By Dr. Samuel K. Ludwin
Within the last 5 years, an exciting new tool in molecular biology is being developed, with the potential to enable scientists to delete, modify or add new codes into the genetic makeup (genome) of humans, animals and plants. Although there are numerous ways of modifying the genome already in use in experimental and even clinical situations, the CRISPR technique has enormous advantages over these due to its simplicity, cheapness, accuracy and easy accessibility to many scientists. Progress has been made at almost breakneck speed, bringing with it the promise of curing disease-caused mutations of the genome, such as cancers, inherited genetic diseases and even some infectious diseases, but also accompanied by enormous ethical and safety issues.
CRISPR are composed of genetic building blocks and can be likened to a GPS with an attached laser precision scalpel. The “GPS” component allows the building blocks to home in on the defective gene or parts of a gene with remarkable accuracy, while the “scalpel,” which is an enzyme (called caspase9), excises the unwanted code. The damaged gene can then either repair itself spontaneously, or a new normal sequence can be added to aid this repair.
The CRISPR discovery story is also a fascinating one in science. Scientists working with bacteria, among the simplest forms of life consisting of a single cell, found parts of the genetic code that were unusual. However, they soon realized that these unusual sequences actually formed a primitive “immune system” for the cell that allowed the cell to excise the unwanted genes of any attacking viruses. They then realized that they could make use of this mechanism to excise similar unwanted sequences in all animal and plant life. This is a wonderful example of a common theme in research where investigations in one area, seemingly arcane, can turn out to be immensely useful in many other areas.
Since this discovery, hundreds of labs around the world are working on this issue, and the rate of publications is increasing exponentially. Much of the work is experimental, with only a few attempts at human disease. In animals or in cell cultures in the test tubes, CRISPR has been shown to be increasingly effective at removing defective genes in cancerous or metabolically diseased cells. Its use in whole adult animals is curtailed by the need to find more effective ways of delivering the product to all cells, a situation which is easier to deal with in the test tube where single cells are used. Other issues to be overcome are ensuring that the GPS does not lead the building blocks to parts of the genome with similar but normal sequences.
In children and adults, many diseases may be cured by treating only the affected cells (such as the circulating blood cells in leukemias). However, in inherited genetic disease, the most effective way of using CRISPR is to alter the earliest embryonic cells, namely the fertilized egg, so that all subsequent daughter cells and eventually all the cells in the body are “cured.” This has already been done successfully in mice. However, therein lies the great moral and ethical quandary of altering the genome for generations to follow. What about the misuse of the technique to create perfect offspring, or the science-fiction nightmare of human robots? (Similar scenarios may also be envisioned for altering any other life form in the environment). Most Western countries have forbidden research on human embryos which could result in live fetuses, but there are many places in the world where the ease of access to the technique may tempt people into offering this service. Some of the leaders in the field, as well as international experts in medicine, ethics and law, and prominent lay figures, have come together and published guidelines for the conduct of research to prevent unethical or unsafe research. Let us hope that we will use a marvelous scientific discovery wisely for the good of humanity and the environment— without facing the spectre of terrifying unintended consequences.
Editor’s note: Special thanks to Dr. Ludwin for providing BCA-Qc Connected with this important overview of a new, fast-moving technology that has profound implications for cancer research and treatments. Dr. Ludwin is an emeritus professor in the Department of Pathology and Molecular Medicine (Neuropathology), Queens University, Kingston, Ontario, Canada, and a visiting scientist at the Montreal Neurological Institute, Montreal, Quebec, Canada.
<http://www.nature.com/news/crispr-1.17547> [with links to many articles/commentary]