Peter Doherty on Variolation

Two noteworthy media mentions of variolation:

1. The New Yorker features Douglas Perednia talking about controlled infection and variolation, as its Exhibit A on on why conservative media shouldn’t presume to write on health/medicine, as they will only say stupid obviously terrible things:

After the Federalist tweeted it out, Twitter, which has been cracking down on coronavirus misinformation, temporarily locked the Federalist’s account. … He’d submitted it to a number of medical journals and blogs. “They all turned it down with no comment,” … tried the Federalist, almost at random. … The site accepted his article the next day, no questions asked. …

On the site … most commenters found Perednia’s idea absurd, dangerous, hilarious, or all three. … many angry e-mails and calls … Andrew Lover, an assistant professor of epidemiology at the University of Massachusetts-Amherst, told the Times that Perednia’s article was “exceedingly ill-advised and not evidence-based in any way shape or form.” …

Perednia [said] the way to adapt his idea to this reality was to make sure that the infecting was done with ‘the lowest possible dose’ … a concept known as variolation—which, he thought, would cut the death rate among those who chose to take part. (more)

2. A month ago, Adam Ford interviewed me on voluntary infection. Yesterday, Ford posted his interview with Nobel laureate Peter Doherty, author of Pandemics (2012), wherein Ford asked Doherty about variolation. Here are selected quotes from that discussion (fuller quotes below the fold):

47:10 Ford: “Controversially, in leu of actual vaccine that could come, hopefully in 9 months, but maybe even in 18 months if things go okay, if social isolation doesn’t work well enough too, would something like strategic or voluntary small dose low dose infection, like variolation, work in order to gain immunity, or nudge herd immunity? Is that something that we should be considering?

Doherty: (laughing) “Well let’s tell people what variolation was. … What they did was do this in young children, young children had a good immune response, generally survived smallpox, so what they were doing essentially is giving them smallpox, and they survived, whereas if they got it when they were older, they’d have a much worse disease. … So its not an unthinkable thing. …

52:40 With Covid19 I don’t know, but it would take a brave soul to be a test candidate, With younger people who are not severely affected, it’s possible. But you’d have to be enormously careful that they didn’t get any dose through their nose. But there would be ways of doing this. …

53:40 Ford: Is this something that could be achieved in the near term, if the vaccine timeline ends up looking like its going to be longer?

Doherty: If it was an absolutely catastrophic situation, if it was like the situation that is depicted in Contagion, where everyone who is within 100 feet of the virus gets it and dies, yes it could be reasonable. But I think for a virus where 80+% of people are definitely mildly infected at worse, or not sick enough to go into hospital, I don’t think you would take risk of that. The thing about a vaccine is that you have to give it to large numbers of normal people. You can’t take risks with vaccines.

You can take risks with end stage therapy. If someone is very very sick, and you’ve got something you think might work, you can try it pretty easily. People will approve that, … But you can’t take risks with vaccines. And the magnitude of the severity of this threat is not great enough to do that. You could say, … we’ll take a vaccine that looks a bit risky, maybe, and we’ll give it to the elderly. These are the people who are at risk, they can try it. … People like me, say would volunteer, I certainly would. I’d give it a go, and see if that works. But I wouldn’t want to be giving a vaccine that had any risk at all to younger people. You know, these are all theoretical arguments. But there is no way anything is ever given to anybody in this sense without going through extremely thorough review processes. … I think it is pretty unlikely.

So Doherty accepts “variolation” as a term that applies outside the context of smallpox. He thinks it could work, but oddly seems to see the main concept as infecting the young, rather than controlling dose, delivery vector, or strain. And he sees it only as justified in extreme circumstances, which Covid19 will never be, as it isn’t deadly enough. Even if the Great Suppression crashes the economy worse than the Great Depression, and even if millions will likely die from accidental infections, in his eyes and those of regulators that’s no excuse for letting healthy people voluntarily take substantial personal risks.

