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We now have a preprint with a great deal of data on the first mRNA coronavirus vaccine candidate from the Pfizer/BioNTech effort. This is actually the first real data set on any of the genetic vaccines, since Moderna’s paper on their Phase I trial has not yet appeared (all we had was a brief press release) and a brief press release is all we got from Inovio’s DNA vaccine work as well.

I’m very glad to see this – some of the other vaccine programs (Oxford/AZ and CanSino, for example) also have been very forthcoming with information, and it’s extremely important that all of the human trial data be made public. I realize that doing so opens the door for a lot of people who don’t understand human trial data at all to wander through it misinterpreting things – no doubt about it – but the dangers of that are far, far outweighed by the need for full disclosure. There are lots of qualified eyes out there, too, and for the public to have confidence in the vaccines that get approved we have to have everything out on the table with no room for suspicion. No one gets a pass: everyone publishes everything if they want to be taken seriously.

So what do we have today? It looks like good news. Recall that this effort actually has four different mRNA vaccine programs: two with modified RNA bases, one with extra uridine bases, and one in the “self-amplifying” category. This preprint covers the initial data on BNT162b1, which is one of the modified-base candidates (incorporating 1-methyl pseudouridine, which should cut down on the innate immune response attacking the mRNA vaccine itself and also increase protein production once it gets into the cell. And it encodes a trimer of the coronavirus Spike protein’s receptor-binding domain (RBD), the most common antigen that is being studied in all the vaccine programs worldwide. The trimerized variant uses a “foldon” protein scaffold that displays three of the RBDs simultaneously in a three-dimensional array – it’s a motif borrowed from a bacteriophage that has been used in vaccine production before.

In this study, 12 patients got 10 microgram doses at Day 1 and Day 21, 12 patients got two 30 microgram doses in the same way, and 12 got a single 100 microgram dose at the start. There were nine placebo-injection patients as a control, and a convalescent serum panel as a comparison group for antibody response.  Male/female almost 50/50, ages from 19 to 54, mean 35 years old. No serious adverse reactions: one patient in the 100 microgram group reported severe pain at the injection site, and several others reported moderate pain or soreness after the first shot (by comparison, 2 of the 9 placebo patients reported the same). Pretty much everyone reported it after the second, which is to be expected. There were reports of headache, fatigue, and fever, which were dose-dependent and also more severe after the second dose, and in fact these are what limited the 100 microgram group to only one initial injection. This is also exactly what you expect from a vigorous immune response.

And that appears to be what the team got. The patients were profiled at Day 7, Day 21, Day 28, and Day 35 (with dosing, as mentioned, at Day 1 and Day 21). RBD-binding antibodies (IgG) were detected at Day 21 after the first dose, and were much stronger 7 days after the second dose (Day 28). In terms of just geometric-mean concentration of antibodies, the levels achieved after the first dose were 1.8x and 2.8x (in the 10µg and 30µg patients, respectively) the levels seen in the convalescent serum panel. After the second dose, these went up to 8x to 50x the convalescent levels (!) The antibody response was further profiled for titers of real neutralizing antibodies – at day 28 (seven days after the second dose) neutralizing antibodies were 1.8x and 2.8x (in the 10µg and 30µg patients, respectively) those seen in the convalescent patients.

That definitely sounds good, since the convalescent patients, remember, had already beaten the coronavirus infection with the levels they’re showing. One variable in this, which we’ll have to address, are the reports that antibody levels in such recovered patients may drop off faster than expected. You might want to try to standardize when you draw plasma from such a comparator group (compared to when they stop showing viral RNA, perhaps). As Matthew Herper noted, the antibody titers in the convalescent patients show a much wider spread than the treated patients from this study. Everyone will of course be monitoring the persistence of vaccine-induced antibodies as these trials go on as well, and we’ll get more data on the topic. Another thing that I hope we see plenty of data collection on in the trials is T-cell response – this recent preprint suggests that this might be an even more sensitive indicator than antibody titer, and that there are indeed people who develop such a response without ever really seroconverting (developing antibodies).

The FDA has published guidelines for such clinical trials, and they look reasonable. The gold standard will of course be protection against coronavirus infection versus a placebo control, and right behind that is the severity of disease in people who do get infected. Blood chemistry/immunology is not addressed in detail because we just don’t have enough predictive detail yet about antibody and T-cell responses (as this latest Pfizer/BioNTech manuscript also notes), but the guidance leaves open the possibility of approval on such markers if we get a clear enough picture later on. Any such surrogate endpoints will have to be tied directly to those clinical endpoints, of course.

