Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing

CHAPTER 1 THE CRISPR CRAZE

“This is CRISPR?”

Bill Whitaker, a correspondent for the 60 Minutes television show, sounds puzzled as he points to a small white plastic tube containing a few drops of a colorless liquid that might as well be water. Indeed, it mostly is water.

Holding the vial under the bright television lights is Feng Zhang, a thirtysomething scientist who has helped ignite a biological revolution.

“It has CRISPR in it,” Zhang says helpfully.¹

The interview is being filmed in Zhang’s laboratory at the Broad Institute in Cambridge, Massachusetts, one of the most elite biomedical research centers in the country. The Broad (rhymes with road) is named after philanthropist Eli Broad and his wife Edythe. It jockeys for space with other ivory towers established by billionaire businessmen including the Koch brothers (cancer), publisher Pat McGovern (brain research), and medical device inventor Jack Whitehead (cell biology). When I first moved to the United States in the late 1980s, working at the Whitehead Institute on the fringe of the MIT campus, the only other sign of civilization was a Legal Seafood restaurant. Today, Kendall Square is the center of the biotech universe, as much a Boston landmark as Fenway Park. A nearby plaque proclaims this to be the “Most innovative square mile on the planet.” Few would argue.

Zhang looks, if anything, younger than his thirty-four years, with black cropped hair and a smooth cherubic face. In a lab photo with about twenty students and research fellows, you could easily mistake him for a grad student. But since 2013, Zhang has become accustomed to media requests and the intrusion of film crews. This is literally a case of déjà vu: a few months earlier he was answering the same questions in front of the same CBS cameras. But the interviewer on that occasion, Charlie Rose, had since been sacked for good reasons,^I so 60 Minutes producer Nichole Marks opted to reshoot the entire segment.

Whitaker stares at the tiny tube disbelievingly. “So this is what’s revolutionizing science and biomedicine?… That’s wild!”

Even if the 60 Minutes cameras could zoom into the contents of that tiny vial between Zhang’s finger and thumb—like a scene from Fantastic Voyage—it would be hard to see what the fuss was about. But CRISPR is a very big deal—a tempest in a test tube. The term CRISPR has a precise scientific definition (more on that later) but in the space of just a few years, this obscure acronym has become a household word, both noun and occasionally verb that epitomizes the revolution in genome editing—the ability to pinpoint and alter a given DNA sequence in any organism.

But Whitaker isn’t letting this go. “So the CRISPR is not the liquid, the CRISPR is in the…?”

“It’s dissolved in the liquid,” Zhang explains patiently. “There are probably billions of molecules of CRISPR in here.”

“Billions…?”

Marks had been pondering a story on CRISPR for a year or two, visiting the Broad to meet Zhang and the institute’s founding director Eric Lander, and attending the major genome editing ethics conference in Washington, DC, in 2015. CRISPR was being trumpeted in the media as the next miracle biotechnology. But for all its medical potential, CRISPR had not yet entered the clinic, let alone cured anyone of a disease.

The tipping point for Marks came in the summer of 2017, when researchers in Oregon led by Shoukhrat Mitalipov became the first American group to successfully edit a gene in a human embryo using CRISPR. Mitalipov insisted he had no plans to use gene editing to produce actual human beings. But it was hard to ignore the possibility that, in the biological equivalent of the Doomsday Clock, we had moved a big step closer to the alarming prospect of designer babies.

The scientific possibilities of CRISPR seemingly know no bounds. By harnessing the components of a prehistoric bacterial immune system, scientists have developed a remarkable molecular cursor that can scan the 3 billion letters that make up the human genome for a specific sequence, cut it, then repair or change it. The Human Genome Project (HGP) was all about reading humankind’s genetic makeup for the first time. We identified more than 20,000 genes that make up the parts list of the human body. We catalogued mutations in fully one third of those genes that are known to give rise to a plethora of genetic diseases. We spent about $2 billion over thirteen years to spell out this rambling string of As, Cs, Ts, and Gs.^II The fruits of that labor are blooming, spurring the development of precision treatments for cancer and many diseases.

