On the one hand, hundreds of thousands of small and medium businesses were forced to shut down, triggering one of the worst jobs crises since the Great Depression. In 2020 alone, workers around the world cumulatively lost $3.7 trillion in earnings — an 8.3% decline.

On the other, a handful of mega-corporations, particularly in the Big Tech and Big Pharma sectors, have made a killing, raking in hundreds of billions more in “pandemic super-profits” than over the previous four-year average. Topping the list are behemoths such as Amazon, Apple, Microsoft, Alphabet (Google), Facebook, Pfizer, Johnson & Johnson, AstraZeneca and Merck.

The success of the Tech giants — Amazon, Apple, Microsoft, Alphabet, Facebook — is easily explained. As people found themselves confined to their homes, they turned to the internet for pretty much everything: shopping, dining, working, schooling, entertainment, socialising, even sex. In other words, what represented a curse for countless small and medium traditional businesses, represented a blessing for a handful of corporate behemoths.

The golden egg for the pharmaceutical companies, however, came later with the vaccines: the companies behind two of the most successful Covid-19 vaccines — Pfizer, BioNTech and Moderna — made combined profits of $34 billion in 2021. And if the “new normal” ends up including permanent booster shots, such super-profits will become the norm. Crucially, these profits are then distributed to shareholders who predominantly belong to the richest 1% of society. It’s hardly surprising then that billionaires around the world saw their wealth increase by $3.9 trillion just in 2020. As Oxfam starkly put it in a recent report: “The wealth of the 10 richest men has doubled, while the incomes of 99% of humanity are worse off”.

To see what this means in practice, one need only turn to Latin America, whose billionaires increased their wealth by 52% during the pandemic. In Mexico, meanwhile, multimillionaires saw their wealth increase by 31.4% in 2021 alone. On the other hand, over the last two years, 78 million people in the region were plunged into extreme poverty, while 13% of children abandoned education altogether.

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In Africa, where low-income countries predominate, the picture is equally stark. A report this month noted that not only had GDP fallen by as much as 7.8% in some cases, but that remittances from abroad had fallen by 25%. In a context where remittances from rich countries accounted for over half of private capital flows to Africa shortly prior to the pandemic, this has had a devastating effect on the daily economy, with over 40 million additional people in extreme poverty.

Couple this with a debt crisis, and it is not surprising that the impact on daily lives has been devastating: in Angola, a recent report described how youth unemployment doubled to nearly 60% in the past two years. Meanwhile, the continent’s billionaires have seen an uptick in their fortunes, as elsewhere; a January report from Nigeria found that Africa’s 18 billionaires had seen their wealth increase by 15% in 2021 alone.

Yet in many ways this is a global phenomenon; on every continent, there has been a hyper-concentration of wealth, and poorer communities have suffered. Wealth has been further racialised, with minority communities suffering the most in rich countries, and poorer continents the worst affected.

Why, then, have Left-leaning commentators supported the policies that have led to these terrible outcomes?

The usual explanation is that these impacts were an inevitable impact of the pandemic. And yet the evidence for this is weak, not least because most of those affected by the virus have been elderly people often beyond an age of active employment. In Africa, a 1% increase in mortality from Covid in a country like Nigeria cannot explain the 20% collapse in formal employment. In fact, Tanzania — one of the very few countries that did not impose Covid restrictions in 2020 — was also almost the only country in Africa to see its GDP increase, by as much as 5% according to some reports. Meanwhile in Sweden, where restrictions were much milder than in the rest of Europe, the country returned to pre-pandemic levels of production by the middle of 2021, in contrast to many other European countries (while registering lower per capita mortality rates than many other countries).

And so it seems that the staggering increase in inequality, and in the concentration of capital, must be the consequence of the Covid response measures, not of Covid-19. What, then, are some of the likely consequences of this massive accumulation of capital by a tiny number of people, expropriated from SME owners and the global working class?

A dystopian future seems to be emerging from the ashes of the pandemic — one in which not only is wealth more concentrated than ever in the hands of a small elite, but in which practically every sector of the economy is dominated by a handful of all-powerful mega-corporations. Perhaps it’s unsurprising, then, that those who have most profited from the pandemic response, such as Bill Gates and Mark Zuckerberg, also supported that response and removed information from their portals which criticised it.

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However, there’s a further element that makes this scenario even more disturbing, if possible, and that is the growing consolidation not only within, but also between, sectors. This becomes evident when we look at the investment funds that actually “own” these corporations. BlackRock and Vanguard are the two largest asset management firms in the world, respectively managing $10 and $8 trillion. That’s 3.7 and 3 times more than the UK’s annual GDP. These two funds are the top “owners” of all the major Big Pharma (Pfizer, Johnson & Johnson, Merck), Big Tech (Facebook, Twitter) and Big Media (New York Times, Time Warner, Comcast, Disney, News Corp) corporations. Even more worrying is the fact that despite having shareholdings of “only” 5-7% in these companies, there is growing evidence that institutional investors such as BlackRock and Vanguard try to influence company management and boards on strategy.

It would appear that these funds also coordinate among themselves. When analysing the voting behaviour in board meetings of the two funds, researchers found that they coordinate it through centralised corporate governance departments. This is hardly surprising if we consider that BlackRock and Vanguard are also each other’s main institutional investors: in other words, they partially “own” each other through cross-shareholding. So, we are effectively in the presence of a single super-entity that “owns” and controls a huge chunk of the Western economy. While this was already the case before the pandemic, the latter has accelerated this trend. More importantly, it has brought to the surface the way in which these funds, through their cross-sector corporate control, can “harmonise” these companies’ behaviour to further their interests.

We can see this in the case of debate around pandemic strategies on social media, and the censorship exercised today by social media platforms against any critical voice, no matter how qualified. A good example might be the removal from YouTube of a video of a senior editor of the British Medical Journal, Peter Doshi, discussing the Pfizer Covid vaccine trial in a US Senate hearing — in which among other things Doshi had questioned the accuracy of the reporting of the Pfizer vaccine effectiveness.

This is worrying in itself. But it becomes even more worrying when we consider that the companies selling the vaccine, the media outlets shaping the mainstream vaccine narrative and the social media platforms enforcing that narrative are, to a large degree, “owned” and controlled by the same two funds: BlackRock and Vanguard, which, incidentally, are raking in billions from the vaccines. This harmonisation among sectors (and between the latter and governments) points to the rise of a new ultra-powerful complex — the techno-media-pharma (TMP) complex. This is evident in increased “synergies” between these sectors: take Google’s growing investments in the health, pharmaceutical and pandemic-prevention sectors, for example, or Amazon’s investment in Covid-19 research.

Of course, none of this would be possible without the active support of governments, which create an enabling environment that rewards participants in the TMP complex. This is evident, for example, in the secrecy, overpricing, cronyism, and inefficiency that has characterised Covid procurement deals: Covid tests, PPE, vaccines, and now vaccine passport technologies have all been parcelled out to transnational corporations without proper tendering processes or legislative oversight. In other words, this is not a scenario in which governments disappear, but rather one that relies on increasingly powerful and authoritarian state apparatuses furthering the interests of big capital.

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This is hardly surprising when we consider the extent to which these corporate giants have meshed with our political systems. The US is a good case in point. Obama was very close to Eric Schmidt, CEO of Google, who later became a close collaborator of the Pentagon in developing military applications of AI. Today, Biden’s economic policies are heavily influenced by the director of the National Economic Council, Brian Deese, a former BlackRock executive. This ultra-elite is now in a position to shape every aspect of our lives — and it’s frankly terrifying.

If the Left is to recover from the catastrophic policies that it has supported during the pandemic, it must begin by recognising that it is lazy and misplaced to denounce those who point out these inconvenient truths: that wealth is hyper-concentrated as never before, that this is as a result of the policy choices during the pandemic, that these choices were unprecedented, and have been supported by those who enriched themselves enormously along the way, and censored any alternative point of view.

If we don’t want a world dominated by a very few ultra-wealthy people, and their vision for retaining that wealth, an unprecedented collective effort will be needed to fight for a different future. The huge TMP conglomerates will have to be broken up and their profits used for the benefit of all humanity, and not just their shareholders. This will be the struggle against the post-pandemic capitalist nightmare — and we are already losing.

But pharma bad behaviour is not new. For example: there’s a thing in patent law called “evergreening”. It’s most famously used by big pharma companies who don’t want their expensive drugs to reach the end of their 20-year patent and become available as a generic, so they develop a very slightly different version of the same drug and get a new patent on that.

Venlafaxine is an antidepressant, marketed as Effexor. As it neared the end of its patent, the manufacturer developed a new version – desvenlafaxine, marketed as Pristiq. Desvenlafaxine is what the body naturally breaks venlafaxine down into; your liver takes the venlafaxine and metabolises it into desvenlafaxine. It is also either less effective or no more effective than the original.

The patent for Effexor expired in December 2008; Pristiq entered the market in early 2009. By 2014, Pristiq was the second most prescribed antidepressant in the US, despite being “a slightly worse version of an older antidepressant with no proven advantages that also costs fifteen times as much”. (A month’s supply of Effexor at the time cost $20; a month’s supply of Pristiq cost $300.)

And it’s not the only bad thing they do. When a drug reaches the end of its patent, other companies can make generic versions. To encourage that, the US FDA says that the first company to do so gets 180 days of exclusivity, so it can establish itself in the market. “Until recently,” says Dr Vishal Gulati, a venture capitalist specialising in healthcare, “it was legal for the original company to pay off the company to not launch the product. Companies would get a license to make the generic, and then be paid to not launch it.” They were literally paying to prevent patients from getting cheaper healthcare.

What’s going wrong here? There’s a very tempting explanation, which is that big pharma is evil. But I never find that satisfying as an explanation. Instead, I’d rather think about incentive structures.

There’s an inherent tension at the heart of any knowledge-based business — anything which develops new technology or information and sells it. You want it to do two things: to create that knowledge, to advance our understanding; and to spread it around, so that the world can benefit from it. Information is a “non-rival good”: if I benefit from it, that doesn’t stop you from benefiting from it too. An example is a lighthouse. If I see the beam, and avoid the rocks, it doesn’t stop you from doing the same. By contrast, a hamburger is a “rival good”: if I eat it, you can’t.

People can make money selling hamburgers. But it’s much harder to do so by operating a lighthouse.

The trouble with knowledge-based businesses is that they are more like lighthouses than like burgers. If you create a new piece of software, or a new technology — or a piece of investigative journalism — then there’s nothing stopping me from simply copying it. And then you won’t make any money off it. That makes it less likely that you’ll spend the time and effort to create any more new things.

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So we created intellectual property laws in order to stop that. Creators of a thing can get a patent or a copyright, and are granted exclusive rights to produce that thing for some number of years — 20 years, in the case of pharmaceuticals.

Problem solved, right? Well, obviously not. Because we don’t just want a world in which new things are created. We also want a world in which everyone can gain access to those things. Intellectual property rights prevent us from making extremely cheap copies of things that we already know how to make. If a foreign correspondent reports human rights abuses in Yemen, it’s best for society if as many people as possible to read that report, so that we can act on it. But intellectual property rights (and their downstream effect, paywalls in journalism) stop that from happening.

This is a direct trade-off. “My mental image of all this is we’re basically squeezing a balloon,” says Owen Barder, a development economist. You can squeeze the top, and move the problem to the bottom. Or you can squeeze the bottom, and move the problem to the top. But the balloon is still there.

And this isn’t the whole problem. We want pharma companies to develop drugs and vaccines for the developing world. But people in the developing world can’t pay as much money as people in the rich world, obviously.

Pharma R&D is expensive: sometimes billions of dollars to research one drug. And for every drug that is successful, there might be 20 that aren’t, and the research into those needs to be paid for as well. That money needs to come from somewhere. At the moment, it comes from patients in rich countries paying sometimes hundreds of dollars for pills that might, individually, cost a few cents to make. The “marginal cost” of each dose is tiny — Jacobin and Oxfam fume that the Covid vaccines, for instance, are priced at many times the manufacturing cost — but that cost needs to cover the “fixed cost” of all the R&D (and marketing, staff costs, etc) you’ve put in.

The ideal solution to this would be selling the drug to everyone at the maximum cost they’re willing to pay. Charge hundreds of dollars in the US, a bit less in the UK and EU, much less in Bulgaria, and almost nothing in Malawi. “If you could perfectly price-discriminate, you’d be charging above the marginal cost in lots of countries, and at the marginal cost for the ones who couldn’t afford more than that,” says Barder.

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But that’s not possible. For one thing, if they tried it, people would buy the pills in Malawi for a few cents and fly to the US and sell them at a profit. But more important, Congress or Parliament (and the press) would kick off – why are our citizens paying hundreds of times over the odds? It would be politically impossible to do. So, instead, they make the drug at a single price, which only rich countries can pay, until the sales in those countries have paid off the R&D costs. “Drug companies are just responding to the incentives we’ve set,” says Barder. “They’re doing the thing we asked them to do.”

The temptation, when faced with problems like these, is to argue that big pharma should be destroyed, and all drug research run by publicly funded university laboratories. And maybe that would work – but it’s a huge gamble. Pharma companies do some bad things, but they objectively do make drugs that are hugely valuable to society. And it’s not that publicly funded bodies are free of bad incentives. Academica has huge problems of its own — academics are rewarded for publishing lots of papers, rather than for necessarily finding out true things. Government’s incentives are to remain popular, rather than to fund the most effective things: it would be easy to imagine lots of money going to fund treatments for picturesque children with cancer, rather than for, say, diabetes, even if it were a much less effective way of saving lives.

Still, it might work. At the moment, as Barder says, there’s a tendency to “socialise the losses and privatise the gains”: private companies get rich off research that is often begun in university departments. A starting point might be to pump lots of money into university research, let them bring drugs to market, and see if they can outperform big pharma. What would be crazy, though, is to destroy big pharma first, and then hope that our new nationalised version can keep new drugs coming through.

