A Crack In Creation

Gene Editing Advances of CRISPR and the Unthinkable Power to Control Evolution

An excerpt by Jennifer Doudna

Jennifer Doudna

My name is Jennifer Doudna. I am a biochemist, and in the past half-decade, I have become involved in a groundbreaking area of the life sciences.

By the summer of 2015, the biotechnology that I’d helped establish was growing at a pace that I could not have imagined. And its implications were seismic.

The biological world is…undergoing profound, human-induced changes. When agriculture emerged 10,000 years ago, humans began biasing evolution through the selective breeding of plants and animals, but the starting material — the random DNA mutations constituting the available genetic variations — was still generated spontaneously and randomly. As a result, our species’ efforts to transform nature were met with limited success.

The Dawn of CRISPR
Scientists have succeeded in bringing this primordial process fully under human control. Using powerful biotechnology tools to tinker with DNA inside living cells, scientists can now manipulate and rationally modify the genetic code that defines every species on the planet, including our own. And with the newest and arguably most effective genetic engineering tool, CRISPR-Cas9 (CRISPR for short), the genome — an organism’s entire DNA content, including all its genes — has become almost as editable as a simple piece of text. As long as the genetic code for a particular trait is known, scientists can use CRISPR to insert, edit, or delete the associated gene in virtually any living plant’s or animal’s genome.

This process is far simpler and more effective than any other gene-manipulation technology in existence. Practically overnight, we have found ourselves on the cusp of a new age in genetic engineering and biological mastery — a revolutionary era in which the possibilities are limited only by our collective imagination.

Gene Editing in Humans
To treat many diseases, CRISPR offers the potential to edit and repair mutated genes directly in human patients. In laboratory-grown human cells, this new gene-editing technology was used to correct the mutations responsible for cystic fibrosis, sickle cell disease, some forms of blindness, and severe combined immunodeficiency, among many other disorders.

Gene editing holds the promise of life-changing treatments and, in some cases, lifesaving cures.

How the Science Works
CRISPR enables scientists to accomplish such feats by finding and fixing single incorrect letters of DNA out of the 3.2 billion letters that make up the human genome. Researchers have corrected the DNA mistakes that cause Duchenne muscular dystrophy by snipping out only the damaged region of the mutated gene, leaving the rest intact.

Because CRISPR allows precise and relatively straightforward DNA editing, it has transformed every genetic disease — at least, every disease for which we know the underlying mutation(s) — into a potentially treatable target. Physicians have already begun treating some.

The Ethical Dilemma
Gene editing holds the promise of life-changing treatments and lifesaving cures. But there are other profound implications of CRISPR technology: It can be used not just to treat diseases in living humans but also to prevent diseases in future humans.

The CRISPR technology is so simple and efficient that scientists could exploit it to modify the human germline — the stream of genetic information connecting one generation to the next.

Yet once it becomes feasible to transform an embryo’s mutated genes into “normal” ones, there will certainly be temptations to upgrade normal genes to supposedly superior versions. Should we begin editing genes in unborn children to lower their lifetime risk of heart disease, Alzheimer’s, diabetes, or cancer? What about endowing unborn children with beneficial traits, like greater strength and increased cognitive abilities, or changing physical traits, like eye and hair color?

The Accidental Discovery
This is unprecedented in the history of life on earth. And it forces us to confront an impossible but essential question: What will we, a fractious species whose members can’t agree on much, choose to do with this awesome power? Controlling the evolution of the human species could not have been further from my mind in 2012, when my colleagues and I published the research paper that formed the basis of the CRISPR gene-editing technology.

Yet in the course of our research on a bacterial immune system called CRISPR-Cas, we uncovered the workings of an incredible molecular machine that could slice apart viral DNA with exquisite precision. The utility of this same machine to perform DNA manipulations in other kinds of cells, including human cells, was immediately clear to us.

By the time scientists employed CRISPR in primate embryos to create the first gene-edited monkeys, I asked myself how long it would be before some maverick scientists attempted to do the same in humans.

What repercussions would we need to prepare for? I was tempted to leave those discussions to the people with actual bioethics training… Yet at the same time, as a pioneer in the field, I felt a responsibility to help lead the conversation on how those technologies could, and should, be used. In particular, I wanted to ensure that the discussion involved not only researchers and bioethicists but also a great range of stakeholders, including social scientists, policymakers, faith leaders, regulators, and members of the public.

Gene editing forces us to grapple with the tricky issue of where to draw the line when manipulating human genetics. Some people view any form of genetic manipulation as a perverse violation of the dignity of life. Others see the genome simply as software — something we can fix, clean, update, and upgrade — and argue that leaving human beings at the mercy of faulty genetics is not only irrational, but immoral.

We hope this book will demystify this exciting area of science and inspire you to get involved.


Excerpted from A Crack in Creation:
Gene Editing and the Unthinkable Power to
Control Evolution by Jennifer Doudna and Samuel Sternberg.
Copyright © 2017

By Jennifer Doudna and Samuel Sternberg. Used by permission of Houghton Mifflin Harcourt Publishing Company. All rights reserved.


“This CRISPR illustration is provided by Synthego, which helps scientists accelerate CRISPR genome engineering research by providing technologies that significantly improve the effectiveness of research while drastically reducing the time required in the lab,” said Kevin Holden, PhD, Head of Synthetic Biology at Synthego. – Kevin Holden, PhD, Head of Synthetic Biology at Synthego.

A Crack In Creation