Trump's Treatments & Nobel Prizes

When Donald Trump caught the coronavirus his doctors put him on a range of treatments, including an experimental antibody therapy from the company Regeneron as well as a number of other drugs and supplements. It’s been unclear how ill he actually is, so it's difficult to judge whether these measures were appropriate; but how do they stack up against the current best practice in COVID treatment? And how much have we learned since the pandemic began? Charlotte Summers is an intensive care consultant at Addenbrooke's Hospital; she also advises the UK government on managing the condition. Chris Smith asked her opinion on Trump's treatments...

Charlotte - I have to say I was quite surprised; they perhaps weren't the first drugs necessarily that I would have reached for had I been one of the doctors looking after him. I think the most controversial is probably the Regeneron therapy that he had, which is a cocktail of two antibodies that are designed to neutralise the virus. And actually the company that makes those had only released the first data on this a few days before they were given to the president, and it was only based on 275 patients, and the clinical trials are ongoing. We don't actually know whether this therapy works or not. So I was slightly surprised that a very experimental therapy - which although it looks promising, isn't proven - was given to the president of the United States.

Chris - The rationale for using antibodies is, of course, that's what your own immune system makes when you have an infection; and if you give people those, perhaps it will help to soak up some virus and bolster your own immune response. Have we not though seen something of a checkered response to the convalescent plasma therapy that has been done for some time since this began, where people are taking blood products from people who have recovered from coronavirus and giving them to people at high risk of severe disease, and it's not clear that that's actually working? So why do we think these Regeneron... or I know AstraZeneca are also making a rival product, aren't they? Why do we think that this is actually worth pursuing?

Charlotte - The issue with convalescent plasma is that everybody makes a different level of immune response. Some people make a very low level of antibody response; some people make much higher. And lots of the data that's been generated with convalescent plasma studies has not been terribly clear about the amount of antibodies in the therapy that's being given. But convalescent plasma has been given by two big trials in the UK that are ongoing at the moment, the RECOVERY trial for people who are hospitalised and the REMAP-CAP trial for people that are in intensive care. So we should get an answer from those fairly soon, I hope. The antibody therapies: we know how much antibody you're given, and we know that they are targeted to try and neutralise the virus, so it's slightly different type of antibodies to the general antibodies you might make in your new plasma in response to having had the virus.

Chris - So there's a slightly higher prospect that they may be advantageous. The other thing that he got was dexamethasone- tell us a bit about that.

Charlotte - Dexamethasone is a steroid treatment and that's quite widely used across a range of healthcare settings. But what was important was that this therapy is one that's got an evidence base. The big UK clinical trial called RECOVERY, that lots of people will have heard of, showed that there was a mortality benefit in people who needed oxygen or who were on ICU ventilators if you were given dexamethasone; so their outcomes and their chance of survival were improved by having this therapy. People who weren't on oxygen: there was definitely no benefit, and possibly even a potential that the therapy did some harm in that group of people. So I can't imagine that they gave the dexamethasone therapy to Donald Trump without him requiring oxygen. And we know that the reports about whether he did or didn't require oxygen have been a little bit confusing at times.

Chris - Theo, you must have been party to quite a lot of data coming across your desk on drugs, including dexamethasone?

Theo - Yes. I think at the moment there are several hundred trials of different drugs and therapies ongoing, and there's also been a lot of claims based on observation, because so many people have been hospitalised and some of them happen to be taking drugs for something else. For example, there was a suggestion that one particular antacid that people take if they have stomach problems... people taking that in China, in the first wave of COVID, appeared to do slightly better than people who weren't taking it. And actually that's one of the cocktail of drugs that Donald Trump seems to have been given, although he may have been taking it anyway.

Chris - This is famotidine, isn't it? The ranitidine-like drug?

Theo - Yeah. But he may have been taking that anyway for some other condition; we don't know. They seem to have sort of thrown a bunch of things at Donald Trump, some of which, as Charlotte said, you would expect to treat severe illness with; and some, like the antibodies, you would treat early in the illness; and it just adds to this confusing picture of how long he's been ill, how seriously ill he was.

