Controversial new research suggests SARS-CoV-2 bears signs of genetic engineering

The claim has yet to be peer-reviewed writes The Economist

Oct 22nd 2022

Astring of about 30,000 genetic letters were all that it took to start the nightmare of covid-19, the death toll from which is likely to be more than 20m. Exactly how this story began has been hotly contested. Many think that covid-19’s emergence was a zoonosis—a spillover, as so many new pathogens are, from wild animals, for it resembles a group of coronaviruses found in bats. Others have pointed to the enthusiastic coronavirus engineering going on in laboratories around the world, but particularly in Wuhan—the Chinese city where the virus was first identified. In February 2021 a team of scientists assembled by the World Health Organisation (who) to visit Wuhan said a laboratory leak was extremely unlikely. However, this conclusion was subsequently challenged by the who’s boss, who said ruling out this theory was premature.

Two recent publications appear to have bolstered the case for a natural origin connected to a “wet market” in Wuhan. These markets sell live animals, often housed in poor conditions, and are known to be sites where new pathogens jump from animal to human. Early cases of covid-19 clustered around this market. But critics counter that there are so many missing data about the epidemic’s initial days that this portrait may be inaccurate.

The opposing idea of a leak from a laboratory is not implausible. The accidental escape of viruses from labs is more common than many people realise. The flu epidemic of 1977 is thought to have started this way. But an escaped virus does not imply an engineered virus. Virology labs are also full of the unengineered sort.

Research such as that done in Wuhan offers a number of ways for a virus to leak out. A researcher on a field trip could have picked it up in the wild and then returned to Wuhan, and so spread it to others there. Or someone might have been infected with a wild-collected virus in the laboratory itself. But some argue that sars-cov-2 could have been assembled in a laboratory from other viruses that were already to hand, and then leaked out.

Into this fray comes an analysis from an unlikely source. Alex Washburne is a mathematical biologist who runs Selva, a small startup in microbiome science based in New York. He is an outsider, although he has worked in the past on virological modelling as a researcher at Montana State University. For this study, Dr Washburne collaborated with two other scientists. One is Antonius VanDongen, an associate professor of pharmacology at Duke University, in North Carolina. The other, Valentin Bruttel, is a molecular immunologist at the University of Würzburg, Germany. Dr Washburne and Dr VanDongen have been active proponents of an investigation into the lab-leak theory.

The trio base their claim on a novel method of detecting plausibly lab-engineered viruses. Their analysis, published on October 20th on bioRxiv, a preprint server, suggests sars-cov-2 has some genomic features that they say would appear if the virus had been stitched together by some form of genetic engineering. By examining how many of these putative stitching sites sars-cov-2 has, and how relatively short these pieces are, they attempt to assess how much the virus resembles others found in nature.

They start from the presumption that creating a genome as long as that of sars-cov-2 would mean combining shorter fragments of existing viruses together. For a coronavirus genome assembly they say an ideal arrangement would be to use between five and eight fragments, all under 8,000 letters long. Such fragments are created using restriction enzymes. These are molecular scissors which cut genomic material at particular sequences of genetic letters. If a genome does not have such restriction sites in opportune places, researchers typically create new ones of their own.

They argue that the distribution of restriction sites for two popular restriction enzymes—BsaI and BsmBI—are “anomalous” in the sars-cov-2 genome. And the length of the longest fragment is far shorter than would be expected. They determined this by taking 70 disparate coronavirus genomes (not including sars-cov-2) and cutting them into pieces with 214 commonly used restriction enzymes. From the resulting collection, they were able to work out the expected lengths of fragments when coronaviruses are cut into varying numbers of pieces.