But back to these latest results: I agree with the paper’s conclusion, which says that its findings “are encouraging and strongly support accelerated clinical development and at-risk manufacturing“. So far, so good, and remember, these folks have three more mRNA vaccines coming along simultaneously. I very much await Moderna’s paper on their Phase I mRNA results for comparison – it’s been six weeks since the press release, guys, an eternity in Covid-time. Bring on the data, everyone!

Editor’s note: Some of our covid-19 coverage is free for readers of The Economist Today, our daily newsletter. For more stories and our pandemic tracker, see our hub

ON SEPTEMBER 2ND 1859 C.F. Herbert, prospecting for gold in south-eastern Australia, saw something sublime in the evening sky. “A scene of almost unspeakable beauty presented itself, lights of every imaginable colour were issuing from the southern heavens,” he would later recall. “The rationalist and pantheist saw nature in her most exquisite robes. The superstitious and the fanatical had dire forebodings, and thought it a foreshadowing of Armageddon and final dissolution.”

Those who saw cataclysm in the auroral display were not exactly wrong: just ahead of their time. The Carrington event, as the geomagnetic storm Herbert observed came to be known, was the result of 100m tonnes of charged particles thrown off by the Sun a few hours earlier slamming into Earth’s magnetosphere, a protective magnetic sheath generated by currents in the planet’s liquid core. The electromagnetic effects of the onslaught did not just produce a truly spectacular display of the Southern Lights (and the Northern ones, too, visible as far south as Colombia). They induced powerful currents in any electrical conductors to hand. Some telegraph networks took on a life of their own, no longer needing batteries to generate signals.

Such effects mattered little 20 years before the advent of the light bulb. In today’s ubiquitously, fundamentally and increasingly electrified world a “coronal mass ejection” (CME) as large as that of the Carrington event could cause all kinds of chaos. Induced currents would topple electrical grids. Satellites would have their circuitry fried or be dragged from the sky as the outer atmosphere, bloated by the storm’s energy, rose up towards them.

How bad the effects of an off-the-charts CME might prove is up for debate. Some say a really big storm would knock the power out in various places for a few hours, as a moderate one did in Quebec in 1989. Others predict something little short of the end of days. That the world will some day find out who is right, though, is beyond debate. Solar physicists put the odds of a Carrington-level geomagnetic storm some time in the next ten years at around one in ten. Eventually one will come.

Geomagnetic storms are one of a small set of events found in the historical and geological record that present plausible threats of catastrophe. Pandemics are another, giant volcanic eruptions a third. Seeing how well—or how poorly—countries are currently coping with the only one of these catastrophes of which they have prior experience raises the question of how they might cope with the others.

Technology plays a crucial role in the hazards such events generate. It can bring surcease, as a vaccine might for a pandemic. It can bring vulnerability, as electric grids have when it comes to geomagnetic storms. And it can also bring forth new risks of its own. The most obvious are the technologies of internal combustion and nuclear weaponry, which made possible catastrophic global warming and war on an unprecedented, environment-shattering scale. It is possible that further techno-disasters may lie ahead—and that they may be the most serious of all, putting the whole human future in jeopardy.

In a recent book, “The Precipice”, Toby Ord of the Future of Humanity Institute at Oxford University defines an existential risk as one that “threatens the destruction of humanity’s long-term potential”. Some natural disasters could qualify. An impact like that of the 10km asteroid which ushered out the dinosaurs 66m years ago is one example. A burst of planet-scouring gamma rays from a nearby “hypernova” might be another. A volcanic “super-eruption” like the one at Yellowstone which covered half the continental United States with ash 630,000 years ago would probably not extinguish the human race; but it could easily bring civilisation to an end. Happily, though, such events are very rare. The very fact that humans have made it through hundreds of thousands of years of history and prehistory with their long-term potential intact argues that natural events which would end it all are not common.

Do you feel lucky, punk?

For already existing technologically mediated risks, such as those of nuclear war and climate collapse, there is no such reassuring record to point to, and Mr Ord duly rates them as having a higher chance of rising to the existential threat level. Higher still, he thinks, is the risk from technologies yet to come: advanced bioweapons which, unlike the opportunistic products of natural selection, are designed to be as devastating as possible; or artificial intelligences which, intentionally or incidentally, change the world in ways fundamentally inimical to their creators’ interests.

No one can calculate such risks, but it would be foolish to set them at exactly zero. Mr Ord reckons almost anyone looking at the century to come would have to concede “at least a one in 1,000 risk” of something like a runaway AI either completely eradicating humanity or permanently crippling its potential. His carefully reasoned, if clearly contestable, best guesses lead him to conclude that, taking all the risks he cites into account, the chances of humankind losing its future through such misadventure in the next 100 years stands at one in six. The roll of a single die; one spin of the revolver chamber.