A more low-key version, says Gulati, might be for academic institutions to become better at demanding equity in pharmaceutical products that are based on their early research. He also suggests that countries such as the UK could negotiate cheaper drugs by offering the NHS as a source of clinical trial subjects — as has happened with Novartis’s new cholesterol drug inclisiran, aka Leqvio. That’s hugely valuable to pharma companies, and it’s something the NHS can do easily and safely, with its huge, centralised, well-protected data systems.

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Those ideas might help make drugs cheaper in the UK and other rich countries: getting them to poorer countries is a different problem, with different solutions. Governments could buy out patents — if a firm thinks it can make $10 billion over the next 10 years for its product, we could say that we’ll give them the $10 billion now (or a bit less) in exchange for the rights to make the drug available at cost.

Barder likes one idea, put forward by the late economist Jean Olson Lanjouw. “Her suggestion was,” says Barder, “that if I’m AstraZeneca and I show up at the UK patent office asking for IP protection for a new drug, the patent office should say ‘Well done. Can you tell me what you expect the market value for this drug to be in all 200 countries in the world?’”

Then AstraZeneca or whoever would say “I expect most of my revenue to come from the US, UK, EU and Japan, and relatively little from sub-Saharan Africa and Bangladesh.” And the patent office would grant them a patent, on the condition that they license it for free use in those countries that make up the bottom 2% of their revenue. “It’s like a tax of 2%,” says Barder, “but those countries might well make up 80% of the disease burden.” It hasn’t been tried, as far as I know, but it’s worth thinking about, and it would avoid the problems of Congress or Parliament demanding that the drug be made cheap here — although it would only work for global diseases that affect the rich world as well as the poor — diseases like cancer, or heart disease, or hypertension. It wouldn’t help incentivise research into diseases like malaria or dengue, which have no impact on the rich world. The “advanced market commitment”, which I discussed here, and involves Western governments promising to give pharma companies a bonus for every dose bought by developing nations, might be more effective for that.

Andrey Zarur, the CEO of the biotech firm GreenLight[1.  I have done several pieces of paid writing for GreenLight over the last two years], who are producing their own mRNA vaccine for Covid at the moment, comes at the whole thing from a different angle“Pfizer was not designed to make low-cost therapeutics available to every corner of the world,” he says: it’s a 150-year-old company with settled investors and a particular way of working.

He compares it to Apple. “You have a $1,000 iPhone 13,” he says. “Who’s that designed for? My children. Idiot teenagers with rich parents.” Poorer countries need smartphones too, but the solution is not to force Apple to sell smartphones to Ethiopia at a discount. “What you need is an innovative company with different processes.” Instead of demanding changes from 150-year-old companies that are very good at the specific things they do, create smaller, newer companies which do the thing you want. “There’s six billion people in the developing world,” says Zarur. “You should be able to figure out a way to turn a reasonable profit with reasonably priced drugs.”

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It’s obviously true that pharma companies have done bad things. It’s also obviously true that they’ve done marvellous things — I have relatives who are alive today who wouldn’t be without the pharmaceutical industry’s products.

Perhaps there are other systems which could have produced those drugs, other than the undeniably cutthroat capitalist system we have today. But any system would have bad incentives and obvious, easy-to-publicise disasters.

The job of government in this situation should be to find the bad incentives, the market failures, and to patch them; to make it work, to decide which end of the balloon to squeeze. The Indian government, for example, decided a few years ago that it would not accept evergreening any more — it passed a law saying that it would only offer new patents on drugs that were sufficiently different from existing ones.

In 2013, the government won a court case against Novartis, which had tried to get a new patent on a cancer drug, imatinib mesylate — a crystalline version of an existing cancer drug, imatinib. The government said that the new version was no better than the existing one and was simply an attempt to squeeze more money out of the healthcare system.

It worked. You could argue (as Novartis did) that it will reduce innovation; but the point is you can change the system, change the incentives, encourage the behaviour you want, without smashing the system entirely.

The Joint Committee on Vaccination and Immunisation (JCVI) explained that this is the result of a risk-benefit analysis. The JCVI’s Prof Adam Finn in a briefing with the Science Media Centre pointed out that “happily the virus very rarely affects children seriously”, and that the very small risks of adverse effects from the vaccine outweigh the risk to a child of getting, and then becoming ill with, Covid. The UK medicines regulator has declared the Pfizer vaccine safe and effective in children, but the JCVI has a more stringent approach.

Similar calculations were made back in March. At the time, a small number of cases of a rare clotting disease were detected in people who had had the Oxford/AstraZeneca vaccine. As a result, the JCVI recommended that it not be used in the under-40s unless no other options were available.

That decision was based on a straightforward risk-benefit analysis. The risk of a blood clot caused by the vaccine is vanishingly small – about one in 50,000, with the risk of severe health impacts lower still. But young people are also at very low risk of getting severely ill if they develop Covid, and the number of people with Covid at the time was very low – only about 6,000 new cases a day, compared to about 60,000 at the January peak. That meant that the chance of a young person getting infected, and then getting very ill, was even smaller than the risk of a blood clot, as the Winton Centre for Risk and Evidence Communication showed.

“Freedom Day” has happened now. It’s far from clear what effect it will actually have. The Government’s Scientific Pandemic Influenza Group on Modelling (SPI-M-O)’s latest modelling paper, published last week, says that by the end of August, we could end up with fewer than 100 hospitalisations a day, or more than 10,000. 

Small changes to our assumptions drive huge changes to the outcomes: will 90% of people stop wearing masks? 70% 50%? Will we all pile into nightclubs and theatres, or only a few of us? We don’t know: these things, or a million others. As the Bristol maths professor Oliver Johnson puts it, “the range of uncertainty around any reasonable forecast probably includes both ‘it’s basically fine’ and ‘we have a very serious problem’.” 

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What we do know, though, is that cases were already growing before Freedom Day. The R value is well above one. If we wanted to reduce the number of cases, to make the line on that chart actually go down, then we would need to reintroduce some (probably quite stringent) measures. That seems unlikely.

But what we can do is get more people vaccinated. And it seems that two obvious ways of doing that are to vaccinate children, and to start using the Oxford/AstraZeneca vaccine in younger people again.

Vaccination makes a huge difference to Covid risk, in every way. Which is why it’s a problem that our programme has tailed off so much. On one glorious day back in March, 844,000 vaccine doses were reported to have been administered across the UK. That was anomalous; but from March until about June, there was an average of between 500,000 and 600,000 doses being administered every day.

Since early June, though, those numbers have sagged dispiritingly. It’s been more like 250,000 for the last few weeks.

So how do we get it back up to higher levels, given that vaccine coverage is more important than ever? 

There are two drivers of vaccine uptake: supply and demand. The most obvious problem, at the moment, is that demand is down. Paul Mainwood, a strategist who has spent recent months looking at vaccine delivery, points out that first-dose vaccine uptake shows a distinct curve. At first, each age group is vaccinated slowly, so the numbers creep up; then it accelerates, and shoots upward; then, as it nears 100%, it levels off again. The curve on the graph is S-shaped..

With the over-50 age groups, that flattening-off happened at above 95% coverage; but as you come down the cohorts, the levelling-off happens earlier and earlier. For 30- to 34-year-olds, the line has flattened significantly and it hasn’t yet reached 80%. For 18- to 24-year-olds, it’s lower still: the flattening is visible and it’s only around 65%.

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That suggests that there is reluctance among younger people to get the vaccine. Whether that’s true anti-vaxx attitudes, or an understandable wariness of feeling rubbish for a day or two in exchange for a reduction in an already tiny risk of death – or an equally understandable, if in my view wrongheaded, concern about the more severe side-effects – is hard to know, although the ONS says that “vaccine hesitancy” is rare. Even among 16- to 29-year-olds, the most hesitant group, only 13% say they are reluctant to take the vaccine. But even if they’re not reluctant, we seem to be running out of people who are noticeably keen.

How you persuade those increasingly hard-to-reach groups is disputed. Finn of the JCVI said that one reason they were being so stringent is that they are worried about “the impact on public trust” if the JCVI recommends vaccines for groups who would not directly benefit from them: I worry about the opposite problem, about the impact on public trust if you tell the public that the vaccines aren’t safe. 

But given that demand is a problem, it does seem that an obvious way to increase demand would be to widen the availability of the vaccine. About 20% of the UK’s population is under 18; roughly 13 million people. Probably about four million of those are between 12 and 18. We can expand demand simply enough by offering it to them.

One question is, of course, whether we could vaccinate those young people quickly enough to make a difference. 

It does seem that the UK is not, right now, struggling with supply. I spoke to Kevin McConway, emeritus professor of statistics at the Open University, and he noted that all his local vaccine centres have walk-in availability for Pfizer, suggesting that it’s not an immediate problem.

But Mainwood estimates that we are bumping right up against our supply with Pfizer. If we were to take steps to speed up vaccination – by offering second doses earlier than eight weeks, for instance, or by allowing teenagers to be vaccinated – we would struggle.

The thing is, though, we have literally millions of AstraZeneca vaccines sitting unused. We bought 100 million. It’s very hard to get detailed breakdowns of which vaccines have been used, something that Professor Sir David Spiegelhalter, who I spoke to, is somewhat annoyed by: but we can’t have used more than 82 million AZ doses, since that’s the total number of vaccine doses administered. Probably it’s more like half that. 

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And since those March days when the AZ risk-benefit calculations were carried out, the situation has changed enormously. Now, the number of cases every day is back up around 50,000, not far off the January peak. The latest ONS infection survey finds that around one person in every 95 has the disease right now. And it’s highest among the youngest age groups – almost 3% of 17- to 24-year-olds have it. The Winton Centre’s analysis suggests that when the numbers are that high, the risk-benefit analysis changes utterly. A twentysomething has about a one in 50,000 chance of a blood clot if they get the AZ vaccine ,but a higher than one in 16,000 chance of going into intensive care with Covid in the next 16 weeks if they don’t.

If we freed up those AZ doses, we could do all sorts of things. For one thing, we could offer people a mix-and-match vaccine dose, so that people who want their booster earlier than eight weeks could do so. The evidence of effectiveness for mixed Covid jabs is now quite good, and it may even be more effective than two jabs of the same dose.

And we could offer vaccines to older teenagers who are willing, with their parents’ consent, to take a very low risk of vaccine side-effects in exchange for a significantly decreased risk of spreading the disease.

People should be able to make these decisions, or in the case of older children, to make them in concert with their parents, just as we allow them to make other decisions about risk and wellness. Perhaps they would need to sign a waiver; but they should be allowed to.

In about seven weeks, children will be going back to school after their summer holidays. The virus will, in all likelihood, still be circulating at least as much as it is now. We will head into winter with few restrictions, possibly with new variants, and still, probably, with a large percentage of the population unvaccinated. We could significantly reduce that percentage if we allow people to make their own decisions about what is important.

Now that Freedom Day is here, we ought to allow people a real freedom: the freedom to choose to be vaccinated.

There’s more. The Moderna vaccine was ready to go last January, within a couple of days of the SARS-Cov2 viral genome being sequenced. But it was not approved in the US until December, after months of testing and regulatory caution. If it had been approved instantly, many hundreds of thousands of lives would have been saved. It could all have been over a long time ago.

But, on the other hand, the history of vaccines is not entirely unblemished. In 1955, a batch of polio vaccine caused thousands of cases of polio, hundreds of cases of paralysis, and 10 children’s deaths. If people had been more cautious then, those lives would have been saved – and perhaps people would be less nervous about vaccines generally. Certainly the incident raised vaccine fears.

Which of these is the lesson we need to draw? Are we too cautious, too risk averse; or is it wise to be risk averse when it comes to vaccines, to avoid driving public panic with rare but real disasters?

A year ago today, on 23 March 2020, we went into lockdown. In the past 12 months, we’ve come to understand a lot of technical concepts – infection fatality rates, vaccine efficacy rates, exponential curves. But the most significant thing is that we have all had to become utilitarians. We all now think in terms of QALYs, utils, the greatest good for the greatest number.

As soon as lockdown began, there were fights over whether it did more harm than good. Both advocates and sceptics of lockdown argued in the same terms. The economic damage would undoubtedly ruin livelihoods; but would it do more harm, as measured in quality-adjusted life years (QALYs), than letting the virus run unchecked?

The argument over lockdown was a version of the famous trolley problem: if an out-of-control train is hurtling down a track towards five rail workers, should you divert it onto another track, where only one person is working? To hugely oversimplify, the utilitarian answer is yes: you save five lives for the price of one.

But not all ethicists are utilitarians. To again oversimplify, deontologists – Immanuel Kant is the best-known example – say you should follow certain rules: some things are always wrong, whatever the consequences. It is generally (though not universally) accepted that Kant would not pull the lever. He would say it is wrong to act to kill the one person, even though it would end up saving four lives on net.

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The great revelation of Covid-19 is that we are all consequentialists, or all claim to be. With lockdown, the argument wasn’t usually over whether it was simply wrong to kill people with lockdown but permissible to let them die from Covid. It was whether lockdown saved more QALYs than it cost. We’re not arguing whether it’s wrong to kill one to save five – we’re arguing about the number of people on each track.

Last week, several countries suspended use of the Oxford-AstraZeneca vaccine because of fears over blood clots. I think it was a terrible decision.

For that matter, so does the European Medicines Agency. It says that whether or not the vaccine causes some small number of clots (which it may do, in a subset of people), the correct decision is to carry on vaccinating people with it as quickly as possible. “[T]he vaccine’s proven efficacy in preventing hospitalisation and death from COVID-19 outweighs the extremely small likelihood of developing DIC or CVST,” it said in its statement. (It’s worth noting that the US trial has now announced its results, which were very positive, and had zero cases of CVST in its 21,000 participants.)

Again: this is stark utilitarian language. If we pause the delivery of the Oxford/AZ vaccine, we will prevent X deaths from blood clots. But it will also lead to Y deaths from Covid because fewer people are vaccinated. If X is smaller than Y, then vaccinating is a good idea. We’re not arguing over whether it is wrong to kill a small number by giving them a vaccine, even if it saves lives; we’re arguing over how many we would save. Again, we’re not arguing about whether we should pull the lever, we’re arguing about how many people are on the track.

(Of course, X could well be zero, and I think it’s very possible that it is. Certainly, X is much, much smaller than Y. But the principle is unchanged.)

