In the UK, we are now suddenly very worried about the “South African variant[1. I’m not going to use the word “variant” any more, because, annoyingly, scientists use it to refer to two different things. Sometimes they use it to mean all the descendants of a particular virus further back in history. But sometimes they mean it to refer to a particular mutation. Instead, I’m going to refer to “strains” or “lineages”, and “mutations” or “changes”.]”, or B.1.351; it is a different thing to the “UK variant”, B.1.1.7, which emerged late last year and which I wrote about over Christmas.

Both the South African strain and the UK strain have several mutations which make them genetically distinct from the earlier SARS-Cov2 virus. But they share one particular mutation, called N501Y. That seems to be what makes the UK one more transmissible – around 50% more likely to jump from one person to another – and the indications are that the South African strain is similarly effective. (There’s an argument over whether it’s more deadly, as well: as far as I understand it, the evidence is too unclear to draw any real conclusions – but as Adam Kucharski points out, being more transmissible is a far bigger problem than being more deadly anyway.)

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What has people alarmed about the South African strain, though, is that various vaccines, and presumably pre-existing immunity from earlier infection, seem to be less effective against it. It has another mutation, E484K, which changes the shape of the spike protein; that appears to be what is driving it. All existing vaccines use the spike protein to prime the immune system to be ready for the real virus when it arrives.

That’s why it’s bad news that several cases of B.1.351 which couldn’t be traced back to South Africa have been found in Britain, suggesting community transmission. 

The Government is rolling out mass testing in nine postcodes around England — which, for avoidance of doubt, is good and necessary. I also wish that we had done more to establish rapid testing and hotel quarantine at borders weeks ago, as Yvette Cooper MP pointed out in a Liaison Committee meeting. But the scary thing, in a way, is not the South African variant itself at all. The scary thing is that the E484K mutation has arisen – twice, independently – in the UK strain as well. Ewan Birney, the deputy director-general of the European Molecular Biology Laboratory, called this “spooky”.

There’s a thing in biology called “convergent evolution”, where evolution hits upon similar solutions to a problem. The eye has evolved several times independently, because it is useful for lots of different kinds of animals to be able to detect light and use it to navigate the world. The common ancestor of birds and bats was flightless, but both evolved wings where their forelimbs used to be, because flight is useful for some lifestyles. When, in evolution, you see two species independently coming up with some similar systems, it’s usually evidence that that system is a solution to some evolutionary problem, not just a random quirk.

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So the fact that the E484K mutation has appeared three times now, always so far in conjunction with the N501Y mutation, suggests that it is, indeed, evolutionarily useful. I’ve seen one suggestion that the mutation in the spike protein helps it “grip” the ACE2 receptor on the outside of human cells; that would be one possible evolutionary advantage it could bestow.

The other possibility is that the E484K mutation is just better at infecting people who already have some immunity, and that gives it an advantage.

For the record, it does seem to be better at infecting people who already have immunity. Again, the data is quite sparse, but it seems that those 90% effective vaccines drop down to 70% or so when pitted against the South African strain. Novavax goes down from 86% to 60%. Johnson & Johnson goes from 72% to 57%. The Ox/AZ, Pfizer and other vaccines will probably have similar numbers. 

It’s worth noting that the “efficacy” of a vaccine means how good it is at preventing symptomatic disease. It appears that they are still extremely effective at stopping severe disease, hospitalisations and death, although the data is much more sparse on those things simply because they are much rarer outcomes.

In the UK, about 15% have had the vaccine and perhaps a similar number have had the disease itself. If the E484K-mutant forms of the virus find it significantly easier to infect those people, then those new forms will have an evolutionary advantage over the older strains. At the moment this advantage is quite weak, depending on how much protection against transmission you get from immunity, but it will get stronger. And if the mutation happens to arise again, which it almost certainly will since viruses mutate all the time, then it will tend to spread.

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Of course, “how much protection against transmission you get from immunity” is a key question. You might naively think – I certainly did – that if immunity reduces your viral load and prevents your symptoms, it’s a safe bet that it stops you from spreading the disease. But, as Dr Al Edwards, a professor in biomedical technology at the University of Reading, points out, it’s not as simple as that. Lots of viruses (including cold coronaviruses) spread very easily without symptoms, and you could reduce viral load an awful lot while still having many billions of virus particles in your system.

