Ridley: CRISPR announcement is great moment in medical history

Baby KJ lacked a working copy of a vital gene

The announcement last week that a nine-month-old baby in Philadelphia has been cured of a rare genetic disorder by gene editing is a great moment in medical history. For the first time, doctors have altered a gene inside many cells in the liver of a living human being using CRISPR, the molecular tool borrowed from microbes that can home in on particular DNA sequences and in some cases alter them.

It reinforces my view that biotechnology, applied to medicine, represents the greatest opportunity for innovation, and the greatest hope for rational optimism in the current generation. More so, perhaps, even than artificial intelligence (AI).

The baby, known as KJ, lacked a working copy of a gene vital for processing protein in food. This meant that even with a very low protein diet, he would probably die young or face mental and physical disability – even if he could get a liver transplant when a little older. Today, after the experimental treatment, he is thriving.

To some, this is an amazingly rapid achievement, coming just 13 years after the first invention of CRISPR as a tool for altering animal genes. To others, it is the end of a frustratingly long delay, coming 33 years after Francisco Mojica first discovered the CRISPR machinery in an archaeal microbe. And 26 years after the tragic death of a patient with a genetic disorder, Jesse Gelsinger, put a stop to a prior, much cruder technique for applying gene therapy to human beings that involved infection with live viruses.

The latest work could not have happened without the invention by David Liu and colleagues at the Broad Institute, of the latest version of CRISPR, known as base editing, in which the DNA is not cut but directly altered. The precision needed to ensure that every change is made in exactly the right place, without “off-target” effects took time to invent. A reminder of my obsession with the notion that innovation is as much (if not more) about perfecting tools as inventing them in the first place. Thomas Edison realised that the lightbulb was no use till it was reliable and affordable.

With the spectre of Jesse Gelsinger hanging over it, the biotech industry had been reluctant to try editing human genes until it was sure it could do so safely, and had been looking for first cases, like KJ’s, where the prognosis was tragically poor without treatment.

Pause to consider just how extraordinary this precision surgery is. Baby KJ’s disease results from just two single-letter changes in his three billion letter-long genome, one inherited from each parent in a piece of bad luck. Even diagnosing this is like finding two single-letter misprints in a document 800 times as long as the bible. The changes are the 1,003rd letter in the CPS1 gene, inherited from his father, where a C has changed to a T and the 2,140th letter, inherited from his mother where a G has mutated to a T. The effect of these changes is to terminate the construction of a key protein prematurely so that it is unable to do its biochemical job.

(I find a lot of science journalism frustrating because it deliberately leaves out such details, thinking they would baffle the reader, and hurry on to platitudes about the politics of science as The New York Times did. The result is coverage that is often far too dull and even harder to follow.)

The scientists then designed a bespoke CRISPR tool that would somehow (and this still boggles my mind) seek out the key phrases where the misprints are and alter them without affecting other nearby phrases. Oh, and to do this in almost every one of the billions of cells in the liver but nowhere else in the body. None of this was imaginable, let alone possible a generation ago.

The particular affliction of this baby is very rare. But the technique can fairly simply now be adapted to almost any inherited disorder, including far more common and also far less lethal ones. That is why this particular experiment is so exciting.

One key point here is that there had been growing pessimism about our ability to fix genes in living beings, so called somatic therapy, as opposed to fixing them in embryos at the start of life, which is much easier. That in turn was beginning to lead to calls for germline gene editing to be tried, hitherto a scientific taboo because it involves creating a change that is heritable.

In a recent article for The Spectator World (see here) I told the story of He Jiankui, who served a prison sentence in China for doing exactly this on twin babies to render them immune to HIV, and who has recently been making controversial and outspoken calls for that technique to be pursued instead of somatic gene therapy.

The new result means we do not need to face this moral dilemma quite so urgently: we can, in other words, heal sick people today rather than prevent people being born with such diseases.

It’s early days. It would be wrong to imply that treatments for everybody with an inherited disease are just around the corner. Or that the technique could be applied to diseases such as cancer, dementia or diabetes. Yet. But given what Crispr has achieved in its first 13 years, imagine what it could do in the next 25. The future is going to be astonishing. Please pass that along by clicking the “Like” and “Restack” buttons below.

---

Matt Ridley is the author of The Rational Optimist: How Prosperity Evolves and most recently Birds, Sex and Beauty: The Extraordinary Implications of Charles Darwin's Strangest Idea.

---