Since then, “Pfizergate” has ballooned into one of the biggest scandals in EU history. Following von der Leyen and the Commission’s refusal to hand over the text messages — not only to journalists, but even to the EU Ombudsman and the EU Court of Auditors — the European Public Prosecutor’s Office (EPPO), an independent EU body responsible for investigating and prosecuting financial crimes, announced in late 2022 that it had opened an investigation into the pandemic procurement process (though not into Pfizergate specifically). It confirmed that it had received “an exceptionally high number of reports and complaints” asking that “it investigate the purchase of Covid-19 vaccines in the European Union”.

Then, in April 2023, Frédéric Baldan, a Belgian lobbyist specialising in EU-China trade relations, filed a lawsuit against von der Leyen before a Liège court, accusing her of usurping official powers, destroying public documents, pursuing illicit interests and committing corruption, and damaging his country’s public finances. Shortly after, Baldan’s lobbyist accreditation was withdrawn by the European Parliament. The story, however, doesn’t end there.

Despite von der Leyen’s clumsy attempts to sweep the case under the carpet, or arguably because of them, Pfizergate continues to rumble on. Since Baldan filed his criminal complaint, several individuals, organisations and even two countries — Hungary and Poland (under the previous PiS-led government) — have joined the lawsuit. With Brussels steeling itself for the EU elections in June, all the signs pointed to a big legal bust-up and an even bigger PR disaster.

But then, earlier this month, von der Leyen’s hearing in front of the Belgian court — to decide whether the EPPO or the Belgian investigators should prosecute the case — was mysteriously postponed to December. This is not a trivial matter. Even though a year and a half has passed since the EPPO first opened its investigation, no one has yet been charged. Indeed, it’s unclear whether the EPPO has actually been looking into the case at all. A few days before the recent hearing in Liège was supposed to take place, Baldan’s lawyer, Diane Protat, visited the EPPO’s offices in Brussels and Luxembourg to request a copy of its case file — standard procedure from a legal standpoint. However, not only was she told that there was no such file, but on both occasions security was called on her.

Such behaviour is typical of the EPPO. For several months after beginning its probe into the EU’s vaccine procurement, it showed little interest in Pfizergate; as far as we know, it didn’t even demand that von der Leyen hand over the infamous text messages. However, shortly after Baldan filed his complaint in Belgium, the EPPO quickly moved to obtain a copy of the document from the Belgian prosecutor’s office — and almost immediately claimed exclusive jurisdiction over the case.

It argues that, if there was any misconduct relating to EU-wide vaccine-procurement deals, this represents a damage to the EU budget, and that under EU law it is up to the EPPO to investigate, prosecute and bring to judgment the perpetrators of criminal offences that affect the EU budget. The complainants see the situation differently: they note that the vaccines were purchased with money that came from member states’ national budgets, not the EU budget — as even von der Leyen herself admitted in a recent presidential debate. That is why they argue that the case should be tried in national courts, such as the Belgian one, rather than by the EPPO.

As for the immunity from legal proceedings that von der Leyen enjoys as president of the Commission, the complainants suggest this applies only with respect to acts carried out within the scope of her defined function as Commission president. Suffice it to say that whether carrying out billion-euro deals behind closed doors, and then leaving member states and taxpayers to foot the bill, falls within the purview of her role is questionable. That said, the plaintiffs face an uphill struggle: if the case moves forward, the request from prosecutors to waiver von der Leyen’s immunity would be handled by the College of Commissioners — which is usually chaired by von der Leyen herself. However, they have an ally in the Belgian investigating judge, Frédéric Frenay, who has successfully investigated several corruption cases in the past: according to Euractiv, he doesn’t agree with the EPPO taking over the case and is insisting that it remain in Belgian hands.

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But why is the EPPO, after showing hardly no interest in it for several months, now so adamant about taking over the case? Given the organisation’s behaviour since Pfizergate broke, one could be forgiven for wondering if they were ever interested in truly investigating von der Leyen — or whether they were covering up for her. As the German MEP Martin Sonneborn told the Berliner Zeitung: “Why does the EPPO, which reports to Justice commissioner Didier Reynders, who reports to Commission president von der Leyen, need a year and a half to search von der Leyen’s office in the Commission building and confiscate her work cell phone to view the Pfizer SMSs?”

Questions have already been raised about the body’s judicial independence: last year, for example, it attracted criticism after Giorgia Meloni’s government helped install a new prosecutor despite an independent panel of judiciary experts ranking him last among Italy’s three candidates. Previously, other countries had faced criticism for the same reason. As Sonneborn put it, with the EPPO, “another organisation seems to have been created that does not have the interests of the citizens in mind, but rather the shielding of EU officials from their democratic accountability”.

Seen in this light, the EPPO’s efforts to assume jurisdiction over the Belgian complaint could be read as an attempt to stifle an independent investigation into Pfizergate — or at least delay it until after the EU elections and the nomination process for the new president of the Commission. Certainly, if that was the aim, they’ve succeeded. We can rest assured that Baldan’s recent demand for von der Leyen to be sacked and barred from running for office as long as she is the subject of criminal proceedings will likely fall on deaf ears.

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Von der Leyen, however, is far from off-the-hook. After all, the Belgian court may still decide to allocate jurisdiction to the state’s investigative authorities. And who knows, the EPPO might actually decide to start doing some serious investigating itself. Besides, this isn’t the only legal cloud hanging over von der Leyen’s head: another case was filed by the New York Times against the European Commission at the European Court of Justice after they failed to provide them with the text messages, but the court has yet to rule on the matter.

Paradoxically, far from pointing to a well-functioning rule of law, all of these investigations only serve to highlight the complete lack of accountability of EU politicians, and of the EU system more generally: despite all the courts and bodies that have looked into this so far, not one has managed to get von der Leyen to hand over some text messages. But perhaps we shouldn’t be surprised. Ultimately, Pfizergate isn’t an isolated incident, but a reflection of the EU’s true nature: a haven where unelected politicians and corporate leaders can cosy up to each other away from prying eyes, unhindered by obsolete concepts such as transparency and the rule of law. The only difference is that, this time, they might finally be caught out.

Last week, Politico reported that the US Food and Drug Administration might wait until this summer to consider authorising a vaccine for children under five years old. Only a few days earlier, a judge had struck down the nationwide mask mandate on airplanes, prompting angry reactions from some who claimed that the ruling would result in dead children. Some parents have loudly proclaimed that they will continue to shield their kids from social interactions until a vaccine is available. And in New York City, children aged between two and four are still required to mask in schools because they are too young to be vaccinated.

As Covid restrictions and mandates have been dropped across the America and the Western world, unvaccinated kids have become a rallying cause for Americans unable or unwilling to leave the pandemic behind. But the truth is that children under five don’t need to wear masks and don’t need to have their lives put on hold pending vaccination. Hysteria about the risk to them is not just unhelpful but harmful. It deprives them of a normal childhood without any countervailing justification.

A decision on vaccines for young children is probably a few months away, given that U.S. public health authorities want to consider the Pfizer and Moderna vaccine data together. While some parents are understandably angry and frustrated with delay, the FDA is right to be cautious here. Young children are at low risk from the virus and the benefits of vaccinating them are uncertain. Even if the vaccines are approved, it is not clear that they will make a big enough difference to justify placing restrictions on children in the interim.

First, consider that the FDA has not tasked the vaccine makers with proving that their vaccine lowers rates of hospitalisation in kids. Nor do they have to show that the vaccines reduce MIS-C (an inflammatory condition that may arise after infection) or even rates of Covid infection. Rather, the FDA has asked Pfizer and Moderna to prove that their vaccines, at the dose given to kids, generate levels of antibodies that are comparable (or “non-inferior”) to levels of antibodies generated among older, fully vaccinated people. This is a low benchmark, and means that, in practice, the trials being run to clear it are very small. Indeed, they may be too small to detect reliable signals for the most important benefit — reduction in severe Covid — and for harms.

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Yet so far, Pfizer has failed to clear even this very low bar. Two doses of three micrograms of the Pfizer vaccine (1/10th the adult dose) fell short in December of 2020, to the disappointment of many. The FDA allowed the company to take another shot at it, literally, by adding a third dose. In late January of this year, there was buzz that the FDA would take the unprecedented step of authorising the vaccine despite the failed trial because it looked like it might reduce infections, but just a week later, Pfizer announced they would wait for the results of the 3rd dose before seeking approval. The flip-flop generated national news and outrage from some parents and doctors.

