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

by Jennifer A. Doudna

Science does not know its debt to imagination. —Ralph Waldo Emerson

as the tsunami looms closer, my terror gives way to determination. I notice a small wooden shack behind me. It is my friend Pua’s place, with a pile of surfboards scattered out front. I grab one and splash into the water, paddle out into the bay, round the breakwater, and head directly into the oncoming waves.

Before the first one overtakes me, I’m able to duck through it, and when I emerge on the other side, I surf down the second. As I do, I soak in the view. The sight is amazing—there’s Mauna Kea and, beyond it, Mauna Loa, rising protectively above the bay and reaching toward the sky.

beach is a mirage, but the waves, and the tangle of emotions they inspire—fear, hope, and awe—are only too real.

My name is Jennifer Doudna. I am a biochemist, and I have spent the majority of my career in a laboratory, conducting research on topics that most people outside of my field have never heard of.

By the summer of 2015, the biotechnology that I’d helped establish only a few years before was growing at a pace that I could not have imagined. And its implications were seismic—not just for the life sciences, but for all life on earth.

This book is its story, and mine. It is also yours. Because it won’t be long before the repercussions from this technology reach your doorstep too.

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 virtuall...

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.

For example, scientists have harnessed CRISPR to generate a genetically enhanced version of the beagle, creating dogs with Schwarzenegger-like supermuscular physiques by making single-letter DNA changes to a gene that controls muscle formation.

In another case, by inactivating a gene in the pig genome that responds to growth hormone, researchers have created micropigs, swine no bigger than large cats, which can be sold as pets.

Scientists have done something similar with Shannbei goats, editing the animals’ genome with CRISPR so that they grow both more muscle (thus yielding more meat) an...

Geneticists are even using CRISPR to transform Asian elephant DNA into something that looks more and ...

Meanwhile, in the plant world, CRISPR has been widely deployed to edit crop genomes, paving the way for agricultural advances that could dramatically improve people’s...

Gene-editing experiments have produced disease-resistant rice, tomatoes that ripen more slowly, soybeans with healthier polyunsaturated fat content, and potato...

Food scientists are achieving these improvements not with transgenic techniques—the splicing of one species’ DNA into a different species’ genome—but by fine-tuned genetic upgrades involving cha...

While applications in the planet’s flora and fauna are exciting, it’s the impact of gene editing on our own species that offers both the greatest promise and, arguably, ...

To treat many diseases, though, 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.

3.2 billion letters that make up the human genome,

have no doubt, this technology will—someday, somewhere—be used to change the genome of our own species in ways that are heritable, forever altering the genetic composition of humankind.

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.

For the roughly one hundred thousand years of modern humans’ existence, the Homo sapiens genome has been shaped by the twin forces of random mutation and natural selection.

Now, for the first time ever, we possess the ability to edit not only the DNA of every living human but also the DNA of future generations—in essence, to direct the evolution of our own species.

This is unprecedented in the history of ...

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.

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

Would it inadvertently widen social or genetic inequalities or usher in a new eugenics movement?

In mid-2015, Chinese scientists published the results of an experiment in which they had injected CRISPR into human embryos.

The genome—a term coined in 1920 by the German botanist Hans Winkler and probably intended as a portmanteau of gene and chromosome—refers to the entire set of genetic instructions found inside a cell.

Our intrinsic physical traits—eyesight, height, skin color, predisposition to disease, and so on—are the result of information encoded in our genomes.

The genome is made up of a molecule called deoxyribonucleic acid, or DNA, which is constructed of just four different building blocks. Known as nucleotides, these are the familiar letters of DNA: A, G, C, and T, shorthand for the chemical groups (also known as bases) of adenine, guanine, cytosine, and thymine that distinguish the four compounds.

The letters of these molecules are connected in long single strands. Two of these strands come together to form the famous double-helix structure of DNA.

Two strands of DNA wrap around each other along a central axis, with the continuous sugar-phosphate backbone of each one occupying the outside of the helix; together, these form the two side rails of the ladder.

The letter A from one strand always pairs with T on the other strand, and G always pairs with C. These are known as base pairs.

Shortly before cell reproduction, the two strands are separated by an enzyme that “unzips” the double helix right down the middle. After that, other enzymes build a new partner strand for each single strand simply by using the same base-pairing rules, resulting in two exact copies of the original double helix.

DNA, as it turns out, is much like a secret language; each specific sequence of letters provides instructions to produce a particular protein inside the cell.

The proteins then go on to carry out most of the critical functions in the body, like breaking down food, recognizing and destroying pathogens, and sensing light.

RNA acts as a messenger, ferrying information from the nucleus, where the DNA is stored, to the outer regions of the cell, where proteins get produced. In a process called translation, cells use long strings of RNA that are produced by discrete segments of DNA—stretches of code called genes—to construct individual protein molecules.

Every three letters of RNA, when read together, equal one amino acid, and amino acids are the building blocks of proteins. Genes and their corresponding protein products differ from one another by the sequence of nucleotides (in genes) and amino acids (in proteins). This overall flow of genetic information—from DNA to RNA to protein—is known as the central dogma of molecular biology, and it is the language used to communicate and express life.

viruses, for instance, have just a few thousand letters of DNA (or RNA, since some viral genomes contain no DNA) and a small handful of genes. Bacterial genomes, by contrast, are millions of letters long and contain around 4,000 genes. Fly genomes contain around 14,000 genes spread out across hundreds of millions of DNA base pairs. The human genome comprises about 3.2 billion letters of DNA, with around 21,000 protein-coding genes. Interestingly, a genome’s size is not an accurate predictor of an organism’s complexity; the human genome is roughly the same length as a mouse or frog genome, about ten times smaller than the salamander genome, and more than one hundred times smaller than some plant genomes.

the human genome is composed of twenty-three distinct pieces, called chromosomes,

that range in length from 50 to 250 million letters.

Like the cells of almost all mammals, human cells normally contain two copies of each chromosome, one from the father, one from the mother. Each parent contributes twenty-three chromosomes, which ...

Unlike the genetic code found in other chromosomes, mitochondrial DNA is inherited exclusively from the mother.

For example, in sickle cell disease, a genetic disorder of the blood, the seventeenth letter of a gene known as beta-globin is mutated from an A to a T.

One example is WHIM syndrome, in which the one thousandth letter of the CXCR4 gene is mutated from a C to a T; the mutant gene creates a hyperactive protein

the neurodegenerative disorder known as Huntington’s disease is due to a mutation of the HTT gene in which the same three letters of DNA get repeated too many times.