Prof Luke O'Neill leads the way into a sterile room adjoining his laboratory in the Biomedical Sciences Institute in Trinity College, Dublin. This, he says, "is where we grow the bugs."
His team doesn’t usually work on what he calls “really dangerous pathogens” here. By really dangerous ones, he means “P3 pathogens” like HIV. The “p” refers to the pathogen or protection level needed to handle it. “Ebola is P4, which is even more dangerous. We work on P2.”
Covid-19 is a P3 pathogen. So when O’Neill first heard of the new novel coronavirus that had emerged in Wuhan in January, he didn’t anticipate that he would end up working on a possible treatment for it. At that stage, he didn’t expect it to have much of an impact on his life at all.
“I was at a conference in Rotterdam with Sars people. There was a guy there from New York who was the world expert on Sars, and I’m sitting beside him. And he says to me, ‘have you seen this new one? This is going to be bad … Seventy per cent of the world will get infected with this because it’s a brand new virus’.”
O’Neill was not immediately alarmed. He suspected the virus would probably turn out to be mild. “The hope was you’d put it out in a few months, like Sars. But then, it’s different. It’s more troublesome.”
He opens up an incubator and takes out a flask. “There are macrophages in there – the white blood cells in your body. You can grow them in a dish. And then we can study them. What we’re doing is growing those because we’ve got a drug that might be an anti-inflammatory for Covid. We’re testing it on those macrophages.”
Macrophages, he explains, “are your frontline inflammatory cell. They go crazy in Covid-19.” So that is an experiment on Covid-19? Yes, he says, and “we’ve probably ruined it by taking those out.” He puts the tray back, but he doesn’t sound too worried.
When I told people I was going to meet the affable chair of biochemistry and author of Humanology, everyone I spoke to had a question they wanted to ask him. When and where should we be wearing masks? Will we have to learn to live with coronavirus? How does he stay so positive? Is he single?
“The mystery to me and my colleagues is we’ve been doing this for 35 years and nobody cared. I’d be at parties and their eyes would glaze over. Now everybody knows about the immune system.”
He has become known for his calm, reassuring presence on our TV screens, the more optimistic antidote to Tony Holohan's sober nightly broadcasts
He has become known for his calm, reassuring presence on our TV screens, the more optimistic antidote to chief medical officer Tony Holohan’s sober nightly broadcasts.
O’Neill was delighted when a former PhD student contacted him after one of his media appearances recently, to say that when she was working with him, “she’d come into my office devastated because the results wouldn’t have been good, and she said I’d always say, go back out and try it again. She said, ‘you always gave me a boost, and you’re doing it for the whole country now’.”
He’s had to get used to being shouted at in the street. “They mainly say, keep up the good work. Or they’ll shout sometimes, why are you wearing that mask? Some guy the other day shouted ‘you’re a commie’.” He seems quite pleased by that.
The reason O’Neill is able to stay positive is because he’s encouraged by the pace of research and the extent of international collaboration. “We know a lot about this virus, which is incredible, because it’s so new.”
Why didn’t scientists see a pandemic coming? “When I was training in the UK, I knew a lot of virologists. And you’d avoid them, not because you’d get sick off them, but because they were always saying there’s a pandemic coming. You’d be like, shut up about the pandemic. There’s a risk of an asteroid hitting the earth as well. So we kind of ignored it. Looking back at it now how stupid were we?”
The “coronavirus people” were “as obscure as hell.” “They were studying the common cold … it was all a bit boring.”
But even as it was clear a new novel coronavirus had emerged, nobody was clear how troublesome it might become. A large part of that is down to asymptomatic spread. “If you’re unlucky enough to be infected now, you’ll have no symptoms until day seven. But by day four, five, six you’re spreading it, and you don’t even know. And then secondly, it’s very contagious.”
In mid-February, O’Neill was at another conference; this time in Miami. He was there to present his work on the new anti-inflammatory discovered in his lab.
Ninety per cent of science is failing. It's early days. We need the next two months to tell us if there's going to be a prospect
He jumps up to get two cushions from the couch in his office, one of which is embroidered with the chemical symbol for the anti-inflammatory, Itaconate. “That’s the stuff there,” he says, showing off the cushions proudly, a bit like a parent showing off a photo of a newborn. “That’s how the kind of nerds we are. My lab gave me those for Christmas.”
At the conference, he met a German immunologist friend, who warned him again that the virus that had just arrived in Italy was going to be "bad". O'Neill was by this time paying more attention. It was clear, he says, at that stage that it was "something different to Sars" and that older people were going to be most severely affected, along with those with diabetes and obesity.
“If we’d been smart, we would have said let’s protect the nursing homes immediately. I feel a bit guilty myself … Why didn’t we all go, what about the nursing homes here? Again, there’s a blind hope that you could shut them and stop people going in and stop the spread.”
Part of the problem, he suggests, is that so much about Covid-19 is still ambiguous. “The central problem we’ve had all along with this is that science might give you a 50 per cent of the answer at the moment. But you need a 100 per cent decision if you’re a politician. That gap is the problem.”
That same desire for certainty has fed into what some people see as prevarication about the widespread wearing of masks, which O’Neill has been advocating. In the beginning, it made sense only to recommend masks for people with symptoms, especially as there were concerns about supply and “there was some evidence that it increased the spread, if you were wearing it and picking at it”.
But as the evidence about asymptomatic spread became clearer, and the scientific consensus shifted towards masks, he thinks the advice should have been updated. “You teach people how to wear masks, and if a third of them are not doing it properly and two thirds are, that justifies the mask.”
Also, he says, “if we all wear masks, it destigmatises the ones who have to wear him. That’s a great reason.”