Then, on March 23, 2022, Moderna announced that its children’s vaccine — two doses of 25 micrograms, or 1/4 the adult dose — did generate sufficient antibody levels, again raising hopes that FDA approval would be forthcoming. But only limited results have been released so far. We don’t know the full spectrum of adverse effects, nor the impact on the outcomes we really care about: cases, severe disease, hospitalisations, MISC-C, and deaths. These outcomes are especially important for conducting a cost-benefit analysis for Moderna, which has clearly been linked to higher rates of myocarditis in young men than has the Pfizer vaccine.

As the clinical trials have dragged on, moreover, the landscape of kids and Covid has changed. Children have always been at relatively low risk, but newer variants appear to be even less risky for them. A recent preprint from the UK suggests that children infected with Omicron were less likely to be hospitalised with severe disease than children infected with the alpha or delta variants. We have also learned that MIS-C is less common often with the newer variants. Delta was less likely to trigger the condition than alpha, and CDC data suggests that omicron was less likely to trigger it than delta.

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More generally, it makes no sense to be overly cautious about low-risk children at a time when the United States is dropping most restrictions for adults. The risk to an unvaccinated healthy child under five is often lower than the risk to their vaccinated or even boosted parent. Natural immunity is also powerful and prevalent. It protects strongly against reinfection and even hospitalisation after reinfection. Not that the data here is from adults — naturally immune children are so rarely hospitalised that it is difficult to conduct studies on them.

Most kids have already had Covid, even if they and their parents don’t know it. Prior to the omicron wave, up to half of American children had been infected, and the virologist Trevor Bedford estimates that omicron might have since infected 40% of Americans. Although there is surely some overlap between the two numbers, most kids have probably already had Covid at least once, and it would be difficult for a vaccine to offer them any significant further protection. Finally, we have learned that vaccination has rapidly waning protection against symptomatic infection. Some studies report that vaccine effectiveness in those aged 5-11 for symptomatic Covid is less than 20%.

If you put all this together, the story becomes clear. The vaccine trials have been inconclusive. Most children have had Covid already, and the ability for a vaccine to further improve their health is limited. Finally, they are at extremely low risk to begin with. Parents may encourage their offspring to get vaccinated if and when vaccines become available, but they should not be consumed with fear pending FDA approval. Nor should they prevent their children from living a normal life.

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.

Its latest such gambit is a claim that the Office for National Statistics’ data shows “a significant rise in the death rate for adolescent males over the last eight months”. HART have put together an “open letter to Sajid Javid, Chris Whitty, Patrick Vallance and the relevant public health bodies”, saying that “the concern is that this time period coincides with the rollout of vaccinations to this age group”.

There’s a saying in journalism that you should play the ball, not the man. And I will play the ball, but I want to play the man a bit first. HART has form for suggesting that vaccines kill people: on p35 of its ‘Covid-19 Response’, still prominently linked on their website, they suggest that the second peak in deaths “coincided with the mass roll-out of novel mRNA/DNA vaccines” and that “whilst we cannot infer causation from correlation, the mRNA/DNA vaccines had not been tested on this cohort” and it would be “negligent” not to ask whether “the rise in deaths during this period is linked in some way to the vaccine roll-out”. (The second peak in deaths was, in fact, caused by the second peak in Covid cases which preceded it by a fortnight or so.)

HART is populated by odd people who believe strange things: one of its publicly listed members worried, in a since-leaked private chat, that the vaccines were literally making people magnetic. Other leaked messages show a member suggesting that the group “seed the thought that vaccines cause Covid”, and that the vaccine rollout is “a crime against humanity” and part of a plan for “massive scale depopulation”. It’s worth noting that while these people may seem to be cranks, they also seem to have some influence with senior Tory backbenchers.

But let’s look at the ideas, as well as the people. After all, stopped clocks are right twice a day, and there have been plenty of stopped clocks in the pandemic. So: what’s the evidence that vaccines have been killing young people?

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Here’s HART’s case. They say that according to ONS data, there were 402 deaths among 15 to 19-year-old boys between May and December last year, and that that’s about 65 more than the average for that period over the years 2015 to 2019. I’ve looked into it, and these numbers are about right. In fact, they are a slight understatement of reality: you can see the figures for 2021 here, and the five-year average here. This is, the ONS acknowledges, a “statistically significant” increase.

HART thinks, or at least heavily hints, that the extra deaths are caused by myocarditis, an inflammation of the heart muscle which has been seen in rare cases following vaccination with the Pfizer jab: “​​a connection cannot be excluded,” they say, and it would be “a grave dereliction of duty” not to investigate. They took the ONS to the High Court to get them to release more data, including the age, gender, and vaccination information of everyone who died between the age of 12 and 19 since 1 May last year[1. The ONS is looking into it, but they can’t release the data easily: so few people die at that age that if they gave much more information about them then individuals would be identifiable. The High Court agreed that they shouldn’t release it.].

HART are not the only people to worry about this. In the US, there are regular outbreaks of concern around the mRNA vaccines and myocarditis. But is there anything in it?

For the record, HART is right that the number of recorded deaths in that age category is unusually high. I spoke to the ONS, and they agree — a spokesperson told me that there has been an increase of recorded deaths, compared to the five-year average.

That said, it’s not clear that the rise is real. The ONS only becomes aware of deaths when they are officially registered, which — if the death is referred to a coroner — could be weeks or months after the death itself. Young people’s deaths are much more likely to be referred to the coroner, and in 2020, coroners’ offices were under enormous strain from the pandemic. The spokesman also speculated that there might be a simple backlog from the previous year. There may be all sorts of other reasons, and until the coroners’ reports are in we won’t know.

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Another problem for the myocarditis hypothesis is that, although HART says that the “time period coincides with the rollout of vaccinations to this age group”, it doesn’t really. The first mass vaccinations for under-18s didn’t start until August, and even then only began relatively slowly: only about 40,000 people a day were being given first doses in that period, down from a high of 600,000 in March. HART also says that the real risk is second doses, and under-18s wouldn’t have received those until September. Admittedly, 18 and 19-year-olds would have had their jabs somewhat earlier, but not that much earlier: even 30-year-olds were unable to have theirs until the end of May.

And looking at the data that HART themselves cite, there doesn’t seem to be an obvious spike after younger people get the vaccine: while the number of deaths does seem to go up after about May, there’s no spike in August when large numbers of young people started getting vaccinated.

The ONS spokesperson said that there have been adverse vaccine reactions mentioned on death certificates — but only 13 of them, and the ages ranged from 35 to 94. Perhaps there’s been a rash of unreported myocarditis cases, or other vaccine reactions, among young men, but it would be a bit surprising given the attention on the issue.

But let’s grant HART’s premise. Let’s imagine that some percentage of these excess deaths are not statistical artefacts, and are caused by myocarditis. What would that mean?

The main conclusion wouldn’t change: vaccines save lives. Look at this Our World in Data page on the risk of death for vaccinated vs unvaccinated people, in various countries. An unvaccinated American is around 100 times as likely to die as a triple-vaccinated one; an unvaccinated Swiss is about 165 times as likely to die. Similar if less extreme numbers can be seen in Chile and England, although OWID doesn’t yet have data on the effects of boosters in England.

Of course, that’s across all ages. But when you look at 12 to 17-year-olds in the US (the only country where there’s a reasonable amount of data), about one in every 100,000 unvaccinated died each week. That would be about 250 a week, if everyone were unvaccinated. It’s well over ten times the risk to vaccinated children of that age.

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The US CDC assesses the risk like this: if 100,000 children are vaccinated, they’d expect around five to seven cases of myocarditis, likely mild. But if they weren’t vaccinated, they’d expect about 5,500 of them to be infected with Covid in the following three months, and about 50 of them to be hospitalised. Out of the 25 million or so 12 to 17-year-olds in the US, that would be around 12,000 hospitalisations in three months. Perhaps ironically, a fair number of them would develop myocarditis: the UK government says about 18% of hospitalised Covid patients suffer myocardial injury.

The point is: even if some non-trivial number of young people have died of myocarditis because of the vaccine, the odds are that more would have died without it — and likely very many more would have suffered a really nasty illness and ended up with some quite long-term effects from it. And, of course, they’d have been more likely to pass it on to other, more vulnerable, people, including their own families.