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Why don't women feel safe?

By Tom Chivers

Utilitarianism is absolutely how we should be thinking. For one thing, it’s not clear to me that the distinction between killing someone through action and allowing them to die through inaction is even coherent. If I am driving, and a child runs out in front of me, and I don’t press the brake – is that act, or omission? Or, for that matter, is stopping the vaccine rollout the act, or is continuing the vaccine rollout?

The philosopher Jonathan Bennett argues that things should count as an “action” if, of all the bodily movements I could have taken, only a small fraction would lead to this outcome. So pushing a car down a hill to a cliff would count, because I could have done millions of things – tap-danced, written a sonnet, played volleyball – and almost none of them would have made it roll down a cliff. But not stopping a car when it is already rolling towards a cliff would not, because if I’d tap-danced near it, the car would have rolled over anyway; only a small subset of actions, like putting a big rock in front of it, would have stopped it. Maybe that works as a distinction, but I don’t know if it answers my “not pressing the brake” question.

What’s interesting, though, is that true utilitarianism is extremely complex. In the pandemic, mercifully, it’s often been pretty straightforward to work out which of two actions is better. Lockdown almost certainly saved more lives than it cost, because 1) loads and loads of people were dying and 2) if we hadn’t locked down, the economy would have taken a huge hit anyway (as Sweden’s did, almost as much as its neighbour Denmark, despite the lack of a lockdown) because of all the people too scared to go to the shops or the office while a deadly pandemic was raging. Certainly it’s not the case that countries which controlled the virus better had worse economic outputs.

Similarly, rolling out the Ox/AZ vaccine despite some small risk of a small number of clotting deaths is almost certainly a good idea because 1) the vaccine will save so many lives and 2) it turns out that stopping the rollout scared people anyway. It’s not a finely balanced situation. The utilitarian calculus is fairly straightforward.

But this is by no means always the case. Eliezer Yudkowsky is an AI theorist and arch-utilitarian, who argues that a sufficiently enormous number of people getting dust specks in their eye is worse than one person being tortured for 50 years. When I asked him a rather stupid question about utilitarianism, he said that “most people” (he did not say “especially you, Tom Chivers” but it was, I felt, heavily implied) were not “smart enough” to operate on a utilitarian basis, because the real consequences of any given action are so complex and unknowable.

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Will we pass the Boris roadmap tests?

By Tom Chivers

Here’s what I mean by that. If I leave the house and cross the road to go to the shop, I will slightly change the flow of the traffic. Some cars that would have gone through a green light will now have to stop at the red. That small change will slowly affect the entire road network, like the butterfly flapping its wings and causing a thunderstorm. Eventually it will mean that cars which would have been in fatal crashes will now not, while cars that wouldn’t have been now will. Some people will live who would otherwise have died, and vice versa. I can’t possibly predict the outcomes of even a tiny, inconsequential act like going to the shop.

So instead of trying to predict the outcomes of each action in real time, we ought to behave as quasi-Kantians – to establish rules to follow, and then follow those rules: if we try to compute the best outcomes on the fly, it’ll work out worse, because we’re not very good at it. (For one thing, you might end up sitting in your house, alone, unable to go to the shop in case you kill thousands of strangers.)

For instance, go back to X and Y above. If X is smaller than Y – if fewer people will die from blood clots than would be saved by the vaccine – then we might say that the vaccine is a good idea.

But those aren’t the only numbers involved. What happens if a few people die from blood clots, and that bad publicity scares others into not taking the vaccine? Does that mean we should stop the rollout? Or, as it in fact turns out, would stopping the rollout for minor fears scare more people? Those stark X and Y figures are only the surface froth: computing the real “consequences” of any action is phenomenally difficult.

In non-pandemic times, we seem to have a simple rule for this: when a vaccine is linked to some negative impact, we suspend its use and investigate it. Concerns (baseless ones, as it turned out) about mercury in the hepatitis B vaccine led US regulators to stop using it in 1999. Australian concerns over febrile convulsions in children led them to suspend the use of the influenza vaccine in under-fives in 2010.

Is this the right rule? Not all vaccine fears are baseless: remember the polio vaccine deaths above? But that was an old form of vaccine, made by deactivating a live virus; obviously the virus had not been sufficiently deactivated. Modern mRNA, protein subunit or viral vector vaccines are not biologically capable of causing the infection they are meant to protect against, and the process for deactivating viruses when we use them in vaccines nowadays has been vastly improved. And, also, for the vaccine to have reached the public, it must have been through Phase III testing in tens of thousands of people; hundreds or thousands of person-years of testing.

And following that rule has led to some pretty negative outcomes. Suspending the Ox/AZ vaccine, as we saw above, does not seem to have boosted public confidence – rather the opposite. Similarly, the suspensions of the US hepatitis vaccine and the Australian flu vaccine seem to have been associated in both cases with a dramatic reduction in vaccine uptake. The public doesn’t hear “We’re just checking this vaccine is safe, to reassure you;” they hear “This vaccine is dangerous, and we’re taking it offline.”

In the wider world of medicine, regulatory institutions such as the MHRA, EMA or FDA have a rule in place that says something like “You need to do years of incredibly rigorous trials on new drugs, to prove safety and efficacy to some P<0.001 level, before we will roll it out to the public.” That’s because even if speeding up the process would likely do more good than harm, it only takes a few thalidomide-type disasters to damage public confidence.

That makes sense – even in the pandemic, there were lots of very confident people telling us that some drug or another worked; sometimes they were right, and it was tocilizumab, but sometimes they were wrong, and it was hydroxychloroquine. But this need for perfect data has been far too widely applied, and led us to avoid much lower-cost and easily reversible interventions, such as masks, border closures or a ban on mass gatherings like Cheltenham Festival, for far too long.

We’re all utilitarians now, as I say. The pandemic has forced us to be. But the tricky bit will be learning when to be the short-term utilitarian, working out the pros and cons of the individual case, and when to be the quasi-Kantian rule-follower.

Obviously pandemic time differs from peacetime, but I think we should learn to be a bit less rigid in some of our rules. The panicked need to suspend vaccines at the first sign of danger, for instance, can be relaxed somewhat. Modern vaccines are amazingly safe. In any case, when we shut down vaccine programmes out of an overabundance of caution, in the hope of reassuring the public, it seems to have the exact opposite effect.

I’m not saying we should have immediately rolled out the Moderna vaccine the moment it was available, or that we should have carried on giving a lethal polio vaccine to children in order to prevent vaccine hesitancy. But it is ridiculous that Americans still can’t take the Oxford/AstraZeneca vaccine, that it is sitting unused in warehouses even as it is already saving thousands of lives elsewhere; that whole nations have suspended its use in a doomed attempt to reassure the public of something they didn’t need reassuring about. Perhaps, after a year of this pandemic, we finally ought to realise that when it comes to vaccines, the real danger is in being too cautious.

Furthermore, and following the acutely embarrassing Article 16 debacle, an effort was made to reclaim vaccine internationalism for the EU brand. The new line came from the President of the European Council, Charles Michel — whose sanctimonious missive on the matter is a masterpiece of Pecksniffery.

Unfortunately, the EU good guy act didn’t last. Indeed, our neighbours appear to have lost their minds.

Kicking off the March madness was a vaccine export ban to Australia — a pointless and counter-productive move given that the EU could potentially benefit from vaccine imports.

Next, came a completely avoidable diplomatic row with the UK. Ironically, the cause of it was the Michel missive, which in seeking to emphasise the EU’s internationalism accused the British of banning vaccine exports. Except that no such ban exists. Eventually, the EU was forced to admit the truth. There was no apology.

Perhaps we should try to understand the EU’s prickliness. In a Covid-ridden world where vaccines have become an instrument of great power rivalry, the EU is trying to defend a high-minded principle — that of equal access between EU member nations. This is how Monsieur Michel put it in his blogpost: “The goal was to avoid competition and bidding between countries, and to allow all countries to obtain the doses at the same time. Otherwise, the larger or richer Member States would have been the first in the queue and best served…”

Admirable. Except that the joint procurement programme isn’t quite as egalitarian as its billing would suggest. Some countries — including Germany, of course — have exploited its loopholes to serve themselves. Other countries aren’t happy. Last week, the Austrian Chancellor, Sebastian Kurz, led five EU countries — Austria, Czechia, Slovenia, Bulgaria and Latvia — in demanding an EU summit to address the unfairness:

“…the last few weeks have shown that deliveries are currently not being made according to population keys and that this is set to intensify in the coming months. This approach clearly contradicts the political goal of the European Union — the equal distribution of vaccine doses to all member states. If the distribution were to continue in this way, it would result in significant unequal treatment — which we must prevent.”

Kurz has been accused of seeking a distraction from his own government’s mediocre performance, but he makes a valid point. The EU’s vaccine procurement strategy prioritised fairness over timeliness, and has delivered neither.

Meanwhile, across Europe, governments are uniting in the face of an old enemy. Yes, the EU’s least favourite medicament is back on the blacklist: the AstraZeneca vaccine. This time the flimsy pretext is the report of blood clots in a small number of recently vaccinated individuals. Writing for UnHerd, Tom Chivers explains that it’s unreasonable to expect universal invulnerability to death and disease in a population of millions of older people. It’s also worth noting the assurances given by AstraZeneca itself, the UK government, the Scottish government, the World Health Organisation and indeed the European Medicines Agency.

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Everything you know about Europe is wrong

By Ed West

Nevertheless, that hasn’t stopped several EU governments (including the Germans, the French and Italians) from slapping a temporary ban on the Oxford AZ vaccine. For its part, the Irish government claims to be acting upon the “precautionary principle”. But there is nothing precautionary about snatching away a life-saving vaccine from vulnerable people in the middle of deadly pandemic — not without overwhelming proof of a countervailing danger, which they clearly don’t have.

There’s never a good time to commit an act of calamitous self-harm, but this latest insanity comes at an especially critical juncture. Not much more than a month ago, Covid cases in the EU were at roughly the same level as in the UK and the US. Now, they’re roughly twice the American level, and between three and four times the British level. That’s not just because cases are coming down in the UK and US, but also because they’re heading up in several European countries — and across the EU overall.

Furthermore, new variants of the virus such as those first detected in Britain, Brazil and South Africa are now established and spreading in EU countries — underlining the urgency of getting the population vaccinated. And yet instead of ramping up vaccination — as the British are doing this week from an already high base — European governments are choosing this moment to sabotage their own vaccine supply.

And let’s not forget where we are in the course of this pandemic — and what we’ve sacrificed to contain it. In the West, we’re now 12 months on from the first round of lockdowns. As the UK begins to unlock stage by stage, millions of Europeans face a second spring of confinement. Italy — the first European country to lockdown a year ago — is locking down again as cases surge.

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How the EU humiliated itself

By Peter Franklin

Whatever the medical justifications, one has to ask if lockdown is politically, socially or economically sustainable. If Europe doesn’t achieve herd immunity levels of vaccination by the summer, the pressure to unlock regardless will be immense. It will be argued that if enough of the Continent’s elderly and vulnerable people have been jabbed then that will constitute ‘focused protection’ — thereby allowing the less vulnerable population to take their chances with the virus. Wouldn’t it be an irony if something akin to the strategy set out in the Great Barrington Declaration were to be implemented by the Continentals instead of les Anglos?

Of course, that would provide the new variants of the virus with a vast pool of hosts to splash around in freely. Through the use of mass testing and genomic sequencing, the authorities might be able to monitor and manage the spread and evolution of the variants — but this assumes that sufficient capacity to do so is in place. It isn’t. According to evidence given to the European Parliament by the European Centre for Disease Prevention and Control most European countries are not where they need to be in order to do the necessary tracking.

How do they get away with it? The EU’s politicians, I mean. Well, it helps that in Europe there’s always somebody else to blame. It might be another country, another institution or one of the EU’s five presidents. The choice is never ending. It also helps that, in times of crisis, people rally behind their governments. Not unreasonably, they put their trust in those politicians with the greatest experience of governing — a tendency that benefits establishment politicians over their populist rivals.

Nevertheless, there are signs that voters are beginning to lose their patience. In Germany, the ruling CDU — until recently surfing on a wave of support for Angela Merkel — crashed to defeat in regional elections. In France, polls continue to show a disturbingly tight second round run-off between Emmanuel Macron and Marine Le Pen. In Italy, populists account for three of the four main parties — and the non-populist fourth party (the centre-left, pro-European Democrats) are losing ground. In Spain, support for the hard Right Vox party continues to grow — even to the extent of overtaking what had been the main opposition party.

I’d like to think that this week’s renewed attack on AstraZeneca is evidence of a political panic. “Let’s blame somebody else before the voters blame us” would be a logical, if cynical, motivation. However, I fear that it’s not cynicism at work here, but a much more dangerous force: self-righteousness.

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Brexit makes more sense than ever

By Peter Franklin

When you read the words of Charles Michel, a disturbing thought hits you: the people actually believe their own rhetoric. Consider this passage, in which Michel favourably compares the EU to Russia and China: “Europe will not use vaccines for propaganda purposes. We promote our values.”

I wonder, where were these “values” when they tried to impose a hard border on the island of Ireland? Or, now, as they cause millions of people to fear a life-saving vaccine?

But then, for the European Union, self-righteousness is not a character flaw, it’s a necessity. The EU is an enterprise — the “European project”, in fact. As such, it is unlike a real country. A nation, like a family, isn’t defined by what it does and still less what it thinks. It has no need to state its purpose or justify its existence.

The phrase, “my country, right or wrong” is widely regarded as the classic statement of jingoistic nationalism. But properly understood, what it means is that you can admit that your country is wrong, because that won’t change the fact of its existence — or of your belonging to it.

Not so with an enterprise. If it doesn’t work anymore, then it shouldn’t continue — because it is no more or less than it what it does. To fail a test as big as Covid — and in particular the vaccination effort — has existential implications for the European Union.

It is therefore not a question of the EU asking itself whether it’s got this one fundamentally wrong. By its own internal logic, it cannot be fundamentally wrong — certainly not on a matter as important as this one. Rather, the question is how it reconciles this basic assumption with reality.

I really hope the gap between the two narrows, because I fear the next set of answers.