But now, with CRISPR, scientists have a powerful, easy, affordable tool that puts researchers in a position to surgically rewrite the code when there’s a glitch. To “play God.” They can design and engineer the DNA sequence of organisms big and small, from viruses and bacteria to plants (crops, flowers, trees), worms, fish, rodents, dogs, monkeys—and humans. There were other genome editing technologies developed “B.C.”—before CRISPR—that have entered the clinic to treat HIV and rare genetic disorders. And there are already enhancements to CRISPR, even more precise versions called base editing and prime editing that take us closer to the Holy Grail of safe, pinpoint control of the DNA sequence.

There have been some momentous medical revolutions over the past few centuries: sanitation and clean water, anesthesia, vaccines, antibiotics, small-molecule drugs, biologics, in vitro fertilization (IVF) and prenatal diagnosis. In the basic sciences, new tools and technologies continually drive science. Tools to control neurons, map the architecture of the cell nucleus, and conduct a liquid biopsy of DNA fragments circulating in the bloodstream. But CRISPR has changed science in a profound way: the technique caught fire, its simplicity, flexibility, and affordability catching the imagination of researchers around the world in a dazzling democratization of technology.

CRISPR wasn’t the result of a dedicated applied engineering effort. Instead it is the culmination of decades of investment in basic biomedical research, supporting dozens of dedicated scientists working in unfashionable fields, conducting research for the thrill of discovery to better understand the natural world around us. As Nobel laureate Bill Kaelin noted in a piece in the Washington Post championing basic research in cancer rather than razzle-dazzle moonshots: “The CRISPR gene-editing technology that will revolutionize medicine and agriculture emerged from studies of bacteria and their resistance to viruses.”² It is hard to envision a less trendy area of research—or it was until the CRISPR breakthrough.

What can CRISPR do? Treat cancer and thousands of genetic diseases. Simple, cheap, mobile diagnostic tools to detect outbreaks of deadly infectious diseases including the COVID-19 pandemic. Designing heartier, more nutritious strains of crops to feed the world. Creating new breeds of disease-resistant livestock and animals for organ transplantation. Conjuring the notion of “de-extinction,” a way to resurrect extinct species such as the woolly mammoth, while providing a new tool for conservationists to save endangered species. Shaping evolution to control or even eliminate the scourge of infectious diseases. And changing the human gene pool, for better or worse, by editing the DNA of human embryos in a scene straight out of a science fiction movie.

Indeed, it didn’t take long for scriptwriters and novelists to become enthralled by CRISPR. In the 2016 finale of the X-Files reboot, Mulder and Scully search for an antidote to a CRISPR bioweapon that knocks out a crucial gene in the immune system, thereby jeopardizing the human race. Jennifer Lopez was reportedly working on a pilot television show with the working title C.R.I.S.P.R.³ Billed as a police thriller set in the near future, the series would see “mentor and protégé battle for control over the human genome in a game of cat and mouse in which the future of our species may rest.” Tragically, J. Lo has yet to realize her vision of our Crispered future. Writer Neal Baer featured a CRISPR bioweapon pandemic plot line in the third season of Designated Survivor, starring Kiefer Sutherland.⁴

Back in the real world, Lander calls CRISPR “the most surprising discovery, and maybe most consequential discovery, in this century so far.” He’s a little biased, it must be said: Zhang is one of the star faculty at the Broad Institute, Zhang led one of the first demonstrations of CRISPR gene editing in human cells, and has co-founded five companies in five years. Prestige, patents, and prizes are all at stake. Beyond that, a sense of scientific immortality perhaps—the chance to be remembered as the inventor of one of the great discoveries in science and medicine, to be catapulted into the pantheon of science—Pasteur, Einstein, Fleming, Crick, Franklin, Hawking.

But most of the international recognition and early awards for the discovery of CRISPR belong to a pair of female scientists who collaborated to produce what one scientist called an “immortal” paper that appeared in June 2012. Like a short-lived supergroup, Emmanuelle Charpentier and Jennifer Doudna teamed up to program a bacterial enzyme to target and cut any DNA sequence according to the investigators’ whim, laying the groundwork for a game changing, genome editing tool with boundless applications.

