Chinese scientists are again experimenting with mutated coronavirus strains.
Last month, a group of virologists from Beijing cloned and mutated a Covid-like virus found many years ago in a pangolin and used it to infect ‘humanized’ mice.
All eight mice infected with the GX_P2V virus subsequently died, leading to ominous headlines around the world.
The aim of the study, the scientists said, was to determine the danger of new Covid viruses to humans and provide data for the development of a universal vaccine – one that can protect against all coronaviruses.
Given the controversy surrounding the origins of Covid-19, it is perhaps unsurprising that the study, which has yet to be peer-reviewed, fell flat.
Professor Francois Balloux, the director of the UCL Genetics Institute, derided it as “scientifically completely pointless”.
“I see nothing of vague importance that could be learned by forcibly infecting an alien species of humanized mice with a random virus,” he wrote on X. “Conversely, I could see how such things could go wrong…”
But despite the controversy and potential risks, it’s not just Chinese scientists who are poking and prodding at the virus variants in an attempt to better understand them.
Now that the worst days of the pandemic are behind us, there is a boom in research into genetically modifying Covid variants, cloning related pathogens, hunting viruses and more.
While some of it is happening in the East, much of the work is happening in Britain, led by some of the biggest names in virology, as well as in Germany, Switzerland, Japan and the US.
The scientists involved insist there is little to fear and much to gain.
They say the experiments, carried out in safe, high-security laboratories, are essential for better understanding Sars-CoV-2 and the wider coronavirus family to which it belongs.
‘Reverse genetics’
A body called the G2P2-UK Consortium is leading this research in Britain.
It was funded by the British taxpayer and run by Imperial College London. It was founded with the aim of investigating how current and emerging Covid variants adapt in humans, and how they will take over in a population.
It also seeks to determine the role that different mutations (random changes in a virus’s genetic sequence) have on a variant’s characteristics, in terms of its lethality, transmissibility and ability to evade vaccine-induced immunity.
“To understand why different variants of concern behave differently, we need to identify which mutations in the genome confer these properties,” said Professor Wendy Barclay, head of the G2P2 Consortium.
This process typically begins with the emergence of a new Covid variant that has acquired a series of mutations.
The mutations not previously observed will be the focus of the experiments that follow. Their genetic coding will be removed from the Covid strain under study and inserted into the original Wuhan virus that emerged in late 2019, or sometimes into another variant of concern.
This process – called ‘reverse genetics’ – changes the virus’s proteins responsible for its ability to infect and replicate in human nasal cells, for example, or its ability to evade antibodies and other human defense mechanisms.
This modified virus will then be exposed to human cells grown in the laboratory or in hamsters to see if such functions are enhanced or reduced.
By repeatedly ‘mixing and matching’ different mutations through these experiments, scientists can ‘refine’ which mutations cause the variant’s troublesome features, says Professor Stuart Neil, a virologist at King’s College London.
“You can break it down into a single point mutation or a group of mutations.”
Professor Barclay said the work has been crucial in answering many of the unknown questions that surrounded Sars-CoV-2 during the acute phase of the pandemic.
“For example, the original Covid virus replicates less efficiently in human nasal cells in the laboratory than Omicron and its subvariants,” she said. “Why is that? Which ‘pieces’ of the virus are responsible for this property?
“We can now say that these differences are due to the spike protein and in the future we can look for mutations that could affect this property and alert public health officials if necessary.”
At first glance, the work appears to be venturing into the kind of genetic territory that amplifies the characteristics of Sars-CoV-2 – a hallmark of so-called gain-of-function research.
Yet there is a crucial difference: the consortium scientists do not add mutations to the virus that it has not yet learned in the wild.
“We limit our studies to naturally occurring mutations that already exist in the human population, we do not give the virus any function that it did not already have,” said Prof. Barclay.
This differs from gain-of-function experiments that might, for example, fuse the worst traits of two different viruses and see what risk this ‘chimeric’ pathogen poses to humans.
Although the G2P2-UK consortium does not conduct research of this risky nature, and neither do Chinese virologists in Beijing, it ensures that the strictest safety protocols are followed when conducting its own mixing and matching experiments.
All projects begin with a written risk assessment that must be approved by the Health and Safety Executive (HSE), the UK’s workplace safety regulator. If the research is considered too dangerous, permission will not be granted.
Experiments with the Covid virus and its variants, meanwhile, are being carried out in a ‘Containment Level 3’ laboratory – this is an airtight, gas-tight facility that uses a specialized airflow design to prevent the escape of dangerous pathogens.
It is one level below the highest level of laboratory biosafety, CL4, which tackles the world’s deadliest diseases – from Ebola to smallpox.
These facilities and their staff, who are specifically trained to work in a CL3 laboratory, are inspected at least once a year by the HSE – although a Telegraph investigation earlier this year found that recorded laboratory leaks and accidents in Britain have increased by 50 percent since Covid emerged.
It is understood that safety guidelines for laboratory experiments with the Covid-19 virus – including the sharing of mutations between variants – are being reviewed by the HSE.
The regulations for sampling, testing and analysis of Sars-CoV-2 were quickly implemented at the beginning of the pandemic, but were never updated.
The scientific understanding of “what makes the virus tick” has improved dramatically since 2020, an expert involved in the review said, raising questions about whether laboratory protocols for the pathogen should be strengthened – or relaxed.
An HSE spokesperson said: “As scientific knowledge of coronaviruses has now improved significantly, we would like to know whether further risk assessment advice for genetically modified coronaviruses would benefit the scientific community. This reconnaissance exercise is ongoing.”
Risks will of course always exist in this type of work, especially when it comes to the unpredictability of constantly evolving viruses.
Still, advancing our scientific understanding and thereby improving humanity’s preparedness against future biological threats is worth the reward, argues Dr. Benjamin Neuman, a virologist at Texas A&M University.
“Preparedness requires a certain amount of courage, individually for the scientist, and collectively for society,” he said. “But preparedness saves lives.”
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