Chris - And Charlotte, if you had been the physician to Donald Trump and you had to treat him or manage him, how would you have approached it? And also what have we learned about how, when someone comes in and they're acutely unwell with COVID, the actual disease caused by this virus, how we manage them now, compared to how we would have been managing people back in March?

Charlotte - It's slightly tricky to say exactly how I'd have managed him and get it right, because I don't have all of the medical information available to me. I've just got what's in the press. But I would definitely have started with the therapies for which we've got evidence. So if he needed oxygen, I would definitely given him the dexamethasone. And if he was early on, and had signs of pneumonia - inflammation in his lungs on a chest X-ray - I would have given him remdesivir, the antiviral therapy, that he did get, but a little bit later and after getting the Regeneron. And given that convalescent plasma actually has got an emergency use license in the United States, I would potentially have gone with that rather than the experimental Regeneron therapy. Although I would have tried to encourage him to be randomised into a clinical trial so that actually we could have learnt something about the use of these therapies, rather than just giving it on compassionate grounds.

Chris - What about issues with giving people supplementary oxygen early? And also this question about anticoagulation? We've learned, have we not, that quite a lot of people who get this infection have problems with their blood clotting going off?

Charlotte - I'd have given him oxygen if he needed oxygen. And actually there's advice across the world about the levels at which we should start giving people oxygen therapy that vary from between about 90 to 94%, depending on how well you're monitored. So if his oxygen levels had dropped to those kinds of levels, I would absolutely have given him the oxygen, because that's important. Anticoagulation is more tricky and there's actually not strong consensus across the community of hematologists and other healthcare researchers about what the best approach is here. We know that patients with sepsis from any cause actually have an increased risk of getting blood clots. And coronavirus infection, or COVID-19, has had a really big number of people with a sepsis type illness recently. So we've been seeing a lot of people with blood clots, but it's still not definite that the proportion of people with COVID getting blood clots is substantially greater than the people who have sepsis from other causes, but I think it probably is. But we don't have data to back that up.

In terms of what we do about that, there isn't an evidence base to answer that question at the moment. There's an arm of a trial called REMAP-CAP that is looking at hospitalised ward patients in the UK to try and come up with an answer for that. And there are other trials in discussion across the world. But it's something that we don't have good evidence for. Should we give them things like aspirin? Should we thin the blood therapeutically? Should we just give them protection against developing clots? What's the best way to go? It's still a subject of great debate.

Thanks to the pandemic, we’re entering a world that’s more online; and, thanks to what many are calling the ‘fourth industrial revolution’, it’s a world that’s much more automated and data-driven. Jim Gazzard, director of the Institute for Continuing Education at the University of Cambridge, has been on the front line of having to respond. Chris Smith asked him, firstly, whether young people in the UK should have been sent off to university...

Jim - I think it's a very finely balanced decision. You mentioned young people, and I think that's key. These are people who are needing to get on with their life, needing to get on with their education, and they're relatively low risk; so returning to halls of residence, returning to small group teaching, I think is probably on balance the most sensible decision. But I'm interested in adult education; of course it's a little bit different perhaps for people who are in their forties or fifties or sixties, or students with health conditions, so we decided to deliver all of our continuing education, certainly for undergraduate courses, fully online this year.

Chris - How has, though, the response to learning worked out? Because some people have been saying to me that they go home at the end of the day and they're a bit Zoomed out, square-eyed from staring at screens all day.

Jim - Exactly that. If they've been on Teams all day, or Zoom, then it is quite difficult. So we're trying to break up the learning into smaller chunks and to engage in different ways. What we are hearing from students, particularly because of the global recession that goes along with a pandemic, is that there's a real necessity about learning; whether that's about an enforced career change, whether it's actually a concern about whether skills and knowledge are contemporary. So we've seen a real growth in enrollments - we're over 50% up year on year - and I think this is being mirrored globally. I think sometimes it's for positive reasons, because people have used lockdown to really think about what they want to do with their futures. But as mentioned, it's also for some of these more challenging reasons.

Chris - Lee what's been the experience at Wits in Joburg?

