposed to the same kind of organism, you can respond immunologically very, very quickly.

You can respond much more quickly than the time it takes the pathogen to cause the disease itself. And that's why disease is controlled. So it's this combination of acquired immunity and immune memory, which is vital in the process of vaccination. In India, Sanjoy, the Indians had a different idea of the immune system, didn't they? How did that work out when the idea of vaccination, was, began to be more widespread, I mean, began to be forced on people. Well, in India, as in Britain, there was a tradition of seeing health and disease being a result of a certain balance of humours.

So a disease like smallpox was often attributed to an imbalance of these humours. Now, depending on which Indian healing tradition you're talking about, some of them refer to three humours, others refer to four humours, wind, bile, phlegm and blood. So disease, a disease like smallpox, was explained in terms of an imbalance of these humors. And therefore, by getting the balance right, it was assumed that you would then increase your body's ability to counter disease. But I think one of the points I have to slightly disagree with my co-panelists is that there was an understanding of immunization of the concept of immunity and immunization before. But different terms were used. The understanding wasn't our current understanding doesn't mean that understanding did not exist before

and the whole idea about bodily predisposition, bodily balance, humoral balance was actually a widely, widely accepted theory for why smallpox might affect one individual more dramatically and another individual less dramatically why it might kill one person and cause another person to survive. Yes, I agree completely with Sondro and I wouldn't want to suggest that there's no

concept of immunity. And actually the word is used quite commonly throughout the 19th century, but there's no theory of the immune system as we know it today. But the idea of the constitution, one's constitutional predisposition to disease, one's ability to fight off disease, one's ability to actually nurture disease within the body is very, very important to 19th century concepts of disease. And so Sanders absolutely right, there is a concept of immunity, but there's no

immune system, which is really a product of the 1890s. Yes, I'd agree that the understanding of immunity that there was an immune response that could be protective is centuries or even millennia old, and that could be regarded as the beginning of an understanding of immunology. But I would regard the Asian description of the way the body works in terms of humours of one kind or another as rather a temporarily satisfactory way of describing what they're facing, but is not really an explanatory form of immunology and hasn't led to a better understanding of the immune process. But we should also stress that we didn't need to have the scientific theory behind it to have vaccination. That vaccination

as a practice predates our understanding of how it actually works by well over 100 years. And so we don't need the science actually to have vaccination. Of course, the science has improved the process of vaccination and our understanding of immunology enormously. But it's worth pointing out that immunology is still an imprecise science. There's much unfinished business in immunology, and there are many vaccines that we use routinely today that we still really don't understand the mode of action for. True, but the concept of bodily humours is not just an Indian or Asian phenomenon.

It's very much an entrenched part of Western healing traditions as well. But perhaps more importantly, when we start looking at our sources, we realize very quickly that there was not one, One germ theory of disease, but multiple germ theories of disease. And their dissemination, as well as their assimilation, was uneven, and their effect was equally uneven. So just because Pasteo comes to the scene or Jenna comes to the scene doesn't mean that popular medical official attitudes change overnight or pretty quickly.

Often what people do, including medical practitioners, is to accept elements of the germ theory while holding on to older ideas. of Constitution. And that is an integral part of selling a new medical idea. Because I think it's very important for medical practitioners to realize that the patient is an active agent in the act of treatment. So, you know, the scientists can jump up and down as much as he wants or she wants and say that this is great.

You know, I've discovered the cutting-edge technology. But as long as you don't convince the official in the field and, more importantly, the patient, they're not going to accept it. this technology, and I think this comes through immensely, powerfully, in relation to smallpox and vaccination. And that's certainly true in terms of the effect of the anti-vaccination movement, that anti-vaccinators have easily been dismissed as part of the lunatic fringe as Luddites, but actually they're the ones who said, look, this is a filthy practice, you need to make this safer

for us, and the government was forced to do that because the population rejected it. And that's a really important part of the story that I think Sanjoya said. made that point quite eloquently here. Chris Dye, how was smallpox finally eradicated? And I've said at the beginning of the program, it's the only major human disease that has been eradicated. So there's a lot more out there. But first of all, how was smallpox eradicated?

And secondly, why is it so far the only one to have been eradicated? The smallpox eradication campaign was launched by the World Health Organization in 1967. WHO had been created after the Second World War. war like other Bretton Woods institutions and was in a position to coordinate a global eradication campaign. So the campaign began in 1967. The technology was sufficiently well established. The principles of vaccination were sufficiently well established. And the idea was to achieve sufficiently large coverage of a population applying ideas of mass vaccination and herd immunity in order to eradicate the disease. So in the 1960s, when the campaign begun, there were tens of

millions of cases of smallpox every year. But in the space of 10 years or so with this comprehensive campaign, smallpox was eradicated in 1977 was the last recorded case of smallpox in Somalia. It should be said that the basic ideas on which the campaign were founded changed a lot during the course of the campaign. There was a lot of improvisation in a variety of different ways. For example, the initial idea of herd immunity and wide coverage became converted later on in the campaign into one of surveillance and containment. Towards the end of the campaign, the idea was to identify very rapidly cases as they arose in the final pockets and then essentially cordoned them off, keep people isolated, vaccinate everybody in the area.

And because that was done efficiently, smallpox was final. eradicated in 1977. Your second question is, why is it the only one? There are many kinds of answers to that question, but one of them is that although smallpox had spread all over the world, it is only a moderately contagious disease. I was talking earlier on about the number of cases being transmitted from one person to another. In the instance of smallpox, smallpox doesn't generate very many secondary cases. So it's quite easy to stamp out infection in a population by vaccinating with moderately high coverage.

So the other diseases that we're now faced with eradicating diseases like polio, diseases like measles, are much more difficult, in part because they have higher rates of transmission. They have some other difficult characteristics as well. Polio, for example, has many asymptomatic cases, and that wasn't a strong feature of smallpox. and that's one reason why polio has been hard to eradicate. Well, thank you all very much indeed. Thanks to Najid Dabak, Sanjoy Batacharya and Chris Dye, and next week we'll be talking about the great exhibition organised by Prince Albert in 1851

to showcase Britain as the workshop of the world. Thank you very much for listening. Thank you. We hope you've enjoyed this Radio 4 podcast. You can find hundreds of other programmes about history, science and philosophy at BBC.com.uk forward slash radio 4.