Since it’s very likely that you are a British person, and therefore have either recently had or will soon have your first jab – and that it is very likely that that jab will have been the Oxford/AZ vaccine – I can understand if this makes you feel nervous. Especially since the Netherlands, Ireland, Denmark, Iceland, Norway, Spain, Thailand and Germany have all suspended or partly restricted the use of the jab.

It is a stupid, harmful decision; it will predictably lead to some avoidable deaths; and there is absolutely no good reason to think that the Oxford vaccine is linked in any way to blood clots. It’s also dangerous because it will give people the false impression that it is unsafe, even when these countries change their minds.

But it is very instructive. Because it shows us a simple, but common, way, in which numbers go wrong in the news: the failure to ask “Is this a big number?” After all, 37 people getting sick sounds really bad, on its own. But is it more than we would expect? What do we need to know to understand that?

We need two more numbers: one, how many people have been given the Oxford vaccine; and two, how many blood clots we would expect to see in that many people, if we hadn’t given them the vaccine. Luckily, we know those two numbers fairly well. About five million people have been given the Ox/AZ vaccine in Europe (about 17 million worldwide, according to AstraZeneca); and about one person in every 1,000 suffers a thrombosis every year.

So you’d expect to see about 5,000 blood clots among the five million recipients of the jab every year — 14 a day, nearly a hundred a week — even if that jab had nothing to do with blood clots whatsoever. Professor Sir David Spiegelhalter, the Cambridge statistician, goes into a bit more detail here if you’re interested.

On that basis, it’s hardly surprising that we might see 37 thromboses over a few weeks of vaccination. In fact, it’s surprising that there aren’t quite a lot more, although that’s probably because a lot of people had blood clots and didn’t associate them with the vaccine.

Asking that simple question — “is this a big number?” — and knowing how to answer it would have saved a lot of bother, for journalists and for policymakers. But it often doesn’t occur to people.

So I’ve written a book with my cousin David (he’s an economist) in an attempt to correct this: How to Read Numbers: A Guide to Stats in the News (and Knowing When to Trust Them). Because while it’s true that the public needs to be literate in order to participate in democracy, it’s not enough to be able to read words. We also have to be able to navigate numbers.

Is 37 a large number of thromboembolic events? Probably not. But if you don’t know to ask “is it a big number?”, you might end up being scared when you don’t need to be – and be put at risk of Covid, if you don’t get vaccinated.

How about 361, as in “361 cyclists were killed on London roads between 1993 and 2017.” Is that a lot? Obviously it’s tragic for each cyclist and their families. But should I feel unsafe when I cycle, or not? Should I be out campaigning for TfL to improve cycle safety? Well, that depends how many cycle journeys there were in London in that time. Was it 4,000 a day? 40,000? 400,000? (It was 437,000, so about one journey in every 10 million ended in tragedy. Only you can say whether that is safe enough for you.)

By the same author

Why don't women feel safe?

By Tom Chivers

Or: when we say that police-recorded hate crimes have gone up in the last few years, is that the same as saying that actual hate crimes have gone up? Or has the way that hate crimes are reported and recorded changed? (Probably the latter. If you look at survey data, the number of actual hate crimes has been steadily falling. But police-recorded crimes have gone up, because as a society we take them more seriously: so the public has become more likely to report them, and the police more likely to record them.)

It’s important to be able to navigate these issues. You don’t need to be especially good at maths; you simply need to be aware of how numbers can go wrong. It’s more about a way of thinking than about mental arithmetic. It matters, because we make decisions every day — should we have a bacon sandwich? Should we have a glass of wine? Are we safe walking home? — based on numbers which we have seen in the news.

But journalists, too, need to be clearer. We are performing a public service: we hold governments to account; we inform the public. Despite the stereotypes, journalists in my experience are usually well-intentioned and public-spirited. We’re not just out there hawking for clicks; we pride ourselves on finding out things that other people don’t want to be known, or for explaining complicated things to our readers.

Often, though, journalists aren’t traditionally very good with numbers. One of the things I try to do with my columns for UnHerd is explain bad science stories. Often the numbers in these stories mislead not because journalists are doing it on purpose, but because they’re not scientists or statisticians. Questions like “Is that a big number?” “Are we still measuring the same thing?” “Is the study it comes from any good?” simply don’t occur to them. We’ve thought of a neat way to address this: a statistical style guide.

Most publications have style guides. At the Telegraph, the style guide was very concerned with the correct terms of address for aristocracy. (“The Duke of Bedford’s son is the Marquess of Tavistock. Lord Tavistock’s elder son, if he has one, can use the third title of the Duke, and he therefore is Lord Howland.”)

The style guide at BuzzFeed, where I worked after that, was much more concerned with whether or not to hyphenate “butt-dial”, “circle jerk” or “douchebag” (all thus).

The Sunday Sport’s style guide, meanwhile, is extremely particular about how to write “bellend”. (“BOLLOCKS: Full out in copy and in headlines. WANK: Full out in copy, w**k in headlines. BELLEND: One word, full out in copy and headlines.)

Having a consistent style is useful; it helps publications maintain a clear identity. But as far as we know, no publication has a style guide for numbers. Not just in terms of when to write 100 and when to write “one hundred”, but: how should you present statistics in order to avoid misleading your readers?

So we have put together a list of 11 points that we think will help. They’re in our book. We don’t pretend that they’re the final word, and we’re keen to find out how we might improve them. For instance, Evan Davis, the radio presenter, tells us that he thinks we should explain in words that there is uncertainty around an estimate, or that a study is not very robust, rather than explicitly including confidence intervals and sample sizes.

We do think, though, that if journalists follow our guide, we’ll end up with a better national discussion. People will have a better understanding of the numbers in the news, and therefore make more informed decisions. It might also prevent governments from making insane decisions about perfectly good vaccines, putting thousands of lives at risk in the middle of a pandemic.

By the same author

What Covid tests can we trust?

By Tom Chivers

 Our Statistical Style Guide

1) Put numbers into context

Ask yourself: is that a big number? If Britain dumps 6 million tons of sewage in the North Sea each year, that sounds pretty bad. But is it a lot? What’s the denominator? What numbers do you need to understand whether that is more or less than you’d expect? In this case, for instance, it’s probably relevant that the North Sea contains 54 thousand billion tons of water.

2) Give absolute risk, not just relative

If you tell me that eating burnt toast will raise my risk of a hernia by 50%, that sounds worrying. But unless you tell me how common hernias are, it’s meaningless. Let readers know the absolute risk. The best way to do this is to use the expected number of people it will affect. For instance: “Two people in every 10,000 will suffer a hernia in their lifetime. If they eat burnt toast regularly, that rises to three people in every 10,000.”

3) Check whether the study you’re reporting on is a fair representation of the literature

Not all scientific papers are born equal. When CERN found the Higgs boson, or LIGO detected gravitational waves, those findings were worth reporting on in their own right. But if you’re reporting on a new study that finds that red wine is good for you, it should be presented in the context that there are lots of other studies, and that any individual study can only be part of the overall picture.

4) Give the sample size of the study – and be wary of small samples

A drug trial which has 10,000 subjects should be robust against statistical noise or random errors. A psychological study looking at 15 undergraduates and asking whether washing their hands makes them feel less guilty is much less so. It’s not that small studies are always bad, but they are more likely to find spurious results, so be wary of reporting on them.

5) Be aware of problems that science is struggling with, like p-hacking and publication bias

Journalists can’t be expected to be an expert in every field, and it’s hard to blame them for missing problems in science that scientists themselves often miss. But be aware of the various ways that scientists can chop up data to make it look as though there’s something there when there isn’t — or to quietly hide results that don’t support their hypothesis. Also, if a result is surprising, that might be because it’s not true. Sometimes science is surprising, but most of the time, not very.

6) Don’t report forecasts as single numbers. Give the confidence interval and explain it

A lot of the time, the media will report on forecasts and models of the future. For instance, each year the Office for Budget Responsibility will make an economic forecast for how much the economy will grow. Or in early 2020, statistical modellers made forecasts for how many people the Covid-19 pandemic would kill.

If they said “Without a lockdown, Covid-19 will kill 250,000 people in Britain,” they didn’t mean that it would kill exactly 250,000. Instead, that was a best guess, in the middle of a wide range of uncertainty: they might say, for instance, that they were 95% sure that the true figure would fall between 100,000 and 400,000. That is the “confidence interval”.

Often, though, when the media reports on forecasts and models, they just give the central, best-guess estimate, which makes them sound more precise than they are. When reporting on forecasts and models, make sure you give the confidence interval, not just the central estimate.

7) Be careful about saying or implying that something causes something else

Lots of studies find correlations between one thing and another — between drinking fizzy drinks and violence, for instance, or between vaping and smoking weed. But the fact that two things are correlated doesn’t mean that one causes the other; there could be something else going on. If the study isn’t a randomised experiment, then it’s much more difficult to show causality. Be wary of saying “video games cause violence” or “YouTube causes extremism” if the study can’t show it.

8) Be wary of cherry-picking and random variation

If you notice that something has gone up by 50% between 2010 and 2018, have a quick look — if you’d started your graph from 2008 or 2006 instead, would the increase still have looked as dramatic? Sometimes numbers jump around a bit, and by picking a point where it happened to be low, you can make random variation look like a shocking story. That’s especially true of relatively rare events, like murder or suicide.

9) Beware of rankings

Has Britain dropped from the world’s fifth-largest economy to the seventh? Is a university ranked the 48th best in the world? What does that mean? Depending on the underlying numbers, it could be a big deal or it could be irrelevant. For example, suppose that Denmark leads the world with 1,000 public defibrillators per million people, and the UK is 17th with 968. That isn’t a huge difference, especially if you compare it with countries that have no public defibrillators. Does being 17th in this case mean that the UK health authorities have a callous disregard for public emergency first-aid installations? Probably not. When giving rankings, always explain the numbers underpinning them and how they’re arrived at.

10) Always give your sources

This is key. Link to, or include in your footnotes, the place you got your numbers from. The original place: the scientific study (the journal page, or the doi.org page), the Office for National Statistics bulletin, the YouGov poll. If you don’t, you make it much harder for people to check the numbers for themselves.

11) If you get it wrong, admit it

Crucially – if you make a mistake and someone points it out, don’t worry. It happens all the time. Just say thank you, correct it, and move on.

And if you agree with all that, then join our campaign…

How to Read Numbers: A Guide to Stats in the News (and Knowing When to Trust Them) is published on Thursday.

The outrage was the subsequent blame-shifting manoeuvre by the European Commission. While the accusation that AstraZeneca was diverting vaccine supplies from the EU to the UK was absurd, the consequent threat to impose a hard border on the island of Ireland was shockingly irresponsible. Widespread condemnation forced the Commission to back down.

The scandal is what happened next. For a start, and despite the fiasco and the outrage, no one has resigned — least of all Ursula von der Leyen, whose cool-and-calm exterior conceals a heart of beating ineptitude.

Then came a spectacular display of sour grapes. After all the fuss about not getting enough of the Oxford AZ vaccine, various EU powers-that-be have undermined its reputation.

It all kicked off with a report in Handelsblatt on the 25 January. The piece featured a claim — from a mysterious source within the German government — that the vaccine was only 8% efficient among the over-65s. Unsurprisingly, this made headlines around the world.

Could this possibly be true? No, said AstraZeneca, the figure had no basis in their research or anyone else’s. So where did it come from? An investigation for the BMJ by Hristio Boytchev tried to get to bottom of the matter, but all we can say for sure is that an unnamed source in the German health ministry was very keen to get the fake news out there.

In any case, the murkiness soon became manifest. Within days of the anonymous briefing, the German and French governments announced that they would not be allowing the use of the vaccine among the over-65s.

In comments to the press on the 29 January, Emmanuel Macron made it clear what the French attitude would be: “everything points to thinking it is quasi-ineffective on people older than 65, some say those 60 years or older.”

But “everything” did not point to that conclusion. The British had already approved the vaccine (on the 30 December) and had been successfully using it since. On the same day as Macron’s remarks to the press, the European Medicine Agency (EMA) also approved the use of the vaccine — among all adult age groups. Furthermore, they specifically addressed the issue of older age groups:

“There are not yet enough results in older participants (over 55 years old) to provide a figure for how well the vaccine will work in this group. However, protection is expected, given that an immune response is seen in this age group and based on experience with other vaccines…”

As Tom Chivers explained for UnHerd here, it’s entirely reasonable to expect encouraging results from trials conducted mostly on younger age groups to hold true for their seniors, too. And yet the President of France saw fit to state that “the real problem on AstraZeneca is that it doesn’t work the way we were expecting it to.”

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Europe is waiting for its Napoleon

By Peter Franklin

If anything, the vaccine has exceeded expectations. Results from England show that inoculation has cut the risk of serious illness in the over-80s by around 80% — building on similarly impressive results from Scotland. That Handelsblatt claim wasn’t just wrong, but wrong by an order of magnitude.

Note, also, that these results are for a single shot of the vaccine. The second shot should produce even better outcomes. Nevertheless, the degree of protection already achieved has triumphantly vindicated the decision to spread out the shots in order to vaccinate as many vulnerable people as possible. More reason, then, for Macron to eat his words — because as well as pouring doubt on the efficacy of the virus, he poured scorn on the UK’s first shot first strategy, stating: “I’m not sure that it’s very serious.”

Well, it is serious, as are the consequences of the EU’s sour grapes. The irony of the supply dispute with AstraZeneca is that shots of the vaccine are now going unused in the EU, because intended recipients (like the older under-65s and health workers) are worried there might be something wrong with it. In Germany, regional governments are pleading with Berlin for permission to reassign doses to people in lower priority groups who are willing to take it.

The contrast with the British experience becomes more embarrassing by the day. Though one would expect Covid deaths to fall as a result of the UK strict lockdown, they’ve been tumbling fastest among the most extensively inoculated age groups — compelling evidence that our vaccine strategy is working.

