Coronavirus: how the virus changed science

I talked to Jim Smith, interim Director of Research Programmes at the Wellcome Trust and Visiting Group Leader at the Francis Crick Institute. His comments are in italics.

What is different about research on COVID-19?

It’s not an original observation, but in some ways, it’s like being in a war. Not with respect to conflict between nations, but with respect to pulling together when we have to.

I remember being at the RAF museum in Hendon and was struck by the altimeter developed by the ‘Dam Busters’ in World War Two. To reach the right altitude to release Barnes Wallis’s bouncing bomb they used two spotlights, one under the aircraft’s nose and the other under the fuselage, so that at the right height their light beams converged.

In extremis, we can work together to find elegant solutions and do extraordinary things.

What does this wartime footing mean for science?

In the kind of science that I normally do, we spend a lot of time circling a problem because we don’t know how to solve it.

We may need to approach the question from the front, or we may need to sneak up from behind when it’s not looking. This is the way you make discoveries.

But the way we are working now, with COVID-19, is to take advantage of all that exploration to use our knowledge to get the answers as quickly as possible, taking advantage of decades of discovery science to save lives. And that’s really invigorating.

 This is well illustrated by teams doing vaccine development, where the usual approach of working in series, as it were, has been transformed to parallel working, in an effort to get a vaccine as quickly as possible.

In some senses, this is a riskier approach, but it’s exactly the right thing to do in an emergency. To this end, Wellcome has made funding available for the development of new vaccines and treatments and also to help low- and middle-income countries prepare for the pandemic.

What does SIR PAUL NURSE, Nobel Laureate, mean by invoking the Dunkirk spirit?

He was saying in April how hundreds of scientists working in small laboratories across the UK could create a 21st-century scientific flotilla of ‘little ships’ to avert Britain’s threatened coronavirus crisis by increasing testing.

The ‘ship’ of the Francis Crick Institute, directed by Paul and where I have my lab, took up the gauntlet in a way that truly makes me proud. Charlie Swanton, Steve Gamblin and Sam Barrell—and many more—are working in partnership with University College London Hospitals (UCLH) and its diagnostic partner Health Services Laboratories to test NHS staff so they know whether they can go safely to work.

And consistent with what I was just saying, scientists at the Crick have now validated a reverse transcription loop-mediated thermal amplification test for the virus that gives results in just 25 minutes. One of the research groups however has used mass spectrometry to identify proteins that could be used to predict whether a patient is likely to become severely ill with COVID-19.

It’s fantastic the way that scientists can turn their skills, at a moment’s notice, to tackle this global pandemic.

Is science still the most powerful way to understand the world?

That’s for sure. That’s how I live my life!

But you have to do the science properly. You have to design the experiments as carefully as you possibly can, always looking for any alternative reason for that exciting result.

As a developmental biologist, I discovered with Jeremy Green, that cells turned on different genes when exposed to different concentrations of a molecule called activin.

But then I had a sleepless night fretting that when I did these experiments, it might have been increasing concentrations of the solvent that had the effect, not the activin itself. The next day we reran the experiments to check the results were OK, which they were. But you must always be open to alternative explanations.

How is COVID-19 changing the image of science?

A major Government opinion survey published a few days ago shows that attitudes to science had remained broadly the same since an earlier study in 2014, with scientists and engineers being seen as some of the most trustworthy professionals in the eyes of the public. However, the survey was conducted last year.

I spoke to the writer David Aaronovitch recently and we agreed that gruesome though it may be, COVID-19 is waking people up to science, science policy, the nature of risk, and the relationship between science and politics.

This might be inspirational. In the case of Paul Nurse, he traces his science epiphany to a night in autumn 1957 when he ran down the road in Wembley to watch the Sputnik 2 satellite cross the night sky. What the outcome of the pandemic may be in terms of trust in science and scientists, we’ll have to see…

Why the rush to publish half-baked COVID studies?