Fuller quotes (so you can check I’m not quoting out of context):

47:10 Ford: “Controversially, in leu of actual vaccine that could come, hopefully in 9 months, but maybe even in 18 months if things go okay, if social isolation doesn’t work well enough too, would something like strategic or voluntary small dose low dose infection, like variolation, work in order to gain immunity, or nudge herd immunity? Is that something that we should be considering?

Doherty: (laughing) “Well let’s tell people what variolation was. Variolation comes probably about a thousand years old or more. First done by the Chinese. Smallpox was a terrible scourge. …

What they did was do this in young children, young children had a good immune response, generally survived smallpox, so what they were doing essentially is giving them smallpox, and they survived, whereas if they got it when they were older, they’d have a much worse disease. We do the same actually with measles and mumps, the vaccines we give to kids is very safe, but mumps particularly in older men was a real problem, a terrible disease, and hospitalized people for months. Big problem in militaries during WWI and WWII, and a lot of men were left sterile by it. So its not an unthinkable thing. What happened then was the Chinese practice of infecting with smallpox caught on in the Middle East …

That the way people of my generation, were all vaccinated like that, variolated of vaccinated, scratching it into the arm, and it would come up as a little pustule or module, and then go down, and then we’d be immune.

Ford: So, I mean, if

52:40 Doherty: With Covid19 I don’t know, but it would take a brave soul to be a test candidate, With younger people who are not severely affected, it’s possible. But you’d have to be enormously careful that they didn’t get any dose through their nose. But there would be ways of doing this.

Another way of doing that is to actually attenuate the covid19 virus; you would actually knock out some of the genes that allow it to cause the disease and allow it to multiply a whole lot. And then you would have what is called an attenuated vaccine, and that’s really what the mumps and measles vaccines are. The same in polio vaccines. They were just weakened decades ago in a much more primitive way by passing them through tissue cultures. And they underwent mutation to reduce virulence, they were tested very throughly in monkeys, and then they were given to humans.

53:40 Ford: Is this something that could be achieved in the near term, if the vaccine timeline ends up looking like its going to be longer?

Doherty: If it was an absolutely catastrophic situation, if it was like the situation that is depicted in Contagion, where everyone who is within 100 feet of the virus gets it and dies, yes it could be reasonable. But I think for a virus where 80+% of people are definitely mildly infected at worse, or not sick enough to go into hospital, I don’t think you would take risk of that. The thing about a vaccine is that you have to give it to large numbers of normal people. You can’t take risks with vaccines.

You can take risks with end stage therapy. If someone is very very sick, and you’ve got something you think might work, you can try it pretty easily. People will approve that, especially if its a drug that’s approved for use in humans for some other purpose. But you can’t take risks with vaccines. And the magnitude of the severity of this threat is not great enough to do that. You could say, yes well, we’ll take a risk, but only with the people who are really at risk. So you could say, well, we’ll take a vaccine that looks a bit risky, maybe, and we’ll give it to the elderly. These are the people who are at risk, they can try it. Most of them aren’t working anymore. And they are all getting imputation credits, or whatever it is, so here we are.

I’m just being trivial, we don’t want to put anyone at risk of course. But people like me, we’ve had a good long and happy life, and have achieved a reasonable degree of satisfaction. But people like me, say would volunteer, I certainly would. I’d give it a go, and see if that works. But I wouldn’t want to be giving a vaccine that had any risk at all to younger people.

You know, these are all theoretical arguments. But there is no way anything is ever given to anybody in this sense without going through extremely thorough review processes. By our level of institutions, by our medical school ethics committees, and then by your own Therapeutic Goods Administration, and everything is always done along guidelines. Done by the FDA.

So these are policy decisions, if you were going to take any risk at all, with a particular target group,
with a vaccine, I think it is pretty unlikely. But we may end up with a situation where, the majority of people are really out and about because they’ve had an infection or whatever, or because they just have to relax the controls, because there just doesn’t seem to be much virus out there. But people like me will still have to be very careful.
56:40