According to the doyen of DNA, Jim Watson, what Doudna and Charpentier did was “the biggest advance in science since the discovery of the double helix.” But it’s important to use it so that it’s equitable. “If it’s only used to solve the problems and desires of the top 10 percent, that will be horrible,” Watson warned. “We have evolved more and more in the past few decades into an inequitable society, and this would make it much worse.”⁵

In a profile of the dynamic duo for the Time 100, Mary-Claire King called their work “a tour de force of elegant deduction and experiment” that affords scientists “the power to remove or add genetic material at will.” King christened CRISPR “a true breakthrough, the implications of which we are just beginning to imagine.”⁶

Over the past few years, I’ve watched the impact of CRISPR spread like wildfire around the world, commanding attention not only from scientists and the media but also from royalty, politicians, and even the Pope.

Every two years, the Norwegian capital hosts the Kavli Prize, awarded by the nonprofit foundation set up by the late Fred Kavli, a Norwegian inventor who made a small fortune in Southern California. In collaboration with the Norwegian Academy of Sciences, the Kavli Foundation bestows three $1-million awards for spectacular science that is big (astrophysics), small (nanoscience), and complex (neuroscience). The awards may not quite match the luster of the Nobel prize or the purse of Silicon Valley’s Breakthrough Prize, but they are among the most coveted in science.

In September 2018, the Kavli Foundation awarded the nanoscience prize to a trio of CRISPR pioneers—Charpentier and Doudna were joined by Lithuanian molecular biologist Virginijus Šikšnys. The first two came as no surprise. The inclusion of the Lithuanian was belated recognition of his own pioneering work, despite being scooped by the Charpentier-Doudna team in the summer of 2012. My efforts to peek into the jury deliberations were swatted away with amusement by a Kavli program officer, who said I’d have to wait fifty years for the jury notes to be unsealed.

The streets of Oslo are adorned with banners marking the Kavli celebrations. En route to the University of Oslo campus, I ask my Uber driver if he’s heard of the Kavli Prize. He starts to shake his head, but then he remembers: “Oh wait, I read about one of them—he’s from my country! He’s our man! Tell him to book a ride with Raymondias.” Against the odds, I’m being chauffeured by the one Oslo Uber driver who has heard of Virgis Šikšnys.

That evening, the laureates mingle with guests at a reception held in the Norwegian Academy of Science and Letters. A young attaché to the American Embassy asks me for an introduction to Doudna, a late arrival with her husband, fellow Berkeley professor Jamie Cate, and their teenage son Andrew. “How do you pronounce her name? Is it Dood-na?” (It’s not.) Doudna smiles graciously but looks like she needs some sleep. In the buffet line I’m cornered by a Norwegian philosophy professor, who says I should expect plenty of speeches at the formal banquet the following evening. He explains with a little Scandinavian joke. “A Dane, a Swede and a Norwegian find themselves on death row. Each is given one last request. The Dane says, ‘I want a feast, a roast pork dinner with all the trimmings.’ The Norwegian says, ‘I want to give a long speech.’ As for the Swede, he begs to be shot before the Norwegian’s speech.” (Perhaps you had to be there.)

The next day, hundreds of guests file into the Norwegian City Theater for the official prize ceremony. The audience chatter halts abruptly as King Harald V enters the stage. Part Oscars, part Eurovision Song Contest, we’re treated to a gloriously eclectic selection of musical entertainment. The show opens with Mathias Rugsveen, a fifteen-year-old “sorcerer of the accordion,” who crushes a selection from The Barber of Seville. Before the neuroscience prize, Norway’s answer to Adele belts out a version of “Crazy.” At one point, cohost Alan Alda loses his place on the teleprompter but recovers effortlessly: “Hold on, my ad lib is here somewhere!” Finally, it is time for King Harald to present the nanoscience prize to Charpentier, Doudna, and Šikšnys. Only at the ceremony’s conclusion, as Doudna beckons family and friends to join her on stage, do the laureates visibly relax and hug each other.

Later that evening, the laureates make a grand entrance down a long marble staircase in the magnificent Oslo City Hall to the forty-nine bells of the carillon. King Harald joins the laureates at the VIP table. We feast on a menu of salmon and halibut sashimi followed by filet of deer. I’m reliably informed by the president of the Norwegian Student Union that deer has a completely different taste than reindeer, which he hunted as a boy.

