Wednesday, November 15, 2023

Q&A with Fabrice Delaye




Fabrice Delaye is the author of the new book The Medical Revolution of Messenger RNA. A science and technology journalist, he is based in Switzerland.


Q: What inspired you to write The Medical Revolution of Messenger RNA?


A: Obviously, the pandemic--but also the apparent speed to develop a brand new technology: the 10 months it took to make available vaccines based on messenger RNA.


As a science journalist, I was aware of mRNA because Moderna chose Lonza in Switzerland to produce its vaccine in Europe if clinically proven.


I was also aware of a related success of a technology with RNA (that is siRNA) with an American company called Alnylam who obtained market approval for an RNA based therapy (not a vaccine) in 2017.

Still, when mRNA vaccines were approved in December 2020 people were wondering how it could have been so fast, 10 months when normally it takes many years to develop a new vaccine. I thought the question was legitimate and started to search for an answer.


It drove me to look for the scientific and technological history of mRNA vaccines and because I found none I started to reconstitute it myself. I discovered a dramatic story spanning over 60 years. It illustrates how fundamental science is conducted and how it is transferred to make a technology we can use.


Doing that I found the incredible personal stories of the people involved--how they were disregarded by colleagues and big pharma for years. But also how tenacious and inventive they have been.

Q: What would you say are some of the most common perceptions and misconceptions about the Covid-19 vaccines?


A: The main misconception is probably about infection. The common perception is that the vaccine will stop the infection. But for a respiratory disease like Covid, a vaccine, even an mRNA vaccine, does not prevent infection in the upper airway. If you breathe droplets with virus, the virus will infect you.


That is because the immune system in the upper airway is slightly different than in the rest of the body. There is some protection from vaccines at this level but it is not full protection. What matters really then, is where there is real protection. It is further in your body like in your lungs.


Instructed by the vaccine, your immune system will block the reproduction of virus be it with antibodies that will stick to it or because of another more long-lasting defense mechanism named T Cell which will kill the infected cells to stop the spread.


That is why mRNA vaccines are efficient to stop the infection from spreading in the body but can't completely prevent it from entering the body.


Another important point still is that SarsCov-2, the covid virus, mutates. Not at fast as the flu, but a bit like it. Therefore, the immune response instructed by the vaccine will evolve and one may need a booster against a new variant.


Still, it is key to understand these new vaccines will be efficient at blocking virus reproduction in the body. Because the more viruses the more chances there will be of new dangerous mutations.


We are a bit in a race there. If the virus multiplies unchecked it will soon put more people at risk. Vaccines reduce massively that risk but cannot eliminate it completely.

Finally, there is a misconception about side effects. There are side effects with mRNA vaccines as well as with other vaccines. Most are mild, some are more serious and it is certainly a bad outcome for the people who have suffered them. 


The point is the benefits-risks balance. In a pandemic you are in a kind of evolutionary race with the virus. The more uncontrolled you let them be, the more they reproduce.


mRNA vaccines are not perfect but they are our best tool to stop a pandemic that would have otherwise claimed a considerably higher number of direct victims and maybe even more indirect victims because the healthcare system is swamped by the number of sick and infectious patients as we saw when there were no vaccines. 

Q: How did you research the book, and what did you learn that particularly intrigued you?


A: I start with the scientific literature. Science articles make references to previous work so one can follow that thread. Once I had identified the main researchers I started to contact them to get their stories, including their personal stories.


The book is about the people doing the science and through that it offers an accessible and often thrilling way to science itself. It is quite dramatic because these scientists were outsiders often fighting for every penny while their competitors with DNA technology were offered gold. 


Then, there is the business side of the story. There, I started by following the patents’ lead. I used that second set of data to understand also the role of pharma, biotech companies, and clinical trials in this story. I interviewed the entrepreneurs, managers, investors, and clinicians involved.


One thing that was particularly intriguing is that prior to 2020 three big pharma companies could have controlled the mRNA space. They renounced it and at the end it was two start-ups few had heard of that developed the mRNA vaccines for Covid. And now every pharma company has started an mRNA business.


Q: What do you see looking ahead when it comes to mRNA-based vaccines?


A: In the '80s, the first tangible outcome of biotechnology was the capacity to produce proteins, a lack of which in our body can cause disease--for example, recombinant insulin for diabetes and later monoclonal antibodies for cancers. It gave birth to massive companies such as Genentech and Amgen.


Proteins are the active agents in our bodies. They do close to everything. That are proteins that metabolize nutrients and use oxygen to produce the energy we need, that are proteins that carry and interpret messages cells need to function, that are proteins that trigger the immune system to defend ourselves.


mRNA is sort of an information technology, an operating system between the hard drive memory of DNA and the software of proteins.


Now one can hack the DNA step to program a particular mRNA to make a particular protein. This protein will be produced at will directly in the body to supplement the ones lacking or in the case of vaccines trigger immune response.


That opens the possibility of a flu vaccine you take once for all your life and not every year, and also cancer vaccines and even personalized cancer vaccines.


But because mRNA allows you to produce these proteins without entering the nucleus and risking the modification of DNA, the medical possibilities are literally endless. 2023 Nobel prize winner Drew Weissman told me once he still regularly wakes up with a new idea of potential application of mRNA. And he started dreaming of it 25 years ago.


Q: What are you working on now?


A: I am working on the extraordinary story of GLP-1, the anti-diabetes molecules people are now using massively to lose weight. There again it is quite a dramatic multi-continental thriller mixing science, technology, money, jealousy, etc.


I believe telling science through personal stories of scientists, doctors, patients, entrepreneurs, etc., is the way to make it accessible to non-scientists at a time where the power of science and technology is so impactful on our life that it is important to understand it.

Q: Anything else we should know?

A: Nobel prize winner Tom Cech once told me that the development of mRNA vaccines is the equivalent for biologists of putting a man on the moon for engineers.


I hope my book--which I could develop like a thriller thanks to the personal stories I had the chance to learn first in many cases--will help make this story more accessible and this achievement better recognized.


Covid vaccines have unfortunately been politicized. This is hiding the magnitude of the scientific achievement behind them and its medical potential for the future.


--Interview with Deborah Kalb

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