I’m sure that some scientists are so keen to contribute to containing COVID-19 that they’ll publish prematurely so that their results can be applied as soon as possible.

To them, one would say (as I said above) do the science properly. In other cases, well, it is a little-acknowledged fact that scientists are human beings. Some crave attention. Some crave success. Some crave money. So, some will cut corners.

But if COVID-19 sometimes brings forth poor science, it has also brought out the best in people too, whether this is those involved in testing at the Crick, or Wellcome turning its headquarters into a respite centre for local NHS staff.

To repeat the well-worn war analogy, COVID, like war, brings out the best and worst in us.

How about the problem of reproducibility, where it is NOT UNCOMMON IN THE BIOSCIENCES for a striking result not to be reproduced?

As I said, I regard science as the best way to understand the world.

My fundamental principle is that if you do the same experiment twice, you should get the same answer both times. And if you get a different answer it’s because, unknowingly, you haven’t done the same experiment.

One famous example is that rats and mice show different levels of stress depending on whether they are handled by a man or a woman. Would a researcher repeating an experiment know, necessarily, who had handled the animals? Probably not.

But here’s an example where the right response to a different result would be ‘Hmmm…I wonder how my experiments differ from theirs?’.

But I’m not so idealistic that I think we should ignore the question of reproducibility, and Marcus Munafo of the UK Reproducibility Network does a wonderful job. Lots of it comes down again to scientists being human beings.

Some make honest mistakes; others may hurry a piece of work because (especially in the time of COVID) the results may be so significant and the rewards may be so great; and a few may be plain dishonest. In the great majority of cases, though, especially if the results are indeed significant, the truth will out.

I think the use of preprint servers is serving reproducibility well. I know from my own experience that if you send something to BioRxiv you think very carefully before you press submit, because there’s no going back—once it’s out there it’s out there, and anyone can comment.

And I think COVID is making journals more pragmatic. Authors can’t do additional experiments so easily now, especially if they involve mice, so there’s no rush to do that tricky experiment requested by referee 3.

Is the urge to be the first to publish a new finding too strong?

It sure is, and speaking both as a scientist and a funder I hope we can start to judge researchers by more than whether they got their paper out in April and their rivals published in June. This obsession with being first can backfire.

Do you think COVID-19 has changed the relationship between Government and science?

The mantra is that scientists advise and ministers decide. But ministers, like scientists, are human beings, and I just don’t know how well they listen or to what extent they drive the agenda of the scientists.

One day the history of this pandemic will be written, but it’s so hard to know what is going on when you’re in the thick of it, and when knowledge (like the virus) is evolving.

As I said, a clear positive from the pandemic is the way the research community has rallied, and this extraordinary effort shows UK research at its best.

But this research, and the researchers doing it, needs to be protected through the uncertain times ahead—not least Brexit—because there has never been a more important time for science to inform policymaking.

What do you make of some of the scientific arguments, such as the one about the value of face masks?

Every week I have a Zoom conversation with some of my medical mates, and we discussed this quite recently.

I’m no expert, but I can’t imagine how masks would not reduce the shedding of infectious droplets into the environment by asymptomatic or pre-symptomatic people, and I’m pleased that the Royal Society agrees.

As the Royal Society says, the UK is way behind other countries in mask usage. Part of it may be, as its president Venki Ramakrishnan says, because the message has been inconsistent. I do also worry that there may be an element of racism and exceptionalism—’we Brits don’t wear masks.’

Do you think COVID-19 is wiring up science in new ways?

You bet. It’s ironic that while scientists can no longer travel to international meetings, new collaborations have been springing up around the world.

The Coalition for Epidemic Preparedness Innovations (CEPI) has led the way in bringing donors, philanthropists and companies together to make a vaccine and to distribute it fairly and equitably, in an environment in which the drug Remdesivir is being ‘scooped up’ by President Trump.

And scientists are thinking broadly and imaginatively about how their experiments might contribute to our understanding of COVID-19.

