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16 June 2021

Martin Rees and Steven Pinker: Wagering on catastrophe

Four years ago these two eminent scientists bet on the likelihood of a man-made global biological disaster. Is it time to decide a winner? 

By Martin Rees

Advances in biomedicine have vastly improved health and extended life all over the world, including its poorest countries. Over the past 25 years an average human has gained seven years of life expectancy. The gain is more than just staying alive: the number of healthy years she will enjoy has risen too.

The future benefits to humanity could be greater still. According to the Global Burden of Disease project, every year the world loses a total of 1.65 billion years of potential life due to premature death, and another 853 million years of healthy life due to disability and illness. If you have lost a loved one to cancer, heart failure or a degenerative disease, as you surely have, you can appreciate the unfathomable gift of a biomedical advance that would have kept them alive. Multiply that gift by billions and you can begin to appreciate the possible bounty of progress in our battle against disease.

At the same time, this progress creates vulnerabilities and ethical dilemmas, and that will give humanity a bumpy ride through the century. The gulf between what science may enable us to do and what it is prudent or ethical to do will shift, widen and, in many cases, be difficult to discern.

Concerns about biomedicine have loomed large during the Covid-19 crisis, but they are nothing new. Throughout the history of medicine, people have recoiled at innovations that seemed to go against nature, including vaccination, transfusions, anaesthesia, artificial insemination, organ transplants and in-vitro fertilisation. That all are unexceptionable today is a reminder that squeamishness at the new is not a reliable guide to what is ethically defensible.

More recently, people have opposed embryo and stem cell research, and mitochondrial transplants (so-called three-parent babies). And despite genetically modified crops having been consumed by more than 300 million Americans for two decades without harm, they are still severely restricted within the European Union.

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A headline trend in biotech has been the plummeting cost of sequencing DNA. The publication of the first draft of the human genome 20 years ago was quintessential Big Science – an international project with a $3bn budget. But the cost of human genome sequencing has fallen to below $1,000, and soon it will be routine for all of us to get sequenced. At the same time, it has become feasible to synthesise genes and even simple genomes from scratch.

[See also: China’s Covid cover-up?]

Most people distinguish between an intervention that would remove something harmful, which they welcome, and one that would enhance what we already have, which they fear. Whether or not this difference is morally significant (or even, in many cases, meaningful), the actual prospect of genetic enhancement of humans is, perhaps fortunately, remote.

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A few genetic diseases, including Huntington’s, are caused by a single gene that could be snipped out by the CRISPR-Cas9 gene-editing technique. But most, such as schizophrenia or a susceptibility to Alzheimer’s or cancer, are the product of hundreds or thousands of genes, each tweaking the probability of a person having the disease by a tiny amount.

This is even truer of traits and talents such as height, intelligence and personality. Only when the DNA and trait profiles of many millions of people are available will it become possible (using pattern-recognition systems aided by AI) to identify desirable combinations of genes. Not until this can be done will “designer babies” become conceivable (in both senses).

And perhaps not even then. In the 1990s many commentators fretted about the day wealthy parents would be able to insert a gene for intelligence into their unborn children, the ultimate form of inequality. The scenario would feel very different if it consisted of inserting a few thousand genes into a child, each possibly increasing IQ by a minuscule fraction of a point and, because no gene has a single effect, also possibly increasing the probability of brain cancer or epilepsy by a fraction of a point. Moreover, even the most heritable diseases display a lot of unpredictable non-genetic variability, as is clear from the fact that identical twins can have different trajectories of life and health.

In addition to the distinction between curing and enhancing, many people draw a line between genetic manipulations whose effects are restricted to individuals’ own bodily tissues and those that reach into the eggs or sperm and are passed down to their progeny – manipulations that feel vaguely eugenics-like, God-playing or Brave New World-ish.

Yet the concept of a pure germ line (egg and sperm cells) that we alter at our peril is a fiction. Every parent bequeaths dozens of new mutations to their children, and research suggests the number transmitted is increased if the parent is older. The biggest threat to the integrity of the human germ line is not gene editing but middle-aged new fathers.

***

Manipulation of the germ line of other species also forces us to think hard about our ethical intuitions. There has, for instance, been an attempt in parts of Brazil and other areas to sterilise and thereby wipe out the species of mosquito that spreads the dengue and Zika viruses; the trials recorded a 90 per cent reduction in local populations of the species. Is it bad to play God in this way? (Trick question: which wild animal is most dangerous to humans? Answer: the mosquito.) Similar techniques are being proposed that could preserve the unique ecology of the Galapagos Islands by eliminating invasive species such as black rats.