Annoyingly, there isn’t much data on the impact of vaccines on transmissibility. Most of the studies only looked at symptomatic disease, and got people to take a PCR test only if they showed symptoms. But the Oxford study has been getting people to do a swab every week (I know, I’m on it and it’s been really quite unpleasant). Early data from their trial suggests that two jabs reduces transmission by about 67%.

If that’s indicative, which I hope it is, then there is going to be significant and growing selection pressure on the virus to find ways around the vaccine immunity. The E484K mutation appears to be one such way.

That makes it all sound quite scary. I shall now give some reasons to be less scared. First, it’s only somewhat better at evading immunity: being vaccinated still gives you significant protection, especially (it seems) against severe disease. “We expect the potency to drop a bit with the new variants,” says Edwards, “but we don’t expect people to be completely immunologically naive.” Your body will still have a much improved chance of churning out a response quickly enough to stop you from getting really ill.

The other positive thing is that, having made all these vaccines, it’s relatively easy to simply make new ones. In the case of the mRNA vaccines, that’s especially true – they’re extremely plug-and-play, just put a new strand of RNA in and off they go. But, says Edwards, even the adenovirus ones like Ox/AZ are relatively easy to repurpose.

Of course, we’ll need to get better at testing them and licensing them. The Moderna vaccine was ready to go within a few days of the SARS-Cov2 genome being sequenced last January, but it took 11 months to be declared safe and effective. If we want new vaccines ready quickly in response to new strains, we’ll need to be a lot more nimble. The idea of human challenge trials has somewhat dropped off the radar lately, but it might be worth considering doing those in young, healthy volunteers each time you need a new version of a vaccine, because you can get safety and efficacy results so much faster if you don’t have to wait for people to get the disease naturally.

There’s another thing to consider. There are two things that drive evolution: selection and mutation. We’ve just been talking about selection pressures: that is, if there’s some mutation which is better at transmitting, or better at evading immunity, then it will tend to become more common in the population, because each virus will on average have more offspring than its non-mutant rivals. (That’s why the B.1.1.7 virus is so widespread in the UK now.)

But selection needs mutation to work upon. It might be that lions would be even better predators if they had wings and breathed fire, but if such a mutation never arises (which it won’t) then we’ll never find out. 

The way to keep the number of mutations down is to keep the number of cases down. It’s fairly linear: if you have twice as many infected people, all else being equal, you have about twice as many chances for a virus throwing up some dangerous new mutation.

(That is around the whole world, by the way. A new variant arising in Delhi or Rio de Janeiro will be here pretty quickly. We need to vaccinate everyone, everywhere, as quickly as possible.)

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So that means that there is still a very strong case for keeping cases low, even as the deaths and hospitalisations drop. It will be enormously tempting to open up society again once the most vulnerable are vaccinated, but that will mean providing a huge opportunity for the virus to spread and mutate, while also piling the selection pressure on so those mutations will tend to become widespread. We’ll essentially be creating a perfect petri dish for mutant versions.

That might be a price worth paying; perhaps the economic gains (and therefore the real-life gains) will be sufficient to offset the risks, especially given the possibility of making new vaccines quickly. But in general, the lesson of this pandemic seems to have been that more relaxed restrictions backfire. And this government doesn’t have a great track record in actually thinking about the costs and benefits: it has a tendency to just put off eating the shit sandwich as long as possible. 

Testing for the “South African variant” (which I assume, and scientists seem to agree, means not just literally the South African ones, but any with the E484K mutation) is a good thing. Testing and quarantining at the border is a good thing, and keeping cases low is important. But this probably won’t be the last time we see the E484K mutation, or others like it, which help the virus partially escape immunity. Charles Darwin would understand.

That was suddenly impossible. So the phone call urgently said: we need to get the children’s presents to them. So I hopped into the car and rushed off to a motorway service station just outside London, where I met a grandparent, swapped a bunch of hastily wrapped gifts, paid our socially distanced respects, and set off home. What was poignant was that I saw several — five or six, probably — pairs of cars in the car park, boots open, presents ready, doing the same thing. The motorway was much busier than I would have expected on a normal Saturday night. As I was driving home a song was dedicated on the radio to a granddad who was driving from Hereford to Swansea to get his kids their presents. It was gently heartbreaking.