He has met Tony Holohan only once, as a result of the crisis, but credits NPHET with getting most things right. "The lockdown was exactly as it should have been."
The big thing is the testing. If we get that wrong, that's disastrous. The schools is the other big one. That's a really important thing to get right. I would definitely advocate opening up of schools for certain age groups
The real test will come in “the next phase. The big thing is the testing. If we get that wrong, that’s disastrous. The schools is the other big one, though. That’s a really important thing to get right. I would definitely advocate opening up of schools for certain age groups.”
He says he “got into inflammation about 35 years ago” in the same way someone might say they got into marathon running or writing. “Inflammation is central to the immune system. The trouble is it goes rogue. It goes rogue in arthritis; in your skin as psoriasis; in your brain as Alzheimer’s; in your gut as Crohn’s. And we don’t know why. I’ve spent the last 35 years trying to see why that is.”
Inflammation plays a role in Covid-19, and is central to what’s called a ‘cytokine storm’, a severe immune reaction in which the body releases too many cytokines – a normal part of the immune response -- into the blood too quickly. “What killed people in 1918 flu was a massive cytokine storm in younger people,” the same thing that’s killing older people now. “If you took a 25-year-old who died in 1918 of flu, their lungs would look like a 70-year-old’s lungs now with Covid.”
One of the angles of attack on Covid-19 is that scientists might discover a way to switch the inflammatory process off, which is where O’Neill is hoping Itaconate might come in. He starts talking faster as he gets to this part of the story.
“I’m getting all excited. So I’m at this conference in January in Rotterdam. Fast forward six weeks. I get an email from one of the guys at the conference who saw my presentation. He says, we want some of your Itaconate. We need to collaborate.”
But he’s remaining measured about it. “Ninety per cent of science is failing. It’s early days. We need the next two months to tell us if there’s going to be a prospect.”
It is, he says, “another shot on goal…As scientists, we hope we can help. I mean, the big goal for all of us is to make a difference and to make sure our research is making things better. If you’re a scientist, you’ve got a great reason to come to work at the moment.”
We were doing an essay on Keats. And I realised, why am I writing this essay? Everybody has said the same thing about Keats for years. I just thought, biology – now hang on a minute. I might be able to do something new here
O'Neill grew up in Bray, Co. Wicklow. His father was a "a radical, a hippy before his time", who loved Dickens and Shakespeare. Brought up in Salford, England, he had been in the British army in the second World War. "He was conscripted. He didn't volunteer, as he always pointed out, he wasn't a hero for the cause."
O'Neill's grandmother -- who was "very entrepreneurial, a really go ahead business streak" – moved back to Ireland during the war to spare her younger sons being conscripted and bought a B&B on Bray seafront. When the war ended, O'Neill's father was just 21.
He came to Ireland having “seen horrors. My Dad’s war experience damaged him terribly, because half his regiment were killed, and he never had a proper job after it.” He never talked about it to his family.
“It was only towards the end of his life, when I asked him to tell me more, that I realised the horror of it.”
It was at Pres Bray, where “I wasn’t too studious; I was a little bit of a messer”, that O’Neill’s interest in science was sparked. English was his favourite subject until he had an epiphany in sixth year.
“We were doing an essay on Keats. And I realised, why am I writing this essay? Everybody has said the same thing about Keats for years. I just thought, biology – now hang on a minute. I might be able to do something new here, something different.”
He’s happy to be able to combine both now in his writing – there’s another book coming out later this year called, enticingly, “Never mind the b****cks, here’s the science.”
How does he fit it all in? “I don’t watch Game of Thrones,” he laughs. But he is watching Normal People, which he loves. He fits it all in by staying up very late. “I’ll start writing at midnight, and I’ll do two or three hours. Six hours sleep is enough for me.”
It's probably a good thing that his wife, Margaret Worrall, is a fellow biochemist. They have two sons, Stevie and Sam.
The number of vaccines being tested is the same in the total history of malaria. If the vaccine doesn't work, we have the anti-inflammatories, we have the antivirals, and then the other hope is antibodies themselves
I ask him the question I most want to know the answer to. When we say “this too shall pass”, will it actually pass?
“No question,” he says instantly. “The history of all infectious diseases tells us this. The Black Death went away. The 1918 flu went away. Swine flu went away. It’s definitely beatable, this one.
“The number of vaccines being tested is the same in the total history of malaria. If the vaccine doesn’t work, and there’s still a risk of that, we have the anti-inflammatories coming down the pipeline, like our one. We have the antivirals. And then the other hope is antibodies themselves, that we’ll develop immunity.”
On immunity, he says, “the best evidence we have so far is in monkeys. They infected monkeys and they couldn’t reinfect them. Now we’re not monkeys, so it’s not 100 per cent, but there’s no good evidence out there yet that people are not protected from a second infection.”
He is also putting some hope in the BcG vaccine as a possible partial vaccine against Covid-19 , which is currently the subject of seven clinical trials. “It protects against respiratory viruses and it protects against measles. So there’s evidence it does give a kind of a barrier.”
What we’re seeing is the kind of “constant kicking the tyres process that science is sometimes.”
What he’s looking forward to on the other side is a holiday in Marbella, by a pool. “I’m obviously extremely busy. And I’m not bored in any way.” But he missed the “inevitable simple things. What gets me most of all was how much we took all that simple stuff for granted – just going for a pint or having a cup of coffee with a friend.”
He is, he admits, an optimist generally. “I think it’s just the way I am … You have to have hope, haven’t you? Without being stupid. The worst thing is to give people false hope … but I’m very confident that of all these things being tried, all you need is one to work.
“Put it this way, I can’t think of anything else we should be doing.”