It is easy to say “even one death is too many”. Of course, each death is a tragedy; but two deaths is twice as big a tragedy, all else being equal. I hope that the ONS is able to find some hint of what caused the apparent increase in deaths among adolescent males; I sincerely doubt that it’s the Pfizer vaccine. But even if it is, the likelihood is that it saved many more lives than it cost. 

Luckily, I think the battle over vaccines has largely been won — more than 90% of UK adults are now vaccinated. But groups like HART have influence over serious people on the fringes of real power, despite being deeply strange people who think those who advocate vaccines for children “need shooting”.

The trouble is, HART’s data is superficially convincing, and takes work to rebut. There are still many thousands of children, and others, who have yet to have their vaccine: if some of them die unnecessarily because of this nonsense, that really would be a tragedy.

Only 40% of the South African population has been jabbed against Covid — a slow take-up which is euphemistically described as “vaccine hesitancy”. It is anything but: it is enraged rejection.

There are a number of reasons why it is so hard to get South Africans to take the umjovu, the injection: appalling technical management of the outbreak, a prevailing scepticism towards science, wariness about the Government and a wide-spread apprehension by the poor and marginalised that this is at best another form of repression and at worst witchcraft. It is a dangerous brew in a country already in a state of great political, social and economic instability.

In common with the rest of the world, South African epidemiological estimates of fatalities at the outset of the coronavirus outbreak verged on the fantastical. Initial predictions were for between 87,000 and 350,000 fatalities in the first phase. There were 103. Two years later, with the virus in retreat, fatalities attributed to Covid (but by no means vouchsafed) are only now beginning to touch the lowest initial estimates.

Yet the South African Government imposed one of the longest and most severe lockdowns, supported by a baying national and social media. The decision has proved inappropriate in nature, premature in timing and catastrophic in impact. In a country where many depend on ad hoc daily or weekly subsistence wages, the sudden cessation of economic activity wreaked havoc amongst the poor and self-employed. A failing state was unable to deliver on its promise of subsidies, responsible policing or effective containment.

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It took more than a year for the first subsidies to individuals or small businesses to start coming through. And even then they were erratic, corruption-prone, inadequate, and according to many attested reports, distributed on a racially biased basis. Nearly a quarter of small businesses have gone to the wall and unemployment has rocketed.

An entire section of the population was effectively criminalised: in the first four months of the outbreak, 230,000 citizens, 0.4% of the population, were charged with infringement of the Disaster Regulations for breaking the restrictions, 311 of them policemen. All the charges were later dropped: the criminal justice system simply could not cope.

For every reported infection to the end June last year, seven citizens were arrested for breach of regulations; for every 100 infections, one police officer was arrested; and for every 1,200 infections there was a High Court urgent application. Seven people had been killed in heavy-handed enforcement.

When two doctors working in a Government hospital were forcibly interned in one of the state’s make-shift rural isolation camps, the High Court ordered they be allowed to self-isolate at home: it accepted the doctors’ deposition that they stood more chance of dying from the conditions of incarceration than from the virus.

Small surprise, then, that the general population, particularly the poor, headed for the hills. Take-up of the crucial HIV-Aids retroviral dropped from 95% to 30%; malaria medication showed the same path. Attendances for tuberculosis screenings dropped by two-thirds, while consultations with GPs were down 60% and tens of thousands of urgent surgery procedures were postponed for the coronavirus patients who never arrived.

Emergency procurement of personal equipment, meanwhile, opened the door to the corruption lurking in every interstice of the State. The  heir-presumptive to President Ramaphosa has resigned: a state investigatory agency accuses him of directing a R350 million (£16.6 million) Personal Protection Equipment account to friends. The Gauteng Health Department, industrial heartland of the nation, is embroiled in a R560 million (£26.5 million) fraud inquiry. The female whistle-blower was assassinated within days of the inquiry’s launch.

The begging question, whether President Ramaphosa, a decent man, is presiding over a ruling party in the throes of a Robert Kennedy versus The Mob has at least been definitively answered.

At the same time, a public service already perilously compromised by patronage, corruption, incompetence, and the dismissal of key white personnel for affirmative action reasons, went into a long recess. Two years later it has still not properly returned.

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Enforcement of traffic licencing rules have also been in abeyance for 18 months as 500,000 drivers’ licences await clearance. Estates cannot be closed, forensic inquiries completed, crimes prosecuted (including culprits in the so-called State Capture project of former President Jacob Zuma) and property transferred. More than half a million school children have quite simply not returned to school.

As for the burden of this failure of service delivery, it has been carried disproportionately by the poor, mainly black but increasingly also by white citizens, judged by the street corner beggars. There is little doubt that the effect of the containment strategies advocated by South Africa’s warrior scientists facilitated the July Troubles this year, which claimed 357 lives in a scourge of looting, arson and violence and has directly accounted for the drastic decline in ruling party support in last month’s municipal elections.

South Africans have endured, if never condoned, the absurdities and atrocities of this misjudged, exploited and needless panic to date. The ebb and flow of the global debate about the course of the pandemic has been intensely watched here by the literate and online portion of the community.

They have followed, like many others in the world, the way the arrogant scientific certainties that locked up the world are dissolving in the face of measured science and empirical fact. They understand one cannot follow a “science” when the scientists are hopelessly at odds. They are aware of the abuse of both language and statistics, particularly the new phenomena of snatch-stats whereby mortality from other causes is snatched for Covid-19, or the natural path of an expiring virus is used to justify the efficacy of an antidote or Excess Deaths are annexed to justify a lost cause.

They note the irony whereby their government, correctly, tells the world not to be alarmed by the Omicron variant, while it simultaneously contemplates a grievous assault against the rights of its citizens to contain it, egged on by the usual howling suspects who demanded total lockdowns. Citizens have minutely followed recent reports of how Pfizer arm-twisted their desperate government into signing legal indemnities for its product: who ever heard of citizens being forced to be vaccinated when the supplier is absolved of any responsibility for the consequences?

Most South Africans are not conspiracy theorists but their history teaches them one certain thing: uncontained power always gets one screwed. And many feel screwed now by a confluence of forces (not a conspiracy) that — from Big Pharma, to Big Tech to authoritarian governments — seeks rent from this incomparable tragedy.

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By Brian Pottinger

But another, far more important constituency of hesitaters and rejectionists exists. Those who take the time to talk to the black poor and marginalised are astonished by the extent to which, scarred by their lockdown experiences, they regard the current scare as yet another means to oppress them. Curfews, liquor and tobacco bans and the outlawing of political meetings under the guise of fighting Covid-19 support their case. And, for many, the umjovo is nothing less than ubuthakathi or witchcraft.

President Ramaphosa enters dangerous territory here. Take-up of vaccines is higher among the minorities for a variety of reasons and it is a section of the white minority who are the most vociferous supporters of vaccinate-at-all-costs. Banning access to public spaces will instantly translate, as it always does, into a political and racial rumpus. Pieces of paper that permit or restrict certain people’s movements have a terrible record in this country’s history: a bitter resonance for every black person.

Proven and restless forces in South Africa are today looking for chances to reignite the insurrection of July. These are people who do not protest by way of orderly marches, posters and pram-pushing. They seek only opportunity; the consequences brought by the human attempts to contain the pandemic is a revolution.

But revolutions always eventually consume their children. Time will certainly consume the reputations of the architects of this epochal tragedy: the scientists, pharmaceutical companies, politicians and media. And if Ramaphosa isn’t careful, it could also consume the fragile nation of South Africa.

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.

Judging by the stream of recent headlines, petitions and open letters, parents of 12 to 15-year-olds could soon be heading for a showdown over the “right to be vaccinated against Covid”. The UK’s Chief Medical Officers this week announced a plan to offer them jabs — despite the Government’s Joint Committee on Vaccination and Immunisation’s advice that the direct benefits for healthy children were too marginal.

And while parents will be required to give their consent for their child to be vaccinated, a child will be able to override their parents’ refusal providing he or she is deemed to have “enough intelligence, competence and understanding to fully appreciate what’s involved in their treatment” (otherwise known as being Gillick competent).

Covid-19 has always been a crisis in search of a culture war, and the response to this announcement has been no exception. When such luminaries as Gillian McKeith and Laurence Fox, and groups with titles such as Family Defence League and Lawyers for Liberty, start advising parental resistance, you know it’s about more than the scientific specifics of just one jab. Suddenly it is about personal freedom, the rejection of state interference in family life and the principle that a parent should decide what is right for their child. It is about where you stand politically and how you want to be perceived.

