The Trump Organization, run for years by former US president Donald Trump and three of his adult children, is facing multiple New York lawsuits related to its financial reporting MANDEL NGAN AFP

New York (AFP) – The trial of Donald Trump’s family business on fraud and tax evasion charges began in New York on Monday, with the former US president immediately dismissing as it as a political stunt.

In October 2014, virologist Edward Holmes took a tour of the Huanan Seafood Wholesale Market in Wuhan, a once relatively overlooked city of about 11 million people in the central Chinese province of Hubei. The market would have presented a bewildering environment for the uninitiated: rows of stalls selling unfamiliar creatures for food, both dead and alive; cages holding hog badgers and Siberian weasels, Malayan porcupines and masked palm civets. In the southwest corner of the market, Holmes found a stall selling raccoon dogs, stacked in a cage on top of another housing a species of bird he didn’t recognize. He paused to take a photo.

Eight years on, that photo is a key piece of evidence in the painstaking effort to trace the coronavirus pandemic back to its origins. Of course, it’s been suspected since the early days of the pandemic—since before it was even a pandemic—that the Wuhan wet market played a role, but it’s been difficult to prove it definitively. In the meantime, other origin theories have flowered centered on the Wuhan Institute of Virology, a biological research lab which, it’s argued, accidentally or deliberately unleashed the virus on the city and the world.

The overwhelming scientific consensus is that Covid originated in a similar way to related diseases such as SARS, which jumped from bats to humans via an intermediate animal. Figuring out exactly what happened with Covid-19 could prove immensely valuable both in terms of finally disproving the lab leak theory and by providing a source of information on how to stop the next pandemic. “This is not about placing blame,” says Kristian Andersen, a professor of immunology and microbiology at the Scripps Research Institute in California. “This is about understanding in as much detail as we can the origins of the Covid-19 pandemic.”

For the last two years, an international team of scientists including Andersen and Holmes has been trying to pinpoint the epicenter of the pandemic, using methods ranging from genetic analysis to social media scraping. Their research, which attracted widespread coverage in preprint before being published in its final form last week, reads as much like a detective report as an academic study.

First: the scene of the crime. Where exactly in this city of 11 million people did the virus first jump from animals to humans? To find out, the team—led by University of Arizona biologist Michael Worobey—scoured a report published by the World Health Organization in the summer of 2021, which was based on a joint investigation the public health body conducted with Chinese scientists. By cross-referencing the different maps and tables within the report, the researchers obtained coordinates for 155 of the earliest Covid cases in Wuhan, people who were hospitalized from the disease in December 2019.

Most of those cases were clustered around central Wuhan, particularly on the west bank of the Yangtze river—the same area as the Huanan market. “There was this extraordinary pattern where the highest density of cases was both extremely near to and very centered on the market,” says Worobey, lead author on the paper, which was published in Science. Statistical analysis confirmed that it was “extremely unlikely” that the pattern of cases seen in the early days of the pandemic would have been so clustered on the market if Covid had originated anywhere else: A random selection of similar people from around Wuhan were very unlikely to have lived so close to the market.

Even early patients who didn’t work or shop at the market were more likely to live close to it. “This is an indication that the virus started spreading in people who worked at the market, but then started to spread into the local community, as vendors went to local shops, infected people who worked in those shops, and then local community members not linked to the market started getting infected,” says Worobey.

A string 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. ■

Editor’s note: The pre-print “Endonuclease fingerprint indicates a synthetic origin of sars–cov-2” by Bruttel, Washburne and VanDongen, can be found at bioRxiv.

All our stories relating to the pandemic can be found on our coronavirus hub.

Viscount Matt Ridley, who co-authored a book on the origin of the coronavirus, called the new work a “hugely important study”.

“Evidence that strongly suggests SARS-CoV-2 was engineered may have been hiding in plain sight all along,” he said.

Prof Francois Balloux, the director of the UCL Genetics Institute, said it was “the strongest piece of evidence to date against a simple scenario of strict zoonotic origin for SARS-CoV-2”.

‘Highly misleading’

But prominent academics have rubbished the findings, claiming it was a “self-fulfilling prophecy” and the findings are “highly misleading”.

Critics say the signals the authors claim to be evidence of a lab origin are not a smoking gun because these genetic fingerprints are naturally found in many viruses, including the common cold.

Prof Stuart Neil, a professor of virology at King’s College London (KCL), accused the team of “stacking the deck” by cherry-picking their analysis and turning their paper into a “self-fulfilling prophecy”.

“It is confected nonsense put out to create a splash of controversy and become a talking point in the US and UK media,” he told The Telegraph.

Prof David Robertson, head of viral genomics at the Centre for Virus Research at the University of Glasgow, said paper was “nonsense” and “highly misleading”.

‘Poppycock dressed up as science’

Prof Kristian Andersen, evolutionary biologist and professor in the Department of Immunology and Microbiology at the Scripps Research Institute, called the work “nothing more than poppycock dressed up as science”.

