Science is packed with committees deciding on ethics… but there are few that decide whether it is safe
“I am officially launching my new company: Cathy Medicine. We will eradicate diseases in future generations through germline gene editing.” This is one of several strongly and strangely worded tweets sent in recent days from the Twitter account of He Jiankui, a Chinese scientist who served a three-year prison sentence for gene-editing two human embryos. Those embryos are now people: seven-year old twin girls with the pseudonyms Lulu and Nana.
“Good morning bitches,” Dr He wrote on 16 April. “How many embryos have you gene edited today?” “Get in luddite, we’re going gene editing,” he added the next day. And: “I literally went to prison for this shit.” Is it the real Dr He? The journalist Antonio Regalado, who first broke the story of Dr He’s experiment in 2018, contacted him by email to ask if these tweets were from him or had his Twitter account been hacked. “Yes, it’s me,” replied his normal email account.
Germline gene editing of human beings – so that the edits are inherited by their children – is a taboo among scientists. They insist it is neither safe (yet) nor ethical, given the possibility that it could be used to “enhance” people. But they do it to viruses all the time – especially in Wuhan where they specialise in turning bat viruses into ones that can infect humanised mice. It’s a glaring double standard.
The key technology for human beings, known as Crispr, was invented in 2012 by repurposing a tool from a bacterial immune system, which can home in on precise sequences in a genome, cut the DNA and insert an edited version. Before Crispr, genetic engineering and gene therapy meant throwing genes into genomes with viruses in the hope that they landed in a good spot without breaking an existing gene. Good enough for tomatoes, where the deformed mistakes could be discarded, but not acceptable for human beings. The latest iteration of Crispr, known as PASSIGE, invented this year by David Liu at the Broad Institute (a collaboration between Harvard and MIT), can insert a large gene into a precise spot with very few “off-target” mistakes.
It was Crispr that Colossal Biosciences used to create a “dire wolf”, announced earlier this month. It did so by altering around 20 of a grey wolf’s genes to match the genes of extinct “dire wolves”, a larger species with white fur. That is only a fraction of the genomic differences between dire and grey wolves, so many think Colossal is making misleading claims. But that it will soon be possible to generate animals that look almost exactly like extinct species such as mammoths and passenger pigeons is increasingly plausible.
The experiment that got Dr He sent to prison in 2018 involved seven couples in which the father was HIV-positive. Such people can bear healthy children by “washing” sperm in such a way as to remove all traces of the HIV virus with near 100% effectiveness before using IVF. But Dr He offered a further reassurance to the couples. He took their embryos and used Crispr to disable a particular gene, CCR5, without which HIV cannot infect human cells. In two cases, at least, it worked.
(CCR5 is an intriguing gene. It appears to protect against some infections but make you more vulnerable to others, and being without it does not seem to be problematic. A natural mutation that knocks out CCR5 seems to have arisen among Vikings about 700 years ago and spread through Europe where it is now present in around 10% of people, possibly because it gave protection against bubonic plague. Lulu and Nana are therefore likely to be immune to some diseases and prone to others.)
https://pmc.ncbi.nlm.nih.gov/articles/instance/1377146/pdf/9585595.pdf
When news of Dr He’s experiment broke, People’s Daily called it “a historical breakthrough in the application of gene editing technology for disease prevention”. But within days, western and Chinese scientists had reacted with fury. Over 100 of the latter signed a letter that called the work “a huge blow to the global reputation and development of Chinese science”. The experiment was unnecessary because the couples were at minimal risk of passing on HIV, and it touched an ethical third rail.
It soon emerged that Dr He had used private funding and thus avoided scrutiny by the state. He was prosecuted, convicted, fined and imprisoned for three years. Released in 2022, a year later he became director of a new Genetic Medicine Institute at the private Wuchang University of Technology, in Wuhan. Last October he moved to Beijing from where he is apparently sending tweets that seem to promise he will resume germline gene editing of human beings, this time to tackle Alzheimer’s disease. Has the Chinese government decided they like his work after all?
