Chinese scientists let eugenics out of the bottle

What this young and formerly little known Chinese scientist did to make twins Aids resistant this week has left scientists aghast.

Chinese scientist He Jiankui speaks at the Second International Summit on Human Genome Editing in Hong Kong this week. Picture: AFP

He Jiankui let the genie out of the bottle when news broke this week that his team in China had genetically engineered newborn twins to be resistant to the AIDS virus.

Good job, you may think. But the implications of what this young and formerly little known researcher did are staggering.

In creating the world’s first DNA-enhanced babies, He took it on himself to bring the deeply contested science of eugenics into kicking, breathing life.

Like it or not, the future had suddenly arrived.

Despite the absence of peer-reviewed published findings, which by convention would accompany an announcement of this import, the available evidence supports his claim to a place in history, albeit at the cost of violating ethical mores and possibly laws to boot.

Last month the infant girls, Lulu and Nana, were born as part of an experiment involving eight Chinese couples, all with the male partner HIV-positive. Using a gene editing tool known as CRISPR-Cas9, He claims to have disabled the gene that opens the door to the AIDS virus to invade cells and multiply. Without the receptor produced by functional CCR5 genes, the infection may be unable to take hold.

He, 34, said his aim was to modify the twins’ DNA to render them immune. A high-minded explan­ation that he was giving HIV-affected couples, who face entrenched discrimination in China, “hope for life” was drowned out by the tsunami of international criticism.

His own university in Shenzhen disowned him and China’s vice-minister for science and technology, Xu Nanping, suggested he had breached regulations governing genetic research.

The country’s National Health Commission ordered an immediate investigation.

US National Institutes of Health director Francis Collins said altering the human genome was a “line that should not be crossed” and renowned Oxford University bioethicist Julian Savulescu branded the work “monstrous”. Kathy Niakan, a leader in the field from London’s Francis Crick Institute, warned it represented an irresponsible, unethical and dangerous use of the powerful gene editing technology. Their outrage was typical of the reaction.

Here in Australia, prominent ethicist Simon Longstaff worries about the precedent that has been set. “Some of our worst dreams in terms of the possibilities around eugenics could start to be realised,” he tells Inquirer. “You could have whole groups of people who are being fundamentally altered in terms of their futures in ways that society never really gets to think about, talk about or decide because of a scientist going rogue outside the normal conventions of good scientific researching.”

As He discovered when the thunderbolt struck, ahead of his appearance on Wednesday at a drawcard scientific conference in Hong Kong, it is one thing to man­ipulate individual genes and quite another to manipulate the gen­ome, nature’s instruction manual for the 37 trillion cells that make up the human body.

TAUS iNQUIRER gene baby explainer embed

CRISPR and other gene-editing tools are used to cut and paste DNA in the hope of finding genetic fixes for disease. But in these cases, the altered cells stay within the individual’s body.

Editing an embryo, as He did, is very different: it changes every cell in the body, including the sperm or eggs that would pass those modifications on to future generations. This is what responsible scientists are getting at when they caution against unforeseen consequences for the human germline.

Until this week, it was an academic discussion given that most countries, Australia among them, have banned genetic experiments that could result in a laboratory mutation being permanently and heritably etched into the genome.

The Chinese are developing a deserved reputation for cutting corners on the regulation of the fast-moving research. CRISPR has been around for only six years. But in 2015, a lab at the Sun Yat-sen University in Guangzhou ­casually announced that it had used the tool to edit human embryos obtained from a local IVF clinic, though these were non-viable discards that could never have resulted in a live birth. It was a slapdash experiment meant to provoke a response — and it did.

Around the world, scientists reacted with anguish and concern, foreshadowing this week’s vitriol. In the West, researchers have pushed the legal boundaries in the race to stay competitive. Last year, Shoukhrat Mitalipov of Oregon Health and Science University in the US, gene edited viable embryos but stopped short of implanting them. He’s claim to fame is to be the first to own up to doing so, assuming his results are ­verified.

