CRISPR/Cas9 now used in humans

As reported by the journal Scientific American yesterday, researchers at Sichuan University in China used CRISPR/Cas9 in humans to treat a patient with a metastasising lung cancer.

This is the first time that CRISPR/Cas9 was used in humans, although a related genome editing technique, TALENs, has already been used to treat human cancer. Indeed the Chinese trial use of CRISPR was announced earlier, and in July, the Guardian closed a report with the words,

Crispr was approved for human trials in the US by a research group backed by tech billionaire Sean Parker, but if it begins on schedule in August the Sichuan University study will beat them to the punch of being the first of its kind.

A continuation of this patient’s treatment is planned, and nine further patients are scheduled for this treatment, in part on an extended scale. The procedure was approved by the ethics panel of the hospital in June, and originally the researchers hoped to begin the procedure even a few months earlier.

We haven’t learned anything yet about how researchers hope to control for the precision with which such immune cells were modified. Further questions emerge: how have patients been selected and informed? What preparatory studies and experiments were carried out before to ensure maximum patient safety? Does the modification of these immune cells come with side effects? We should hope that more details will be released soon.

Certainly this is fascinating news. At the same time there are at least two things to look out for:

T-cells: the immune system in action (Microbe World: Leukemia treatment, flickr. Image provided by Carl June, the specialist quoted in this post)

Scientific American reports that CRISPR was used to modify cells in the patient’s immune system that curb the immune system by default. Taking off the hand break, as it were, sets the immune system on full throttle. This raises the question why the immune system doesn’t run on full potential in the first place. We’ve come across the fact that the human genome is a fine-tuned interaction of various components, and this is true for the overall human organism as well. The consequences of interventions in a fine-tuned system are especially hard to predict, so it is well in order to consider the Chinese trial an experiment. Of course there is hope that this will help control or even cure cancer, but the inherent risk in this procedure is that unleashing the immune system might make it more aggressive even towards healthy cells. Autoimmune diseases have attracted a lot of attention more recently, being compared to cancer themselves.

Sputnik. (Vintageprintable1 at flickr)

Further, Carl June, a specialist in immunotherapy who works on therapeutic uses of genome editing, is quoted as saying, “I think this is going to trigger ‘Sputnik 2.0’, a biomedical duel on progress between China and the United States, which is important since competition usually improves the end product”. June alludes to the first earth satellite that was put in orbit by the Soviets in 1957, which came to be hailed as a demonstration of Soviet scientific prowess. Eventually, US politicians took Sputnik as a challenge to step up US efforts in science and space exploration. This side of the Cold War is often associated with excitement about innovation, American hegemony, and new options for Western consumers.

But at this point certainly greater reservation would be in order. It is possible that the opposite of June’s positive evaluation is true. In a post at her “Making Science Public” blog at the University of Nottingham, Brigitte Nerlich discussed the prospect of the CRISPR “race” that we’re just seeing unfold, and recalled:

Between 2004 and 2005 there was a race between two teams of scientists, one team working in Newcastle (UK) and the other in Seoul (South Korea). The prize was being first in achieving a breakthrough in stem cell therapies based on therapeutic cloning. That race did not end well, as we know, especially for the South Korean team led by Woo Suk Hwang, a cloning specialist initially celebrated as a pioneer and hero.

If there is a race, what are the contestants racing for? The Cold War race about arms and scientific achievement had positive effects, but were there other effects as well? Just a week ago, there were reports about a diver who may have stumbled over a nuclear bomb that had gone missing during the Cold War, and up to fifty nuclear warheads are believed to have “disappeared” during the arms race frenzy. Remember also that the patents debate surrounding CRISPR involves venture capital amounting to over a billion US$. Is venture capital a good driver for responsible scientific achievement?

Certainly at the moment there are no indications of clear misdemeanours, and I’m not raising any accusations. But a “race” contributes to a heated atmosphere that may very well be conducive to oversights, lack of attention to ethical issues, and yes, even the possibility of fraud. Let’s hope the cooler heads will prevail. But we should also keep an eye on the possibility of a “lock-in”, as discussed by the Nuffield review on genome editing. What they mean with this is that new therapeutic CRISPR developments might forge ahead with such speed, capital, and a powerful grip on public attention that they may crowd out alternative approaches based on sheer marketing power. The “Sputnik” theme adds to this the excitement of pioneering endeavour. In sum, such early approaches might then be disproportionately privileged, and society may find itself at a loss to explore alternative, better uses of CRISPR and other methods.

Edit: Nerlich’s post is not about an “arms race” but merely a “race”.