Dr. Patrick Harrison:

I thank the committee for this opportunity. As mentioned in the Chairman's prefatory comments, my interest in gene editing is for medical purposes.

Sixty-five years ago scientists discovered that a single specific mutation in the sequence of our DNA was enough to cause the genetic disorder sickle cell anaemia. The same is true of cystic fibrosis, muscular dystrophy, spinal muscular atrophy and 4,000 other inherited disorders. Collectively, these diseases affect 7% of the world's population. It is not rare to have a rare disease but it is extremely rare to have an effective treatment.

In 1970 the concept of gene therapy was proposed. The idea was to add a corrected copy of the defective DNA sequence into cells of an affected individual. In 1993 the technology finally caught up with the idea and the first clinical trials began. However, three decades and 5,000 clinical trails later, with remarkable advances, we still have only two gene therapies that have been licensed. Peter Marks of the Food and Drug Administration recently stated that it would take 600 years to increase that number to 100 approved medicines if we were to continue with existing tools at the current rate.

Rather than paper over the cracks in the genome, can we delve into the genome, find those mutations and fix or edit them? Yes, but I ask the committee to consider for a moment the magnitude of the problem. The book I am holding up contains about a million letters or bits of information; our genome contains 3 billion bits of information, or 3,000 of these books stacked on top of one another. That is the height of the Spire of Dublin, which, by coincidence, is overlaid with the double helix pattern of DNA. However, the mutation we need to fix is just one letter in those 3,000 volumes, and all that information is in the DNA of a cell that cannot be seen without a microscope, so it is quite a challenge.

In 2005 scientists in California described one of the techniques already mentioned, with the first precision gene-editing technique to correct a mutation in cells from a patient with severe combined immune deficiency. The symptoms of that disease are as bad as its name suggests. A few years later my lab in Cork became the first to use that technique to correct the most common cystic fibrosis mutation in cells. However, progress with these early editing techniques was slow and we really needed a paradigm shift.

The breakthrough, as mentioned, came in 2012 with CRISPR-Cas9, a programmable RNA-guided DNA endonuclease. It was the missing piece of the puzzle. CRISPR-Cas9 could target any mutation in any gene in any organism. For academic labs it was free and easy to use. Within a year a new CRISPR study was being published every day. Currently, a new CRISPR study is published every 60 minutes. These research publications are describing proof-of-treatment studies for hundreds of rare diseases in animal models and in human cells. The first ethically approved clinical trial of CRISPR reported its results in The New England Journal of Medicine, the most prestigious medical journal in the world, for a handful of patients with a rare liver disease just last summer. There are many more clinical trials ongoing as we speak, and more sophisticated and refined CRISPR strategies are constantly emerging with improved specificity and safety. We require additional tools to target specific tissues in patients, and those will need to be underpinned by appropriate medical, regulatory and access frameworks to pay for them. However, for individuals with these diseases - cystic fibrosis, sickle cell disease, muscular dystrophy, certain types of cancer and thousands of other conditions - there is now real hope and real prospects because of CRISPR.