That’s because CRISPR is not especially difficult to use, which is one of the attractions of the technique. “You don’t need a lot of equipment or super-duper expertise,” says Robert Brink, a senior principal research fellow at Sydney’s Garvan Institute of Medical Research. The system is an ingenious adaptation of the defence response evolved by bacteria to attacks by viruses: a biological switchblade to deliver co-ordinated slashes to the genome of the invading pathogen. Once scientists realised the mechanism was programmable, they harnessed the bacterial protein, Cas9, to target selected genes, thereby mutating them at will.

In this sense, it was probably only a matter of time before someone made this the means to an inevitable end: genetically enhanced people. Yet to regard He as some kind of lone wolf would be a grave mistake. The young man may have grown up on a farm in southern China but his higher training was conducted in the US, where he earned a PhD in biophysics from Rice University in Texas in 2010, capped off by a year as a post­doctoral research fellow at Stanford, incubator of some of the world’s brightest biotech talent.

He was lured home in 2012 to set up a lab at the Southern University of Science and Technology in Shenzhen under a well-funded program run by the Chinese government to retain promising researchers. The added attraction was he could do work there that was not possible in the US, most of Europe or Australia.

China banned human cloning for reproduction in 2003 but He told US wire service AP he believed gene editing of human embryos resulting in live births was legal because the country had no law specifically forbidding it.

He also had tapped his contacts in the US. His mentor at Rice, physics professor Michael Deem, reportedly was involved in the research and sat on the scientific advisory boards of He’s two genetics companies (Deem now is being investigated by the Texan university.) Other American scientists were brought on to the team in Shenzhen. Their role and knowledge of what he was up to no doubt will be raked over. But the man himself made his priority clear, telling AP he wanted to be the first to deliver a gene edited child. “There will be someone, somewhere, who is doing this,” He said in a recent interview. “If it’s not me, it’s someone else.”

The researchers looked at targeting the PCSK9 gene that helps regulate cholesterol in the bloodstream before settling on the HIV pathway. They ran trials on mice and monkeys, and turned to a Beijing-based AIDS advocacy group Baihualin to recruit the couples. He is adamant all the subjects gave informed consent, having been exhaustively briefed on the “off target” risks. While CRISPR is cheap and easy to use, it is far from foolproof and can set off dangerous changes in genes other than the ones intended; cancer is among the possible consequences.

To begin with, the sperm from each HIV-positive man was “washed” to neutralise the virus and then injected into eggs extracted from their partners. The embryo, when only one to four cells in size, then was treated with the CRISPR “machinery”, painstakingly introduced by an embryologist using a tiny pipette.

At 500 cells — barely a smear in the test tube — the enhanced embryos were tested to check if the gene editing had worked. At this point, the scientists could see most of the genome to anticipate any off-target effects. He now has revealed that a second woman was implanted, without providing details. Little Lulu and Nana are said to be thriving in the care of their unidentified parents.

Addressing the Second International Summit on Human Genome Editing in Hong Kong, He said his only regret was that news of the babies’ arrival had leaked to the media before he could get the research published in an academic journal. “For this specific case, I feel proud, actually,” he said on Wednesday.

The irony is that He and four collaborators did manage to place an article in this month’s edition of the respected CRISPR Journal — an ethics statement on “fundamental human values” to frame, guide and, yes, restrict germline gene editing, but that makes no mention of the contentious work in Shenzhen.

Among the five core principles enunciated is “mercy” for families in need and respect for the child’s autonomy: “A life is more than our physical body and its DNA,” they write. Yet Brink, who confines himself to working on lab mice at Garvan, wonders what the future holds for those two special babies He helped create.

You see, there’s a reason nature gave us the CCR5 gene. As Brink says: “HIV takes advantage of it, but its presence is important to the functioning of the immune system.” The veteran Australian researcher says the infants’ engineered resistance to the AIDS virus may be a good thing in isolation, but in the greater scheme of things it also may make them susceptible to infections that a properly functioning immune system will defeat.

Who can say what will happen in their course of their lives, let alone those of the children they may have and untold generations to follow? Let’s hope this is a cautionary case, not the harbinger of an even more uncertain future.