London School of Hygiene & Tropical Medicine

Where did the idea of inoculation against disease come from?

Before vaccination, there was the technique of inoculation by variolation, in which scabs and pus were taken from someone suffering from smallpox would be inserted into cuts in the skin of a healthy person. This could induce a mild infection that offered protection against the more virulent form of the disease.

As you can imagine, the thought of being infected with someone else’s pus didn’t always go down well. When variolation became popular in Europe in the 18th Century nobody understood sterile techniques or sterilised needles. It wasn’t very safe but it worked most of the time.

When did modern techniques of vaccination begin?

Some might say modern vaccination began with Edward Jenner, who realised that injecting people with the milder cowpox virus gave some protection against lethal human smallpox. But it’s very unusual to find an animal pathogen so similar to a human pathogen so Jenner’s technique isn’t something that could be replicated with many other diseases.

Louis Pasteur developed the principle of exposing someone to a pathogen to trigger immune memory to it, so I’d say modern techniques started with him. His ‘isolate, attenuate, inject’ doctrine is the basis for all subsequent vaccine development. These days his ‘attenuate’ step, reducing the effect of a pathogen, has been expanded into all sorts of different ways to derive a vaccine from a pathogen. Pasteur insisted on using the term vaccination, which means literally ‘of the cow’, in honour of Jenner’s work.

What were public attitudes to vaccines in the early days?

Today, Jenner is revered but he was burned in effigy multiple times in his lifetime. People objected to being vaccinated for a variety of reasons including worries around safety.

At the time vaccine development involved a lot of experimentation. Pasteur, for example, tried to develop a rabies vaccine by giving injections of a progressively more virulent form of the pathogen to build up a resistance. It probably contained very little live virus and although he didn’t really know what he was doing, it did work in some cases.

There were also instances of forced vaccination that provoked resistance: for example, vaccination of Mexican people in the USA with cowpox in the late 19th Century, not recognising that many people in Mexico were already vaccinated against smallpox as children. Public resistance dwindled when they stopped doing that sort of thing.

In Britain in the early 20th Century, most of the resistance to vaccination came from within the medical establishment. Gaston Ramon invented the diphtheria toxoid vaccine in the early 1920s and it was adopted all over Europe but not in Britain. He talked about ‘Angleterre refractaire’, which could mean ‘refractory Britain’ or ‘backward Britain’ depending on how generously you translate it.

How did attitudes to vaccines change during the 20th Century?

They varied a lot from one country to another. Up to the 1980s, Britain was often among the last high-income countries to roll out new vaccines.

Britain was also where the 1970s scare about the whooping cough vaccine originated. It revolved around the use of a whole cell vaccine, in which the whole of a dead bacterium is injected. Perhaps because it generated the biggest immune reaction of the vaccines given to children at the time, it was blamed for a whole host of early childhood conditions. Wrongly, as it turned out, but it took several large-scale epidemiology studies to establish that.

In Japan, Yuji Sato led the development of an acellular vaccine for whooping cough that used just a few proteins so didn’t cause the same type of immune reaction. However, public concern about the whole-cell vaccine evaporated long before the acellular vaccine was introduced. These concerns can be fickle, which makes them very difficult to predict.

The 1990s saw a sudden shift in attitudes in Britain. Suddenly we wanted to be first in the queue when new vaccines became available. That was when conjugate vaccines, against pathogens like Hib and pneumococcus, were becoming available and many of them had their first population-level assessment in Britain.

Of course, there were also the widely discredited false claims that the MMR vaccine causes autism, a controversy which I wrote about but that could take up a whole book by itself.

What do you think history can teach us about the future of vaccines?

That’s a difficult one to answer because pathogens that causes serious disease tend to have unique ways to evade the immune system, which means that an effective vaccine against them needs to be unique. In the early days of vaccination, a single new technique could often be used against multiple pathogens but now, the low-hanging fruit have been plucked. The pathogens we don’t have vaccines for are the difficult ones, hence new vaccines tend to be the result of new approaches to making a vaccine.

As future vaccines are likely to be technically complex, each will have its own implications in terms of cost, developmental pathways and possibly reactions they cause. However, I’ll stick my neck out and say that there are likely to be a couple of constants.

The first is that there’s never any shortage of people insisting there can’t possibly be an effective vaccine against any given pathogen until the day a vaccine is proved effective. Admittedly, that doesn’t mean there can be an effective vaccine against every pathogen; after all, there are plenty for which the naysayers have yet to be proved wrong.

Another constant is that as vaccinology targets more difficult pathogens, vaccine development is going to get more expensive and take longer. A consequence of that is that resources tend not be available for a pathogen until it becomes a problem in high-income countries. Remember how the 2013-2016 Ebola outbreak led to experimental vaccines being yanked out of the freezers they’d been languishing in as soon as it infected a few people in Europe and North America.

We saw the same phenomenon with COVID-19, which showed us how fast a vaccine can be developed when you cut out the time spent waiting for committees to meet. Admittedly, Ebola and SARS-CoV-2 are more amenable than, for example, HIV, but they do show us the realpolitik of funding.

‘How Vaccines Work’ is published on 9 March 2023 by Little Brown. Find out more about the book on the Little Brown website.

Image: UK Ministry of Health diphtheria vaccination poster.