A New Era in Medicine Begins: mRNA Vaccines!

Nobody knew whether mRNA technology would work against the novel coronavirus — but it does! This is an extraordinary moment for science.

What is mRNA?

The past few months have taught the public several scientific terms. We have had to understand R0(a virus’s reproduction number) and PCR(the polymerase chain reaction testing method). Now comes mRNA.

This last term has featured heavily in recent news because two new mRNA vaccines have produced excellent results against coronavirus. If you have even a basic knowledge of biology, you may know that mRNA stands for “messenger ribonucleic acid”, but if you do not, there is no everyday equivalent for the term.

Even in vaccine research, if you had said as recently as 10 years ago that injecting people with mRNA could protect them against infection, you would have received astonished looks.

In fact, mRNA is a molecule used by living cells to translate gene sequences in DNA into proteins, the building blocks of all essential structures. A piece of DNA is copied into a piece of mRNA (transcription), which is then read by the cell’s machinery to synthesize proteins.

What does an mRNA vaccine mean?

In an mRNA vaccine, mRNA that will produce viral proteins is injected into muscle. Our own cells then read it and synthesize the viral protein. The immune system responds to this protein as if we had been infected with the virus, but the proteins cannot cause disease on their own. This produces a protective response that we hope lasts for some time.

It is so elegant and simple that it is almost science fiction. But last week, we learned that it was real. It is extraordinary to translate observations originally made in cell cultures in a Petri dish into real life.

Two new mRNA-based COVID-19 vaccines

At the same time, phase-3 clinical trial results from the first two COVID-19 vaccines to report them came from mRNA-based vaccines, which is not entirely surprising.

Companies working on this technology had already cleared the first hurdle because they could begin producing the virus’s mRNA as soon as the SARS-CoV-2 genetic code became known (published by the Chinese in January 2020). Conventional vaccines take much longer to make.

The development process and mechanism of action of Moderna’s mRNA vaccine are shown below.

The impressive performance of these new vaccines is likely to overshadow other vaccines already in development. This depends on how effective the alternative approaches become and how quickly and extensively their results begin to emerge.

Could this approach be used for all future vaccines?

Beyond this, however, lies the question of whether mRNA represents the future of all vaccines. If a coronavirus vaccine can be made so well and so quickly with mRNA, why not use this approach more generally? In short: Will mRNA become the default platform for vaccines from now on? This would be a major turning point in disease prevention.

We will have to wait and see. Even assuming that the full details of the results confirm the headlines when they emerge, some things can be revealed only by time. How long will protection last, especially in those at greatest risk? Are these vaccines effective enough not only to prevent recipients from becoming ill when exposed, but also to prevent infection altogether — or reduce transmission to others?

Safety is the key criterion by which we assess any new vaccine technology. Unlike medications given to treat people who are ill, vaccines are offered to everyone. Side effects can be tolerated if they are only very mild and short-lived — most people will accept a slightly sharp ache in the upper arm and feeling unwell for a day or two, though not everyone will. Above all, vaccines must not cause serious illness, or may cause only a very rare condition that also resolves quickly.

At first glance, mRNA should be safe. After all, it is abundant in all our cells all the time. It is also a very fragile molecule. It breaks apart easily and is rapidly degraded by proteins designed to do this, which are found everywhere. Working with mRNA in a laboratory is a nightmare because it keeps disappearing. On this basis, it should not linger in the body for very long after injection.

The fact that mRNA is genetic material may raise the possibility of genetic side effects. However, although human cells regularly copy DNA into RNA, the reverse does not occur — RNA cannot turn it back into DNA and alter our genes. (In fact, making DNA from RNA — a process called “reverse transcriptase” — is something certain types of virus, such as HIV, can do.) Ultimately, confidence in vaccine safety comes from experience, and the same will apply to mRNA. It is reassuring that it has already been safely tested in tens of thousands of trial participants. Soon this will become millions, and — assuming no unexpected problems emerge — confidence will grow.

The mRNA technique for future vaccines

Whether or not mRNA now becomes the preferred way to make new vaccines, it is clear that a global disaster on the scale of a pandemic encourages innovation at a much faster rate. This is not only the result of funding and resources provided to those with solutions that might ordinarily face greater skepticism; it is also driven by the remarkable things people can accomplish when given a shared purpose and the right circumstances. Although we like to celebrate individual heroes and leaders, scientific advances such as mRNA vaccines are always the product of collaborative efforts by many people with different skills and backgrounds. Bringing vaccines into clinical use also requires many brave and selfless volunteers to participate in trials.

Conclusion

Stepping back, one fact stands out. At the beginning of November, we still did not know whether any vaccine would help us overcome this terrible disease. As the month drew to a close, we became confident that they could. With that, mRNA vaccines are entering the history books, which is remarkable in itself. Human ingenuity, invention, and sheer hard work mean that we are finally on the way out of this disaster.

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