Advances in reading and writing are very important. But if I could only read and write this book without an ability to edit, search, and replace, the result would never see the light of day. So too with genome engineering, or editing: It allows scientists and even nonscientists to rewrite the genetic code as easily as I can change money to honey or gnome to genome on my computer.
In 2014, I was invited by the Nobel laureate Jim Watson to help update a popular science book that he’d written with Andrew Berry a decade earlier, simply called DNA.21 As I reflected on the major advances in genetics, there was no escaping CRISPR. In November 2014, at the annual Breakthrough Prize ceremony, televised live from a NASA hangar in California, I watched Cameron Diaz handing Doudna and Charpentier the most lucrative science prize in the world, worth $3 million apiece.IV Barely thirty months after their landmark study, the scientific establishment and the titans of Silicon Valley had crowned the women as scientific royalty.
Neither Doudna nor Charpentier were physicians, but CRISPR holds the prospect to taking gene therapy to a new level. Both women launched biotech companies to deliver CRISPR-based therapies designed to fix mutations that cause sickle-cell disease, blindness, DMD, and many other disorders. “For the past decade, I’ve been making GMO humans,” says Fyodor Urnov, a colleague of Doudna’s who helped develop genome editing at Sangamo Therapeutics in California. In 2019—seventy years after Linus Pauling proposed sickle-cell anemia as the first “molecular disease”—Victoria Gray, an African American mother from Mississippi, became the first American patient to receive a gene-editing therapy for sickle-cell disease.22 A year later, she is healthy, blessedly free of complications, her blood cells rejuvenated. Many more genome editing trials are getting underway, mostly using CRISPR. We are truly on the verge of a new era in medicine.
But genome editing has gone much further. The actions of He Jiankui crossed a red line, a scientific Rubicon that virtually all scientists deemed sacrosanct. Heritable genome (or germline) editing is no longer the domain of dystopian science fiction movies and panicked stories of designer babies. The genie is well and truly out of the bottle and cannot be put back. Will germline editing find a niche in treating genetic disorders? Will couples want to use CRISPR to genetically enhance their children? Why should we stop at correcting genetic diseases? Can we not entertain the idea of applying CRISPR technology for enhancement? How about tuning a gene to reduce the amount of sleep we need, or provide protection against the onset of dementia, or shield astronauts against radiation poisoning? Or is heritable genome editing, as Urnov argues, “a solution in search of a problem”?
CRISPR “is a remarkable technology with many great uses,” said Broad Institute director Eric Lander. “But if you are going to do anything as fateful as rewriting the germline, you’d better be able to tell me there is a strong reason to do it. And you’d better be able to say that society made a choice to do this—that unless there’s broad agreement, it is not going to happen.”23
Editing Humanity is the story of one of the most remarkable scientific revolutions we have ever seen—the CRISPR revolution. My original intent in this book, supported by a science writing fellowship from the Guggenheim Foundation, was to focus on CRISPR—the science and the scientists. In 2017, I conceived the launch of a new journal called The CRISPR Journal, and began meeting the scientists leading this exciting research. Our journey begins with the stories of a band of unheralded microbiologists and biochemists—the true “heroes of CRISPR”—trying to fathom the function of obscure lines of genetic code in bacterial DNA. CRISPR demonstrates emphatically the immense value of funding basic academic and investigator-driven research. Big science consortia like the HGP can do great things, but lest we forget, so too can humble scientists with modest financial support. Few could have predicted that studies of how bacteria vanquish their viral nemeses would spawn a multi-billion-dollar industry that could cure disease and alleviate world hunger.
In Part II, I discuss the rise and fall of genetic therapy, which is undergoing a renaissance after years of despair. One of the great hopes of genome editing is the possibility of treating patients with a wide range of debilitating diseases including muscular dystrophy, hemophilia, blindness, and sickle-cell disease. The term “Holy Grail” is overused in science, but if fixing a single letter in the genetic code of a fellow human being isn’t the coveted chalice of salvation, I don’t know what is.
In the second half of the book, I turn to the CRISPR babies and the extraordinary story behind this reckless experiment. I lift the veil on He Jiankui’s secretive ambitions. I question whether He Jiankui was the rogue scientist that he has been painted and assess the fallout of his actions. In the closing chapters, I present some of the exciting new directions that CRISPR might take us, from gene drives to eradicate malaria to de-extinction to resurrect species we have lost, and separate truth from fiction in the debate over designer babies.
This is biology’s century. As Urnov points out, there is a huge gap between a genius idea and its practical realization. In 1505, Leonardo da Vinci designed a model of an ornithopter—a flying machine. It was almost four centuries later, in December 1903, when Orville Wright defied gravity for twelve seconds and the length of a baseball diamond (120 feet). It took several decades more for that landmark flight to usher in commercial air travel, let alone carry the first man into earth orbit and beyond.
Siddhartha Mukherjee says it well in The Gene: “The challenge with all these technologies is that DNA is not just a genetic code, it is in some sense also a moral code. It doesn’t just ask questions about what we will become. Now that we have these tools, we have the capacity to ask the question, what can we become?”
This book is about the origins, development, uses and misuses of CRISPR, the technology adapted from some of the most ancient organisms on earth, which bring us to the precipice of editing humanity.
I. In the mid-1980s, Francis Collins posed for a newspaper photographer in a lab coat holding a needle in front of a large haystack—the literal metaphor for DNA detectives scouring the genome for a single spelling mistake among three billion letters.
II. Both professors, Shankar Balasubramanian and David Klenerman, have since been knighted.
III. In nanopore sequencing, the DNA is unzipped to allow a single strand to be threaded through a nanopore—a bacterial protein shaped like a ring donut. By measuring the electrical current as the DNA speeds through the pore like a subway train, Oxford Nanopore can translate those electrical squiggles into the underlying DNA sequence.
IV. The annual Breakthrough Prize of $3 million per recipient is worth about ten times a one-third share of the Nobel Prize, which has a total purse of $900,000.
PART I
O, wonder! How many goodly creatures are there here!
How beauteous mankind is!
O brave new world,
That has such people in’t!
—William Shakespeare, The Tempest
“You can’t just boss bacteria around like that,” said the younger Mrs. Hempstock. “They don’t like it.”
“Stuff and silliness,” said the old lady. “You leave wigglers alone and they’ll be carrying on like anything. Show them who’s boss and they can’t do enough for you. You’ve tasted my cheese.”