Genome Editing: Risks and Rewards 

Fifty years ago, the recombinant DNA revolution begun with the discovery of restriction enzymes which provides bacteria with innate immune system. These enzymes gave rise to the modern biotechnology industry.

Ten years ago, scientists discovered that bacteria also harbor adaptive immune system now known as CRISPR-Cas9 system which cut invading DNA that matches “guide RNAs” encoded in specific bacterial genome regions containing clustered regularly interspaced short palindromic repeats. Now this system is thought to have the potential for editing the genome in living human cells. It holds great therapeutic promise. For example, we can use it to delete the CCR5 gene in a patient’s immune cells, conferring the resistance to HIV. In normal population 1% of population lacks the functional copies of this gene and are thus naturally resistant to HIIV virus. CCR5 gene encodes a membrane receptor and this receptor is a requirement for the HIV virus entry as the virus binds to it. Thus, no functional receptor, no virus binding and no intrusion and free viruses are cleared away from the circulation by immune cells, mainly by macrophages. This pose no unique ethical issues because it affects only a patient’s own somatic cells.

However, the technology also raises eyebrows when it comes to editing human germ line DNA, in which changes cause permanent, heritable changes and may be to used in highly unethical applications such as for “designer babies” or “genetically modified humans.”

Various potential applications in germ line editing, however, must be considered. The most common argument for germline editing concerns preventing devastating monogenic diseases, such as Huntington’s disease. Though avoiding the roughly 3600 rare monogenic disorders caused by known disease genes is a compelling goal. Genome editing would add substantial value only when all embryos would be affected — for example, when one parent is homozygous for a dominant disorder or both parents are homozygous for a recessive disorder. But such situations are vanishingly rare for most monogenic diseases. For dominant Huntington’s disease, for example, the total number of homozygous patients in the medical literature is measured in dozens. For most recessive disorders, cases are quite infrequent (1 per 10,000 to 1 per million). 

It has been only about a decade since we first read the human genome. We should exercise great caution before we begin to rewrite it.

From: Brave New Genome, Eric S. Lander, Ph.D., The Broad Institute. A lengthier version of this article was published on June 3, 2015, at NEJM.org.

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