The paper, which as a preprint has received no formal peer review, and which has not been accepted for publication in a journal, will be picked apart in the coming days—as well it should be, for this is the way that science works. Early reactions, though, have been deeply divided. Francois Balloux, a professor of computational systems biology at University College London, said he found the results intriguing. “Contrary to many of my colleagues, I couldn’t identify any fatal flaw in the reasoning and methodology. The distribution of BsaI/BsmBI restriction sites in sars-cov-2 is atypical”. Dr Balloux said these needed to be assessed in good faith. But Edward Holmes, an evolutionary biologist and virologist at the University of Sydney, said that every one of the features identified by the paper was natural and already found in other bat viruses. If someone were engineering a virus they would undoubtedly introduce some new ones. He added, “there are a whole range of technical reasons why this is complete nonsense.”

Sylvestre Marillonnet, an expert in synthetic biology at the Leibniz Institute for Plant Biochemistry, in Germany, agreed that the number and distribution of these restriction sites did not look quite random, and that the number of silent mutations found in these sites did suggest that sars-cov-2 might have been engineered. (Silent mutations are a result of engineers wanting to make changes in a sequence of genetic material without making changes to the proteins encoded by that sequence.) But Dr Marillonnet also said that there are arguments against this hypothesis. One of them is the tiny length of one of the six fragments, something that “does not seem logical to me”.

The other point Dr Marillonnet makes is that it is not necessary for the restriction sites to have been present in the final sequence. “Why would people introduce and leave sites in the genome when it is not needed?” he wondered. Previous arguments in support of the possibility of a lab leak have stressed that a manipulated virus would not need to have any such tell-tales. However, Justin Kinney, a professor at Cold Spring Harbor Laboratory, in New York, said that researchers have created coronaviruses before and left such sites in the genome. He said the genetic signature indicates a virus ready for further experiments and said it needed to be taken seriously, but warned the paper needed rigorous peer review.

Erik van Nimwegen, from the University of Basel, says there are only small scraps of information and it is “hard to pull anything definitive out of that”. He adds, “one cannot really exclude at all that such a constellation of sites may have occurred by chance”. The authors of the paper concede this is the case. Kristian Andersen, a professor of immunology and microbiology, at the Scripps Research Institute in La Jolla, California, described the pattern, on Twitter, as “random noise”.

Any conclusion that sars-cov-2 was engineered will be hotly contested. China denies the virus came from a Chinese lab, and has asked for investigations into whether it may have originated in America. Dr Washburne and his colleagues say their predictions are testable. If a progenitor genome to sars-cov-2 is found in the wild with restriction sites that are the same, or intermediate, it would raise the chances that this pattern evolved by chance.

Any widely supported conclusion that the virus was genetically engineered would have profound ramifications, both political and scientific. It would put in a new light the behaviour of the Chinese government in the early days of the outbreak, particularly its reluctance to share epidemiological data from those days. It would also raise questions about what was known, when, and by whom about the presumably accidental escape of an engineered virus. For now, this is a first draft of science, and needs to be treated as such. But the scrutineers are already at work.

Rishi Sunak’s first job? Clearing up his own mess

 A clever man, with a penchant for bad ideas writes The Economist

Oct 25th 2022

Rishi sunak entered Downing Street clutching an invisible dustpan and broom. “Mistakes were made,” declared the new prime minister on October 25th, all but rolling up his sleeves. “I have been elected as leader of my party…to fix them.” The voice was passive but the identity of the culprit was clear—Liz Truss, Mr Sunak’s hapless predecessor, who managed just 49 days in the job. It is the morning after the night before in the Conservative Party. The grown-ups have returned to find the house has been trashed. Now Mr Sunak must start the clean-up.

There is just one problem with this narrative. Mr Sunak is a cause of the problem as well as the solution. The new prime minister is helping tidy up a mess that he helped create.

When the Conservative Party has erred in recent years, Mr Sunak has nearly always been in favour of the mistake rather than the fix. There were many reasons to support Britain leaving the eu. Mr Sunak, however, picked the worst one: he thought it was a cracking idea. Britain will be “freer, fairer and more prosperous outside,” wrote Mr Sunak in 2016. It was a pragmatic decision, not a romantic one. The fundamental problem at the heart of his own government will be a policy for which he long campaigned. Likewise, Mr Sunak was comfortable with a “no deal” Brexit so long as Britain actually left the eu. Mr Sunak has pledged a more constructive relationship with the bloc. Better not to have broken it at all.