Lee - The teaching has been very good, but we have in the developing world a different challenge: that our students can't afford the bandwidth in the way that the developed world can. Wifi, internet, is not as freely available. So all of our teaching tends to be recorded in advance and we limit the interaction, and I think that's a really sad thing, because like many of you I miss that one on one interaction; it's the things that happen during the course of a lecture, as you follow the students and they challenge you, that is the point of higher education.

Chris - You were quite early to this party though, because when you started making the stupendous discoveries that you have in South Africa, rather than squirrel these findings away in a lab and work on them in isolation for the rest of your career, you actually said, "no, I'm going to scan them, and I'm going to put all this data on the internet so people can download and 3D print their own Homo naledi or Australopithecus sediba," and people are!

Lee - That was just trying to move some of the fighting in this field of palaeoanthropology by showing the evidence, making the evidence available. We were also there very early in going live with the science, experimenting with "how do you go live? How do you communicate science in an authentic way, that also doesn't lose the trust in science, because we make mistakes along the way?"

Chris - Here is the UK's chancellor Rishi Sunak; let's hear what he had to say earlier this week...

Our economy is now likely to undergo a more permanent adjustment. We need to create new opportunities and allow the economy to move forward. And that means supporting people to be in viable jobs which provide genuine security.

Chris - I suppose, Jim, that those sorts of statements are both an opportunity and also a curse for someone in your position, because some things that you may have been anticipating training people for may not actually exist as viable jobs, in Rishi Sunak's words; but there may now be new opportunities, new things potentially, that people want training in, which someone delivering online and adult education... it's an opportunity there.

Jim - Yeah, I think you're right, Chris, there are opportunities and threats. If we want to be serious about science and technology, not only do we need to continue training PhD level scientists, but we need to think about technician level science support. So I think there's going to be some very exciting opportunities in those areas in life science, in physical science, and looking at data analytics, looking at coding. But yes, I think there's going to be creative destruction that's being accelerated around COVID. And we're seeing so-called white collar jobs, that would be exciting professional opportunities even only 10 or 15 years ago, that technology is overtaking with algorithms and machine learning. As an educationalist interested in life wide and lifelong learning it is a really interesting time, but I understand it's a really scary time as well, when I think the norms of employment within an economy in the UK, for example: they're going to change very rapidly, and we have to be ready to respond to that as universities, and education and training providers.

Chris - What's your view on this Theo?

Theo - As has just been said, it's going to be so interesting to see how computers get better at doing the menial things that we do, ranging from driving a car to assessing an X-ray; and how are we going to train people to work around the changing world of work, particularly unfortunately when we face a global economic crisis brought on by COVID.

Chris - It's interesting that both you and Jim just before you brought up computers and coding, because that also made headlines this week, didn't it unfortunately...

Public Health England have admitted tonight that nearly 16,000 cases of coronavirus between the 25th of September and the 2nd of October were not included in daily figures for that period and not transferred to the contact tracing system...

Chris - I think one word springs to mind Jim: whoops. How did that happen?

Jim - That is a really interesting point. I mean, if we are to believe what we've been told, this was about an Excel spreadsheet that hadn't been transferred into the main data repository. Obviously I don't know how it happened, but I would bring this back to skills and training. We need people who have digital skills and we need to be able to design systems that work properly.

Chris - And just very briefly, with your eye on your crystal ball - which I'm sure you have there in your office - what do you foresee as where we will be, from a university point of view, as the university sector, in a year's time? Do you think that organisations like the one that you're running will be at the forefront and it's going to very much be online, or do you think we'll solve this COVID problem and it will be bums on seats back in lecture theatres? Are these changes here to stay?

