First US based human trial of CRISPR

The University of Pennsylvania has announced it has started the first formal US human trial using the technique.

Two patients, one with multiple myeloma and one with sarcoma, both of whom are said to have relapsed after standard treatment, are now being treated with CRISPR techniques.

The once soaring reputation of CRISPR had hit some serious turbulence in the last 18 months. First came warnings from Wellcome Sanger Institute (WSI) that CRISPR may be making random unwanted changes to DNA sections at points away from the target area.

Then Chinese researcher, Professor He Jiankui, caused controversy when he used CRISPR to tamper with genes of human embryos which he then re-planted in the mother who gave birth to genetically modified twins. There was a storm of indignation and anger in the scientific community and the news raised global concerns of irreversible changes to the human genome.

Professor He Jiankui is said to be facing severe sanctions from the Chinese authorities with some reports suggesting he is under a form of house arrest.

But the news from Penn University will give some relief to the CRISPR community. It means the methodology is gaining some traction in terms of rigorous medical research.

The first human trial started in Germany last year ago using CRISPR to treat ?-Thalassaemia. In that case haematopoietic stem cells, taken from the bone marrow of trial participants is to be genetically modified in the laboratory. In theory the modified cells should be able to produce high-levels of foetal haemoglobin. Then they will be re-infused in the patients.

A third trial using CRISPR is also about to be launched by Editas Medicine and its Dublin-based development partner Allergan. It will focus on a common form of childhood congenital blindness, Leber's congenital amaurosis T10.

LCA is a type of inherited retinal condition (with similarities to retinitis pigmentosa). It causes the specialised light-sensing photoreceptor cells at the back of the eye to stop working properly which causes vision loss. It affects about 1 in 80,000 people and is the most common form of inherited sight loss in children.

The LCA trial is unique because it is the first-time researchers have tried using CRISPR to edit genes while they are inside the human body.

Legal wrangles

CRISPR has been the centre of bitter legal wrangles since its discovery and development and continues to cause havoc in the scientific community over its ethical use.

In a recent essay published in the Boston Globe, psychologist Steven Pinker said he believed bio-ethicists should “get out of the way” and scientists should just do whatever they want.

According to Pinker: “A truly ethical bioethics should not bog down research in red tape, moratoria, or threats of prosecution based on nebulous but sweeping principles such as dignity, sacredness, or social justice.”

“Of course, individuals must be protected from identifiable harm, but we already have ample safeguards for the safety and informed consent of patients and research subjects.”

However Jennifer Doudna, the scientist many credit with discovering CRISPR, responded to Pinker last month in a speech on campus at Berkeley California. She said that in her view Pinker goes too far and also revealed her feelings about Chinese scandal.

She said: “We need to be thoughtful about putting in place appropriate guidelines, and frankly I would say regulations. We really need to establish a set of principles where there’s some price to be paid if you cross that line. The challenge is how to do that.

She was scathing about Chinese Professor He in changing embryonic DNA and then implanting altered embryos so that they resulted in live births.

She said: “The twins, which were born, now have changes to their DNA that have never been tested. It’s really a profound thing to think about.

“When I was sitting in the audience of that meeting in Hong Kong when it was announced, I literally had the hairs on my neck were standing up. It seemed so horrifying.”

The World Health Organization has been prompted to act in the wake of the debate, announcing that it has convened an international forum of scientists charged with thinking hard about where we go from here with CRISPR.

The results of the current formalised new trials will be eagerly awaited.

By Dermot Martin