How Covid changed the world for the better

Second draft of history: what lessons are there from the extraordinary experience of the last two years? This week Reaction marks the lifting of the final Covid-19 restrictions in England with an assessment by our writers of how the lockdown and the pandemic reshaped our politics, medicine and attitudes to risk.

As Albert Einstein once said: “In the midst of every crisis lies great opportunity”. Admittedly, to search for the silver linings of the coronavirus pandemic – after it has claimedover five million lives – might feel glib. Yet undeniably, despite the scale of loss, there is cause for optimism amongst the misery. 

The past two years have been a time of unprecedented scientific achievement. We have witnessed the largest public health effort in history. Scientific progress already underway has been fast-tracked and the rapid development of a new generation of vaccines has been a remarkable feat. Our entire health ecosystem has evolved to become more efficient, more collaborative and more innovative. If we embrace these evolutions long-term, it raises the hope that we could save millions of lives far beyond Covid-19.

When the pandemic first struck, many scientists would have thought it impossible to create an effective, safe vaccine in less than a decade. It has often been said that it takes 17 years to move medical research from bench to bedside; in other words, this is the average time lag from starting research on a drug to its adoption in clinical settings. The measles vaccine, which progressed from identification of the disease to the onset of vaccine testing in just over ten, was the former record-holder.

And yet, in the space of just a year, we witnessed the development and approval of three safe and effective new generation vaccines for Covid-19. Over 10.4 billion doses have been administered globally, saving an estimated half a million lives the world over – a stunning achievement.

As we look to the future of medicine, the Pfizer-BioNTech and Moderna vaccines are, in many respects, an especially remarkable success story. The rapid development of these two particular vaccines was powered by a cutting-edge and highly promising technology: mRNA, or messenger ribonucleic acid. Before Covid struck, no country had ever authorised an mRNA vaccine. The pandemic has raised hope that other mRNA vaccines will be developed in the near future to treat a host of other diseases and to transform cancer treatment.

Vaccination is a form of immunotherapy. And mRNA vaccines work by instructing our cells to create a protein that resembles the real virus protein. Our immune system then trains itself against this (harmless) protein so that later on, if we confront the real virus protein, our bodies recognise it and are primed to destroy it. 

Uğur Şahin and Özlem Türeci, the husband-and-wife mastermind duo who founded BioNTech, give a helpful analogy: “It’s like showing our immune system a wanted poster of an outlaw”. This helps our immune system to swiftly eliminate the outlaw when he shows face. 

This notion of “stimulating the body’s immune system to control and eliminate an invading pathogen” is likely to bring dramatic advances in cancer treatment, according to Kate Bingham, the vaccine tsar who chaired the UK’s Vaccine Taskforce. After all, “cancer is a failure of the immune system.” 

“Immunology is the fundamental basis of how we are going to change medicine around the world”, Bingham says, since it shifts the focus of healthcare to preventing illness, as opposed to treating symptoms once they’ve already occurred. 

We do already have some preventative jabs for cancer. But at the moment they are limited totargeting viruses that can cause cancers, such as the HPV and Hepatitis B jabs. The hope with mRNA cancer vaccines is that they could train our immune systems to eliminate cancerous cells. 

In October 2021, BioNTech announced it had initiated phase 2 trials for mRNA vaccines to treat patients with head and neck cancers, melanoma and colorectal cancer. Moderna, meanwhile, has progressed to phase 2 trials for its personalised mRNA cancer vaccines and pharma giant CureVac is only one step behind, after expanding its phase 1 trial for a melanoma vaccine. The early clinical trials suggest all of these vaccines are safe and successfully shrink cancerous tumours. 

BioNTech is trialing two types of mRNA cancer vaccines. The first would prevent the growth of cancer cells by identifying specific proteins commonly found in the tumours of many cancer patients and then destroying them. 

The second type of vaccine is highly personalised, with the aim of preventing cancer relapse. They would identify, and target, cancer mutations unique to every patient. After surgery to remove a tumour, roughly 60 per cent of cancer patients are cured. For another 30 to 40 per cent, however, the tumour will regrow. Certain cancers, such as liver and lung cancer, are especially prone to post-surgery regrowth. mRNA vaccines could be instrumental in preventing relapse. 

Another reason for all of the hype around mRNA vaccines is the speed at which they can be produced and tweaked. According to Türeci, the process of tumor biopsy to finished product could be achieved in just four to six weeks. 