So I understand the anger at the new London lockdown, so late in the day, after so many Pollyannaish pronouncements and positive messages about “saving Christmas”. The new restrictions are being blamed on a new variant of SARS-Cov2 which has arisen in the South-East of England. In my more cynical moments, I had started to wonder whether they were overstating the importance of the new variant, that it was simply a convenient peg to hang the inevitable U-turn on, and I was not the only person to think that. But having spoken to some people, I have decided that was unfair. 

Here’s what I’ve learned. In short: it’s real; we need to take it seriously, and watch it closely, and it will likely make life harder; but it’s not panic stations, and there’s no major reason as yet to think it will, for instance, stop vaccines from working. Also, we’ve been oddly lucky with the testing.

First: there really is a new, noticeably different strain. Ewan Birney, the deputy director-general of the European Molecular Biology Laboratory, points out that all viruses mutate, all the time. Some, such as HIV and influenza, mutate incredibly rapidly, making it very hard to create vaccines against them. SARS-Cov2 is “pedestrian” by comparison, he says, but still, new mutations arise all the time, and we don’t bother with a press conference for every one. “If we did, we wouldn’t be able to move for press conferences,” he says.

The new strain, though, really has mutated significantly more. Here is a useful chart (below), from a preprint study released over the weekend. Each blob on the chart represents one time a SARS-Cov2 virus was sequenced, so that scientists could see its genome. The higher up it is, the more it has mutated away from the original version detected in January. The further right it is, the later the date it was collected.

The lighter grey blobs represent the familiar SARS-Cov2 virus, slowly changing at a fairly steady, predictable rate. But the darker blobs are the new strain, B.1.1.7, which was first detected in September. You can see that although it too is changing at a steady rate, at some point before it was detected, it diverged from its parent strain significantly: it has roughly twice as many mutations per location on its genome.

Of course, we don’t care about mutations for their own sake, so it might be worth talking about what this means. A “mutation” is simply a copying error. The virus gets into your cells and commandeers them to make new copies of itself. Sometimes, as it does so, it gets it slightly wrong: random errors appear in the RNA, its equivalent to our DNA. Those errors may slightly change, for instance, the shape of a protein that it makes.

It’s wrong to think of viruses as mutating “for” something: the errors are random. Most will do nothing, or have a negative effect, like randomly adding or deleting words in a recipe. But every so often, one might do something that is useful for the virus. Perhaps it might make its protein spike a little more suited to opening up cell membranes, or help the virus evade antibodies a little more effectively. Then that version of the virus will tend to spread a bit better than the older one, and copies with that mutation will become more common in the population.

What will be helpful for the virus, of course, depends on its environment. So different viruses (or any living thing) face different “selection pressures”. For instance, if a new antiviral drug is used, then those copies of the virus which are most resistant to that drug will tend to spread better. 

With viruses that have recently jumped from another species, such as SARS-Cov2, says Birney, there are usually two main pressures driving change. One is obvious: viruses that can jump more easily between hosts will tend to spread better, so viruses tend to become more efficient at transmission. Another is perhaps less so: viruses tend to become less deadly, because if your disease kills your host in two hours, you won’t have much time to get to the next one. “Viruses when they jump, usually do two things,” says Birney. “They end up mutating to transmit faster, and often to cause less disease. That’s the pathway to becoming an endemic virus.”

So the question is whether either of these things has happened in the B.1.1.7 strain, and the answer is: it’s hard to know, but probably, at least on the transmissibility point.

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It’s not that you can look at a viral genome and say “Ah yes, that one’s better at spreading.” And if you notice that a particular variant is spreading faster, that may be because the variant is better at spreading, or it may just be, for instance, that it happens to be prevalent in an area where there’s a lot of transmission. There’s a lot of regional variation in what strains are where; if a new strain happens to arise in a place where, say, fewer people can work from home, then it will look like it’s good at transmission when in fact it’s just lucky. That happened early on, says Birney: the D614G mutation became the dominant one in Europe after it arose in May. It may have had a slight growth advantage, he says, although “the jury is very much still out” on that; “it’s hard to work out if it was just random chance that got it to the top or not”.  

In this case, though, there are reasons to think that it probably is more effective at spreading. The New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) looked at four strands of evidence and they all centred on the B.1.1.7 strain being around 70% more effective at transmission, although there is a lot of uncertainty around that figure. 

