About a decade ago, He Jiankui visited a village in central China…
It’s a notable place for very unfortunate reasons.
Back in the 1990s, the area saw a surge in the sale and distribution of HIV-infected blood, resulting in more than 30% of the population contracting HIV.
While visiting, He Jiankui noticed a kindergarten that was only for the children of HIV parents. The stigma around HIV was so bad that children were effectively segregated from their peers at public schools.
Witnessing this would become the motivation for He Jiankui’s genetic engineering research. His goal was to assist HIV-infected parents to have children who were immune to the virus.
And that’s exactly what he set out to do.
A scientific team led by He at the Southern University of Science and Technology in Shenzhen recruited HIV-infected couples who wanted to have children.
He and his team believed that they could either eliminate or edit the CCR5 gene using genetic editing technology. There is a known natural mutation to this gene that HIV cannot attach to. If that mutation can be recreated by a genetic edit, doing so would, in theory, make the children immune to HIV.
The foundational research for CRISPR genetic editing technology was published in late 2012. It opened up a world of possibilities to cure all diseases caused by unwanted genetic mutations.
That research took the scientific community by storm. The science was elegant in its simplicity. And it held the potential to “program” human DNA almost as if it were software code.
Shown below, CRISPR technology can be used to deliver a corrected DNA sequence (in yellow) by using a guide RNA (in orange) to deliver the desired DNA sequence to the correct location in plant, animal, or human DNA.
Source: Editas Medicine
The guide RNA and the desired DNA sequence are delivered with an enzyme like Cas9 (CRISPR-associated protein 9 – shown in gray). The enzyme is used to cut the DNA strand allowing the edits to be made.
Where He and his team crossed the line with the scientific community was with the nature of their experiment. Their clinical trial used CRISPR genetic editing technology to modify human embryos prior to implanting them in the mother’s uterus.
This is known as germline editing, whereby the embryo is edited and whatever genetic edits caused by the editing will be passed down to future generations. That’s something the international genetic editing community has long taken a strong stand against.
Despite the questionable ethics of the trial, He and his team didn’t ask for permission. They went forward with their research and modified the human embryos for three sets of parents, which resulted in three births.
The world’s first CRISPR’d babies.
The outrage was everywhere. Germline editing was taboo… and is still taboo. And given how new CRISPR genetic editing was to the scientific community at the time, there was just so much that wasn’t well understood.
One of the biggest risks was unintended off-target editing and the potential unwanted side effects it could cause.
He and his team’s research was published in 2018, the children were born, and all hell broke loose.
He Jiankui in 2019 | Source: The Guardian
He was found guilty in China of “illegal medical practices” which resulted in fines and three years in prison. And his CRISPR’d babies kicked off widespread ethics discussions resulting in ethical frameworks for the genetic editing community.
And perhaps, a not-so-surprising thing happened.
Despite what had occurred, many scientists were anxious to know how the CRISPR’d children were doing.
Were they healthy? Had they experienced any side effects from the germline therapy? Was it safe and effective?
It was only three children, so it wasn’t like a large-scale clinical trial. But again, it was so early in the CRISPR therapeutic development stage, the community was keen to learn from any developments.
The children and the parents involved in the small trail were closely guarded. So for years, there have been far more questions than answers.
In the spring of 2022, He was released from Chinese prison after he and his family suffered greatly, paying the price for his own doing and scientific curiosity. Not surprisingly, he was unwilling to talk after the dilemma… leaving many to wonder what, if anything, he would do next.
But now we know.
In a rare interview a few days ago, He confirmed he had resumed his research in a private lab in the Hainan province. He made it very clear that his work is only focused on genetic editing as it pertains to monkeys and non-viable human embryos.
Naturally, he was asked about the condition of the three CRISPR’d children that resulted from his original work that got him in so much trouble. In fact, that was the very first thing that he was asked.
Fortunately, He shared that all three children are “healthy and living normal, peaceful, undisturbed lives.” He has maintained a “constant connection with their parents.”
Unfortunately, it appears that he has not been able to conduct any further scientific study on the children’s blood to confirm that their DNA is resistant or immune to HIV. Hopefully so, and hopefully the children won’t have any unwanted side effects either as they grow.
He and his team had originally structured their trial to collect the umbilical cord blood at birth, which they did. The plan was to test the blood in a laboratory against the HIV virus. But when the uproar occurred after his research had been published, he wasn’t able to conduct the test.
Clearly, the original clinical trial was risky, reckless, and unethical. There was no way for He and his team to know if the edits were safe and effective back in 2018. Editing viable human embryos and implanting those edited embryos into the mothers’ uteruses was highly unethical. It was the equivalent of rolling the dice with the lives of three children.
It’s impossible to roll back the clock though. And according to He, there are three healthy children who are hopefully immune to HIV.
It’s easy for us to be skeptical of He’s claim that they’re doing fine without the scientific research and analysis of the blood to confirm it. And yet, if I had to guess, it’s true.
The early success that both academia and biotechnology companies have been having with CRISPR technology has been remarkable in the last six years. We’ll take a look at some of that tomorrow.
While He and his team’s approach to research was reckless and dangerous, there are clearly ways to work with CRISPR responsibly and safely. And that’s exactly what has been happening in the U.S. and Europe.
The empowerment that CRISPR genetic editing technology provides for the life sciences industry is as significant as artificial intelligence is for computing. And it will have an equally significant impact on the human race.
The Bleeding Edge is the only free newsletter that delivers daily insights and information from the high-tech world as well as topics and trends relevant to investments.
The Bleeding Edge is the only free newsletter that delivers daily insights and information from the high-tech world as well as topics and trends relevant to investments.
