Read between September 12 - September 12, 2020
Our greatest scientists are those who, despite their expertise, remain free to think differently.
The ‘dirty little secret’ is that vaccines only work well when so-called ‘adjuvants’ are added.
The first recorded ‘clinical trial’ in the history of immunity10 was performed on ‘volunteers’ who had been recruited on the basis that they could either participate in the potentially deadly trial or face the certain death of judicial execution.
The event was covered by all the newspapers and led to considerable interest in inoculation
The term ‘vaccine’ was coined a few years later by a friend of Jenner to describe the process he had discovered, from the Latin word for cow, vacca
vaccine. How come the pus from cowpox blisters worked well as a vaccine, Janeway wondered, whereas protein molecules such as diphtheria toxin, which had been isolated from germs, did not?
Glenny’s team found that when diphtheria protein was purified by a chemical process that involved combining it with aluminium salts, it became an effective vaccine.
But still, there was no obvious common feature that explained why they worked.
This might explain why protein molecules separated from their originating germ were ineffective as vaccines, but a molecule such as LPS, from the outer coating of bacteria, worked well as an adjuvant.
He suggested that distinguishing between self and non-self was not enough: the immune system has to be able to tell when something is likely to be a threat to the body before an immune reaction takes place, and that therefore the immune system must, he reasoned, be able to detect telltale signs of actual germs or infected cells.
What Janeway predicted was that this is not the whole story. Specifically, he predicted that there must be receptors (which he called pattern-recognition receptors) that are not randomly generated and then selected, but rather have fixed shapes that interlock specifically with germs or infected cells (or rather with molecular patterns that are found only on germs or infected cells).
One virus-infected human cell can produce a hundred new virus particles. This means that just three copies of a virus going through four rounds of replication – taking a few days or so – leads to 300 billion new virus particles.
the TLR4 gene encodes for a protein molecule that is able to interlock with a component from the outer wall of bacteria (LPS).
The innate immune system doesn’t just detect the presence of germs but can recognise the type of germ present and direct the immune response accordingly.
what did become clear was that adjuvants are important because they switch on the innate arm of our immune system.
replied confidently that many scientists have one big idea, which they stick with throughout their entire career. Janeway, however, like all creative people, had many ideas, and above all he was never afraid of being wrong.
how does the body decide to make an immune response with the right level of caution
As the scientist who discovered vitamin C, Albert Szent-Györgyi, famously put it, the trick is ‘to see what everybody else has seen, but to think what nobody else has
This was no trivial task – it took him five years to hit upon a procedure that worked – and again, those who happened to work upstairs played a crucial role.
‘I have roamed through living cells, but with the help of a centrifuge rather than of a microscope,’ de Duve said when accepting the Nobel Prize with Palade in 1974.
how does the body decide to make an immune response with the right level of caution? Steinman had discovered that dendritic cells were potent in starting an immune reaction, but he didn’t know why, how or what this meant for the working of the immune system as a whole.
dendritic cells in tissues such as skin, lungs or the gut were found to be immature – while those in the spleen or lymph nodes were mature.
We don’t give up, we scrutinise the details: understanding how the same cells initiate a reaction sometimes but stop it at others required us to understand the precise mechanism by which dendritic cells interact with other immune cells.
Steinman’s broader vision that new medicines could work by harnessing the power of the immune system remains very much in vogue.
We once thought that the positions of stars affect our health, but the truth is even more fantastical: our body is locked in an everlasting arms race with minuscule germs.
It began with a feeling of dissatisfaction. It had recently been established that an immune response involved many different cells – emphasised by Steinman’s discovery of dendritic cells
With around 10 billion B cells in the average person’s immune system, each of us has the ability to make around 10 billion differently shaped antibodies, each of which is able to recognise something that hasn’t been in the body before, ensuring that antibodies can be produced against virtually any structure alien to the body.
years ago the great British explorer George Mallory, who was to die on Mount Everest, was asked why did he want to climb it. He said, “Because it is there.” Well, space is there, and we’re going to climb it, and the moon and the planets are there, and new hopes for knowledge and peace are there. And, therefore, as we set sail we ask God’s blessing on the most hazardous and dangerous and greatest adventure on which man has ever embarked.