Genetic manipulations are by no means the only ethical challenges that will confront us as biomedical science advances. We will also face acute dilemmas about treating those at the beginning and those at the end of their lives. Everyone treasures the prospect of living out more healthy years, while most people dread the prospect of being kept alive in pain or with severe disability or dementia. Yet we have little in the way of a coherent ethical framework that would allow us to deal with this devil’s bargain. Likewise, the ability to treat premature babies can be miraculous, but it might also mean saving children who will never flourish, laying out an ethical minefield.

Research on viruses raises dilemmas that are both incendiary and timely. In 2011 a research group in the Netherlands and another in the US showed it is surprisingly easy to make the H5N1 influenza virus both more virulent and more transmissible – defying the evolutionary dynamic that ordinarily trades one of these diabolical talents against the other (since a virus that kills its host can no longer use that host to spread itself).

These Faustian “gain-of-function” experiments were justified as a way to stay one step ahead of natural mutations, allowing us to prepare vaccines in good time. But many critics argued that this theoretical benefit was outweighed by the risk that dangerous viruses might escape the lab accidentally, or that bioterrorists might release them intentionally.

In 2014 the US government stopped funding “gain-of-function” experiments, but in 2017 the ban was relaxed. In 2018 a team in Edmonton, Canada, reported it had synthesised an extinct horsepox virus, which implied that a smallpox virus could be constructed, too. Some scientists, unsurprisingly, questioned the justification for this research. Others argued that even if the experiment could be justified, the findings should not have been published: if there is such a thing as “dangerous knowledge”, this surely is it.

In 1975, in the early days of recombinant DNA research, the world’s leading molecular biologists met at the Asilomar Conference Grounds in California and agreed on guidelines on which kinds of experiments should not be done. This seemingly encouraging precedent has triggered meetings, convened by national academies, journal editors and government officials, to discuss recent biotechnologies in a similar spirit of proactive caution.

But more than 40 years after the first Asilomar meeting, the research community is more globalised, and more influenced by commercial pressures. Whatever regulations are imposed – on prudential or ethical grounds – cannot be effectively enforced worldwide, any more than drug or tax laws can be. There is the risk that if something can be done, someone, somewhere, will do it.

That is the stuff of nightmares. In contrast to the elaborate, conspicuous special-purpose equipment needed to create a nuclear weapon, biotech involves small-scale, dual-use technology. Indeed, biohacking is burgeoning as a hobby and competitive game. And there are many hundreds of laboratories around the world in which dangerous pathogens are being studied and modified.

***


Illustration by Edmon de Haro

Although a non-expert, one of us (Martin) first wrote about these hazards in 2002, and realised some better-informed colleagues thought a catastrophe was even more likely to happen than he did. On the Long Bets website he wagered that “bioterror or bioerror will lead to one million casualties in a single event within a six-month period starting no later than 31 December 2020”.

This is a bet he fervently hoped to lose, but he was not surprised when, in 2017, the other author of this piece (Steven) took him up on it, with a $400 stake (with the winnings going to charity). Steven had written two books documenting historical declines in violence, poverty, illiteracy and disease, and contrasted the data on those declines with the gloom of commentators whose view of the world was informed by non-random samples of the worst things that happened every day – which is to say, the news.

Martin has argued that these trends, though real, can lull us into undue confidence. In the financial world, gains and losses are asymmetric; many years of gradual gains can be wiped out by a sudden loss. In biotech and pandemics (as with cyber threats), the overall risk is dominated by the rare but extreme events. Moreover, as science empowers us more and more, and the world becomes increasingly interconnected, the magnitude of the worst potential catastrophes has grown unprecedentedly large, and many are in denial about them.

[See also: Are new Covid variants more harmful to children?]

Steven agreed that many hazards, such as wars and pandemics, fall into distributions with a “thick tail”: catastrophic events are unlikely, but not astronomically unlikely. But on the Long Bets website, he ventured that “moral market forces distort the odds: pessimists are seen as serious and responsible, optimists as complacent and naive”. He noted that doomsday predictions are easy to make but have all proved false (such as the supposedly civilisation-ending “Y2K bug” in late 1999). And he suggested that “if an extreme and specific category of event has never before happened, the odds are stacked against it”. Moreover the number of people eager for senseless destruction is small – smaller still if multiplied “by the fraction with the knowledge, skill, intelligence and discipline to engineer a superbug”.