The Europe Union is now waking up to what it needlessly missed out on. Worried EU governments are now desperately reassuring their populations that the Oxford AZ vaccine is safe and effective. The French have just relaxed the restriction on the vaccine’s use among the over 65s. The Germans are likely to follow suit. Thomas Mertens, head of Germany’s  expert panel on vaccine use, has promised an “update” to the current regulations. He was at pains to point out that the existing restriction were never about safety concerns and added that “somehow the whole thing went kind of badly wrong.” Yeah, “somehow”.

In the latest blow to European solidarity, Denmark and Austria have chosen to go their own way, obtaining vaccines via Israel; Slovakia has joined Hungary in acquiring the Russia Sputnik vaccine, believed to be safe although yet to be approved by Brussels; while Poland is considering a deal with China.

And yet the EU’s leaders continue to send the wrong signals. Last week, Angela Merkel said that she would not take the Oxford AZ vaccine herself. Her British defenders point out that this is only because she is 66 and thus just above the age at which the current restrictions kick-in. But, as usual, her apologists miss the point. The rules — which she is ultimately responsible for — are ridiculous and should not exist in the first place. As leader of her country, millions of people will follow her lead.

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Of course, hers is not the only screw-up in this pandemic. There isn’t a country in the world that hasn’t got it wrong repeatedly — and the UK is clearly no exception. However, it’s important that we distinguish between the different kinds of mistake.

About a year ago, Britain should have gone into lockdown at least two weeks before it actually did. However, our Government was acting on official scientific advice that was unfortunately wrong. Other failures arise out of the sheer scale of the challenge, test-and-trace being a prime example. We can test at scale, but tracing is supremely difficult when transmission is so widespread. It might have helped if we’d closed our borders at the outset — but that’s an illustration of a third kind of mistake, those that happen when governments are faced with impossible dilemmas. Choosing the lesser of two evils isn’t easy when they’re both overwhelmingly horrible.

The mistakes made by Brussels, Paris and Berlin over recent weeks have been of a different type, and were entirely avoidable. In deciding policy towards AstraZeneca and its vaccine, the scientific advice (from the EMA) wasn’t wrong, the challenges weren’t insurmountable and the choices far from impossible. There was no question as to the safety of the vaccine. There was a degree of uncertainty as to its effectiveness, but good reason to expect a beneficial outcome. After all, for millions of elderly and vulnerable Europeans the alternative isn’t a better vaccine, but no vaccine — a famously ineffective treatment.

The mistake made in this matter was not an honest one. There’s only one motivation that fits with the facts — spite.

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By Bruno Macaes

As an institution, the EU displays a pattern of behaviour that in an individual would be diagnosed as petty narcissism. We all know the type of person: the character flaw isn’t obvious at first, but they soon give themselves away. In place of the usual give-and-take of a healthy human relationship, they think they’re doing you a favour just by allowing you to interact with them. Furthermore, you will be expected to pay for the privilege. This means abiding by their rules; having to guess what they want without being told; prioritising your relationship with them above any other attachment. Resist their nonsense and you’ll be accused of being the unreasonable one.

If an impasse is reached or you walk away, they won’t wish you well. Indeed, like Jean-Claude Juncker insisting that “Brexit cannot be a success”, they’ll want to you fail without them. And, of course, that’ll be your fault, not theirs. It’s abusive and manipulating, but ultimately self-destructive.

Instead of bullying and then belittling AstraZeneca and the UK, the EU could have chosen the path of cooperation. Even if they genuinely did have questions about the vaccine and the UK’s vaccination strategy they could have kept an open mind — and thus the option to follow suit. As it is, they’ve ensured that any change of mind can only come with a maximum of political embarrassment and humiliation.

Well, never mind — let them pay with their blushes. After all, their people are paying with their lives.

In the year and a bit since then, there haven’t been many opportunities to write straightforwardly upbeat things. So it is with great relish that I write that the vaccines are now unambiguously saving British lives.

One (so far not peer-reviewed) study looking at 5.4 million people in Scotland — that is, basically all Scottish people — found that vaccinated people were 85% less likely to end up in hospital than unvaccinated ones. The Oxford/AZ vaccine and the Pfizer vaccine were statistically indistinguishable; despite ridiculous and confected European concerns about the Oxford vaccine, it is stopping people from dying just as well as the Pfizer one. And in Scotland the AZ vaccine has been mainly used in older people, to great effect.

Another smaller, UK-wide study looking at infections in healthcare workers found that the Pfizer vaccine was about 70% effective at reducing infections 21 days after a first dose, and 85% shortly after a second dose. Further analysis suggests that even if you do get infected you’re about half as likely to get seriously ill or die, suggesting that it’s somewhere up in the 80-90% region against severe disease.

We’re not mucking around trying to reverse-engineer pharma industry press releases and proxy immune responses any more; this is the vaccine out in the field, doing what it was made to do, and doing it well. One of the most heartening graphs showed that the number of severe cases in the elderly was dropping at a far faster rate than cases in younger age groups; when we came out of Lockdown 1, they stayed stubbornly high for a long time. There was some slight concern in the Scottish data that the response started to weaken a bit once you got past 28 days from the first dose, but it wasn’t clear and it didn’t seem to appear in the other study, so I’m not very worried about it.

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When you add in that cases are dropping day by day – the seven-day rolling average is down to around 11,000 positive tests a day, the lowest it’s been since the beginning of October – I think we are allowed to be cheered.

All that might make you think that the road ahead is clear — but there are still reasons to be cautious.

The chief scientific adviser, Sir Patrick Vallance, in a briefing to journalists ahead of the release of the roadmap, said that it is important, as we come out of lockdown, to do it in stages: open up a few things, wait for a few weeks, and watch how R changes; the basic scientific thing of changing one variable at a time.

Schools are the big unknown. It’s nearly a year since schools were closed in the first lockdown, and despite them being opened and closed again since, we still don’t really know what impact they have on transmission. I think it’s pretty clear that they do drive R upward somewhat, but it’s not clear how much. I get different answers depending on which scientists I ask.

In the roadmap, we will open schools on 8 March (plus a few other things which are probably fairly inconsequential from a transmission point of view), and then see what impact that has. Vallance suggested we should leave four to five weeks between new measures, in order to see what the impact is: under the roadmap, we’re leaving just three weeks before further measures are introduced on 29 March, which disease models presented to SAGE suggest would be “unlikely [to] allow the effect of step 1 to be clearly discernible before step 2 takes place”.

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The measures introduced on 29 March seem unlikely to be major causes of transmission: the reintroduction of “the rule of six” outdoors, outdoor sport starting up again. And they will coincide with the start of the Easter holidays. More major changes will come at least five weeks after the schools reopen. But still, this isn’t being overly cautious: if anything, it’s sailing somewhat close to the wind. 

You might, reasonably, say that it doesn’t matter that much whether schools raise R that much, because the vaccines will stop people dying. But not everyone will be vaccinated, and the vaccines are not perfect, so a huge outbreak will lead to a gigantic surge in cases. The SAGE models suggest that if we were to reopen fully all at once, we would end up with the NHS overwhelmed far more than it was even at the peak of spring 2020. 

Slower relaxation, obviously enough, leads to slower growth in cases. And given the uncertainty, especially around schools, coming out slowly is obviously wise. I understand the wish to come out of lockdown quickly: by one measure, we currently have the most restrictive measures in the developed world. But I’d suggest that’s probably at least partly a result of coming too quickly out of previous lockdowns, not a reason to come out quickly now.

There’s another concern, which is that the more infections there are, the more chances there are for the virus to mutate. There are already somewhat vaccine-resistant strains out there. “If we see big outbreaks and exponential growth,” says Rupert Beale, leader of the Cell Biology of Infection group at the Crick Institute, “you might get a more complete vaccine-escape mutant. It’s relatively unlikely, but each new infection is like giving the virus a lottery ticket.” It only needs to be lucky once.

So the roadmap seems sensible: finally Boris Johnson has learned how to pass the inverted marshmallow test.

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A couple of points, though. First, it is baffling that it is “irreversible”, as briefed a few weeks ago. If we reopen schools, they drive R way above one, and we find ourselves in an unexpected new surge, then the sensible thing to do will be to close schools again. It will be awful for a lot of people, but better than a huge second outbreak and the need for a much longer lockdown.

Second, there are missed opportunities here. The number of cases is falling, and that’s a good thing. But as Adam Kucharski of the London School of Hygiene and Tropical Medicine points out, it means that we have only a short window to find things out about the virus. When there are very few cases in the community, it becomes impossible to tell what effect your interventions have: if you tested a vaccine on a population with no disease, then you’d get zero cases in your placebo arm and in your treatment arm. The same applies if you are trying to see the effect of, say, lateral-flow testing.

So now, while there are still a reasonable number of cases, would be an excellent time to do some randomisation. Try lateral-flow tests in schools in a randomly selected 50% of boroughs. Or try new ventilation techniques in half of schools but not in others. Then measure the impact. It is very unlikely that this will be the last we see of Covid, in either this form or some variant; knowing more about how it spreads, what we can afford to leave open and what we definitely need to close will help us when numbers come back up again. 

Third, there was something that Vallance said which caught me up short. We can’t expect the vaccine to be entirely successful, he said, because even if it’s 80% effective, we’re only vaccinating 80% of the population – adults – and 80% of 80% is only about 65%.

Which is of course true, but it made me think: perhaps … we … ought … to … vaccinate … children?

It’s just a thought, but 100% of 80% is 80%. The vaccines are amazingly safe in adults, and I don’t know of any reason why they’d be less safe in children. I was worried that there’d be some Joseph Heller-style situation where we can’t do safety trials on children because we don’t know that it’s safe to do so, but it turns out that Pfizer have already recruited participants. We’re going to have to live with this disease for a long time. Vaccinating people on their 16th birthday forever is not ideal, especially if it’s still circulating in schools. It might not be the most immediate priority but I’d like to know if it’s safe.

I sincerely doubt that this will be the last time I write “coronavirus” in my life, or even the last time this week. But the vaccine news does make me think that, if we do come out of things cautiously, then perhaps this time next year, I’ll at least be writing it less often.

The “British variant” had many mutations, but its key one affected its ability to spread: it was about 50% better at jumping from person to person than the original Covid. More recently, different strains have arisen, with that same mutation — but also another one, which appears to make it harder for vaccine-primed immune systems to fight against. One of these arose in South Africa, hence the talk of the “South African variant”, but the same extra mutation has arisen twice, independently, in the British strain too. The idea of the vaccines not working, after all this time waiting for them to save us, is genuinely chilling.

So: what’s the reality? Do the vaccines work against the new variants? This week more bad news came in: a study from South Africa finding that the Oxford/AstraZeneca vaccine “fails to protect” against mild and moderate cases of the mutant strain first detected in that country. 

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It’s worrying, of course, but there are complicating factors. I think there are some reasons to be less worried than the headline suggests.

First: this is an extremely uncertain finding. As the virologist Müge Çevik points out, the study was small: it had 1,700 participants, which sounds reasonable enough, but your study’s statistical power comes from the number of cases, not the number of people in the study. And there were only 42 cases of coronavirus in the control and the treatment arm put together.

Of those 42, 19 had been given the real vaccine, and 23 had the placebo. The study itself isn’t available, but screenshots taken from an online briefing say that it is believed to be 22% effective. But because of the small numbers, the uncertainty around them is huge: the 95% uncertainty interval stretches from 58% to -49% efficacy.

So, while it is very likely that the vaccine is less effective against the South African strain than against the more old-school varieties, it is still likely to give some protection against mild to moderate disease, and it is very possible that it gives much better protection than this study suggests.

An aside

I wanted to have a somewhat tangential, but serious, grumble at this stage. It is ridiculous that we only learnt about this study via a Financial Times story (and, later, a Times story). It is even more ridiculous that the only reason we have any of the data at all is because a couple of enterprising journalists took screengrabs from the briefing. 

There are all sorts of problems with scientific publishing. One of them is that peer review, as well as being flawed in many ways, is slow: it takes time for (unpaid) scientists to review a paper before it can be published in a journal. But the rise of the internet has meant that it is possible to avoid that problem, by publishing on preprint servers, and letting the peer review process happen in its own time. In the Covid era, that speed is vital; days or even hours might matter, might save hundreds of lives, if some discovery is made about whether some drug or intervention works or doesn’t work.

There have been tens of thousands of Covid-related papers published on the biomedical preprint server MedRxiv in the last 12 months; some of them have been absolute garbage (the XKCD comic reminds us that it probably makes sense to simply refer to them as “PDFs”, rather than “unpublished studies”), but at least it is possible for other scientists, and science journalists, to look at the data. 

So why on Earth wasn’t the South African study made available on preprint? It’s not that the paper hasn’t been written: the FT story was based on a pre-peer-review, i.e. preprint, version, and the slides were clearly written from a written-up paper. It’s just baffling to me. The Oxford vaccine is likely to save millions of lives; its scientific team should rightly be lauded as heroes, as should everyone involved in its manufacture. But communicating science is part of science, and this has been a big failure. I’ve asked the Oxford press team to see if they can help me understand it; if they respond with something interesting, I’ll add it in here.

Back to the point 

As I was saying. My main reason for worrying slightly less than the headlines suggest is because the headlines say that it doesn’t protect very well against mild to moderate disease. The study only looked at younger people — the median age was 31 — so there were no severe cases at all, in either the treatment or the control groups.

Intuitively, you might think that if a vaccine doesn’t protect against mild disease, it won’t have a chance against severe disease. But that’s not how it works. “Most severe disease is a consequence of someone’s immune system not dealing with the level of viral load,” says Stephen Evans, a professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine. “If you drive the viral load down in someone they’re less likely to get severe disease.” It may not be enough to stop them from developing a PCR-detectable, or even a symptomatic, case of the disease, but it might stop them from ending up in hospital.

Or at least that’s the theory, according to our understanding of virology. But it’s not actually been easy to show in the case of Covid because severe disease is, mercifully, rare. Even in the main Lancet study into the safety and efficacy of the Ox/AZ vaccine, there were only 11 severe cases, including one death, among the 11,600 participants in the study. Ten of them, including the death, were in the control group, suggesting a greater-than-90% efficacy against severe disease; but the uncertainty interval (determined using an odds-ratio calculator) is huge, from 99% to 22%. Pfizer’s results are similar; Moderna’s are a bit more robust, but still hard to draw firm conclusions from.

