The beauty of CRISPR is that it is easier, faster, and much cheaper than earlier genome editing platforms. Researchers have edited a Noah’s Ark of plant and animal life: fruits and vegetables, insects and parasites, crops and livestock, cats and dogs, fruit flies and zebrafish, mice and men. Do-it-yourself biohackers began experimenting on themselves and their pets. A tsunami of research papers appeared in the most prestigious science journals as scientists CRISPR’d anything they could get their hands on. “The CRISPR Craze,” as Science dubbed it, swept over the popular press.6 The Economist’s cover featured an innocent crawling baby with a menu of potentially editable traits, including perfect pitch, 20/20 vision, and no baldness.7 The Spectator riffed on that with “Eugenics is back,” featuring a cartoon baby sitting on a petri dish (“not ginger” was the hair preference).8 MIT Technology Review labeled CRISPR “the biggest biotech discovery of the century.”9 And a WIRED cover story by Amy Maxmen stated: “No hunger. No pollution. No disease. And the end of life as we know it.”10
When I was training as a geneticist in the 1980s, I was part of a team desperately searching the human genome to find the faulty genes that cause Duchenne muscular dystrophy (DMD) and cystic fibrosis (CF). We were literally genetic detectives, hunting for clues to the whereabouts of genes and mutations that compromise and curtail human life.I We met patients in our lab at St Mary’s Hospital in London, including teenagers with CF who would be lucky to see their 20th birthday. The identification of the genes mutated in patients with CF, DMD, and other disorders gave us hope that cures were just around the corner. “From gene to drug” and “From bench to bedside” were the memes of the day, heralding a revolution in molecular medicine. Every few years the future of medicine would get a new name—personalized medicine, precision, genomic, or individualized medicine, as if changing the name would change fortunes.
In 1990—the year of the launch of the HGP—I hung up my lab coat for the last time. My personal eureka moment came when I chanced upon a classified advertisement for a job with Nature magazine. Well, I thought, that’s one way to get my name in the pages of the world’s most famous science journal. I was offered the job by the editor, Sir John Maddox. Two years later, Maddox handed me the chance to helm the first spin-off journal bearing the Nature nameplate—Nature Genetics.11 At a conference in 1993 to mark our first birthday, I mingled with a handpicked all-star cast, including Francis Collins, Craig Venter, and Mary-Claire King, who over dinner inspired me to write my first book.
Written with my friend the late Michael White, Breakthrough told of the brilliant Berkeley geneticist who, in 1990, mapped the so-called breast cancer gene, BRCA1. A few weeks after Myriad Genetics scooped King in the race to isolate the gene in 1994, the organizers of a major genetics conference in Montreal convened a plenary session to celebrate Myriad’s highly publicized success. King stole the show, presenting the results from multiple families in which her team had documented specific BRCA1 mutations capable of wreaking what the British journalist John Diamond called the “cytological anarchy of cancer and death.”
King insisted she didn’t care who won the race to identify BRCA1: win or lose, her team would be in the lab studying mutations in families. It was important, she said, to distinguish reality from the media frenzy. “Fantasy has been New York Times profiles, 60 Minutes, guys on motorcycles in Time magazine”—a jab at Francis Collins, her former collaborator. Reality, she said,
is having the gene, not knowing what it does, and the realization that in the twenty years since we have been working on this project, more than a million women have died of breast cancer. We very much hope that something we do in the next twenty years will preclude another million women dying of the disease.12
King received a standing ovation. Two decades later, a lawsuit that stemmed from a dispute over BRCA1 genetic testing resulted in the U.S. Supreme Court outlawing gene patents in a unanimous decision.13
My next book, Cracking the Genome, covered the biological equivalent of the moon landing—the HGP—which became a fierce partisan feud between the international consortium led by Collins and a privately funded hostile takeover led by Craig Venter.14 The command center at his company, Celera Genomics, looked more like the bridge of the starship Enterprise, with two massive video screens streaming DNA sequences rather than photon torpedoes. With the draft sequence in hand, we had the parts list of the human body and could systematically identify the mutations that underlie not only dominant and recessive (Mendelian) disorders but also begin to crack the genetic basis of more common diseases such as asthma and depression.
The ink had barely dried on the genome project when I heard Venter call for a new sequencing technology to speed-read DNA that could deliver the “$1,000 genome.” As the first draft had cost $2 billion, this really did sound like science fiction. But the seeds were sown one Sunday afternoon in February 2005, when Clive Brown emailed his colleagues at a British biotech company called Solexa with the subject line: “WE’VE DONE IT!!!!” Using a new technology invented by a pair of Cambridge University chemistry professors,II Brown’s team had sequenced the genome of the smallest virus known, ΦX174. The next year, another company, Illumina, acquired Solexa, setting it on course to reach the mythical $1,000 threshold a decade later.15 By then, we saw the first cases of genome sequencing saving lives, ending the diagnostic odysseys of patients like Nicholas Volker suffering mystery genetic diseases. The plummeting cost of sequencing was accompanied by major advances in speed. For example, Stephen Kingsmore at Rady Children’s Hospital in San Diego recently set a Guinness World Record by sequencing and processing the complete genome of a newborn baby in just twenty hours.16
Each of these stories chronicled a massive leap forward in genetics propelled by advances in sequencing DNA. We are on course for the $100 genome, with new sequencing platforms offering incredible new possibilities for speed-reading DNA.III 17 One in particular, nanopore sequencing, is housed in a portable device smaller than a smartphone and has found its way onto the International Space Station.
Along with reading DNA, we are also seeing tremendous progress in synthesizing or writing DNA. Church and other scientists have digitally encoded books and films in DNA sequences18 and engineered a yeast cell by fusing the organism’s natural complement of sixteen chromosomes into a single mosaic chromosome.19 Synthetic biology has an exciting future designing DNA circuits and customizing organisms for a host of applications from bioengineered fragrances and petrochemicals to the next generation of antibiotics and antimalarial drugs. Scientists have even expanded the original four-letter genetic alphabet by synthesizing novel chemical building blocks that can substitute for the naturally occurring ones in the double helix. This paves the way for designing synthetic proteins containing novel building blocks.20