I’ll be honest: I do not want to be standing alongside Laurence Fox. I know which “side” of this debate I am meant to be on — which one suits both my political persuasions and my parenting style. And it is that, more than any in-depth medical knowledge, which tempts me to declare myself fine with my own children overriding my consent (were it not for the fact that this in itself constitutes a form of giving consent — the eternal paradox of liberal parenting).

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I find the idea of a child ending up in mediation with their own parents over the right to be vaccinated not just unlikely, but bizarre (the idea of slammed doors, mealtime sulks, plaintive cries of “but EVERYONE else has had one!”). Yet for others, the anxiety is real, with schools being inundated with letters from parents fearful that vaccinations will take place behind their backs.

Perhaps I’m unusual, but ever since I was allowed — just allowed! — to take my firstborn home from the hospital, I’ve been sceptical about the idea that parents know best.

Parental decisions are informed not just by love, but politics. We know this, though we tend to tell ourselves it is those other parents — those of the opposing political tribe — who are getting it wrong. This inconsistency is particularly glaring in current debates on the treatment of young people with gender dysphoria. There are parents who support social transition, the prescription of puberty blockers and/or the use of binders, and parents who don’t — with both sides insisting they are motivated by an understanding of their child inaccessible to anyone else. In accounts of raising trans children, or opposing a child’s desire to transition, “I know what’s best for my child” merges with “any loving parent in my position would make the same choice” (or, at the sharp end, “any parent who would not make the same choice obviously wants their child dead”).

It is uncomfortable to admit that your love, and what is in the “best interests of the child”, is tainted by your own background, self-image, friendship groups and even personal traumas. Yet I know mine is, even when I think I’m right. Indeed, it is by watching the Covid vaccination debate play out that I’ve felt, more than ever, how much more attractive it is to cling to our slogans rather than admit how little we know.

I have my own self-defeating list of things that I, as a parent, should and should not be allowed to do. Not allowed: smacking children; restricting access to contraception and abortion (providing safeguarding checks are made); vetoing access to good sex education (I decide what “good” is). Allowed: vetoing access to dodgy sex education (I decide what “dodgy” is); intervening where a treatment constitutes self-harm (I decide what “self-harm” is).

I know this is provisional and shaky, riven with qualifications, making the bodies of my children (and yours) a testing ground for my politics. I do think there are areas — such as the administration of physical punishment, or the use of breast binders — where it is possible to make a more objective case for harm being done, but the template of “parents’ rights” is unhelpful. With the proposed Covid vaccinations, the situation is different still; the play-off is not between potential losses and gains for one’s own child, but potential gains for other people, perhaps even yourself.

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Here we have an example where the primary beneficiaries of a treatment may not be — indeed, most probably are not — those receiving it. As a result, the simplistic concept of individuals, or their parents, knowing what’s best for them falls apart. Writing in The Independent, Victoria Richards argues in favour of “competent” children making the final decision on vaccination using the principle of “knowing best”:

“Some children under the age of 15 will be deemed “Gilick competent”, some won’t… Parents or carers know their children best — so chances are, you know which camp your child would likely fall into. If you’re a parent who’s vaccine-hesitant, I can understand why you might feel upset – even angry — about such a scenario. But what I really feel is that we should trust our kids; many of whom are mature, intelligent and information-savvy well before the age of 12.”

I think my children are mature, intelligent and information-savvy; the trouble is, I don’t think the debate over having a Covid jab is a test of these qualities. This is a complex situation, hijacked by narratives about state control, science and freedom. It is also one in which moral pressure is being exerted on children, one that might come from schools, but which could also come from parents who want their children to be vaccinated. Coercing children — however subtly — to do something with their bodies which isn’t primarily for their benefit is questionable. But so, too, is making that body the site for spurious, abstract arguments about liberty and parental infallibility. Neither side is coming off well.

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Richards goes on to invoke the principle of “my body, my choice”: “We can’t very well teach our children that they have the right to say “no” to unwanted physical contact one minute, and then demand they kiss an aged aunt the next… And if we are teaching our kids that their bodies (rightly) belong to them, then that should go for whatever it is they decide about the vaccine, too.”

But this is a reversal of our usual message regarding consent, because the focus is on the right to say “yes”, not “no”. There’s something telling in the way that liberal leanings push us towards making the dominant message “you have the right to override your parents if they say no”, rather than “you have the right to override them if they say yes”. It smacks — just a little — of an uncomfortable political division on consent, whereby some of us only want to focus on the giving rather than the withholding. For all the accusations of illiberal moral panic one might throw at those raising alarm about the vaccine, “my body, my choice” is a slogan that would seem to me to apply better to the children saying no for themselves. Suddenly, unexpectedly, I find myself veering, ever so slightly, Laurence Fox-wards.

I am not going to fight with my children over the vaccine; they want to have one and I will not stop them. But there are bigger questions to ask, not just about what influence parents should have, but what we are using our children for. Children have been asked to make significant, necessary sacrifices for adults; it is not necessary to use them to fight our own culture wars.

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.

Israel has emerged from a year of strict restrictions and, after a huge wave of Covid-19 cases at the beginning of the year, exacerbated by the spread of the more infectious B.1.1.7 UK variant, things are now almost back to normal — in large part due to the most successful vaccination programme in the world.

One man who can justly claim credit for Israel’s vaccine success is Prime Minister Benjamin Netanyahu, who secured enough doses from Pfizer to vaccinate Israel’s entire population. Netanyahu reportedly called Pfizer CEO Albert Bourla 30 times until they agreed to make Israel the “world’s lab”, the global poster child for how mass vaccination can beat the coronavirus. So far, all signs are that it’s working.

Yet as polls open around the country, there are two competing narratives hanging over today’s election. One is the story of Netanyahu, “King Bibi”: the ultimate survivor at the height of his power who is approaching his thirteenth continuous year of his second period in office, having beaten the record of Israel’s first Prime Minister, David Ben-Gurion. Despite multiple attempts to oust him, he remains in the PM’s residence on Jerusalem’s Balfour Street.

According to this account, the man nicknamed “the magician” surely has a trick up his sleeve. Netanyahu, after all, has in the last year signed “normalisation deals” with the United Arab Emirates and Bahrain, and begun peace talks with Sudan, ushering in a new era of Israeli-Arab cooperation. His relationship with Donald Trump, meanwhile, brought the US embassy to Jerusalem and Western recognition of Israel’s Golan Heights annexation. And then came his vaccine success, the envy of the world, rounding off Israel’s most peaceful and prosperous decade. Surely, goes this story, he’s going to storm to a romping victory today.

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By Shany Mor

But there’s another, far less optimistic, narrative underscoring this election; one which warns that as Israel holds its fourth general election in just two years, Netanyahu is in deep trouble. For despite his vaccine success, the polls suggest his Likud party will lose several seats, leaving him unable to form a government. Even in the best scenario, he looks set to just about scrape together an unstable coalition with a majority of one seat, making him the hostage of every Knesset member and their whims.

At the same time, this second narrative points out, let’s not forget that Netanyahu remains on trial for bribery and corruption (the trial was suspended for the election, or he’d be facing witness testimony now), and faces an uncertain future and possible prison term if convicted. Moreover, a planned election in the Palestinian Authority in May threatens to elevate Hamas and destabilise the West Bank and Gaza. And in America, with Trump out of office, President Biden is ready to re-enter the Iran deal, an accord that Netanyahu worked hard to sabotage. Now he’s being forced into another election after failing to pass a Budget. “King Bibi”, this narrative suggests, has never been so besieged.

But which of these narratives is true? The truth, I suspect, contains elements of both. Few doubt that Netanyahu’s key political skill lies in his ability to make surprising political moves that alter the playing field. Whenever things look bad, Bibi always finds a way to come out on top.

When, for example, the Likud party won fewer seats than challenger Benny Gantz’s Blue and White party in September 2019, Netanyahu forced the Knesset, Israel’s Parliament, to dissolve itself before Gantz could be asked by the President to form a government. Then, in the election that followed, Netanyahu was able to convince Gantz to join a crisis coalition to fight the coronavirus, with the promise of a rotating premiership that nobody believed would ever come to pass. The move split Blue and White in half.

