A Crack In Creation: A Nobel Prize Winner's Insight into the Future of Genetic Engineering

by Jennifer A. Doudna

In just a few simple and routine steps, Martin and I had selected an arbitrary DNA sequence within the 3.2-billion-letter human genome, designed a version of CRISPR to edit it, and watched as the tiny molecular machinery followed through with its new programming—all inside living human cells. With that success, we had validated our new technology that offered scientists the remarkable ability to rewrite the code of life with surgical precision and astonishing simplicity. In what felt like no time at all, CRISPR had already caught up to almost twenty years of research and development in other gene-editing technologies.

Sangamo Therapeutics.

Editas Medicine

Juno Therapeutics

Intellia Ther...

Our DNA is constantly changing, roiled by random, naturally occurring mutations. These natural mutations are the very drivers of evolution, but they are also how inheritable genetic diseases can arise. Every time our cells duplicate their DNA during cell division, somewhere between two and ten novel DNA mutations creep into the genome. Every person experiences roughly one million mutations throughout the body per second, and in a rapidly proliferating organ like the intestinal epithelium, nearly every single letter of the genome will have been mutated at least once in at least one cell by the time an individual turns sixty. This mutational process begins from the earliest moment of fertilization, and as the single-cell zygote

goes on to divide into two cells, then four, then eight cells of the growing embryo, the new mutations it has acquired will be faithfully copied into the genome of every descendant cell in that growing person’s body. Even the sex cells that create the embryo—the mother’s egg and the father’s sperm—have incorporated new mutations that never before existed in either family’s germline. As a result, each one of us begins life with fifty to a hundred random mutations that arose de novo (“anew”) in our parents’ germ cells.

Any mutations that CRISPR might make—intentional or not—would almost certainly pale in comparison to the genetic storm that rages inside each of us from birth to death. As one writer put it, “Genetic editing would be a droplet in the maelstrom of naturally churning genomes.” If CRISPR could eliminate a disease-causing mutation in the embryo with high certainty and only a slight risk of intr...