Mr Ord is part of a movement which takes such gambles seriously in part because it sees the stakes as phenomenally high. Academics who worry about existential risk—the trend began, in its modern form, when Nick Bostrom, a Swedish philosopher, founded the Future of Humanity Institute in 2005—frequently apply a time-agnosticversion of utilitarianism which sees “humanity’s long-term potential” as something far grander than the lives of the billions on Earth today: trillions and trillions of happy lives of equal worth lived over countless millennia to come. By this logic actions which go even a minuscule way towards safeguarding that potential are precious beyond price. Mr Ord, one of the founders of the “effective altruism” movement, which advocates behaviour rooted in strongly evidence-based utilitarianism, sees a concern with existential risk as part of the same project.

Risks that are merely catastrophic, not existential, do not tend to be the subject of such philosophical rumination. They are more amenable to the sort of calculations found in the practice of politics and power. Take the risk of a nuclear attack. According to Ron Suskind, a reporter, in November 2001 Dick Cheney noted that America needed new ways to confront “low-probability, high-impact” events. “If there’s a 1% chance that Pakistani scientists are helping al-Qaeda build or develop a nuclear weapon,” the vice-president said, “we have to treat it as a certainty in terms of our response”. Such responses included new wars, new government agencies (the Department of Homeland Security) and new executive powers, including warrantless surveillance.

If every perceived 1% risk were met with such vigour the world would be a very different place—and not necessarily a safer one. But it is striking that some risks of similar magnitude are barely thought about at all. Imagine Mr Cheney was considering the possibility of losing a city over a 20-year period. What else puts a city’s worth of people and capital at a 1% risk every few decades? The sort of catastrophic risks that crop up every millennium or so, threatening millions of lives and cost trillions. Perhaps they should be treated equally seriously. As Rumtin Sepasspour of the Centre for the Study of Existential Risk at Cambridge University puts it: “Governments need to think about security as just one category of risk.”

Carrington events are a good example. The most devastating effect of a really large CME would probably be on the transformers in electrical grids: gigantic, purpose-built machines that step voltage down between the long-range transmission grid and the distribution grid which runs lower-voltage power into homes, businesses and hospitals.

Strong enough induced currents could damage some of these transformers beyond repair. Because it typically takes between six and 12 months to get a replacement transformer made—and only a few countries have the industrial capacity to make them—that could leave grids crippled for some time. “If you simultaneously lose the ability to pump water, to pump fuel, to communicate, lose eyes in the sky, you pretty quickly get into territory that’s never really been explored before,” says Dan Baker, the director of the Laboratory for Atmospheric and Space Physics at the University of Colorado, Boulder.

Stockpiling backup transformers could help mitigate some of those problems. But large transformers are not commodity items. “They don’t have a big warehouse holding these things ready to roll out,” says Mr Baker. Redundant local supplies, such as backup generators, would also help. Mr Baker is not sure, though, that enough is being invested in them.

Sudden impact

In general, scientists and policy wonks who think about these things suspect that grid operators are not as prepared as they should be for a Carrington level storm. But some see progress. William Murtagh, who works at the Space Weather Prediction Centre in Boulder, says American policy on space weather has come a long way, to the point where there are now bipartisan bills going through Congress and that grid operators are being required to certify the excess voltages their systems can cope with.

America does, at least, have a solid plan: the National Space Weather Strategy and Action Plan, published in March 2019. It also has an early warning system. The National Oceanographic and Atmospheric Administration, which runs the space-weather centre in Boulder, also runs a satellite called DSCOVR. Rather than orbit the Earth, DSCOVR circles a point on a line between the Earth and the Sun—the point about 1.5m kilometres inward from Earth where the two bodies’ gravitational attractions balance each other out. Conceived of mainly as a way of looking back at an Earth spinning in eternal sunshine, DSCOVR also measures the stream of charged particles flowing past it from the Sun. When a storm passes by, the satellite’s operators down in Boulder will hear about its approach from DSCOVR between 15 minutes and an hour before the brunt of it hits the magnetosphere, depending on its speed.

There is little planning anywhere for what to do in response to a volcanic eruption large enough to cool and dry the climate around the world, as the eruption of Tambora, a volcano in Indonesia, did in 1815. The fact that the stratospheric sulphate particles which bring about such cooling leave a distinctive residue in glaciers and ice sheets reveals the frequency of these eruptions (see chart 1). But there is no pattern which says when another one might be due.