As promised, there are speeches—no fewer than six. The keynote is Marcia McNutt, an ocean scientist and president of the U.S. National Academy of Sciences. She approves that Kavli recognized more female scientists than men. “For every little girl who dreams of rising to the pinnacle of scientific achievement, your future awaits.”^III The director general for research for the European Commission, Jean-Eric Paquet, praises the winners’ curiosity, tenacity, and willingness to take risks. “Fortune favors the bold,” he says, citing another famous risk-taker, polar explorer Ernest Shackleton. Before his first expedition to Antarctica, Shackleton ran a newspaper ad: “Men wanted for hazardous journey. Low wages. Bitter cold. Long hours of complete darkness. Safe return doubtful.”

As it was for Shackleton, instant success was rare for the Kavli laureates. “Tonight, we see only the result, the exceptional achievement,” Paquet remarks. “What we don’t see tonight are the years of hard work, the setbacks, the failures, and the times when they each had to pick themselves up and carry on. In the end, these men and women achieved so much not because they avoided the risk but because they allowed their curiosity to guide them in spite of it—just as Shackleton did.”⁷

The party continues into the wee hours with cognac and a live jazz band, but the Doudnas—having already enjoyed audiences on the prize circuit with the emperor of Japan and the king of Spain—have an early wake-up call. Doudna’s son has to get back to California for school. For the Kavli laureates, there are more events as they head north to Trondheim to give talks at the country’s leading scientific university. Speculation is mounting that, as the scene shifts a few hundred miles to Stockholm, CRISPR will soon be crowned with a Nobel Prize. It’s only a matter of time, but it is not to be this year.

Two weeks after her excursion to Norway, Doudna was back home on the big island of Hawaii. She receives a rapturous welcome as she walks on stage wearing a traditional Hawaiian garland, or lei, featuring the red ohia lehua of the island. It’s a much more down-to-earth affair, followed by a celebratory dinner at Ken’s House of Pancakes.⁸ It was just another whistle-stop engagement for the scientist who, perhaps more than anyone, embodies CRISPR—the woman who literally has DNA in her name.

In the summer of 2017, U.S. senator Lamar Alexander was enjoying a fishing vacation in Canada, off the grid and only listening to the radio for the weather forecast. One day however, he happened to catch a story about CRISPR. We should have a hearing on this, he thought to himself. Luckily, as the chair of the Senate Health, Education, Labor and Pensions (HELP) committee, that was his prerogative.⁹

After running between U.S. Senate buildings trying to obtain my press credentials on a crisp November day, I made it to the hearing room just in time to hear Senator Alexander hailing CRISPR as “just one of the amazing discoveries that has come from basic research funded in part by the federal government.”¹⁰ But he was alarmed by “designer baby” headlines and a report from James Clapper, the former U.S. head of national security, that genome editing had been classified as a potential weapon of mass destruction.

Testifying before the HELP committee were three CRISPR experts—a CEO, a physician, and a bioethicist. “There are a few times in our lives when science astonishes us—this is one of those moments,” said Katrine Bosley, the CEO at the time of Editas Medicine, the first CRISPR biotech company to go public. There are some 6,000 known genetic diseases, Bosley testified. “What if we could repair those broken genes?” she asked. “We owe a responsibility to patients and their families.” But Bosley cautioned it would be a long road ahead. “Cures” was a big word, and Bosley, speaking on behalf of the biotech industry, didn’t want to overpromise.

Most of the Senators stayed only long enough to ask their individual questions before ducking out for more pressing business. Susan Collins, senator from Maine, came out swinging: “It would be possible for genes to be edited that could affect intelligence or athletic ability. We live in a global world; it seems that the scientific advancements have outpaced the policy in this area. How do we ensure this exciting breakthrough in gene editing is used for good by scientists in countries like China or Russia, as well as in our own country?”

I rolled my eyes and winked at science writer Emily Mullin. We’d barely started the questions and already the predictable “designer baby” trope had come up. But Jeffrey Kahn, a bioethicist at Johns Hopkins University, agreed that science advancement usually outpaces policy. “We do have robust structures for oversight that these technologies are used for purposes we intend. International dialogue is happening,” he said reassuringly. “A much smarter approach is to restrict control to allow careful responsible science to go forward, within our borders, not to push them out.”