In 2020 we had Covid-19, which was far more devastating than the threshold event Martin had envisaged. But Martin had phrased the bet to exclude naturally emerging pandemics, and Steven would not have taken it up if he had included them. Both of us agree that these are an ever-present threat, and probably a growing one because of more congested living and more virus-spreading air travel. Though the development of vaccines within a single year is surely one of our greatest scientific achievements (remember that after 40 years there is still no vaccine for Aids), Covid-19 has plainly been a wake-up call that should impel us to be better prepared for future natural pandemics.

But do we know that Covid-19 was a natural pandemic? In the first week of this year, our bet became due, and we conferred by email on how to reckon it. Our agreement was instantaneous and total.

Though the consensus in the first week of January was that the disease was zoonotic – that is, it had jumped from animals to humans, perhaps through an intermediary host – (which would make Steven the winner), we agreed the possibility of leakage of an altered coronavirus from China’s Wuhan Institute of Virology could not be dismissed. Defying Martin’s hopes for losing, Steven’s hopes for winning, the expert consensus at the time, the satisfaction of bringing closure to an “adversarial collaboration” (an ideal of scientific dispute resolution) and even the possibility of accusations of anti-Asian racism, we agreed to defer settling the bet until the scientific evidence was clearer.

It’s a good thing we did. In the past month the consensus has unravelled and the lab-leak theory has gained traction. In the Bulletin of Atomic Scientists, the veteran science journalist Nicholas Wade prosecuted the case. He reported that the Wuhan Institute was conducting “gain-of-function” studies; that Sars-Cov-2 bears signs of such a human-made gain; that three laboratory workers in the institute fell mysteriously ill in autumn 2019; and that no plausible source for zoo-notic transmission has yet been identified.

Though most experts still think zoonosis is the more probable origin story, no open-minded scientist today could insist the case is settled. Anthony Fauci, the US infectious disease chief, has added his voice to those suspecting a cover-up and seeking more openness from the Wuhan scientists. On 27 May Joe Biden called for a report from US intelligence officials to be returned within 90 days.

***

Realistically, given the scientific uncertainty and the deliberate opacity of Chinese authorities, our bet may never be settled. Though this would be enormously frustrating (not so much for us as for science and public health), it is not without some comfort. Proof of a lab leak could, as the legal scholar Stephen Carter noted, “give the coronavirus saga what it’s lacked: a villain”, and “the formless fear that has immobilised most of the world for the last year and a half, at last given a target, might coalesce into fury”. It could also turn people against science and invite crippling, overbroad regulation, slowing progress against disease, death and disability.

Whatever the origin of Covid-19, we can’t rule out lab leakage in the future (recalling, for example, that a serious foot-and-mouth outbreak in the UK was caused by a leakage from the Pirbright laboratory in Surrey in 2007). There is surely a case for enhancing security and independent monitoring of laboratories researching lethal pathogens.

Nor can we rule out the intentional release of a dangerous pathogen. To be sure, governments, and even terrorist groups with specific aims, will always be inhibited from releasing bioweapons because no one can predict where and how far they can spread. The real nightmare is a deranged loner with biotech expertise who believed, say, that there were too many humans on the planet and didn’t care who became infected, or how many. The ultimate bioweapon would combine high lethality, the transmissibility of the common cold and a long asymptomatic period allowing large-scale spreading before countermeasures could be taken.

As Steven has noted, the odds militate against this worst-case scenario. In the real world, technological feats are rarely pulled off by a single evil genius, and complex plots tend to be derailed by mishaps, incompetence, defection and surveillance. But, as Martin has noted, even one feat is too many if its damage cascades globally.

The growing empowerment of tech-savvy groups (or individual hackers) by bio- and cyber-technology will pose an unprecedented challenge to governments and amplify the tensions between freedom, privacy and security.

Despite our bet-worthy differences, we agree that the world was underprepared for Covid-19, however it originated. More broadly, it is unprepared for the intellectual, moral and practical challenges posed by burgeoning biotechnology. These challenges call for clear thinking and well- crafted policies that recognise both its stupendous potential boon to human flourishing and its stupendous potential risk to human safety. l

Martin Rees is the UK’s Astronomer Royal and author of “On the Future: Prospects for Humanity” (Princeton). Steven Pinker is a cognitive scientist at Harvard University. His most recent book is “Enlightenment Now: The Case for Reason, Science, Humanism, and Progress” (Penguin)

[See also: Leader: An avoidable delay]

This article appears in the 16 Jun 2021 issue of the New Statesman, The Cold Web