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T.The past few months have brought a number of scientific terms to the attention of the public. We had to digest R (virus reproduction number) and PCR (the polymerase chain reaction test method). And now there is mRNA. The latter has appeared heavily in recent news due to the spectacular results of two new mRNA vaccines against the coronavirus. It stands for “messenger ribonucleic acid,” a fairly familiar label if you’ve studied biology at level O or GCSE, but otherwise hardly a household name. Even in the field of vaccine research, if you had said up until 10 years ago that you could protect people from infections by injecting them with mRNA, you would have caused perplexed looks.
Essentially, mRNA is a molecule used by living cells to transform gene sequences in DNA into proteins that are the building blocks of all their basic structures. A segment of DNA is copied (“transcribed”) into a piece of mRNA, which in turn is “read” by the cell’s tools to synthesize proteins. In the case of an mRNA vaccine, the mRNA from the virus is injected into the muscle and our own cells read it and synthesize the viral protein. The immune system reacts to these proteins – which alone cannot cause disease – just as if they were carried by the entire virus. This generates a protective response that will hopefully last for some time. It’s so beautifully simple that it almost feels like science fiction. But last week we learned that it was true.
It is extraordinary that the observations originally made in cell cultures in a petri dish have been translated into real life. At the same time, it’s not entirely surprising that the first two Covid-19 vaccines to announce Phase 3 results were mRNA-based. They were the first to get out of the way because, as soon as Sars-CoV-2’s genetic code was known (it was released by the Chinese in January 2020), companies that had worked on this technology were able to start produce the mRNA of the virus. The production of conventional vaccines takes much longer.
It is possible that the impressive performance of these new vaccines will eclipse that of others currently in development. It depends on the effectiveness of these alternative approaches and the results will start coming quickly. Beyond that, however, there is the question of whether mRNA could represent the future of all vaccines. If a coronavirus vaccine can be created so quickly and so well with mRNA, why not use this approach across the board? In short: will mRNA become the default platform for vaccines from now on? This would mark a huge step forward in disease prevention.
We’ll just have to wait and see if that happens. While we assume that all the details of the results, when they arrive, corroborate the figures on the front page, there are things that only time can reveal. How long will the protection last, especially in those who are at greatest risk? Are these vaccines effective enough not only to prevent recipients from becoming ill when exposed, but also to prevent them from becoming infected at all, or failing that, to reduce transmission of the virus to others?
The other key parameter by which we judge any new vaccine technology is safety. Unlike drugs, which are given to treat sick people, vaccines are offered to everyone. Side effects are only tolerable if they are rather mild and short-lived – most people will accept a second of sharp pain followed by a tender arm and feel a little off for a day or two, but that’s about it. Serious diseases caused by vaccines should preferably be non-existent, or at least irretrievably rare.
At first glance, mRNA should be safe. After all, it is found in abundance in all the cells of our body all the time. It is also a very fragile molecule. It breaks down very easily and is quickly broken down by the proteins designed to do so, which seem to be everywhere. Working with mRNA in the laboratory is a nightmare because it keeps disappearing. On this basis, it should not remain in the body for long after it is injected.
The fact that mRNA is genetic material may lead you to think that there is some risk of genetic side effects. However, in human cells, while DNA is regularly transcribed into RNA, the reverse does not happen: RNA cannot go back into DNA and alter our genes. (In fact, making DNA from RNA – so-called reverse transcription – is something that only a certain type of virus, such as HIV, can do.) Ultimately, however, confidence in the safety of vaccines is something that comes from experience and will be the same with mRNA. The reassuring thing is that they have already been tested for safety in tens of thousands of study subjects. In a short time, they will become millions and, assuming no unexpected problems arise, the sense of reassurance will grow.
Whether or not mRNA becomes the preferred way to produce new vaccines, it is clear that a global disaster of the scale of the pandemic spurs innovation at a much faster rate. This is not just the consequence of all the resources and funding made available to those with solutions that could usually be viewed with more skepticism; it is also guided by the extraordinary things that human beings can achieve when they are brought together by circumstances and have a common purpose. While we like to showcase individual heroes and leaders, scientific advances such as mRNA vaccines are always the product of the collaborative efforts of many people with diverse skills and backgrounds. Bringing vaccines to the clinic also requires a large number of brave and selfless volunteers to take part in clinical trials.
Taking a step back, one fact stands out. At the beginning of November we still didn’t know if whatever the vaccine could help us overcome this terrible disease. As the month draws to a close, we’re confident they can. However mRNA vaccines go down in the history books, this in itself is something to be surprised about. Human ingenuity, invention and hard work mean we are finally on the way out of this disaster.
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