African American senator Tim Scott, from South Carolina, wanted to know about the prospects of curing sickle-cell disease (SCD). The third witness, Stanford University physician-scientist Matthew Porteus, said he was preparing to enroll some “very brave” volunteers in a groundbreaking clinical trial. His team would harvest the patient’s stem cells, use CRISPR to edit the gene that carries the sickle-cell mutation—correcting a single letter in the three billion letters of the human genome. They would next return about a billion edited stem cells via IV to the patient. These fixed cells would find their way back to the bone marrow and reconstitute the patient’s blood. With any luck, the patient will no longer have their disease. “That’s pretty cool,” said Scott. And then he left.

Virginia senator Tim Kaine asked if CRISPR had any relevance for Alzheimer’s disease, but Bosley wasn’t so optimistic. New therapies were further out, she said, because the genetics was more complicated than say SCD. Kaine also asked about regulatory oversight. Kahn pointed to the UK, which has strict control processes that allows the country to license emerging biotechnologies. “People don’t want to go to jail for ten years” for violations, Kahn said. “We lose in multiple ways when we drive science underground.” Nor did the U.S. want to cede its leadership and competitiveness in gene editing to anyone else.

No one could have predicted that, one year later, Kahn’s hypothetical warnings would come kicking and screaming to life.

Six months later, in April 2018, the CRISPR road show landed in a most unlikely location—the Vatican. The “Unite to Cure” conference is the brainchild of Robin Smith, president of the Cura Foundation, in conjunction with the Pontifical Council for Culture. Smith’s rolodex is ridiculous: among the guests were TV personalities Dr. Mehmet Oz and CNN’s Sanjay Gupta, with cameo appearances from A-list celebrities including Katy Perry (the power of meditation) and Jack Nicklaus (stem cells). At times, the meeting felt uncomfortably like a late-night infomercial. Billionaire Ed Bosarge bought a clinic in the Bahamas and was receiving experimental injections that would cross the blood-brain barrier to combat memory loss and aging. “My goal is to be healthy and fit and playing tennis at 120,” he said with deadly seriousness.

Then there was Peter Gabriel, the first rock vocalist I ever heard (on Genesis’s Selling England by the Pound). Gabriel treated us to an unplugged concert, although he was a bit rusty as evidenced by a false start on “Solsbury Hill.” He emotionally dedicated the set to his wife Meabh, who had recovered from an aggressive form of non-Hodgkin’s lymphoma following CAR-T therapy. Later he said: “Rich people will live forever and poor people will die in their billions. The trickle-down model isn’t going to change that.”

With so many celebrities in attendance, a panel discussion between the CEOs of the three public CRISPR biotech companies was almost an afterthought. All three companies were launched by scientists at the heart of the CRISPR drama: Zhang and Doudna co-founded Editas Medicine, but Doudna quit over a patent dispute and later joined the founders of Intellia Therapeutics. Meanwhile, Charpentier launched her own company, CRISPR Therapeutics. Katrine Bosley said CRISPR was “the biggest thing to happen in biology in a generation,” moving beyond science fiction to treat genetic diseases. The CEO of CRISPR Therapeutics, Sam Kulkarni, said CRISPR had captured the imagination of millions of people because it was so easy to use. “It has completely democratized [gene-editing] technology.” Intellia’s CEO, John Leonard, said CRISPR clinical trials were imminent, and he predicted CRISPR would be the “standard of care for sickle-cell in short order.”

Bosley conceded there was a dark side to CRISPR. Technology is neither good nor bad, “it’s what we do with it,” she said. That was also the theme of a speech by Pope Francis, delivered in a private audience with a few hundred conference attendees in the stunning Audience Hall, the interior of which resembles a snake’s visage. The Pontiff spoke of the need to protect the environment and exercise caution in the application of gene editing. He acknowledged “the great strides made by scientific research in discovering and making available new cures,” especially in rare autoimmune and neurodegenerative diseases. But science, he said, has opened up new methods

to intervene in ways so profound and precise as to make it possible to modify our DNA. Here we see the need for an increased awareness of our ethical responsibility toward humanity and the environment in which we live. While the Church applauds every effort in research and application directed to the care of our suffering brothers and sisters, she is also mindful of the basic principle that ‘not everything technically possible or doable is thereby ethically acceptable.’¹¹

It was a well-manicured statement, crafted in consultation with Bosley and other CRISPR company executives. And it was soon forgotten as Katy Perry and other VIPs lined up for a chance to kiss the Papal ring. Nobody—not even the Pope—knew that halfway around the world, a Chinese woman was in the first weeks of pregnancy. She was carrying twins whose DNA had been sculpted not by God but by the undivine hands of an ambitious genome engineer with an assist from his embryologist.