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In this election, Netanyahu’s shrewd realpolitik has seen him campaigning for Arab votes, even visiting Arab towns and promising direct flights from Israel to Mecca (just as soon as there’s a peace deal with the Saudis, of course). It marks a dramatic change from his anti-Arab campaigning of recent years; his party passed a Nation State Act that downgraded the status of the Arabic language and filmed undercover footage in Israeli Arab polling stations to suggest voter fraud. Could this be just another ploy to see him retain power?

Whatever the truth, the reality is that Netanyahu’s position remains insecure. Israel’s election polls are notoriously inaccurate, but Likud will still be watching them with unease; the result, whatever it is, is going to be close. Several parties are on the cusp of the four-seat threshold, and if one or more of them drops below it, the coalition calculus shifts. Pollster Camil Fuchs believes that there could be 15 seats’s worth of undecided voters (there are just 120 seats in the Knesset), certainly enough to swing the election one way or another.

So how did Netanyahu find himself in such an uncertain position? Partly, he’s still damaged by the pandemic. On the face of it, that sounds faintly ridiculous, given that he has overseen the most successful vaccination programme in the world. But the truth is that, by and large, his initial Covid response — typified by strict restrictions — was deeply unpopular. Unlike in many other countries, no Israeli political party supported tougher national coronavirus restrictions. Even as infections soared and deaths rose, politicians on all sides pushed for a relaxation. And this was mirrored in the wider public: one poll in January suggested that just 24% of Israelis supported the Government’s measures.

Nationwide criticism was further inflamed by Netanyahu’s apparent capitulation to pressure from Ultra-Orthodox parties, which led to large parts of the Jewish religious education system remaining open while other schools were closed. Enforcement of lockdown rules in Ultra-Orthodox towns was almost non-existent, despite the extremely high Covid rates in those communities. At times, it felt like the whole country was being forced to suffer lockdowns except for the Ultra-Orthodox areas.

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Yet most damaging, perhaps, was the revelation last year that Netanyahu flouted the strict nationwide lockdown he imposed, hosting his son at a Passover seder while the rest of the country celebrated alone. The sense of hypocrisy and injustice cut through far more than the political criticisms levied at him.

But more generally, a palpable sense of weariness has taken hold. Twelve years is a long time to be Prime Minister, especially when they’re marked by the Prime Minister being put on trial. In Israel — where, like so many countries, the old labels of Left and Right feel well-worn — politics today isn’t really about anything other than Netanyahu or Not Netanyahu. No doubt that’s partly why Likud has stopped publishing a manifesto altogether. The manifesto is Netanyahu, and shouldn’t that be enough?

Judging by a number of last-minute campaign stutters, that remains to be seen. Opposition canvassers have been beaten by Netanyahu supporters and required hospitalisation, while several last-minute election stunts have also fallen through; Pfizer CEO Albert Bourla cancelled his planned trip to Israel, and the United Arab Emirates objected to an election-eve Netanyahu visit to Abu Dhabi.

Yet for all this, Netanyahu retains one major advantage. As the incumbent, he stays Prime Minister until a new government is seated. If his rivals are unable to form a coalition to replace him, which seems likely, then Israel will head to a fifth election in the autumn, likely delaying his corruption trial further and giving him yet another chance to win.

Can the ultimate survivor pull off his most audacious win of all, building another coalition that can both keep him in office and, perhaps even legislate to stop his trial? Election Days are certainly Netanyahu’s speciality, but I’m not convinced. Either way, whatever the result of today’s election, it will probably be some time until we learn if Netanyahu has managed to triumph yet again.

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.

Probably it is. But maybe it isn’t, and one thing I should have learnt by now is that, in this pandemic, the “maybe” is important. Maybe we can slow the spread of a new form of the variant; maybe that maybe is worth it. Last  March, we thought masks probably wouldn’t help – but we should have thought maybe they would. We need to think not in terms of certainties, but in terms of costs and benefits, gambles and payoffs. It’s an approach that’s all the more important as the vaccine starts to roll out. 

There was a piece in the New York Times about the British regime which illustrated this rather well. “Britain Opts for Mix-and-Match Vaccinations, Confounding Experts”, said the headline (later changed to “Britain Opens Door To…” etc). The British government, said the piece, was going to allow doctors to give patients a dose of one vaccine (for instance the Pfizer/BioNTech vaccine), and then a booster shot of a different one (say the Oxford/AstraZeneca one). This was, according to experts quoted, not a method supported by science: they “seem to have abandoned science completely now and are just trying to guess their way out of a mess”, said one.

British people, especially those with some understanding of how the British vaccination regime actually works, got understandably annoyed. “This is a complete misrepresentation,” said one fairly typical response; “fake news … false information spread by reputable media organisations”, was another.

That’s probably fair. As the NYT story did say, but didn’t make clear in its headline, the “mix and match” approach is a legitimate one of last resort: the guidelines tell vaccine administrators that “For individuals who started the schedule and who attend for vaccination at a site where the same vaccine is not available, or if the first product received is unknown, it is reasonable to offer one dose of the locally available product to complete the schedule.” 

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It is not saying “Go to it lads, throw the vaccines around like you’re mixing drinks at a stag do”; it’s saying “If you can’t get hold of the vaccine you originally gave, it’s probably better to give a different one as a booster than none at all.” The BMJ has written to the NYT asking for a correction; the drug safety researcher Anthony Cox has written an excellent piece on why the story is unhelpful and dangerous.

So, bad NYT, do better, etc. But there’s a more interesting question: will the mix-and-match vaccinations actually work?

There’s a stock answer to this if you take a certain view of science and knowledge: they won’t. Or, at least, we don’t have any evidence to suggest that they will. It’s not “data driven”, says one expert quoted in the NYT piece. “There are no data on this idea whatsoever,” says another.

This is all true, of course. There have been no randomised controlled trials into whether a Pfizer prime and Ox/AZ boost works, or vice versa. And, traditionally, in medical science, if you haven’t got an RCT showing that your drug regimen works, then you haven’t got any evidence that it works.

But I want to argue that this sort of thinking doesn’t work in emergency situations like the one we’re in. More than that: it’s been a repeated problem throughout the pandemic that we have relied on this “we have the evidence/we don’t have the evidence” binary, meaning that we have moved slowly, waiting for rock-solid confirmation; but moving faster, making decisions on imperfect information, would have saved a lot of lives.

So what do we know? First, it’s worth noting that although the Pfizer and Oxford/AZ vaccines — and the Novavax, and the Moderna, and whatever else — all work through different mechanisms, at quite a fundamental level they all do the same thing. They all present the immune system with an antigen – a little thing that looks like a part of the virus, so that your body produces antibodies which will fight the real virus when it arrives. And in all cases, the antigen is the same thing: the spike protein, the little protrusions that come out from the surface of the virus.

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In the case of the mRNA vaccines, such as Moderna’s, and Pfizer’s, the spike protein isn’t in the vaccine itself; the vaccine contains little lengths of RNA which get into your cells and tell them to produce it. The Oxford vaccine does something similar, but uses a genetically modified chimpanzee cold virus to get into your cells. Others, such as Novavax’s, use the spike protein itself. (You can read more about different kinds of vaccine here, should you wish.) But at base, they all work by making sure that your immune system will recognise the spike protein when it sees it for real.

So there are good theoretical reasons to think that a shot from one vaccine will work in combination with another. But there’s another reason as well: analogy from other vaccines. Stephen Evans, a professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, told me that “heterologous prime-boost vaccinations” — that is, mixing and matching the two doses — have quite a long history: they were first proposed in 1992.

“The idea has mainly been studied in diseases for which we do not have an effective vaccine,” he said. “In HIV or malaria, or in dengue, where there is a single vaccine but it’s not very good.” In many cases, heterologous vaccinations like this can be more efficacious than homologous ones, he says (and there are papers to back him up). Most of the time, you don’t really need to get your vaccine efficacy up, because most vaccines are amazingly effective, hence their use in situations where the vaccines don’t work very well.

Of course, all those other heterologous vaccinations are backed up with RCTs. “We clearly do not have randomised trial evidence confirming efficacy of this,” says Evans. 

But those other vaccinations aren’t being carried out against a backdrop of about 500 people dying every day in the UK alone from a disease for which we have a working vaccine. “This is not an ideal, to do it until we’ve done the trials,” says Evans. “But in a situation of crisis where we’re not able to get people vaccinated with the same dose of the vaccine, it seems a reasonable thing to do to go beyond where we have trial evidence.”