The promise of mRNA vaccines extends beyond cancer treatment. In March 2021, Yale researchers patented an mRNA-based technology to vaccinate against malaria – a disease that has long evaded effective treatment and kills over one million people in Africa every year, according to WHO estimates. 

Many researchers are similarly hopeful about the promise mRNA technology holds for treating autoimmune diseases. An autoimmune disease is when the body starts to attack itself because the immune system mistakes the body’s own healthy cells for foreign invaders and tries to eliminate them. 

To return to the “wanted poster” analogy, we can modify the message mRNA technology sends to the body. Instead of preparing the body to identify and attack a potential outlaw, it’s possible that we could treat autoimmune diseases by sending the opposite message: one that tells our body to do nothing when it sees a certain protein. 

It’s important to point out that mRNA technology wasn’t entirely new terrain before Covid-19. A small group of scientists have been plugging away for years, looking at mRNA vaccines as a possible treatment for illnesses like cancer. But the pandemic has almost certainly fast-tracked progress in this area by years. 

Thanks to the runaway success of Covid mRNA vaccines – and the hundreds of millions of people around the world who’ve been safely dosed with Pfizer and Moderna jabs – investors are piling in and funding has skyrocketed. Before 2015 there was less than $500 million in funding for mRNA therapeutics and vaccines. By 2020 that figure had topped $9 billion.

As Tal Zaks, the former chief medical officer at Moderna, points out, the triumph of the coronavirus vaccines didn’t change the science, rather it enormously boosted public acceptance of the technology.

The future of mRNA is bright. But, as we look ahead, will it be possible to carry forward all of the progress made over the past two years?

Aside from promising developments in cutting edge technology, drug development timelines have been dramatically sped up. This has been achieved through adapting clinical trial designs and accelerating the regulatory approval process. Will these changes stick?

Some of them are likely to be temporary. Under urgent pandemic circumstances, drug regulators have acted quickly to approve drugs, without demanding as much paperwork. This flexibility is unlikely to stick. As Peter Marks, from the FDA, points out: “The current breakneck pace of regulatory work has been essential to reduce the burden of disease due to Covid-19, but this intensity of work cannot continue indefinitely.” Massively refocusing resources on the virus, he explains, “has come at the cost of delaying the development of other crucial medical products.”

Having said that, elements of change can be carried forward. For instance, national drug regulators have co-operated much more across borders to jointly evaluate drug safety. And this is proven to speed up the process. “Increasing international convergence of regulatory requirements has been a useful lesson from Covid-19 that could be further built upon,” says Marks.

What’s more, the embrace of a new and speedier clinical trial model could make it faster to trial other drugs in the future too. 

Randomised clinical trials typically take about seven years to complete. But time-pressed Covid researchers have been straying from this traditional model, looking instead to a model known as an adaptive clinical trial. While adaptive trials first emerged in the 1990s, they’ve been slow to gain traction. Yet they provide some clear advantages: they are both faster and more flexible. The design enables those running the trials to adjust factors such as the sample size, drug dosage and patient selection criteria, based on emergent findings. And this flexibility to make such changes massively reduces waste in clinical trials. Covid-19 has drawn attention to the merits of adaptive trials, providing scope for greater implementation of this innovative study design. This shift could drastically reduce the time it takes to bring a whole range of new medical treatments to patients in the future. 

More crucially still, a culture of collaboration has emerged during the pandemic – not just across borders but also across government, industry and academia, all of which has helped to speed up the drug development process. “We have traditional competitors working together in new ways,” says Esther Krofah, executive director of FasterCures, a Washington DC think tank.

To take but one example, an alliance of over a dozen companies — including Gilead in California, Novartis in Switzerland, and WuXi AppTec in Shanghai, China — has been working to discover and test antiviral treatments by sharing data about early results and basic science, as well as collaborating on designs for clinical trials. If these group efforts bear fruit, they may well continue, predicts Krofah. 

Paul Hudson, CEO of French Pharma giant, Sanofi, agrees. “We have models for unprecedented harmonious collaboration” he says, not just between otherwise competitive private companies but also between the private and public sectors. “We’ve seen what happens when we share information and data. We’ve proven that timelines can be shortened.”

The coronavirus has brought about rapid developments in medical science. We are emerging from it strengthened by the scientific innovation spawned in this turbulent time. These medical advances are already powering change in the pandemic’s wake. Long may it continue.