It was a most maculate conception.

Fears that a renegade scientist might dare to rewrite the genome’s Holy Script have existed for decades, albeit more in the fictional realm. But a 2015 study by a Chinese group showed for the first time that scientists were prepared to fix a disease gene in a human embryo just hours after in vitro fertilization. In ethical terms, it was a giant leap over the mythical red line that supposed that human beings would never play God with their genetic destiny. Over the next three years, various august medical societies and committees published dozens of erudite reports on the ethical pros and cons of genome editing.¹² While scientists and ethicists debated, Australian geneticist Daniel MacArthur tweeted, “My grandchildren will be embryo-screened, germline-edited. Won’t ‘change what it means to be human.’ It’ll be like vaccination.”

Several groups, mostly in China, reported experiments on human embryos, without any plans of implanting those edited embryos. But a young Chinese scientist who had spent five years training in the United States dared to take the next fateful step. He Jiankui assumed that his groundbreaking work would be celebrated at home and abroad, published in the world’s premier journal, putting him on a pedestal with his scientific hero, Nobel laureate Robert Edwards, the co-inventor of IVF.

But there was no celebration, no acclaim, and no Nature paper. Instead, outrage and fierce, near-universal condemnation. The work was sloppy, irresponsible, rash, unethical, and possibly criminal, leaving serious questions over the health of two babies. He Jiankui’s career crumbled overnight as he was placed under house arrest, sacked by his university, and eventually sentenced to three years in prison. Undeterred, a Russian geneticist announced his intent to take matters into his own hands and use CRISPR gene editing to help couples with inherited deafness. “We keep advancing where this line is and, in effect, there is no line,” said Regalado.¹³

The director of the National Institutes of Health, Francis Collins, is steadfastly opposed to any attempt to tamper with the DNA of human embryos. “Evolution has been working toward optimizing the human genome for 3.85 billion years. Do we really think that some small group of human genome tinkerers could do better without all sorts of unintended consequences?” he said.¹⁴ Many leading scientists have called for a temporary moratorium to give scientists and other stakeholders time to explore the rationale and circumstances under which germline editing might be approved.¹⁵ But others find little to fear about the prospect of germline editing. Harvard’s George Church, a veteran genome engineer, is keeping an open mind. “I just don’t think that blue eyes and [an extra] 15 IQ points is really a public health threat,” he told a British newspaper. “I don’t think it’s a threat to our morality.”¹⁶

In his final book, the great physicist Stephen Hawking predicted that we were heading toward an era of what he termed self-designed evolution. “We will be able to change and improve our DNA,” Hawking wrote. “We have now mapped DNA, which means we have read ‘the book of life,’ so we can start writing in corrections.”¹⁷ But for Hawking, the slippery slope didn’t stop at curing devastating diseases such as his own affliction, a slowly progressive form of amyotrophic lateral sclerosis. Hawking believed scientists would use techniques such as CRISPR to modify or enhance traits like intelligence, memory, and longevity—violating the law if necessary. These “superhumans” would be available to wealthy elites, putting them in conflict with natural humans. Hawking continued:

Once such superhumans appear, there are going to be significant political problems with the unimproved humans, who won’t be able to compete. Presumably, they will die out, or become unimportant. Instead, there will be a race of self-designing beings who are improving themselves at an ever-increasing rate.

There was an immediate fear that the abhorrent actions of one scientist could derail the remarkable progress in using CRISPR and other editing techniques for gene therapy in children and adults. As I talked to friends and scientists in the audience, I heard one genome editing luminary portray the numerous concerns over the CRISPR babies as an “existential threat” to the future of therapeutic genome editing.

Thankfully, those fears have not yet come to fruition. Although still early days, genome editing is showing genuine promise in the clinic for patients with cancer, blood diseases, hereditary forms of blindness and many other disorders. The training wheels are coming off, says Fyodor Urnov. “The world gets to see what CRISPR can really do for the world in the most positive sense.”¹⁸

I. #MeToo

II. The genome project’s dirty little secret is that the human sequence is still incomplete. Portions of the genome have proven just too difficult to read using current DNA sequencing technologies.

III. There will be no such speech in 2020: all seven Kavli laureates were men.