Dr Zania Stamataki, a viral immunologist at Birmingham University, told me much the same thing. “We wouldn’t do this if we weren’t in a dire situation,” she said. “If we didn’t need to vaccinate as many people as possible as quickly as possible to save lives, we’d stick to the on-label advice. But at the moment we don’t have the luxury.”

It’s worth emphasising that this will only happen in extremis: if, say, the Pfizer vaccine has run out locally, or someone’s records are lost. “We’re anticipating that we stick to the regimen, and only in situations where we’ve run out supplement it with other things,” says Stamataki. But both Stamataki and Evans say that it’s a reasonable thing to do in those extreme cases. “Because the [the spike protein antigen] is the same,” says Stamataki, “we anticipate seeing the same result.”

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Of course, it may not work. Babak Javid, an immunology lab director at the University of California San Francisco, says that the Moderna vaccine and possibly the Pfizer one introduced a small mutation to the spike protein to “stabilise” it, and that as far as he knows the Oxford vaccine didn’t; so the antigen may not be exactly the same. Will that affect it? Perhaps. It’s vital that we carry on monitoring; in an ideal world we might even do some randomisation, saying that certain GP practices should give the mix-and-match dose to patients where the original vaccine is unavailable, while other practices leave them on single doses.

But the point is that even though we don’t have 20 RCTs and a meta-analysis showing that heterologous vaccinations work for Covid-19, that’s not the same as saying that we don’t have any knowledge or evidence at all. There are reasons, from theory and from analogy from other vaccines, that it should work fine. As Robert Wiblin, the director of research at the evidence-based charity 80,000 Hours, says in this wise Twitter thread, there is a widespread attitude among certain decision-makers that “if a study hasn’t been done on a particular question we have ‘no data’, and therefore no basis on which to form beliefs or act”. But that is flat wrong, and dangerous.

It’s that form of thinking which led people — not just ordinary people, but the UK Chief Medical Advisor and the US Surgeon General, among many others; top, highly credentialled experts — to say early in the pandemic not just that we don’t know if masks work, but that masks don’t work, and to advise against them. They were right that there weren’t any good RCTs. (There still aren’t, really.) But there were theoretical reasons to think that masks might work, and reasons from analogy: we all accept that surgeons wear them to prevent infection during surgery, for instance. And as social interventions go, masks are relatively low-cost, compared with nationwide lockdowns or closed schools. If you multiply the good it might do by the chance that it works, and subtract the costs, the expected value looks pretty good.

You can understand the “no RCTs, no evidence” attitude. Over the last century or so, medicine has established a norm where the only evidence that really counts is lots of RCTs. There is an excellent reason for that: doctors’ intuition as to what worked and what didn’t was often extremely flawed, because doctors are people. So it is very important to show that your new drug or your surgical intervention does more good than harm before you introduce it.

But we simply can’t afford to wait for that level of certainty. Evidence, a wise man once said, is like money: “Obviously it’s useful to have as much evidence as possible, in the same way it’s useful to have as much money as possible. But equally obviously it’s useful to be able to use a limited amount of evidence wisely, in the same way it’s useful to be able to use a limited amount of money wisely.”

That means looking at the evidence you have, and making your best guess at the costs and benefits of one course of action versus another course of action. The costs of, say, closing schools are considerable. Meanwhile, the benefits are very hard to be sure about – how much do they influence transmission? How much are teachers at risk? But we can’t wait for more evidence to come in; we have to make decisions now, as best we can.

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Similarly, there’s been a bit of a hoo-hah about another British plan to delay the booster jab for up to 12 weeks, so that we can get as many people the first dose (and some level of protection) as possible. Again, there are no specific RCTs looking into that – Pfizer only tested its booster three weeks after the prime, although the Oxford study did look at various different regimens including up to 12-week gaps. But again, we don’t have the luxury of demanding certainty and perfect evidence. The question is: do we think that a longer gap will work reasonably well, and if so, do we think the benefits of giving many more people their first dose outweigh the possible costs in efficacy? The MHRA obviously thinks so, and my own suspicion is that it’s pretty clear-cut. “We haven’t got the data” is partially true, but, again, it doesn’t mean we know nothing.

And in the case of mix-and-matched vaccines, once again, it’s true that we don’t have an RCT that says they’ll work. But we have good reasons to think they’ll work; perhaps not as well as the on-label regimen, but well enough to save lives and prevent severe disease and hospitalisations. 

And we know that the likely costs are low — there’s no evidence of any safety issues with heterologous vaccinations, and if the alternative is simply not giving the patient a booster at all because you’ve run out of the original vaccine, then this seems a reasonable course. “I don’t know of any instance where the heterologous prime boost has led to particular harms or to lesser efficacy,” says Evans, “although it hasn’t always led to higher efficacy.” This seems an obvious bet, in the rare cases when the original vaccine is unavailable.

With a bit of luck, we’re near the end of this. I’m sceptical that the Government will meet its target of getting the first dose to the four most vulnerable groups by mid-February, but March should be doable (and Nilay Shah, a professor of chemical engineering at Imperial, told the Science Media Centre that it the February target is “ambitious” and “needs everything to click every day”, but that it is “achievable”). 

So we’re no longer talking about delaying Covid deaths; we are talking about actually preventing them, if we can keep people from getting the virus for a few more weeks. And that means making decisions quickly, making decisions that are good enough rather than perfect, making decisions with limited information rather than waiting for the perfect RCT that shows that giving the vaccine in a red room works just as well as giving it in a blue one.

The NYT’s concern about the vaccine dosing is understandable: it is simply applying the same standard that medical science applies all the time, under usual circumstances. But we aren’t under usual circumstances. In this case, it is inadvertently propping up a decision-making system which has meant that we didn’t introduce masks until too late and which meant that we didn’t lock down or close borders until the virus was already spreading.

I got it wrong by saying that border closures “probably” wouldn’t stop the new variant; I should have talked about how likely I thought it was, and what the costs and benefits would be if it did. The MHRA, by allowing mix-and-match vaccines and a 12-week gap, is thinking in those terms, and doing the right thing. You can’t “follow the data” when there is none: you have to use the information that you have.

This week, of course, it was the Oxford/AstraZeneca vaccine, one week after Moderna announced their results and two weeks after Pfizer’s. 

The headline efficacy results of the Oxford trial are lower than for the other two vaccines. But it’s still great news, and it may be the case that the headline result is not the thing we ought to be looking at. And, most important, the Oxford vaccine, compared to the other two, can be made in far larger quantities far more quickly, can be stored and distributed much more easily, and will be available at a fraction of the cost.

The team is submitting its data to a journal probably around the time you read this, and it will be in the public domain in a week or so. At the moment we have no real data to look at — and, in fact, even the scientists who worked on it have not had access to all of it. So I thought it might be useful to try to collate what we can know, so far.

First, that headline result. The Oxford vaccine is, apparently, 70% effective (the announced result is 70.4%), compared to the 90% or higher for Moderna and Pfizer’s offerings. Except it’s simply not.

There were two groups in the vaccine study: one of about 9,000 people who were given a standard dose and then a booster shot of the same volume a month later; and a second group of about 3,000 people who were given a half-sized dose, and then a standard-sized booster. We should note at this point that the plan to divide the trial like this was in the original trial protocol, so we can be pretty confident that they haven’t just chopped the data up after the fact to make things look good. (EDIT: Although it is all quite complicated; see here.) 

The vaccine appears to have been 62% effective in the first lot, and 90% effective in the second. But if you’re given the vaccine, it will be either a full-dose/full-dose regimen or a half-dose/full-dose one, not some average of the two. So it’ll either be about 62% effective or about 90% effective, assuming those numbers are accurate.

Of course, “assuming those numbers are accurate” is the key phrase. We know there were 131 cases in total in the trial, and we know that there were 100 cases in the control group, and 31 among people who had the real vaccine. But only about 30 or so were in the half-dose group, and the smaller sample size means greater uncertainty.

Incidentally, it’s not completely clear why the smaller dose first is more effective. Andrew Pollard, the chief investigator, speculated in a Science Media Centre briefing on Monday morning that the smaller dose may have “primed” the immune response in some way. I’ve seen other scientists wondering whether it’s because the larger dose pushes the body to develop an immunity to the genetically modified virus that’s used to deliver the antigen. The immune system is complicated; I imagine we’ll find out more about what’s going on in the coming weeks.