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Evans had an idea, though, which I thought would be interesting: what if you aggregate the results from the main vaccine studies? It would obviously have many problems — the various studies have slightly different endpoints; they looked at different populations; and of course they are different vaccines with different effects. And still the sample size is small: across the Pfizer, Moderna, AstraZeneca and Novavax trials, there were only 52 cases of severe disease or death, of which only two were in vaccinated people. (Notably, 29 of them came in the Moderna placebo group, so that vaccine’s results are overrepresented.)

But it would, nonetheless, be somewhat reassuring to find that the vaccines are, on average, more protective against severe disease than milder disease. I did that, and found that they are: 96% effective against severe disease, compared to 87% against mild or moderate. 

(Confidence intervals 99% to 84% for severe, 90% to 83% for mild/moderate; full data here. Prof Evans hopes to write a rather more professional version of this up as a short scientific paper in the future.. He tells me that the comparison between mild and severe disease is a bit more complicated than this, because the data aren’t entirely independent, but I think it’s OK for a crude comparison.)

I don’t want to make too much of this — the fact that those confidence intervals overlap mean we can’t be too sure that the effect is real — but it seems likely that Covid vaccines are better at keeping people out of hospital than they are at stopping them getting the disease at all. So even if the Oxford vaccine isn’t brilliant at stopping you getting the South Africa variant, I’d expect it to be somewhat better at stopping you dying of it.

This doesn’t mean that the South African data (or what we can see of it) isn’t bad news. The 22% efficacy finding is still unnerving; and even if it is better at preventing severe disease, there’s still plenty of room for “better” to mean “still not great”. And it is probably less effective at stopping transmission, so the disease can carry on spreading, and mutating, and eventually becoming even better at evading vaccine-primed immune systems. In separate bad news, the South Africa strain was found to be less susceptible to antibodies produced in response to the Pfizer vaccine, which doesn’t mean it won’t work – there’s more to the immune system than antibodies – but isn’t a great sign.

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But on the other side of the ledger, we now have several approved vaccines that can easily be repurposed for newer variants – Sarah Gilbert, of the Oxford study, was saying on Andrew Marr’s show that they are already preparing a new version, just as they started preparing this one back in January last year. This time it won’t take so long to get approval – there are protocols in place for the flu vaccine, which changes its target slightly each year to keep up with new variants, and doesn’t need full-on Phase I, II, III trials each time. The mRNA vaccines are even easier to make new versions of, and new vaccines are going to keep on coming for the next couple of years. And we have all the factories up and running already. The vaccination process might have to go on a bit longer, but this isn’t a disaster.

Of course, by then there’ll be new new variants. The South African one will be a distant, nostalgic memory, which we look back on with inappropriate fondness. But the same facts will apply.

Some countries were praised for the way they were able to flatten the curve. Others seemed to compete only to avoid being last. There were long debates about the most appropriate metrics to evaluate relative performance and elaborate explanations of why some excelled while others failed. For a while, Sweden seemed to be a winner. Months later it was declared a loser. Germany went from exceptional to average, but New Zealand kept surpassing itself, announcing by the end of the year that it was now reaching the benchmark for coronavirus elimination. One newspaper wrote about Italy, in lines evoking a story worthy of the Olympics, how “Spooked by the dramatic death toll in the Lombardy region, the government of Prime Minister Giuseppe Conte sprang into action, using the license he won through emergency decrees to get the country’s famously sclerotic administration moving. That helped Italy flatten the curve more quickly than anyone thought possible.”

Morbid league tables multiplied. They were criticised, of course, but most often because the picture they offered was too static to reflect the realities of the ongoing competition. With the arrival of the vaccines, state competition took a new form, but not a milder one: an ugly global race for enough doses in which the losers are denied a quick path out of the pandemic.

Suddenly, the laggards from the previous iteration of the game seemed for the first time to be ahead. The United Kingdom was the first jurisdiction to approve the new vaccine and quickly pulled ahead of other large advanced economies in the race to vaccinate its population, a rare pandemic success for the country. The United States followed, with the European Union falling behind, but none could match the success of Israel. In just two weeks in December the state succeeded in vaccinating close to 20% of its citizens, leading the world by a very large measure and drawing on its origins as a tightly-knit small nation fighting for survival. The country is now very close to the 70% mark that experts deem enough to put an end to infection growth.

The vaccine wars quickly escalated. When the European Union received a string of bad news about interrupted or reduced supplies from both Pfizer and AstraZeneca, it responded by threatening to block vaccine exports across the channel (a plan to reestablish a hard border in Northern Ireland was later dropped). This was the perfect background for the intense competition between the two jurisdictions that Brexit had set up in advance. On 29 January, a febrile day in European politics, Brussels put forward a legal mechanism requiring that vaccine exports be subject to an authorisation by member states.

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Without the production of a valid authorisation, the export of such goods will be banned. The instrument states that it was “not the intention of the Union to restrict exports any more than absolutely necessary”, a stirring admission that it can in fact be used to stop the flow of vaccine doses to the United Kingdom. More damaging, the measure was intended to win a political or even an intellectual dispute, but it promised little in terms of actually delivering more vaccine doses.

It was surprising to see such a carnivore approach from a political bloc that detests carnivore behaviour and, more important, has never excelled at it. It could have been avoided had a forceful approach been adopted much earlier. There is a lot that went wrong with the European Commission’s vaccination strategy. But before everything else, there was complacency.

Back in the summer, the predominant feeling in Brussels and many European capitals was that the virus could be controlled through savvy policy measures. The contrast with the health calamity in the United States made European officials forget that the pandemic was in fact a state of emergency requiring a decisive approach to vaccination. Instead, most believed that vaccines would eventually be needed to root out the problem, but the process could be conducted against the background of a waning pandemic, at least in Europe. There was no urgency in signing the necessary contracts with the most promising manufacturers, with protracted haggling over prices further delaying the process.

We now know that time was of critical importance and that the sooner procedures could be tested and perfected, the sooner a high yield of vaccine doses could be expected. The lack of urgency was also reflected in the attempt to bring a number of exogenous considerations into the process. For many months the European Union seemed more interested in scoring political points on solidarity, market power and negotiating clout than in focusing laser-like on the task at hand: getting as many vaccines as fast as possible into the arms of its citizens. It was easy to see all these problems coming. They were like bad omens and they kept piling up.

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The vaccine wars are an instance of the broader genus of technology wars. The reason one could easily guess the European Union would struggle to find its footing is that the bloc has an old-standing problem with technology, seeing it more as a threat than an imperative. And it misses the fundamental nature of the imperative.

First, advanced technology is by definition scarce and competitive. It cannot be normalised: there is always a better way to obtain the same outcome through superior methods. The pandemic was a great teacher in this respect, showing that technology can always move faster and achieve more, or that we are chasing a moving frontier — but the lesson is applicable to normal times as well. During a pandemic, it makes a vital difference whether vaccines are available now or in two month’s time, both in terms of saving lives and resuscitating the economy. This was never understood in Brussels, with the Commission insisting it had secured billions of doses but forgetting to consider when these doses would be available. Even in normal times, being able to lead in key technological areas will sooner or later be translated into more visible forms of global power.

Second, the European Union as a whole — its officials, politicians and organic intellectuals — seems unable to understand that technology is political. You cannot keep it out of politics and this means that politics must adjust to technology at least as much and probably more than technology must adjust to politics. There is no way to be a technological leader without taking risky decisions, without embracing the possibility of failure and without being generous with money and rules — two higher divinities the European Commission will never sacrifice.

It is revealing that, while Britain placed a venture capitalist at the head of its vaccine programme, the European Union opted for a trade negotiator. It was a puzzling choice. What does vaccine procurement have to do with the creation of legal rules? Or consider the news report about how Matt Hancock was impressed by the end of the movie Contagion, in which vaccines are not enough for everyone and have to be awarded by a lottery. One advisor told Sky: “He was always really aware from the very start, first that the vaccine was really important, second that when a vaccine was developed we would see an almighty global scramble for this thing.” You may smile, but whether it comes from movies or scientific papers, a “technological imagination” is the necessary beginning of good policy today.

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The main question posed by the pandemic will be the one concerning technology. The responses adopted by governments around the world seem to fall into two main categories. Those countries able to leverage new and emerging technologies to fight the virus have done better in limiting the number of cases and fatalities, while managing to keep most of their economies and societies operational. The countries unable to use technology had to rely on lockdowns, quarantines, generalised closures and other physical restrictions — the same methods used to fight the Spanish Flu more than a century ago and, in many cases, with the same slow, painful results.

I now fear that the European Union will find itself in the impossible situation of having to prolong some of the existing restrictions beyond the summer, while both Britain and the United States start to normalise. That is the cost of the vaccine delays: a very high cost in lives, prestige and further economic losses.

The current crisis has the potential to spiral out of control. The imperative was to reduce the risks of that happening, no matter what the immediate financial cost. But again, to think technologically rather than legally is something that Brussels struggles with. Economies of scale, exponentials, tail risks — all foreign concepts. If we come out of this crisis with a single widely shared belief, if some previously ignored idea could become a new consensus, it will likely be a recognition that the history of technology is far from concluded.

There is no way to stop technological progress, even if, by hypothesis, one were happy with the current plateau. How these troubling facts force a revolution in our political ideas will be an interesting story to follow. Nowhere will it take sharper tones than in the European Union, where politics and technology continue to be at loggerheads.

That is slightly how I feel about reports coming out of the EU saying that 1) the Oxford/AstraZeneca doesn’t work and 2) complaining that they haven’t been given enough of it.

We’re all desperate for the vaccine to arrive, and to release us all from this year-long limbo. The desperation is making us jumpy: people are panicking, convincing themselves that this vaccine doesn’t work, there are side-effects, the rollout is taking too long. It’s not true; the vaccines work, they’re safe, and here in Britain, at least, the rollout is going remarkably smoothly. But the tension is real.

It’s not just in the UK. In the last couple of days, a vaccine trade war has been threatening to break out: AstraZeneca not supplying the EU with all of the vaccine it promised, and the EU threatening to sit on its own supplies of the Pfizer vaccine in response. People in the biotech industry have muttered to me about the possibility of this conflict shutting down supplies of raw materials. Vials, reagents, nucleotide bases and so on are all made in different places, and if countries stop cooperating, it suddenly gets much worse for everyone.

And where all this started was a bitter little row about whether or not the Oxford vaccine works in older people. On Monday, it was reported in the German newspaper Handelsblatt that the Oxford vaccine was only 8% effective in people over 65. 

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This is simply false. The 8% figure is biologically implausible and entirely without sourcing, and Oxford University, AstraZeneca and the German health ministry have all said that it is wrong. It’s really important to stress this, because there are already people who should know better out there saying silly things about the vaccine being more risky than the disease. The vaccines work; they work in all age groups; if you get offered one you ought to take it.

There is, it is true, very little clinical data on the Ox/AZ vaccine in older people. That is because they were recruited later to the trial and in smaller numbers. But there is good clinical data in younger age groups. And you can analogise from those younger groups to the older ones by “immunobridging”. 

To do this, the Oxford/AstraZeneca trial looked at other measures: whether the numbers of neutralising antibodies, T-cells, B-cells and so on go up after the dose. You do that in older people as well as younger people. With some diseases and vaccines – notably flu – the immune response is much weaker in older people than in younger people; but with Covid, or at least with the Ox/AZ vaccine, the immune response remains surprisingly consistent.

The trouble is that you don’t know whether these proxy measures really correlate with protection. Often they do, but without clinical data you don’t know.

So you “bridge” from a group in which you have both the clinical data and the immunogenicity data — in this case younger people — to a group in which you only have the immunogenicity data – in this case older people. You assume (with good reason, because it has worked so often in the past) that that will give you a reasonable picture. And that isn’t an 8% efficacy.

My understanding is that the figure is one of, essentially, two things: someone taking a figure from a very wide uncertainty interval; or someone simply reading a number wrongly. The later is what’s being floated by the German health ministry. They apparently suggest that 8% of the total number of participants in the trial were between 56 and 69, and that someone has misinterpreted that as the efficacy level in over-65s.

That seems an implausibly basic mistake to me. It does fit with the numbers in the December Lancet paper: 56-to-69-year-olds made up 974 out of a total of 11,636, or 8.37%, of the total. But as far as I can tell the thinking is literally just “they said 8%, here is an 8% in the paper, are they the same?” It’s not even the right age group. 

Besides, a Handelsblatt journalist denies that’s what’s going on, and the newspaper has doubled down on its claim, quoting a “high-ranking official” saying “It is impossible to mix up the numbers. According to the data we have so far, the effectiveness in people over 60 is less than ten percent.”

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My preferred hypothesis is that someone has looked at some clinical data in the over-65s, with a very small number of cases and therefore a very wide confidence interval, seen 8% at the bottom end of that confidence interval, and leaked that. It must be unpublished figures, because the Lancet papers had no “over-65s” group, and besides, they only had five cases in over-55s, which is not really enough to give any sort of estimate. But even so, it doesn’t make sense since the “immunobridging” data lets us be confident that it is reasonably effective in older groups. 

So the 8% figure appears to be bunk. But it’s interesting bunk, because it fits into a wider tension between AstraZeneca and the EU, with the UK either caught in the crossfire or engaged in the conflict itself, depending on who you ask. 

The German newspaper Bild reports that the European Medicines Agency will not approve the use of the AstraZeneca vaccine for the over-65s, out of fears that it will be less effective. And at the same time, there are manufacturing problems at a Belgian factory making the vaccine on license. The EU may get 60% fewer vaccine doses than it asked for; around 31 million instead of around 80 million by March.

(“This vaccine is terrible!” “Yeah, and such small portions.”)

In an interview for La Repubblica, Pascal Soriot, the CEO of AstraZeneca, explains some of this. The production of viral-vector vaccines like the Ox/AZ one is a biological process, like fermentation, not a straightforward chemical engineering. Slightly different processes will end up with different outcomes. The Belgian plant, which makes the batches of vaccine to be taken somewhere else and put into vials, found that its batches were coming out with a lower-than-expected yield of the active ingredient, the adenovirus, in the solution. 