For example, my colleague Andreia Bernardo is not the only one who has suggested using iPS cell-derived heart muscle cells, called cardiomyocytes, to understand why patients infected with SARS-CoV-2 have signs of heart injury (iPS cells, or induced pluripotent stem cells, are adult cells that have been taken back in time to an embryonic state from where they can then be directed to form different adult cell types).

Similarly, many of my other colleagues in the Francis Crick Institute have used their expertise to inform our understanding of SARS-CoV-2 infection.

Don’t you think it is wrong that some vaccine research has been made public in the form of a press release, rather than a peer-reviewed paper?

Of course. Follow the money.

How else has science been altered by COVID-19?

The way we publish our research has been changed forever by the internet, and the way we interact as scientists may be changed for a long time by COVID-19. Repeating my refrain that scientists are human beings, there will always be a desire to meet at conferences and discuss results and new ideas.

But nowadays I can present my results worldwide on BioRxiv at the touch of a button, speak to colleagues on Zoom, and get access easily to much of the data I need. We should all be grateful to the Wellcome Trust and other funders for sharing human genome data in real-time, and really democratising scientific research.

I hope we’ll learn from these lessons in the future. Video conferences can be more inclusive—for some disabled scientists, for those who lack childcare, and for those who face travel restrictions.

And with climate change in mind, we really need to cut down on travel. At some point, we will need to ask ‘What is the point of a conference?’

Has COVID-19 changed the people doing science?

The point I’d make is that COVID-19 has highlighted the importance of equality, diversity, and inclusion. I helped found an organization called EDIS—equality, diversity, and inclusion in science and health.

We have to make sure that science as a career is open to everyone, and that everyone benefits from the research that is carried out. It is now that science has to get its house in order.

With this in mind, there’s one really important thing that has become apparent during the pandemic. Female scientists, and those with young children, are simply not able to devote as much time to their research as before—and of course, this is particularly marked for female scientists with young dependents.

As evidence for this, preliminary data show that the rate at which women post to preprint servers is declining. We recognise this at Wellcome, of course. The section of our grant forms that allows applicants to describe events in their career that may have affected their CV, such as parental leave, sick leave, part-time working, and time away from research, has been changed to mention specifically the impact of COVID.

Our external peer reviewers and committee members have become very experienced in managing this information during the application process, and our staff ensures this section is considered properly during any meeting.

Has COVID-19 changed our view of MATHEMATICAL MODELS?

It hasn’t changed mine. Mathematical models are fine when you’re doing mathematics, and when you’re doing those areas of physics or astronomy that can be described mathematically, but to follow up my comment above, not only are scientists human beings, but so are human beings.

We are, as individuals, unimaginably complex; we are as a population very diverse; we respond to changes in circumstances in different ways; we interact with each other in different ways; and so on.

I am often astonished at how useful models of human behaviour are, and I pay tribute to my colleagues in the field! And to return to another comment I made earlier, this complexity and heterogeneity of human beings might underlie some of the apparent irreproducibility seen in behavioural experiments.

So much so obvious, but one final comment is that it’s very difficult to modulate human behaviour in the time of COVID, to make the subtle changes in the course needed to navigate the waters between health and the economy.

Pubs, shops, businesses, and schools are open or closed. We can make some tweaks, like restricting the number of people in our local fish and chip shop, but we can’t say that if your surname starts with H you have to stay at home today but if it starts with S you can go to your lab!

HOW CAN I FIND OUT MORE?

The latest picture of how far the pandemic has spread can be seen on the Johns Hopkins Coronavirus Resource Center or Robert Koch-Institute.

You can check the number of UK COVID-19 lab-confirmed cases and deaths along with figures from the Office of National Statistics.

There is more information in my earlier blog posts (including in German by focusTerra, ETH Zürich, with additional information on Switzerland), from the UKRI, the EU, US Centers for Disease Control, WHO, on this COVID-19 portal and Our World in Data.

The Science Museum Group is collecting objects and ephemera to document this health emergency for future generations.