There’s another point, which is that the headline figure also doesn’t tell us the impact on asymptomatic cases. The Pfizer and Moderna trials only looked at symptomatic cases: the  Oxford trial, on the other hand, asks all its subjects to swab themselves in the throat and nose every week (I’m on it, so I can vouch for this particular unpleasant duty), so it should catch anyone who’s got the virus, symptoms or no. The results don’t affect the headline figures — those only refer to symptomatic cases — but they are used to establish the effect of the vaccine on transmission. 

It is theoretically possible (but not very likely) that a vaccine could stomp heavily on the symptoms of a disease, so almost no one gets sick, but not stop people from actually getting the virus. By regularly swabbing asymptomatic people the study can see whether that’s the case. All we know so far is that there is an impact on transmission, but until all the data has been released, we won’t know how big that effect is; again, even Prof Ewer of Oxford hadn’t seen those numbers, and nor had Pollard, when he spoke to the SMC briefing.

There’s another level, as well, which is that no one who had had the actual vaccine — whether they got the half-dose or the full-dose regimen — got a “severe” case of Covid. Admittedly “severe” is defined as requiring hospitalisation, and obviously you can have quite a nasty case of Covid without ending up in hospital; but given how lethal this disease can be, it is nonetheless good news that no one ended up dying or in the ICU.

You may rightly say that all this sounds a bit woolly, and it kind of is. Here’s what we know: the vaccine, if administered correctly, probably works about 90% of the time on symptomatic cases, but we can’t be all that sure; it has some effect on asymptomatic cases, but we don’t know what; and no one who took it ended up in hospital, although we don’t know yet whether that means everyone just had a mild case of the sniffles or something more. It’s all good news, but very vague good news.

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So here are some bits of good news that are not vague. First, several million doses of this vaccine — which, as we’ve seen, definitely works, by the targets set — have already been made, and there is lots and lots more on the way. According to Pam Cheng of AstraZeneca (again speaking on the SMC briefing), by the end of December there will be enough actual vaccine to make about 20 million doses for the UK alone, of which about 4 million will already be in vials, ready to go. She thinks there will be about 200 million doses’ worth of material ready worldwide by the same time.

By the end of the first quarter of next year — so the beginning of April — she says there will be enough material for about 700 million doses worldwide, and about 40 million doses ready to go in the UK. And by the end of the year, they expect to have made 3 billion doses. The Serum Institute in India, the world’s biggest vaccine manufacturer, has a licence to manufacture it, so that’s a plausible number. Ewer said that it is estimated that something like two-thirds of the world’s children have received a vaccine made by the Serum Institute: “They are manufacturing on an enormous scale,” she said. “This is exactly what they specialise in, and that’s why we worked so hard to get them on board, because they can do large-scale cheap manufacture.”

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Better still, if the half-dose/full-dose regimen gets licensed, then that means it takes 25% less vaccine per patient. So your 40 million doses would vaccinate about 26 million Britons, instead of 20 million. Your 3 billion doses at the end of 2020 would vaccinate 2 billion people worldwide, not 1.5 billion.

That’s nowhere near enough for herd immunity, especially if the efficacy is on the lower end of the estimate, but it’s enough to vaccinate a huge chunk of at-risk groups and essential workers such as healthcare staff. And AstraZeneca and the manufacturers it has licensed the vaccine to will continue to churn out hundreds of millions more a month.

On top of this the Oxford vaccine, as has been widely reported, can be stored at normal fridge temperatures — between 2° and 8°C. It’s not that it would have been impossible to get huge amounts of the Moderna and Pfizer vaccines to, say, rural Malawi, with their -20°C and -80°C storage requirements, but it will be a damn sight easier with this one.

And, perhaps best of all, the Oxford vaccine looks as though it will sell at something like £2-3 a dose, according to Ewer. Pfizer is expected to sell its vaccine at about £15 and Moderna at more like £25. It is simply much more plausible that this can be bought and distributed in the large numbers required for use in the developing world. This is, says Ewer, partly because the viral vector vaccine technology is older – Johnson & Johnson has one for Ebola which is already being used — so “all the background work on deployment has been done”, while the mRNA vaccines are entirely novel (if exciting).

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I don’t know what this will mean for Britain in the short term. I was speaking recently to a senior scientist who helps advise the government about the mass testing that’s been piloted in Liverpool, and he mentioned that one possibility is that people who test positive have to isolate for a week, but then get a six-month passport saying they’ve had the disease and are safe. He suggested that the same system could be used for vaccines; it sounds plausible to me, with caveats, but whether it actually happens is anyone’s guess.

But the takeaway is that this, like the Pfizer and Moderna announcements in previous weeks, is fantastic news. More vaccines will come, and may be better in various ways, but this is a mass-availability, cheap, effective, easily-stored candidate that does everything you want. It will form the backbone of Britain’s response, and the world’s, and I’m really excited by it.

Now, I just can’t wait to find out what we get next Vaccine Candidate Announcement Day. See you next Monday!

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.

The big response, of course, is vaccines. All the rest of it, all the rapid testing, track and trace stuff, can help control the virus with fewer restrictions on our daily lives. Only vaccines hold out the realistic possibility of getting rid of it altogether, and (eventually) returning to normal.

So it is potentially extremely good news that Pfizer-BioNTech have announced that early results from their trial show that their vaccine candidate, an mRNA vaccine, is around 90% effective. How close, then, is that return to normal?

Boris Johnson says that we have awaited “the distant bugle of the scientific cavalry coming over the brow of the hill” and that now “that toot of the bugle is louder”, but that it is still some way off. The turn of phrase may be tooth-grindingly irritating, but he is basically right.

In short: this is very exciting; the vaccine almost certainly works, although it would be nice to have a bit more clarity about what “works” means; and it’s worth remembering that, beyond just proving that it works, producing it in large quantities and getting it to where it’s needed are real challenges as well. But, mainly, it is completely okay to be excited, as long as you realise that it’s still a few months to wait. 

I think, though, we can be pretty confident that the vaccine actually works. It would be understandable to be sceptical because there has, as yet, been no scientific paper released, or even very much data, beyond one simple number: 94. 

That figure is the total number of cases in both arms of the trial. There were 43,538 people on the trial; according to the study protocol, half of them were given the real vaccine, and half a placebo. Three weeks later, all but 4,000 or so received a booster shot, of the same jab (either the vaccine or the placebo) they had before.

According to the Pfizer press release, there were 94 cases in total, and “the case split between vaccinated individuals and those who received the placebo indicates a vaccine efficacy rate above 90%”.

What that means is that the vaccine prevented at least 90% of cases, so there were 10 times as many in the placebo group as the real vaccine group. Say there were 100 cases in the placebo group and 50 in the other: that would mean that it was 50% effective; if there were 100 in the placebo and ten in the real vaccine group, that would mean it was 90% effective.

In this case, if there are 94 cases in total, there can’t have been more than eight cases in the real-vaccine group, and 86 in the placebo group, for it to be “above 90% effective”. And we also know that the vaccine is astonishingly safe, given no major adverse events in the 20,000 people who were given it.

Again, we have no further data, and it’s always sensible to be wary when ‘pharma company puts out press release saying pharma company’s product is great’. But the results weren’t released by Pfizer — they were put out by an independent monitor, the Data and Safety Monitoring Board (DSMB), so it would be pretty astonishing if they have just made this up.

What might seem more worth worrying about is whether this could be a fluke result. This isn’t, after all, the final analysis, and if you release data from a trial before it’s finished, it’s reasonable to be worried that it’s wrong. 

Let me explain, with this excellent analogy from Tim Harford’s new book How to Make the World Add Up. Imagine that two basketball teams are playing a game, and you want to determine which team is the best. You could just say “whoever wins is best” but it might just be a fluke. So you say beforehand: let’s draw an arbitrary line. If one team wins by a given number of points — let’s say 20 — we’ll say they’re the best. Otherwise we’ll say the results are “not statistically significant”. The higher that number, the more certain you can be when someone does reach it, but also the more times you’ll have to say “we don’t know” because they don’t.

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That’s pretty much how scientific studies work. They say: “If the vaccine does better than the placebo, that could be fluke. So we’ll draw an arbitrary line and say if it does this much better, then it works well enough and we’ll use it.” The arbitrary line was 50% — so if there were 50% fewer cases in the real arm than in the placebo, they’d say it worked well enough.

But if, in the basketball game, one team was 20 points ahead in the second quarter, and then that team’s manager said: “Okay, let’s end the game there”, you wouldn’t think that was a fair assessment. Showing results from the trial early could be doing the same as that.