After the referendum triggered three years of political deadlock, Mr Sunak supported an extraordinary solution to the mess: Boris Johnson. That decision can be put down to cynicism. Mr Johnson was likely to win regardless of whether he was endorsed by Mr Sunak, at the time a junior minister in the department for local government. But intellectual contortions were required to join the bandwagon. Theresa May was competent and diligent yet also a total failure, ran Mr Sunak’s logic, so it did not matter that Mr Johnson was neither competent nor diligent. In July Mr Sunak resigned from his position as chancellor of the exchequer, prompting a cascade of ministerial departures that ended Mr Johnson’s reign. But why put him in Downing Street in the first place?

Mr Sunak embodies the tension between the Tories’ lust for low taxes and their habit of making big-state promises. Colossal spending programmes during the pandemic made Mr Sunak briefly the most popular politician in the country. Yet these were also the decisions he most resented; he tried to curtail schemes such as furlough prematurely in a bid to save cash. In the spring of this year, Mr Sunak similarly dragged his feet on offering support for ballooning energy bills. He is, at heart, a small-state Conservative, even if he has showed a commendable ability to overcome his natural instincts when urgent need arises.

If fiscal conservatism comes first for Mr Sunak, what comes after is much more erratic. As an ambitious backbencher Mr Sunak supported low-tax “freeports”, which shuffle economic activity around rather than generating it. As chancellor Mr Sunak championed the “Eat Out to Help Out” scheme, when the government in effect paid unvaccinated people to sit together during a pandemic and infect each other. Mr Sunak pushed the Royal Mint to issue a non-fungible token this summer, just as the market for these digital assets crashed. Support for quixotic policy is the norm for Mr Sunak rather than the exception.

In politics, however, luck sometimes masquerades as judgment. Losing the leadership contest to Ms Truss this summer was a big stroke of fortune. During that campaign Mr Sunak predicted that Ms Truss would be a disaster, and she was. He warned that reckless spending commitments would force mortgage rates higher; his campaign team even put together a calculator, pointing out the high bills that would hit households if rates hit even 5%. Yet mortgage rates were heading up regardless of Ms Truss’s rash budget. Her errors have obscured the fact that, had Mr Sunak won in the summer, rising interest rates would have left him with tricky questions to answer. Instead he can pin it all on Ms Truss.

During the summer campaign, and throughout his time on the front benches, Mr Sunak has taken a path long followed by the Conservative Party, which has governed in its narrow political interest rather than the national one. Pledges to curtail onshore wind and solar development please a few zealots but make it harder for Britain to reach its climate goals. Slashing fuel duty as chancellor provided a few days of positive headlines, but failed to put much money in people’s pockets and did not help the environment. There is little evidence that Mr Sunak will take on the vested interests, often in his own party, that hold back Britain’s economy.

Standing on the shoulders of dwarves

The prime minister is a cut above most of his peers. But this is as much a function of a Conservative civil war that killed off competent colleagues as Mr Sunak’s own talents. Elected only in 2015, Mr Sunak has not been doing the job very long. Inexperience, even with copious intelligence, is always a problem. Yet the Conservative Party had nowhere else to turn. It would be comforting to think of Mr Sunak as a clever cynic, a gambler who bet big on Brexit and Mr Johnson and (with a helping hand from Ms Truss) became the youngest prime minister in two centuries. A more worrying analysis is that he is a bright and decent man with bad ideas.

On this reading Mr Sunak does not mark a change from the Tory policies that have left Britain in such a state. Rather he personifies them. The rot in the Conservative Party did not begin with Ms Truss. Britain’s departure from the eu, which Mr Sunak supported, is the thing that acts as a handbrake on the country’s economic prospects. Mr Johnson’s chaotic reign, which he also supported, caused even more ruin. It is the Conservative Party’s failure to take on its supporters that does so much damage to the country. Mr Sunak may be the only available man to fix the government’s errors. But he also helped make them.

