Michel Morange: “vaccination is a typical case of a technique developed before being scientifically understood”

In your book, you place the fight against Covid-19 in the long history of biologically based medicine. What are the biological strategies used against the virus?

There are three, which go back at least a century: chemotherapy, serotherapy and vaccination. The first consists of fighting the infectious agent with synthetic molecules, or extracted from plants or other organisms. Begun in the 1920s, it experienced its first major successes in the 1940s with penicillin – a broad-spectrum antibacterial. Faced with Covid, however, we unfortunately only had a few antiviral molecules, despite what some charlatans have said.

The second, serotherapy, involves reducing infection by injecting a patient with serum, that is, the antibody-rich protein fraction of the blood of recovered patients or immunized animals. It dates back to work at the end of the 19th century on diphtheria. It was used successfully in a few exceptional cases at the start of the pandemic, for example in that of the President of the United States! However, it is difficult to apply to entire populations during an epidemic, and it is often not very effective, unfortunately.

And vaccination?

It consists of the injection of a variant with attenuated virulence of the pathogen. This technique, which dates back to Edward Jenner’s work on smallpox at the end of the 18th century^e century, then to those of Louis Pasteur on rabies a century later, led in the case of Covid to RNA vaccines. It is this approach – the oldest – which has provided the greatest service!

You emphasize in your book that this ancient technique was misunderstood for a long time, which contributes to the fact that it remains so…

Indeed, because vaccination is a typical case of a technique developed before being scientifically understood. But this phenomenon is banal: for example, we made fire hundreds of thousands of years before understanding the chemistry of combustion or even built steam engines almost a century before developing thermodynamics. Pasteur himself did not know why his vaccination worked, and he successively proposed several explanations, which are not validated today.

Has vaccination evolved significantly once its principle was discovered?

Yes, especially from the 1970s and 1980s, thanks to the rise of molecular biology, which raised the hope of finally fully understanding the immune system. Molecular biology has made it possible to better control the vaccination process, by using not an attenuated pathogen, but a part of this pathogen: a protein triggering an immune reaction, or even a nucleic acid coding for this protein. This principle, that of RNA vaccines, has been implemented for almost forty years. This is why I strongly disagree with those who claim that messenger RNA vaccines were developed too quickly to be reliable.

What about the hopes of finally fully understanding the immune system?

Unfortunately, they were rather disappointed. Our efforts to better understand the immune system through molecular biology, and therefore the side effects of vaccines, have above all led to an additional complication of its description, already very complex, but without us achieving a truly better understanding.

You write in your book that scientists and doctors hate to admit that they do not understand a technique, a therapy, even when they work very well…

I am not saying that researchers hide their uncertainties from themselves, but that they too often hide them from the general public, so as not to undermine confidence in science. A tactic that I disapprove of, because I think it is better to admit one’s ignorance than to assert a certainty which one will then have to come back to. To restore confidence in the scientific institution, it is time for scientists to recognize that there are things they do not understand; while, of course, doing everything to understand them!

Thus, I find that there is too little research on the serious side effects of vaccines, which are considered accidents, exceptions in the statistical series. For example, we are unable to explain why the AstraZeneca vaccine sometimes – very rarely – triggers thrombosis, while the Pfizer-BioNtech vaccine has the very rare but serious side effect of causing pericarditis. It should be publicly stated that these issues are priorities.

You speak of research “priorities” but describe the evolution of vaccine techniques as “busy”. So should this bush be pruned so that it grows better?

On the contrary, I think that it is best to let him have his wildness. Small branches that seem fragile today will be able to develop if circumstances change. Research on RNA vaccines stagnated for two decades, before proving to be an excellent approach against Covid-19. If we had stopped it, we can appreciate the difficulties that would have been ours during the pandemic. Research must progress on its own, without setting too precise objectives a priori.