There is a theoretical reason to think it’s more transmissible, as well. The new strain had 17 “non-synonymous” mutations when it was first detected — that is, mutations which actually affect its output (there are a further six “synonymous” ones, which don’t). It’s not clear, by the way, how B.1.1.7 ended up with so many mutations. But often, multiple mutations are seen when a virus infects someone with a compromised immune system. In those patients, the virus can stay in the system for weeks and months, rather than a few days; they are often then treated with convalescent plasma. The preprint speculates that something like that may have happened here. 

Birney, and Babak Javid, an immunology lab director at the University of California San Francisco, all think that is plausible, although there is no direct evidence for it. Adam Kucharski, a mathematical epidemiologist at the London School of Hygiene and Tropical Medicine, draws an analogy with antibiotic resistance: if you nuke a microbe with a full course of antibiotics, it will just die, so it won’t mutate into a resistant form. If you don’t give it antibiotics at all, it will have no pressure to mutate. But when you use antibiotics for a bit, those microbes which are a bit more resistant will tend to survive, and resistance will emerge. It’s where there are half-measures, weak selection pressures over a long time, that pathogens mutate into new forms: a virus that lives for a while in someone with a weak immune system and treated with partially effective treatments will throw out new, experimental mutations. It’s well documented.

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Whether or not that’s exactly what happened, B.1.1.7 definitely has several mutations, and the most notable one is a deletion: two RNA “letters” found in the main SARS-Cov2 strain have been removed.

That same mutation, 69-70del, has cropped up in a few other places. One was the Danish mink outbreak that was reported a few weeks ago; it has also been spotted in Lyon. But they are different lineages: the same mutation has happened independently. That is, says Javid, reason to think that the mutation is making the virus more transmissible. “I was sceptical,” he says, “but the same mutation has arisen in several places. If it’s random mutation it’d be less likely to keep appearing, so that’s strong evidence.” Another mutation found in B.1.17 has also cropped up in another new variant seen in South Africa.

Javid’s suspicion, and it’s only a suspicion, is that the mutations make the virus a bit harder for your immune system to kill, so it survives a little longer in the bloodstream. If you have the virus for 10% longer, then, all else being equal, you’ll be 10% more likely to pass it on. “My gut instinct is that this increases the contagious window by six hours, or 24 hours, or something,” he says. “I’m trying to think of biological ways this might result in more contagiousness, and my working hypothesis is if it’s very slightly more resistant to neutralisation by antibodies.”

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It’s worth talking about testing, which is where we got a bit lucky. Testing for whether someone has a virus, using a PCR test, is usually just Y or N: the test finds the viral RNA or it doesn’t. Meanwhile, to track the spread of different variants of that virus, you have to get samples and sequence their genome, which is a longer and more involved process.

But PCR tests work by looking for a few short lengths of the viral RNA, not the whole thing. And by lucky chance, the standard PCR test looks at three different chunks, one of which happened to include the two areas removed by 69-70del mutation.

This doesn’t mean that the PCR tests don’t work. The tests look at three sites “precisely to have belt and braces” when hunting the virus, says Birney. So PCR tests which return positive results on two of the sites, but are negative on the 69-70 site, are probably telling us that the patient has B.1.1.7, not the original SARS-Cov2 strain. This means it’s been much easier to keep track of the virus. That’s why, says Birney, Patrick Vallance was able to give so much detail in his presentation of where it has spread in the UK.  It’s also part of why we can make any sort of estimate about the increase in R. If we were relying on genome sequencing, even though the UK has genuinely world-leading genomic surveillance, we’d have much less info.

(The PCR tests will have to be redesigned, because the whole point is to have redundancy against mutations, and now they’ve lost some of that redundancy. But it’s been useful, nonetheless.)

So the question is: what does this mean? For our tier system, for the vaccine, for our getting back to normal? And is this strain more deadly as well as more transmissible?

For one thing, says Birney, it explains a few things about why the virus kept spreading in Kent and Essex despite them moving into Tier 3 a few weeks ago. It was working elsewhere, but not there. “This is an explanation,” he says. “Quite whether it’s the whole explanation is hard to tell.” It may mean that restrictions have to be tougher, if the new strain really does spread more easily. Essentially, Tier 3 and the new 4 are meant to bring cases down; if that’s harder to do, then we have to work harder.

For the vaccines, we can be reasonably hopeful, I think. Birney points out that there were already many strains in circulation when the vaccines were being tested; the fact that they were so effective is reason to think that they must have worked against the large majority of them. It’s not definitive — “that argument is not fully watertight,” says Birney, “because currently other strains are rare”, but it’s reassuring.