Why Britain cannot build enough of anything

 The problem is bad rules, not bad people opines The Economist

Sep 1st 2022

Duncan sandys, a Conservative minister in the 1950s and 1960s, has two reasons to be remembered. The first is that he was the “headless man” being fellated by the Duchess of Argyll in a Polaroid photo, which emerged in divorce proceedings so vicious that they were turned into a bbc One drama earlier this year.

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The second reason is less salacious. In 1955 Sandys issued a circular that fundamentally changed Britain. It implored local councils to forbid building on the edge of cities in order “a) to check the further growth of a large built-up area; b) to prevent neighbouring towns from merging into one another; or c) to preserve the special character of a town”. The authorities had tried to restrict urban growth since the reign of Elizabeth I. Now they could.

Today all four nations of the United Kingdom have green belts. About 13% of England is so designated, including the surroundings of every major city. The girdle that encloses London is three times the size of the capital. A stroll through it takes in scrubland, pony paddocks and petrol stations. In “The Blunders of our Governments”, a book by Anthony King and Ivor Crewe, the policy is held up as a rare example of legislation achieving exactly what was intended.

The green belts do their jobs well, pushing development into the rural areas between them (see maps). Indeed, most parts of the planning system work as intended. Councillors retain democratic control over the planning system. Environmental watchdogs enforce their mandates fiercely. Stringent rules protect bats, squirrels and rare fungi. Courts ensure that procedures are followed to the letter. But the system as a whole is a failure. Britain cannot build.

In total, about 10% of gdp is spent on building, compared with a g7 average of 12%. England has 434 dwellings per 1,000 people, whereas France has 590, according to the oecd, a club of mostly rich countries. There is little slack in the market. In France, about 8% of dwellings are vacant at any one time. In England, the rate is barely 1%. Britain also struggles to build reservoirs and (despite boasts from successive prime ministers) nuclear power stations. With almost 500,000 people, Leeds is the largest city in Europe without a mass transit system. What has gone wrong?

The problem starts with the Town and Country Planning Act, which nationalised the right to build on land. Where once owners could do almost as they pleased, after its passage in 1947, local councils controlled what was built where. They have never relinquished that power. The planning system has more in common with an old eastern European command economy than a functioning market, argues Anthony Breach of Centre for Cities, a think-tank. “We do not have a planning system, we have a rationing system,” he says.

Even when councils approve development, other outfits can stop it. Natural England was created in 2006 with the aim of protecting flora and fauna. After a European Court of Justice ruling in 2018, it was tasked with ensuring “nutrient neutrality”, meaning any development could not increase phosphate or nitrate pollution in rivers. Natural England came up with a blunt solution: building could not go ahead unless developers could prove it would not lead to an increase in nutrient levels, a stipulation that few could provide.

The result was a near total freeze on house-building. Local politicians and developers, who had spent years in painful negotiations, were caught out. In total, about 14% of England’s land faced extra restrictions. One industry group argues that 120,000 houses were affected, or 40% of Britain’s annual housing target. Liz Truss, the likely next prime minister, has promised to scrap the requirement, but details are scant.

Newts present as many problems as nutrients. Anyone who harms a great crested newt while building can be jailed for up to six months. Bats are a nightmare for anyone renovating or developing (enterprising nimbys sometimes install bat boxes in order to attract them to a potential site). Protected under law, it is a crime to harm a bat or destroy its roost. A full report, which involves ecologists scouring a property with bat-hunting microphones plugged into iPhones, can cost £5,000 ($5,800).

If a roost must be destroyed, a like-for-like replacement must be installed. hs2, a railway line, was forced to build a £40m bat tunnel to stop the creatures being squished; its route is lined with bat-houses, which are large enough for humans. For developers, the rules are an expensive annoyance. For bats, however, the legislation has been a success. Numbers of the common pipistrelle have almost doubled since records began in 1999.