“In plain language – this is uninformed nonsense and it’s simply not worth engaging with this b*******,” Prof Anderson said. 

The academic also said the paper is “so deeply flawed that it wouldn’t pass kindergarten molecular biology”.

The pre-print claims to have found telltale signs that the coronavirus was sliced up in a lab and stitched back together again, leaving behind “a very subtle but identifiable fingerprint”.

The team believe they have spotted “sticky ends” on the end of DNA fragments that have been moved around using enzymes. 

‘It makes a caricature of the whole situation’

But Dr David LV Bauer, a group leader at The Francis Crick Institute and expert in RNA virus replication, said this is impossible.

“Imagine that you’ve seen a train pulling into a station. They are identifying that they see the little couplers linking the carriages together. That’s what they claim to see,” he told the Telegraph. 

“What they’ve misunderstood is that the Golden Gate system is like the fancy new trains on the Elizabeth Line which don’t have any visible couplers.”

The analysis of the paper is also guilty of selective data interpretation, according to Dr Bauer, who says the authors “fixed” various aspects deliberately to only get the results they wanted and the findings will be unlikely to pass through peer-review.

“The result of the analysis has been constrained in such a way that they only ever see an outcome that they want and also there are all the red flags about how they don’t understand how this actually works,” he told The Telegraph.

“The problem with this kind of stuff is that it is perfectly legitimate to ask whether [Covid] came from a lab, whether it was tracked in or out on somebody’s shoe or whether it was engineered. These are perfectly legitimate questions to ask.

“But at the end of the day when you then put out this kind of stuff it just makes a caricature of the whole situation. It makes it really difficult to have any kind of reasonable discourse.”

‘Tinfoil hat bonkers’

Dr Benjamin Neuman, professor of biology at Texas A&M University, said the study “is the molecular equivalent of phrenology or numerology” and “tinfoil hat bonkers”.

“It’s about as illuminating an approach as converting the genome to digits, adding up the digits, and comparing that to the ‘number of the Beast’,” he said.

“The neatest thing is – look at the affiliations. We have someone who works at a gynaecology clinic, a business management efficiency analyst, and an Alzheimer’s researcher. As far as I can tell, none of these has ever worked with a virus before now, or studied virology, or been on a virology paper of any kind.”

NATO defence ministers took stock on Wednesday of its supply effort to war-torn Ukraine to date and debated ways to encourage the defence industry to ramp up production in short order.

The US-led 30-nation military alliance has been treading a fine line since Moscow’s full-scale invasion began, providing only non-lethal support and defending its own territory to avoid being dragged into a wider war with a nuclear-armed Russia.

Yet individual allies continue to pour in weapons and ammunition, including armoured vehicles and air defence or anti-tank systems.

Speaking to Euronews, Dr Patrick Bury, a senior lecturer in security at the University of Bath, said, “I think that both sides are essentially trying to find pressure points on each other and are then succeeding in doing so.”

“If you look at the Kerch bridge attack, which preceded the Russian bombardment of Ukraine and the other cities, it obviously had its military objectives trying to cut or at least slow down logistic supplies to the forces, especially in the Kherson region of occupied Ukraine,” Dr Bury said.

“I think the response, and, what we were expecting actually from the Russians for a while, had been increased attacks on critical national infrastructure using missiles.”

Nuclear arms threats and attacks against civilians spike

Allies are also training Ukrainian troops, building on the lessons NATO has taught Ukraine’s military instructors since Russia annexed the Crimean Peninsula in 2014.

At the same time, national military stocks and arsenals are being depleted.

Some countries are growing reluctant to provide Ukraine with more weapons when they are no longer entirely sure that they can protect their own territories and airspace.

However, following the gains Ukraine’s counteroffensive has made on the eastern frontline and the failed annexation of four occupied territories, the war has entered a new stage.

“In response to the Kerch bridge attacks, Putin would have felt a lot of damage to his personal prestige and pride, and so, some of the targets selected in that latest bombardment were also cultural ones that Ukraine would feel hurt by in a similar way,” Dr Bury, who is also a former NATO research analyst, added.

Putin’s attack on a sovereign country without provocation and his threats to use nuclear weapons to defend seized territory have made many allies neighbouring Russia and Ukraine further concerned.

The United States and its partners want to boost weapons production by sending clear signals to the industry as they pool resources and deliver Ukraine the hardware that it needs, all while ensuring that no major gaps appear in national stockpiles.

“Ukraine is a big country, with many cities. So we need to scale up to be able to help Ukraine defend even more cities and more territory against horrific Russian attacks against their civilian populations,” NATO Secretary-General Jens Stoltenberg told reporters in Brussels on Wednesday.

Stoltenberg said that following the apparent sabotage of the Nord Stream pipelines between Russia and Germany, NATO has “doubled our presence in the Baltic and North Seas to over 30 ships, supported by maritime patrol aircraft and undersea capabilities.”