However, that’s not quite what has gone on here. The plan was always to release data after 32 cases were detected, then again after 62 and 92. (See Table 5.) For reasons that they don’t make clear, but which were “after discussion with the FDA”, Pfizer decided not to release its findings after 32 cases; by the time those discussions were complete, they’d already reached 94 cases. The study will continue until they reach 164 cases, but releasing early data was always part of the plan — so I don’t think it being released now should undermine our confidence at all. 

The other possibility would be that this result is a freak of some kind, that more people happened to get the virus in the placebo group than in the vaccine group. But that’s probably not a serious concern, and we can pretty much rule out the possibility that the vaccine does nothing. If it did, then seeing an 86-8 split would be as unlikely as tossing at least 86 heads in 94 coin-tosses, which is so unlikely that it’s essentially impossible. A one-in-some-number-of-quadrillions chance. 

The real number could be slightly more or slightly less than 90%, but realistically, not very much more. We’re talking no worse than 80%, at the outside. So I think it’s fair to say that the vaccine probably works, and is very effective. The next question is: what exactly does it do?

That might sound stupid — it stops Covid, of course. But what’s not completely clear to me is whether it stops Covid from infecting you or it stops Covid from making you ill. 

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In the trial I’m on, of the Oxford-AstraZeneca vaccine, I have to do a nasal and throat swab every week to see if I have the virus. So it’s very unlikely that I’d get infected and not know about it.

That’s not what happens in the Pfizer-BioNTech one. They seem to only swab people when they come in for follow-up appointments every few weeks or months, or when people get symptoms.

Robin Shattock, who runs Imperial College London’s own vaccine programme, describes it as “a symptom-directed endpoint that requires virological confirmation”. Nilay Shah, a professor of chemical engineering at Imperial, agreed: “My understanding is that the 94 cases must be both symptomatic and RNA-positive to be counted.”

What that could mean is that lots of people in the vaccine group are becoming infected — as in, some detectable amount of virus has entered their bodies and started replicating — but that they are not getting ill, so they’re not getting tested. Shattock told me that even people with mild symptoms, “runny nose, headache, fatigue etc”, would be tested, but still, it could easily miss some infected people.

Obviously it would be better if people were definitely being protected against infection as well as disease, since asymptomatic people can spread the virus. But even if the vaccine has literally no impact on infection rates at all, stopping 90% of symptoms is a big deal. What’s more, asymptomatic people probably spread the disease much less, and besides, it’s very unlikely that the vaccine will have no effect on infection. 

I spoke briefly to Vishal Gulati, a biotech investor and former virologist, and he said that even if the vaccine only protects against disease, it would be “nice to have”, but that he thinks it’s amazingly unlikely that it doesn’t have an effect on the viral load itself. “It’s just not possible that someone who is not sick is producing the same amount of virus over a significant period as someone who’s getting sick,” he said.

It may be that the vaccine is a really good one to give to older and more vulnerable people, to keep them safe, and that later vaccines that are more effective against infection should be given to younger people to stop the spread. According to the protocol, the study is doing antibody tests, so hopefully when the full data is released we’ll know more about the impact on infection as well as disease.

So it probably works well, and most likely reduces the effects of the disease as well as infection. The next problem is going to be making enough of it.

RNA vaccines like the Pfizer one, although completely untried, do have some big advantages. 

One is that making RNA is quite easy. If you have the ingredients – a big soup of nucleotide bases – you can get your length of RNA that you want, and it will essentially replicate itself. You can do it with relatively low-tech materials and at small scale, and each time you need a new length of RNA (for a different vaccine, perhaps), you can reuse the same facilities. Also, the doses are quite small, so you can make more doses per litre in your bioreactor. 

But you still need a lot of doses. Let’s be optimistic and say that it does protect against infection, and that you need to vaccinate 60% of the population to get herd immunity. (For a discussion of what “herd immunity” is, see here, but essentially, it’s the percentage of the population you need to vaccinate to get the R below 1. So if the R is 2, you need to vaccinate 50% of the population, so it’s twice as difficult for the virus to spread.)

In the UK, you’d need to vaccinate about 42 million people. But we’d need two doses per person, so that’s 84 million doses. And, remember, the vaccine is probably only around 90% effective, so about 10% of them won’t work. You’ll end up needing about 94 million doses to vaccinate the whole country to a herd immunity level. If we actually need 70% coverage, then that number is 110 million.

The UK government has ordered 40 million doses from Pfizer. That’s a big deal – it should be enough to vaccinate about 18 million people successfully. If we concentrated that on healthcare workers and the most vulnerable, then it would significantly reduce the number of deaths. But it won’t stop the spread of the disease itself. 

Of course, when the AstraZeneca vaccine is licensed, we’ll end up with another 30 million in short order and 100 million eventually. So UK herd immunity will probably happen. But even so, it is only a temporary reprieve if the virus is still endemic in the rest of the world. To immunise the entire world to herd immunity levels, you’d need about 10.5 billion doses.

Pfizer thinks it can make about 1.3 billion doses next year. Moderna, who are making another RNA vaccine, say a similar sort of figure. But what’s not clear is whether those two estimates take into account the fact that both companies will need the same raw materials; if both companies are ringing the same suppliers and trying to buy all their nucleotides, then one of them is going to be disappointed. I go into a bit more detail about the problems here.

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This is why we simply cannot make do with just the Pfizer vaccine. The Oxford one, for instance, is a viral vector vaccine, and won’t need quite the same chemical components as the Moderna and Pfizer ones, so their supply chains won’t interfere with each other so much.

There’s another problem which is that RNA vaccines such as Pfizer’s need to be kept at -80°C for all but the last day or so before they’re administered; Moderna’s needs -20°C. Other types of vaccine just need to be kept at normal fridge temperature, between 2°C and 8°C. This isn’t an insurmountable difficulty, especially in the UK, but it does mean that you couldn’t, say, bring a batch to a GP’s surgery on Friday and administer it on Monday, unless the surgery had a really high-tech freezer.

In the developing world, that will be an even greater challenge, but it is worth noting that the novel Ebola vaccine developed during the 2014-15 outbreak required a -60°C cold chain, and it was rolled out rapidly to hundreds of thousands of people in the middle of a war zone. These cold chains can be established fast.

There’s one more thing that’s worth mentioning. Donald Trump Jr, among others, is floating the possibility that the vaccine announcement has been delayed in order to help Joe Biden get elected. And you might be tempted to believe him – remember that, earlier on, we mentioned that Pfizer were going to release some preliminary results after 32 cases, and again after 62. But they didn’t end up releasing anything until they’d reached 94 – which, as it happened, was just a few days after Donald Trump Sr had lost the US election.

You can understand people’s suspicions. But it’s worth noting that Pfizer couldn’t have known that the results were positive, because they wouldn’t have had access to them. The only people to have access to the unblinded data – that is, the only people who knew which test subjects had the real vaccine and which the placebo – was the DSMB, the independent body supervising the study. And it’s not Pfizer or BioNTech who decided to release the data: it’s the DSMB.

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It’s not that it’s impossible that this panel of independent scientists were conspiring to help Joe Biden win the election, it just seems unlikely. Gulati thinks the most likely explanation is simply that the DSMB decided that releasing the data early, when the statistical power was still very low, would have reduced public trust in the vaccine. Also, it might have made recruitment for the trial more complicated, if it was obvious that the vaccine outperformed placebo — telling people there’s a 50% chance they’ll be in the placebo arm would not be hugely popular.

To sum up, then: this is a really big deal. It looks like the first vaccine will arrive soon, and that it will work – much better than expected, although with slight question marks over how well it “works” on infection as well as symptoms. And it’s really reassuring that vaccines work at all.

What it doesn’t mean is that we’ll all have the vaccine tomorrow, or even this year, or perhaps even next year. And it certainly doesn’t mean we can stop developing and producing the other vaccines, because each kind of vaccine will have different strengths and weaknesses — some will be easier to manufacture, some will work better in different groups. (There’s a useful Twitter thread on this topic from the CEO of the biotech company GreenLight.)

The best-guess timeline, that most people will probably not see a vaccine until late next year, is still reasonable. And, of course, it would be really nice to see the data from this Pfizer study, rather than just a few bullet-points and self-satisfied quotes in a press release.

Nonetheless, it’s exciting. It’s a light at the end of the tunnel. And finally, it gives a nice straightforward answer to what it is that lockdown is supposed to be buying time for.

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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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.