Some schemes do not survive contact with environmental objections. A planned nuclear power station in north Wales was rejected by the planning inspectorate in 2019 partly on the ground that it might affect a local population of terns. Inspectors ruled that “it cannot be demonstrated beyond reasonable scientific doubt that the tern colony would not abandon Cemlyn Bay”. That the terns had existed next to a previous nuclear power station was little defence. Inspectors also worried about the effect construction would have on the dominance of the Welsh language.

Even small housing estates now require reams of impact assessments and consultations. A planning application used to involve a single thick folder, says Paul Smith, the managing director of Strategic Land Group, which helps customers win planning permission. Now it is a thicket of pdfs, often running to thousands of pages.

For a development of 350 houses in Staffordshire, a developer had to provide a statement of community involvement, a topographical survey, an archaeological report, an ecology appraisal, a newt survey, a bat survey, a barn owl survey, a geotechnical investigation to determine if the ground was contaminated, a landscape and visual impact assessment, a tree survey, a development framework plan, a transport statement, a design and access statement, a noise assessment, an air quality assessment, a flood risk assessment, a health impact assessment and an education impacts report. These are individually justifiable, yet collectively intolerable.

See you in court

Make an error, however, and a legal challenge will follow. Anyone affected by a decision and able to afford a judicial review can challenge a planning decision. For a group of motivated, well-off nimbys, whipping together £20,000 for a review is easy enough. In Bethnal Green, in east London, a mulberry tree blocked the conversion of a Victorian hospital into 291 flats. Dame Judi Dench, an actor, was roped in to support the tree, which was so frail it required support from a post haphazardly nailed onto one of its branches.

After a campaign, the mulberry was in 2018 designated a veteran tree, which gives it special legal rights. (The number of signatories to save the tree matched the then population of Bethnal Green.) Although the developer had proposed moving the plant, a judge ruled that the council had not properly considered the danger that it might not survive: “A policy was misinterpreted; a material consideration was ignored.” The site sits derelict today.

Councils behave rationally when it comes to development. They levy no income tax or sales tax, and cannot even fund all their operations from property taxes, known as council tax. In all, local government imposes taxes worth less than 2% of gdp, according to the oecd. So more development does not equal much more money for better services. But it does equal more complaints. Councillors often enjoy majorities of just a few dozen votes. A well-organised campaign can replace an entire council, as happened in Uttlesford, in Essex. The result is that local councils are “a bottleneck on national economic growth”, argues a joint paper by the Centre for Cities and the Resolution Foundation.

The government in Westminster can usually override local objections. “When the state decides to act, it has unlimited power,” says Andrew Adonis, a Labour peer, who oversaw the introduction of hs2. Projects such as hybrid bills allow the government to bypass the planning system, turning Parliament into a kind of planning committee. The process is so arduous that sitting on the committee is often a form of punishment from the whips who enforce party discipline. But the benefit is that courts do not challenge primary legislation. Judicial review claims bounced off hs2 like stones off a tank.

Even when the government acts, it is often cautious. A plan to turn a quarry in Kent into a settlement of 15,000 homes was one of the most ambitious schemes, when announced by George Osborne, the then-chancellor, in 2014. Yet it is around a seventh of the size of Milton Keynes, a maligned but highly successful new town begun in the 1960s.

Larger schemes, such as a push for a million homes stretching between Oxford and Cambridge, with a new railway and motorway linking them, have been ditched due to local opposition. “We were a bit out of puff,” admits a cabinet minister. Greg Smith, a Tory mp, had already put up with hs2 slicing through his constituency, and it seemed unfair to subject him to more building. In Britain, pork barrel politics works in reverse, with mps keen to keep things out of their constituencies.