Jim - Yeah, I think this is going to change universities profoundly. I think there's been probably 20 or 30 years in the UK and Western economies where we perhaps, I don't know, lost our way a little bit. I think we've got to redefine what universities are for. We need to train the next generation of technicians, as I've mentioned; and really thinking about the fourth industrial revolution, what new jobs, what new roles, will be created. Perhaps half of the jobs that will be around in 10 years don't currently exist right now. So what we have to think about in universities is critical thinking and synthesis of ideas, and creativity, and working with new ideas in different ways; and I think that means we perhaps have to get out of discipline silos and think interdisciplinary learning. So I hope universities will view this as a real opportunity - I genuinely think it is - but I think we've got to think about learning as a life wide activity. The skills that we learn at university, if you're 18 or 19... the half life of those skills now might be three or four years, so you're going to have to learn again in your mid twenties, your early thirties, your forties; you might have to change career in your fifties or sixties; and we might have to carry on working until we're 70, 75, or 80. So I think we've got to recondition our learning and the way that we think about learning to respond to how society and technology is changing.

A cluster of genes that is linked to more severe cases of COVID-19 appears to have originally come to us from Neanderthals, according to a report in Nature. Chris Smith asked Sean Carroll, Theo Bloom, and Lee Berger to unpack the story...

Lee - So Neanderthals are both a lot like us, and a lot different from us. They're more robustly built, they're shorter, they're stockier; and they were considered an absolutely separate species. In fact, scientists used to get in bone fights over whether or not we wouldn't run away from each other, and they'd ever even met. And then ancient DNA came along, and that plays into this story because we mapped out the Neanderthal genome, and suddenly we found out that most humans - including many Africans - had some levels of Neanderthal DNA, something between 1% and 5% within us. And that's where this story comes in.

Chris - And Sean, would you judge that in the book as a fortunate event - the interbreeding of us with Neanderthals - or not? When it comes to coronavirus, it sounds like it might not be...

Sean - Might not be. No one can tell the future; and so really natural selection only operates in the present. So probably the reason why this block of DNA is in a significant number of humans is that there was some positive selection for it, but now here's this new pathogen and it's a disadvantage. And that's a very common story about human genetics. We know, for example, that there's a very rare variant that makes people impervious to HIV. The HIV virus is perhaps a century old, but this variant we can find in bronze age bodies buried in Europe. So these genetic variants have been around for a long time, and perhaps they were favoured by certain other pathogens; they may have conveyed resistance to other pathogens, but now they're either advantageous or disadvantageous to new ones that come along now.

Chris - Theo, what's your reading of Sean's fortunate events? He made reference to our parents gonads, and he's getting at basically the rearrangements of genes in there that render us unique on Earth - unless we have a twin or we've cloned ourselves.

Theo - Yeah. So this notion that, although we're initially taught that genes all behave independently, actually they're inherited in blocks along chromosomes that are inherited together simply by proximity. And this example of the piece of Neanderthal DNA that seems to have an effect on COVID resistance: who knows what genes it may carry, or why it was selected for at some point during evolution. At this point we don't know; we just know that there's a linked box of DNA that's come to us from our Neanderthal ancestors, and it seems to be differently distributed among different groups on Earth at the moment, and may even underlie some of the differences in susceptibility to COVID. But really we're very early in understanding that story, I would say.

Chris - Do we have any idea why those Neanderthals had those genes, and what they did for them?

Sean - The first answer to that is a flat out no, we have no idea. And the second answer to that is a lot more complex. No, they didn't have to have an advantage. They might've just been there and we might just carry them. We need to be cautious about direct attribution, particularly in the middle of a pandemic, because as Theo would absolutely know - I'm sure you were inundated with these ideas - we don't know this right now. It will have to prove the test of time. Don't think that if you carry Neanderthal DNA that you're at some higher risk of this, or if you don't, you're at lesser risk; keep wearing your mask, keep social distancing. Those are the things that work until we get a vaccine.

Chris - And Sean Carroll, the author of A Series of Fortunate Events, I suppose it was another fortunate event that you were able to come on our program today! So thank you for joining us and thanks for telling us about the book. What do you think the next most fortunate event is going to be? A vaccine?

Sean - Yeah, well, that's not fortunate. That's just science, and scientists working very hard. And I have a little inside insight to that through a documentary film that we're making; and there are people whose names you don't know who've been working tirelessly around the clock, in an unprecedented challenge to develop this vaccine. So I think that's a nice side effect of our big brains, is the practice of biomedical science. So hopefully that'll get us all in person in 2021.

An additional interview with the author of the Neanderthal study appeared in the Naked Genetics podcast.