Last week [18 April] Dr He says he married Cathy Tie, a Canadian biotech entrepreneur (after whom his new company is presumably named) who is herself also in a hurry to start gene-editing babies. She tweeted in February that “despite CRISPR being a valid scientific tool, scientists haven’t figured out a harmless method to deliver genetic changes into a patient’s body. Embryos are a different case. Delivering a genetic change to a single cell embryo can be done with one injection.” She argues that Big Pharma prefers to develop expensive and largely useless drugs to treat conditions that could be prevented before birth.
Wuhan is where the worst scientific accident of all time happened in 2019. The White House has now joined the CIA, FBI, German intelligence, the French national science academy and many others in confirming what we have all known for four years to be likely: that a reckless experiment to make coronaviruses better at infecting human cells resulted in the deaths of more than 20 million people.
But whereas the scientific world – in China and the west – was alarmed by Dr He’s cloning experiments, they continue to close ranks to this day around Dr Shi Zhengli’s far more dangerous gain-of-function experiments at the Wuhan Institute of Virology. Why is Shi more acceptable than He?
There is no other place on the planet than Wuhan, and no other period in history than 2017-2019, where and when anybody was doing uncannily suspicious experiments on the exact kind of bat-borne SARS-like coronavirus that caused a pandemic. Coincidences do happen but not on this scale.
Dr Shi Zhengli’s laboratory was collecting coronaviruses from bats in southern China on a huge scale, bringing them a thousand miles north to Wuhan, sequencing their genomes, swapping their spike genes and infecting humanised mice with them sometimes with dramatically increased infectivity as a result. And boasting of doing these experiments at low biosafety levels to save cost. They had the nine closest relatives of Covid in their lab at the time of the outbreak. In 2018 they planned to put a furin cleavage site into a SARS-like virus for the first time, this being the very feature that made Covid so uncontrollable, and which has never been found in any others of this kind of virus before or since.
Yet the reaction of the scientific community in China and the west to Dr Shi has been exactly the opposite of that to Dr He. Those of us trying to find out what happened in the Shi lab in Wuhan have been slandered, abused, censored and called conspiracy theorists by scientists and told to stop casting aspersions on a great Chinese scientist. Yet Dr He hurt nobody, not even the subjects of his experiment, whereas it is highly likely that the reckless and pointless experiments done in the Shi lab killed millions and caused global chaos.
To give an example of just how far people still go to censor and prevaricate on this issue, the following wording appears in Wikipedia to this day: “There is no evidence that any genetic manipulation or reverse genetics (a technique required to make chimeric viruses) of SARS-related bat coronaviruses was ever carried out at the WIV”. Yet several of Shi’s own published papers and an unpublished report from her lab openly boast in detail of inventing reverse genetics techniques, manipulating virus genomes and thus gaining them the function of increased infectivity in humanised mice.
When I pointed out the error, Jimmy Wales, Wikipedia’s founder, seemed genuinely surprised, apparently unaware that the entire entry on the origin of Covid is aggressively policed by a pro-China squad of enforcers of the dogma that it cannot have started in a lab.
I am not defending Dr He, who was recklessly premature at the very least; I am pointing out the inconsistency. A better case can be made for doing germline gene therapy to prevent people being born with life-limiting diseases, where the impact on everybody else is limited, than for training souped up bat viruses to infect human cells, where the downside risk is global.
The simple explanation of the double standard is that Dr He’s transgression was ethical while Dr Shi’s was a biosafety one. Science is packed with committees that decide whether a planned experiment is ethical; there are few such committees that decide on whether it is safe. Bioethics is a career; biosafety is not. Virologists argue repeatedly that it is offensive even to ask them to submit to extra biosafety regulation because “you can trust us”.
Self interest also played a part. Anthony Fauci in Washington approved the funding of the experiments; Peter Daszak in New York channelled the money to Wuhan; Ralph Baric in North Carolina shared the expertise of how to do the work – and the humanised mice. Western scientists would have egg on their faces, at the very least, if they had to admit that an egregious scientific error caused the most lethal preventable accident in the history of humankind.
I reached out to Dr He and Dr Shi for comment.