Careful remote monitoring of the world’s volcanoes, including those that are apparently dormant, should reveal if one is likely to blow in a big way. Again, satellites can play a key role. A technique called radar interferometry makes it possible to see when mountains start to deform as a result of the pressure of the magma building up beneath and within them. Scientists at the University of Bristol are using such data from past eruptions to train machine-learning systems on how to see future ones. Very large eruptions should be fairly easy to anticipate; but quite how large one will prove, and thus quite what effects to expect, will be hard to say in advance.

There are also projects devoted to looking for potentially hazardous asteroids. Here, though, the threat is not what it was. When people began to worry about asteroid impacts in the 1980s, the focus was on events smaller than the dinosaur-killer—too rare to worry about—but still big enough to disturb the climate in the way a very large volcanic eruption does, and thus do damage worldwide rather than just wiping clean some random, and probably sparsely inhabited, part of the planet’s surface. Theoretical models of the population of near-Earth objects suggested there might be 1,000 or so big enough to wreak such havoc, of which only a hundred or so had been discovered. Subsequent observation has found most of the rest of them, and they are all, at the moment, keeping a safe distance. As of 2019 the data suggested that only around 43 near-Earth objects of a potentially climate-changing stature were still to be discovered, according to Alan Harris of MoreData!, a research outfit.

As the need to worry about big asteroids has diminished, though, interest in spotting smaller ones has grown—as has an urge to be able to swat them aside. Next year America will launch a space mission called DART (Double Asteroid Redirection Test) which will change the orbit of a small asteroid orbiting a larger one, thus demonstrating the first step towards a “planetary defence” capability. It is an exciting, dramatic idea. If your aim were to effectively fund ways of lowering the death toll in future catastrophes, though, it would probably not strike you as the best use of $300m. Investing in early-warning systems for pandemics (see article) would seem a much better bet.

Every which way

It is possible to imagine better early-warning systems for pandemics, solar storms and volcanic eruptions, and carefully considered plans which would use that knowledge to reduce the hazard. What of the other big bads?

Existing anthropogenic risks are already quite well dealt with. There are aspects of climate change that could and should be better monitored—methane sources, for example, and changes in soil moisture—but the subject is hardly systematically understudied. It is in the nature of nuclear weaponry that its possessors spend a great deal of time monitoring each other’s capacities and intentions. As for those trying to develop nuclear weaponry covertly, the Comprehensive Nuclear-Test-Ban Treaty Organisation operates a remarkably acute network of monitoring stations that brings together seismometers, radioisotope sensors and detectors of low-frequency sound waves which makes setting off a nuclear weapon of any size without being noticed effectively impossible.

Hazards that do not yet exist but may soon come to pass present a harder problem. The prospect of synthetic biology producing advanced bioweaponry is a fitting target for traditional intelligence methods, coupled with the sort of monitoring that might be used to detect novel natural pathogens, too. Countermeasures might emerge from “precision medicine” approaches built around platform therapies which can be reprogammed for various diseases. Deadly AIs, though, are a different kettle of pseudofish. Today’s AI systems, powerful as they are at recognising patterns, are worrying only to the extent that people use them in worrying ways; in themselves they are no more dangerous, or sentient, than stamp collections. That may change. Most in the field seem to think that one day AIs will be able to give humans a real run for their money. But their views as to when vary widely (see chart 2). Such disparity does not mean no threat will emerge. It does suggest that no one really knows what it may look like.

As a field and a threat, though, AI, like synthetic biology, does have the advantage of emerging from an open academic culture. Its expert practitioners eschew closed publication and discussion. This makes it plausible, at least, to monitor both fields.

Getting such risks taken seriously will never be easy. It is to some extent contrary to human nature. Humans assume that the future will be like the past; they prepare for things they have experience of. Mr Murtagh says that grid operators at high latitudes take solar storms more seriously than others do because of experiences like that of Quebec in 1989. Countries hit hard by SARS have, by and large, done better against covid-19 than those which never had to get to grips with the previous pandemic. When it comes to the truly novel, no one will have that core of experience to build on.

Where experience fails, though, science and imagination may sometimes fill in. Humans often look to the future like Herbert’s superstitious and fanatical mates staring up at the Carrington event’s strange skies, filled with “dire forebodings”. But it can be seen in other ways. You do not have to believe in trillions of people living the good life for ever. Just that there are things to come which are worth caring about, and worth protecting from those threats that reason reveals.■

This article appeared in the Briefing section of the print edition under the headline "What’s the worst that could happen?"