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For the record: it would make sense for the EMA not to use the AstraZeneca vaccine in older people, since they have loads of the Pfizer vaccine and good data that it works in older people, and not so much of the AstraZeneca one and no clinical data. The cost-benefit equation is different in the UK, because we have loads of the AZ vaccine and (for the reasons discussed above) good reason to think it will work in older groups. 

But the shortage has led to a row about whether AstraZeneca ought to deliver some of the doses it produces in its UK factory to the EU. At the moment, all the UK-produced doses will remain in the UK; in response the European Commission is tightening controls on exports of the vaccines it does have, such as Pfizer. The Commission says it won’t sue, because that takes time, but they’re not happy. 

Rob Blackie, a strategist who works with biotech firms, thinks that AstraZeneca will have been behind the decision to keep UK-produced doses here: “I don’t think it’s a government decision,” he says. “The implication of lots of things people have said is that the drug companies are in control. My assumption was that it would be strange to do anything so nationalistic, because the problem of pissed-off governments is so big.” But a biotech industry source speculated that there was probably significant pressure from the UK government, because it has bet so heavily on AstraZeneca.

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Soriot, in his La Repubblica interview, says that AstraZeneca’s contract with the UK was signed three months before its contract with the EU, and that their contract with the EU simply demands that they make their “best effort” to provide as many doses as possible. But, clearly, emotions are running high – hence the strange German claims about 8% efficacy (Soriot sounds baffled by it) and the simmering threat of a trade war.

It’s not just about the EU stopping exports of Pfizer. If this develops into a full-blown vaccine trade war, then entire supply chains could end up getting disrupted. My biotech source agreed that this is not an implausible outcome. AstraZeneca has a stockpile of the raw materials for its vaccine, but some of those materials keep better than others, so it may become difficult if supply dries up. Even small delays in the vaccine rollout could cost thousands of lives, so this matters.

Avoiding a vaccine trade war, then, seems a really good idea. AstraZeneca says it can produce 300 million doses a year in its Wrexham plant – that’s 25 million a month. Elsewhere it says it should be producing two million a week already. If these numbers are anything like accurate, then it seems unlikely that the main bottleneck in vaccine distribution will be the manufacture. 

According to Soriot, the contract with the British government called for the doses from the Wrexham plant to go to the UK first: “As soon as we have reached a sufficient number of vaccinations in the UK, we will be able to use that site to help Europe as well.” But that implies that the UK government could offer to give some to Europe first; as my biotech industry source says, “In vaccine manufacturing, possession is nine-tenths of the law. If the vaccine vials are sitting in the UK, we can choose to how use them.”

I can understand the UK being wary — vaccines are made in batches, millions of doses at a time, not on a production line; so if one batch goes wrong, you lose a hefty chunk of your supply. But enlightened self-interest seems to suggest that we keep the EU sweet rather than start a war, so if we do have spare vaccine, handing some of it over with a smile on our face seems a wise idea. The food actually isn’t terrible, but it would be good if we can give them larger portions.

Still: even though Gates was wrong on the specific case, he is bang on when he suggests that there is a market failure. The pharma industry has done many wonderful things. To pick one example that is very salient to me, metastatic melanoma was essentially a death sentence 20 years ago; now I have two relatives who are alive and healthy, several years after diagnosis, because immunotherapy has made it manageable, if not curable.

But there are real problems with the pharma industry. While it is amazing at developing drugs for chronic conditions for rich people in rich countries, it is less effective at producing medicines — notably, but not limited to, vaccines and antibiotics — which are not profitable in the short term but which are socially beneficial in the long term. It’s also not well set up to produce cheap drugs for poorer countries, even if those drugs are relatively easy to make and distribute. People are dying of treatable diseases because it’s not profitable to cure them.

This is the backdrop to an article by Owen Jones in the Guardian last week, in which he pointed out that Pfizer will stand to make a profit of £9.8 billion from their Covid-19 vaccine. That is, he says, unethical. He quotes activists saying that Pfizer’s patent on its vaccine – and, I assume although he does not say, other firms’ patents on their vaccines – should be suspended, so that cheap, generic versions can be produced and rolled out to the developing world. As it is, biotech patents stand for 20 years; until then, firms essentially have monopolistic power, and can set prices how they like.

I have a lot of sympathy for Jones’s sentiment. He has identified a real problem. But his proposed solution is a bad one, and I worry that it would lead to disaster. You want pharma companies to distribute their products in as equitable a way as possible, but you also want them to continue to make those products. And taking away their profits when they make a good one will not encourage them to do the same next time. So what is the best course of action?

First, it’s worth noting that £9.8 billion is not in fact very much money. Obviously it’s quite a lot of money, on the human scale. But in terms of the global economy it’s peanuts. A paper by the economist Larry Summers estimates that even if we control the virus by the end of 2021, it will still cost the US economy alone about $16 trillion (£12 trillion), if you account for the deaths and misery as well as its simple economic costs. The IMF is more optimistic, putting it at a mere $9 trillion worldwide, although that doesn’t take into account the non-financial costs.

Take the latter, lower figure. If Pfizer making a profit reduces the impact of the virus by one-tenth of one percent, then it will pay for itself, even before we start thinking about the lives lost. I think it is a safe bet that the vaccine will have a much greater effect than that; Pfizer will only see a tiny fraction of the total benefits the vaccine will bring the world.

(It’s also worth noting that AstraZeneca have said that they won’t make a profit from their vaccine “during the pandemic”, although they reserve the right to say when “the pandemic” is over.)

But the main point is that there is a real, and to some extent unresolvable, tension in what it is that we want pharma companies to do. On the one hand, we want them to produce new drugs that save our lives. On the other, we want them to manufacture those drugs cheaply and get them to as many people as possible.

Imagine that a drug firm produces a vaccine for some deadly disease that is affecting people in both the developed and the developing world. Roughly speaking, a new vaccine costs about a billion dollars to get to market, after putting it through animal trials, Phase I safety trials and Phase II and Phase III efficacy trials, applying for licensing, and so on. Let’s imagine it costs about a dollar a dose to make. So if you only made enough of the vaccine to dose one person, the cost of that dose would be $1,000,000,001.

But if you make two doses, the average cost per dose is $500,000,001. If you make four, it’s $250,000,001. If you make a billion, it’s $2. The more doses you make and sell, the closer your average cost per dose gets to your marginal cost of making a single dose.

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The socially optimal outcome is that we charge everyone the marginal cost, $1, so it can reach the maximum number of people. But if we do that, the pharma company will never cover its fixed costs: it will be $1 billion in the red, and probably won’t want to make any more vaccines. 

On the other hand, if you let pharma companies charge the market value — that is, the amount that people are willing to pay — then it will cover their losses, because people in rich countries want to be vaccinated against this disease. But poorer countries will not be able to afford it. People who would be willing to pay the marginal cost are priced out of a vaccine. 

The cost that will encourage industry investment R&D, and the cost that maximises the number of people covered by the vaccine, are different. It’s a simple tradeoff. “It’s obvious that, if your financial model is to sell to rich consumers at above cost price, you’re going to do R&D on products that you can do that for,” says Owen Barder, a development economist who has worked on pharma incentives. “The patent model suffers a really big problem.”

One obvious solution would be to take the whole business out of pharma companies’ hands, and let governments and philanthropic organisations run the whole thing. But the profit motive is very good at one particular thing: making pharma companies drop a product that isn’t working. “I think the key skill of a pharma company is knowing when to exit,” says Barder. “And, to a gross generalisation, governments are rubbish at exit.” 

Most candidate drugs don’t work, or don’t work very well. So most of the time you have to abandon research, after spending a lot of money on them. But it is very hard for a government to say “This thing that we’ve spent £100 million on doesn’t work, and we’re going to throw all that money away.” It’s easier to throw another £100 million in and avoid the question. Drug companies, we all agree, are extremely good at making money. And part of being good at making money is not throwing good money after bad. Publicly funded research is great for blue-skies, open-ended questions that help us understand things, but it is less effective than private firms at developing specific products, because of this exit problem.

Instead, says Barder, what you need to do is separate the fixed cost from the marginal cost. You need to find some way of encouraging pharma companies to sell their products at a low cost to poor countries, while also incentivising them to keep putting money into R&D.

There are several ways of doing this. One example is a financial prize: we (governments, philanthropic agencies, etc) will give whoever comes up with the first vaccine some large amount of money: perhaps $1 billion, on the condition that they then agree to make it in large quantities and sell it at close to marginal cost to the developing world.

That’s a useful model, but it has a disadvantage. In the last two weeks, trial results for two Covid vaccines have been announced: the Pfizer one and, this week, the Moderna one. Initial signs suggest that Moderna’s one is a bit better than Pfizer’s: it appears slightly more effective, and it can be stored at normal freezer temperatures for months, while Pfizer’s needs to be kept at -80°C.

If we had put in place a prize system, so that the first group to develop a working vaccine got a billion dollars, then (assuming Pfizer’s vaccine gets licensed first) Pfizer would get the whole lot, even though it appears Moderna’s product is slightly superior. Depending on what costs remained, it might well make financial sense for Moderna to abandon the project, because they would not get the reimbursement that would make it viable. But, obviously, if a superior product comes out a week later, you still want to be able to buy it. (And you may want lots of different vaccines anyway, because each will have different advantages and disadvantages.)

But there is a better way. The pneumococcus bacterium causes meningitis, pneumonia and septicaemia; this Lancet paper estimates that it killed about 800,000 children in the year 2000 alone. The pharmaceutical industry — Pfizer, as it happens — developed a vaccine, Prevnar. But it was only suitable for the strains of the disease found in Western countries, not in the developing world. Creating a version that worked for the strain found in poorer countries was perfectly possible, but the financial incentives just weren’t there.

To solve the problem, in 2004, the economist Michael Kremer — he of deworming fame — and the British economist Rachel Glennerster proposed something called an “advanced market commitment”, or AMC. Five national governments and the Gates Foundation put aside $1.5 billion dollars. They promised the pharma industry that, if they developed a new vaccine for the developing world, then for every dose that the companies provided at the marginal cost of $3.50 a dose, they would reimburse them a further $7.

Unlike a prize, an AMC rewards both speed of development and quality of product. If your vaccine is first to market, you can sell it and make money without any competition; but if you know your vaccine is better than the one that’s first to market, you can carry on developing it without worrying that it will be rejected because all the money has gone to the earlier, but inferior, product.

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Better yet, it keeps all the risk on pharma companies. If they know a vaccine isn’t likely to work, then they will abandon it, because it won’t make them money — it won’t meet the requirements. If governments or philanthropic agencies were funding the research directly, they’d have the problem of exiting after spending lots of money on it. The funding bodies never have to pay for a product that doesn’t work (although they do have to pay a premium for the ones that do).

With pneumococcus, it was a roaring success. By 2016 the vaccine was being distributed in 60 countries, and more than 150 million children had been vaccinated; Gavi, the body that oversaw the AMC, estimates that it will have saved 700,000 lives by the end of the year.

To be clear, the AMC model won’t work for everything. In the case of Covid, for instance, the problem wasn’t that companies weren’t investing in R&D — they knew that there was a market. But building a vaccine factory takes months and millions of dollars, and pharma companies, understandably, don’t want to invest millions of dollars in a product that very possibly won’t work; they’d rather build it at small scale until they’ve done the testing, then scale it up afterwards. 

Most of the time that works fine. But in the Covid case, the costs to society of making a few factories that ended up not being used were negligible compared to the cost of waiting even a few more weeks for a vaccine. So it became worthwhile for the UK government (for instance) to start paying for manufacture of the Oxford-AstraZeneca vaccine even before it had released its results, and why Bill Gates (again: one of history’s greatest heroes) invested billions of dollars building seven factories for different vaccine types, knowing that some, or even most, would not work.

And AMCs wouldn’t work for antibiotics. Antibiotics are a special case: we need lots of new antibiotics so that we can combat antibiotic-resistant microbes, such as MRSA. But we don’t really want people to use them, because then microbes will become resistant to the new ones, as well. Most of the time, if a pharma company brings a new drug to market, it will win a significant chunk of that market — if you make a new cancer drug or antidepressant that works better on some group than the existing ones, then it will be prescribed for that group. But with antibiotics, most of the time, doctors will continue to prescribe doxycycline or methicillin, and will save your new drug for when they encounter drug-resistant bacteria.

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So there is very little incentive for pharma companies to invest in antibiotics, because — essentially — your new antibiotic will rarely be prescribed, so it will rarely be sold, so you’ll make very little money. According to Jeremy Knox, policy lead in antibiotic resistance at the Wellcome Trust, there’s an additional problem that, for hard-to-explain reasons, antibiotics command low prices anyway. “So you have this toxic combination of very unpredictable small volume markets and very low prices,” he says: “and both of those things combined means that if you’re a producer you’ll probably forecast making a loss.” An AMC that paid them for each dose sold wouldn’t help, because not many doses will be sold even at low cost.

There are models in place that get around this. Jim O’Neill, who was the antibiotics tsar under David Cameron’s government, suggested a lump sum given to each pharma company that brings a novel antibiotic to market. Wellcome and the British Government are also looking at what Knox describes as “the Netflix model”, where bodies like the NHS agree to pay a fixed sum a year to the manufacturers, and are then given as much as they need. So if you only need to use five doses all year, you pay X million; but if you need 5,000 doses, or 5 million, you still pay X million.

It means that pharma companies aren’t incentivised to sell as many doses as they can, and the decision to prescribe can stay in the hands of doctors. (It is worth noting that the UK Government, and the health secretary Matt Hancock in particular, have been quick to take up this model; I rarely have nice things to say about Matt Hancock, so I will flag this now.)

There is also a funding scheme, CARB-X, which supports the R&D of new antibiotics. It’s not enough — Knox thinks we need about 10 new antibiotics every decade, and that at the moment we might be lucky to see two or three. But it’s an improvement.