As a result, Britain’s most productive region is shackled. Burgeoning life-sciences firms fight for scarce lab and office space while world-class researchers live in cramped, expensive homes. The average house price in Oxford, £474,000, is about 12 times average incomes. Given the opposition of local councils and local mps to housebuilding, though, it can hardly be said to be against voters’ will.

Britain is rare in that the Treasury functions as both a finance ministry, keeping a close eye on spending, and an economic ministry, investing for the future. Thriftiness tends to trump investment. “[The Treasury] can add up but they can’t multiply” as Diane Coyle, an economist, puts it. It shackles big infrastructure projects, balking at upfront costs even if there are large returns later on.

The result is false economies. hs2, a £100bn project to connect London to Birmingham and then Manchester, Sheffield and Leeds, was intended mostly to add capacity to Britain’s crowded railways, not (despite the name) to speed journeys up. The government recently cut the eastern leg of the scheme to save money. That it was the most beneficial part of the scheme—the eastern leg to Leeds and Sheffield had a benefit-to-cost ratio of nearly 5.6:1, compared with 2.6:1 on the western leg between London, Birmingham and Manchester—was overlooked. Joseph Bazalgette, the Victorian responsible for London’s sewer system, is said to have argued that: “We’re only going to do this once and there’s always the unforeseen”. Now, the opposite principle applies.

Political capital is less fungible than the financial kind. When it comes to building things in Britain, there is usually no alternative scheme ready to go. If a big project is scrapped, the political capital spent on forcing through its approval cannot be instantly reallocated. The slow process of winning support at a local and national level must start anew. In the meantime, nothing is built.

And Westminster can be capricious. In 2022, after years of argument, Transport for London won permission to build 351 flats on land it owned at Cockfosters Underground station. Grant Shapps, the transport secretary, blocked the development because it removed too many car parking spaces. The Leeds Supertram Act was passed in 1993. Three decades later, Leeds possesses no tram, super or not, as a series of governments refused to fund the project. In 2016 the government rejected a proposal for a trolleybus, in part because it did not think the route would reduce inequality within the city.

Scepticism among nimbys is often justified. Post-war town planners botched city centres, bulldozing through objections. Birmingham’s Victorian centre was carved up to make way for ring roads that still throttle the city. London narrowly avoided a similar fate. New developments, such as Nine Elms, manage to be expensive while looking cheap. Outside big cities, development is often limited to boxy housing estates, which are notorious for poor building quality. A Welsh property surveyor has amassed 560,000 followers on TikTok by angrily taking viewers through snags in newbuilds. (“Check out what this absolute melt has done with this hinge,” he almost screams in one video. “That is absolutely ridiculous.”)

In Oxfordshire a group of residents have spent almost a quarter of a century fighting attempts to build a reservoir. The Environment Agency and a public inquiry sided with the residents over Thames Water. The objectors are shrewd, motivated and well-versed in water regulation. The chairman of the Group Against Reservoir Development (gard) is a retired nuclear scientist; his predecessor was a brigadier. But after a summer of drought, in which Thames Water had to implement a hosepipe ban, the victory rings a little hollow.

Efforts are being made to convert the unbelievers. New planning legislation offers residents the chance to propose their own development and, in effect, approve it themselves via street votes. The government is trying to improve design standards, hoping that beautiful buildings will attract less opposition. Those who put up with infrastructure, whether wind turbines or a reservoir, may benefit from free energy or water bills under one scheme floated by ministers.

Officials are also toying with a net-zero trump card. Projects deemed crucial to making Britain emissions neutral by 2050 would be able to ride roughshod over many obstacles. At the moment policy aimed at protecting the environment hinders projects that should help the climate. The government protects flora and fauna because voters want it; circumventing such rules can only be done in the name of the environment, runs the logic.

Building is binary, however. If something is built, those who oppose it will be unhappy; if it is scrapped they will be delighted. There is little incentive to meet halfway, or to accept a payoff. “This is not some sort of poker game where we demand huge compensation,” said Derek Stork, who chairs the reservoir-killing gard. Britain cannot build. But that is just the way voters want it.