More theoretically, we can take heart from the way the immune system works. As well as B-cells which make antibodies, we have two other kinds of T-cells. One kind I think of as Stasi-like secret policemen. “They basically knock on the door of every cell and say ‘show me segments of all the proteins you have inside you’,” says Birney. “And if it finds one it hasn’t seen before, it decides it’s a virus and presses the ‘please commit suicide’ button’.”

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The other kind goes up to B-cells. Each B-cell produces a unique antibody; when those antibodies destroy a pathogen, the cells keep some of chopped-up parts of those pathogens inside themselves, like prisoners, or trophies. The second kind of T-cell goes up to them and demands to see all the trophies. If it finds one it recognises, it orders the B-cell to make loads of copies of its unique antibody, stimulating a rapid immune response.

Because the T-cells only look at very short segments of protein, any single T-cell could be confused by a single mutation — if one T-cell recognises the 69-70 spot, then it wouldn’t pick up the B.1.1.7 variant with the 69-70del mutation. But because there are millions of T-cells, each remembering a slightly different bit of a protein, it’s unlikely that even quite a few mutations would remove T-cell immunity. We normally measure immunity by looking at B-cells, because they’re easier to test for, which is partly why immunity looks like it drops off quickly in Covid patients. 

But T-cell immunity is longer lasting. Javid thinks it’s quite likely that the new strain could have a slightly shorter period of B-cell immunity, because of his hypothesis about resistance to antibodies, but it’s very unlikely that we’d lose T-cell immunity altogether. Kucharski adds that, in general, while the flu evolves so rapidly that antibody resistance fades in months, with seasonal coronaviruses that process takes years. Hopefully that will be true of SARS-Cov2 as well.

(There’s the added point that the new mRNA vaccines are much more plug-and-play than older ones, so in theory, you could make new vaccines for new strains pretty quickly. But I don’t know how quickly you could get new safety approval from regulators.)

Of course, this is all speculation: we need evidence, rapidly. That’s why surveillance is absolutely vital. If some new strain does outwit the vaccine, we need to know about it immediately.

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Two last points. One, there’s the question of whether the new strain is more deadly, or less deadly. And the evidence is weak either way; as I said at the beginning, often you get selection pressure for viruses to become less virulent, but in the case of Covid-19 it’s in an awful sweet spot where it isn’t very deadly for most people and can spread via presymptomatic and asymptomatic people, so the selection pressure isn’t great, but it’s still very deadly among vulnerable people. 

Birney says that “hospitalisation rates in the South-East [where the new strain is widespread] are not a million miles away from what you’d expect given the infection rate”, so at the moment we can only say that it’s probably not loads more or loads less dangerous. Javid says that one mutation is similar to one found in a Singapore strain which seemed to cause less deadly disease in animal trials, but again, he says, that’s speculative. 

And secondly, the immediate reaction from our European neighbours has, understandably, been to close their borders with the UK. Kucharski makes the point, though, that there is a good chance that they’re shutting a stable door on a long-bolted horse. Britain has the best genetic surveillance of disease in the world, as measured in viral genomes sequenced per capita; that’s not a boast, it’s simply the case. It is very possible that the new strain is spreading rapidly in France, the Netherlands, Belgium and so on, but the surveillance is less effective at spotting it. It’s another reason why we need to improve surveillance everywhere.

At the beginning, I said I was wrong to be cynical, and to think that the new strain was being over-egged to hide the government’s own mistakes. It’s a real new strain, it seems to be more transmissible, and although it doesn’t change anything fundamental, it does make life harder. Javid describes it as an “amber light”.

But I do think there is some blame to be attached here. It might not have been obvious that things would go wrong in this way, but it was surely very possible that things could go wrong in some way. I think that it was ridiculous to think back in November that we could give any confident message about Christmas being opened up. It seems mad that millions of families have been told they can meet up, and then, five days before with the turkey already ordered, told they can’t. A more responsible attitude might have been to be much more cautious early on, to say that an open Christmas was an aspiration rather than promise. 

But perhaps I’m still just sad about all those open car boots, all those presents passed from grandparent to child via an intermediary after another small hope was raised and dashed. There have been an awful lot of sacrifices, but that little indignity felt like it could have been avoided.