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Coming back to Owen Jones’s article, it’s worth noting what I think is a factual error. It’s a minor one, but I think it’s instructive. He says that vaccine companies “abandoned” research into a vaccine for Sars in 2003 because it was not “immediately profitable”. But as I understand it, the reason that the pharma industry stopped work on a Sars vaccine was because Sars (somewhat mysteriously) disappeared. If people weren’t getting infected, then you couldn’t tell if your vaccine stopped infections. In fact, Mike Osterholm, the US epidemiologist, says that the pharma industry invested hundreds of millions of dollars in Sars vaccine research, and then when it went away, the US government and philanthropic agencies left them “holding the bag”, and wary about future investments.

I think it’s instructive because most of the scientists working at pharma companies want to save and improve lives, just as scientists do at universities or other bodies. But just like the scientists at those other bodies, they have to navigate the incentive structure that surrounds them. For university scientists, it’s publish-or-perish – your work is useless if it doesn’t get you journal articles and citations, regardless of how true it is. For industry scientists, it’s profit. 

The trick in both cases is to help the incentives align with what we want out of the research they do. In the case of the pharma industry, we want them to keep producing new drugs and vaccines, but also to provide them at a low cost to the people who need them. If we remove the pharma companies’ patents, and stop them making profits, then we might be able to provide this drug at a low cost, but we’ll be less likely to see the next one. Instead, we need to come up with clever ways of incentivising them to do what we want, so that we continue to spend more on curing malaria than we do on curing baldness.

I don’t want to downplay these developments. They’re important, and if one or both of those is authorised, then we could start seeing people being vaccinated relatively soon. But I did want to talk about some of the difficulties and complexities involved. It is perfectly possible that one vaccine is already in production, and that another will soon be approved for emergency use, and that still, you, ordinary British person[1. I’d say “you and I”, but since I’m on the Oxford trial, I’ll get the real vaccine if/when it’s declared efficacious, if I haven’t had it already.] will not see either for over a year; and that most of the world will not see one for another year after that.

First, let’s talk about the different kinds of vaccine. All vaccines work on one basic principle, which is presenting the immune system with something (an “antigen”) that looks like the thing you’re vaccinating against, usually a virus. But there are different ways to make that antigen.

There are, depending on how you want to break it down, essentially four different kinds. The traditional method – which goes back to Louis Pasteur – involves getting hold of the actual virus you’re vaccinating against, killing or weakening it somehow, and using that as an antigen. These are known as “killed virus vaccine” and “live attenuated virus vaccines”, but I’ll refer to them both as traditional vaccines.

The second involves using a part of the virus, a “subunit”, as the antigen. In the case of coronaviruses, the part involved is the spike protein, the lumpy bits outside the body of the virus. In modern subunit vaccines, you can use a genetically modified virus to infect yeast cells and get them to produce the protein, so it is faster.

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The third and fourth, viral vector vaccines and RNA vaccines, also both use the protein spike as the antigen, but instead of producing it in a factory, they recruit the body to do that for them. Viral vector vaccines use a genetically modified virus to infect the body’s cells and make them produce the spike protein, just as the actual virus co-opts the body’s cells to force them to make copies of itself.

RNA vaccines do much the same, except instead of using a genetically modified virus, they simply use tiny lengths of RNA, which – once snuck inside a cell membrane, in a tiny blob of fat called a lipid nanoparticle – commandeers the cell’s machinery and starts it making the spike protein.

All of these have different strengths and weaknesses. Traditional vaccines are reliable; they’re a mature technology and tend to give good immune responses. But they are slow to make – they need to be grown in insect cells or hens’ eggs, so a batch can take a couple of weeks. The exact process for each one is subtly different, so you can’t easily repurpose a factory. And it takes a lot of infrastructure – a lot of steel in the ground – to make a factory.

Subunit vaccines are pretty well field-tested now; they’ve been around for a few decades. They’re somewhat faster than the traditional ones to make, and the factory hardware is more interchangeable because you can get your yeast to produce any protein you like, but they still need large vats.

Viral vector vaccines, like traditional ones, require the growth of actual virus particles in some biological substrate, such as hens’ eggs or mammalian cells. But unlike traditional vaccines, you don’t need to make a different virus each time – you can just grow the same virus (in the case of the Oxford-AstraZeneca vaccine, a member of a family of viruses called adenoviruses) for each vaccine, and paste in the genetic code for the particular protein you want it to build. They are, however, very much untried – as far as I know, only one has been used in humans before, for protection against Ebola.

RNA vaccines are much faster to produce – it’s “a chemical rather than a biological process”, according to Al Edwards, a professor in biomedical technology at the University of Reading. They also require far smaller doses, so you can get many more out of, say, a 200-litre bioreactor, and, like viral vector vaccines, you can paste in the RNA sequence for whatever protein you need: you can use the same equipment for a vaccine for any given virus. It can also be very small scale, with relatively low-tech equipment; Imperial College is planning to make a small demonstration plant in rural Uganda. But RNA vaccines have literally never been used before, and, inconveniently, while all the other kinds of vaccine can happily be kept at normal fridge temperature (2°C to 8°C), the lipid nanoparticles that are used to get RNA vaccines into the machinery of the cell are very unstable, and need to be kept at -80°C.

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There are about 200 vaccines currently in development for the SARS-Cov2 virus. All of the above kinds of vaccines are represented. However, the two we mentioned at the top, the Pfizer and Oxford/AstraZeneca vaccines, are the two most advanced – both are in Phase III trials (that is, large trials to show that they are not merely safe in humans, but actually work). They are an RNA vaccine and a viral vector vaccine, respectively. Moderna, Johnson & Johnson, and Novavax also have vaccines in Phase III trials, but are not, I think, quite so far along.

As a bit of an aside, something strange has happened with the Oxford/AstraZeneca vaccine. Two patients got ill. The first was with MS, and the vaccine study declared on its consent form that it was unrelated, so the trial continued after a brief pause. The second was transverse myelitis, an inflammation of the sheath around the spinal column; again, the trial paused, and, while it restarted in the UK, Brazil and South Africa, in the US, it did not.

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That is extremely unusual, according to Stephen Evans, a professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine. Usually, drug trials are monitored by independent groups called Data and Safety Monitoring Boards (DSMBs). If a patient gets ill, these boards look at the situation – often, as in the AstraZeneca case, pausing the trial to do so – and decide whether the illness was caused by the vaccine, and, if so, whether the risk outweighs the benefit. If it does, they might recommend to the regulator that they end the trial.

But normally you only have one DSMB for the whole trial. In this case, there are apparently two – one for the UK, Brazil and South African parts of the trial, and one for the US. And while the UK one decided it was safe to carry on with the trial after a brief pause, the US one has not. The US Food and Drug Administration (FDA) is now investigating it and not allowing it to restart. “It’s a very strange thing to have two different DSMBs for the same vaccine,” says Evans. “I’ve not known it to happen before.”

Andrey Zarur, the CEO of the RNA biotech company GreenLight – who have their own RNA vaccine in animal trials, and for whom, full disclosure, I’ve been doing some writing over the past few weeks – thinks that the UK regulators have been very lenient. “AstraZeneca have had very favourable treatment in the UK,” he says. “They say the myelitis is unrelated, but the FDA says BS.” It’s a fairly rare condition, and he thinks it’s likely that it’s connected; he thinks “you may get partial approval” in the UK, but it won’t be approved in the US, at least not soon. Evans is more hopeful, and thinks that the FDA is being “super-cautious”. He notes that a previous vaccine candidate developed by the Oxford team for the MERS virus also saw a serious adverse event. That one was also declared unrelated, but Evans speculates that the coincidence might be enough to make the FDA more wary.

Either way, AstraZeneca are confident enough that they’ll get approval – in the UK, at least – to start production; the UK government has ordered 30 million, with an option for 70 million more. And if Pfizer does get enough data to apply for emergency use approval, they’ll start manufacturing too, at least at small scale.

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So let’s talk about manufacturing. All the vaccines currently under development look like they’ll need two doses each. It’s one thing making 10,000 or 20,000 doses for a clinical trial – in order to get the world to herd immunity, even assuming that the vaccines all bestow complete immunity after the booster shot, we are going to need to vaccinate more than four billion people, twice each. Eight billion doses is an awful lot. A normal bioreactor for traditional vaccines might be 200 litres and able to make a million or so doses in a period of weeks; you’ll need a lot of them.

You can’t simply use a bigger vat, says Edwards. It’s like making a cake: if you can make a cake 20cm across and 10cm deep in your oven, that doesn’t mean you can make a cake 20 metres across and 10 metres deep in a much bigger oven. “It would be burnt on the outside and soggy in the middle.” Making live viral vaccines is a biological process, with lots of steps that depend on precise temperatures and chemistries. “The bigger your batch, the more you have to change your system of production,” he says, “so if you’re making it in a big batch, you have to check you’re still making the same thing. One disaster is that if you make it a different way, it can have a different effectiveness or even not work.” You can make lots of smaller reactors, but obviously that is expensive and difficult.

That’s true for traditional virus vaccines, but it’s also true for the modern viral vector ones, which similarly have to brew up a virus. “Making an adenovirus particle has never been scaled,” says Zarur. The only medical treatments which use similar technologies, gene therapies, have only been used on “single-digit thousands” of patients, he says. AstraZeneca says that it can create two billion doses by the end of next year, but Zarur is sceptical: “there just aren’t enough reactors in the world” as it stands.

RNA vaccines can be made more easily, and because they need much smaller doses, you can get more doses out of the same-size reactor. But Zarur points out other problems. Moderna and Pfizer, both developing RNA vaccines, have each said they can produce around a billion doses by the end of next year. But, Zarur says, that’s an estimate based on how much of their raw materials they can get hold of. “When Moderna says they’re going to make a billion doses by the end of 2021,” he says, “it’s about calling on suppliers and saying how much nucleotide can you make.” And the suppliers of nucleotides might say, we can build enough to make a billion doses. “But those are the same suppliers that Pfizer is calling! Those materials, the nucleotides and the enzymes, are in very short supply.” RNA vaccines, he says, have enormous upsides, but there just isn’t a supply chain in place for them yet.

It is, Zarur says, “a twist of fate” that “the vaccines that are in the lead are also the ones with the least developed supply chain”. The Coalition for Epidemic Preparedness Initiatives (CEPI), the global body established to prepare vaccines for new viruses, estimates that even putting all the pharma companies together, globally there is only capacity to make between two and four billion doses by the end of 2021; even in the most optimistic scenario, we will only have about half of what we need.

(It’s worth noting here that the Oxford-AstraZeneca vaccine trial will be declared a success if there are half as many infections among people given the real vaccine as among those given the control — so if there were 100 in the control arm and 50 in the vaccine, that would be enough. This means it may be that “successful” vaccines only prevent 50% of infections. If that were the case, we’d need to vaccinate a lot more than half the world.) 

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By Stuart Ritchie

Manufacturing the vaccine isn’t the end of the problem. “After you’ve made billions of doses,” says Edwards, “you have the opposite problem: we’ve got factories making tonnes of these vaccines, now you’ve got to get them into little tubes, stick them in a fridge, get them all around the world and put them in needles and stick them in someone’s arm.”

It is a huge logistical challenge. Recently, I spoke to Toby Peters, a professor of cold-chain economy at the University of Birmingham, and Nilay Shah, the head of the chemical engineering department at Imperial College London, about the difficulties of mass rollout of vaccines. At the moment, we vaccinate only a subset of the population at a time: small children, vulnerable people, pregnant women. Now, though, we need to vaccinate everyone, fast. To get a sense of how much the system needs to be scaled up, at the moment, about 50 million vaccine doses – for measles, polio, things like that – are distributed every month in India. There are nine different vaccines, so that’s about 6 million people. But, he reckons, we’d need to get that up to about 200 million people a month. The vaccines need to get from the factory to the clinic to the patient without spending more than a day or so at room temperature.

This “cold chain” delivery is a significant enough challenge if you’re working in a city, but to get to people living in rural parts of India, or sub-Saharan Africa, you will need infrastructure. You’ll need trained people to deliver it, especially if you’re putting several doses in a single vial, which will save money but will mean the healthcare workers need to know how to safely take the right dose out while keeping the remainder sterile and secure. And the vaccine needs to reach a majority of the population. So, Shah points out, you need to get it to them – it needs to be walking distance at most for everyone. We can’t expect billions of people to travel long distances; in underdeveloped areas, that might mean mobile vaccination stations in trucks.

Peters points out that millions of tonnes of food are transported chilled around the world, and that that cold chain is extremely effective and has huge capacity, so it’s not impossible; but it will require a major effort, not least to find out how many fridges and things are available in the developing world, and second to design a cold-chain system, separate from the existing vaccine cold chain. Even in the UK, this is going to be a non-trivial problem. “One thing that bothers me slightly,” says Edwards, “is that a mass vaccination programme is as difficult as a mass testing program, and that” – this last with admirable understatement – “hasn’t always run as smoothly as we hoped.”

Again, RNA vaccines can be made at a smaller scale, so more locally. But then if you want to keep them for more than 24 hours or so, you need to keep them at -80°C. “You can do that in London or New York,” says Zarur, “but how are you going to get it to Laos or Sao Paolo? And unless you vaccinate those populations, you’re wasting your time.” He is hopeful that the second generation of RNA vaccines, including GreenLight’s, will be made in small, almost popup factories anywhere you can get some cheap chemical ingredients and an electrical supply, and then in the 24 hours you have before it degrades, you can get it to where it needs to be. “You couldn’t get it from Cambridge, Massachusetts to France,” he says. “But you could get it from Mexico City to Chiapas.” But that won’t be true of the first-generation ones, which will require more complex and expensive ingredients.

None of this is to say that it’s not important that vaccines are starting to roll off the shelf. It is. Even if only a few million doses are built at first – even if, as Zarur says, “it’s enough for the football players, the Trumps, and the healthcare workers” – that’s a big deal. As he points out, in the first wave, “healthcare workers were dying in the hallways”, and the shortage of medical professionals caused by illness was part of the reason it killed so many others – people weren’t getting treated properly. And as we vaccinate the most at-risk populations, the susceptible population will be reduced, so the virus will find it harder to infect people, and the death toll will come down, and slowly the situation will improve for all of us.

But it absolutely will not be: we get a vaccine in December and we’re out of this by February. The light is real, but the tunnel it’s at the end of is still pretty long.