Masterminds: Genius, DNA, and the Quest to Rewrite Life

(#ulink_0b2da616-1dd2-54c9-94df-a3a82903636b) Laid alongside the wonders of the last century, the dangers of modern science and technology are accepted by people in an ongoing Faustian bargain that has become a cliché of B movies and science fiction novels. Mary Shelley helped launch the notion of the modern mad scientist in 1810, inventing the character of the young idealist who sets out on a quest to understand the intricacies of nature and life and ends up with Boris Karloff in green makeup with bolts in his neck.

This bargain is tempered by a demand that governments remain vigilant against future Frankensteins and Mengeles, while ensuring safety whenever possible as science moves forward. Watchdog agencies such as the U.S. Food and Drug Administration and ethics committees in universities, hospitals, and businesses have been assembled to oversee experiments and the release of new products and hopefully to head off anything that might prove dangerous. The tension between how safe is safe and the pressure from scientists to test new discoveries is one of the defining aspects of modern science and culture. Most scientists insist on a code of ethical conduct in keeping with current norms of human rights and dignity, keenly aware that despite science’s power and clout, the public has little patience for errors that endanger people or overtly imperil the environment. They have no tolerance at all with scientists who would delve into the territory of a Mengele or a Frankenstein, even inadvertently.

This is reassuring, up to a point. Yet as we plunge into tinkering with the basics of life, can we know for sure what they—and we—are doing, and what its impact will be?

Most scientists tell me not to worry: that we humans have not yet destroyed ourselves or the planet, and that on balance science has been an overwhelming force for the good. Yet others worry that we are entering unchartered territory without really understanding the implications. “We have to decide soon what kind of society we want,” says the Oxford neurogeneticist Susan Greenfield, a baroness and member of the House of Lords, and an author who writes about the brain and the social impact of genetics. “For instance, do we want a world where everyone takes Prozac, uses Botox, and plays with Gameboys? We could be heading into a designer-baby world where we sit passively in front of our screens and live in a virtual world. Do we want that?”

The other day I reread the self-description of Victor Frankenstein in Mary Shelley’s classic, who early in the story describes his intentions. “It was the secrets of heaven and earth I desired to learn; and whether it was the outward substance of things, or the inner spirit and the mysterious soul of man that occupied me, still my enquiries were directed to the metaphysical, or, in its highest sense, the physical secrets of the world.” Shorn of the stigma of being spoken by the lips of Dr. Frankenstein, these words could easily describe many of the subjects of this book.

Yet we hardly know the scientists and others sweeping us into this new world, the Stefanssons, Greenfields, and Venters. Their names are mostly obscure outside molecular biology. In part this is because journalists tend to write articles trying to explain the intricacies of proteomics, genetically modified organisms, ribonucleic acid (RNA), transgenic animals, and therapeutic cloning—and the ins and outs of start-ups, initial public offerings (IPOs), and roiling markets. We mention characters like Kari Stefansson, scratching out quick, throwaway descriptions, treating them as secondary to the science and the spreadsheet. Science writers scribble endless books on the solving of the human genome, stem cells, and cloning, often failing to delve seriously into the phenomenon of an age that is producing, all at once, a remarkable profusion of brilliant, quirky, charismatic, possibly dangerous scientists whose work will profoundly impact life itself.

Who are they? Are they megalomaniacs with supersized egos, or individuals of high ethics and morals who will do what one of them, Stanford’s Paul Berg, did when he was in the middle of an experiment in 1971? Berg was creating a hybrid molecule by combining a common bacterium with a monkey virus. He planned to insert his hybrid into Escherichia coli, a benign bacterium found in the stomach of nearly every human on Earth. But the monkey virus, SV40, had been shown to cause cancer in mice and might cause cancer in humans—or not. No one at that time knew for sure, though they now know the virus is most likely harmless in humans. Back in 1971, another scientist alerted Berg to the possible danger of this hybrid molecule’s escaping his lab and infecting E. coli in the stomachs of his lab workers, and possibly beyond, potentially unleashing a cancer plague. This scenario was remote, but Berg could not eliminate the risk 100 percent. So he shut down the experiment, wanting to be cautious about the implications of what became known as recombinant DNA—now used as a basic component of genetics and biotechnology. Would this method of using one organism to produce the proteins of another lead to freakish disasters?

Berg took this question to a famous conference in 1975 at Asilomar, near Monterey, California, where he and others persuaded their fellow geneticists to cease certain recombinant DNA experiments while safety issues were tested and guidelines for containment of dangerous experiments could be formulated. This process led to thirty years of recombinant DNA experiments without a single accident. Berg’s experiments won him the Nobel Prize, with Walter Gilbert and Fred Sanger, in 1980.

Berg was careful, when another scientist might have forged ahead despite the dangers. For instance, his fellow geneticist James Watson argued forcefully against a self-imposed moratorium on recombinant DNA work at the 1975 Asilimar conference, insisting that the process could remain contained and safe in the lab, and that a moratorium would frighten the public and might lead to a ban by the government. (This nearly happened.) Personality played a critical role in this debate between Berg and Watson.

The science emanates from their minds, and from their personal stories, but also from who they are: their hopes and fears; their humility, their arrogance, and the ambition that drive them forward into discoveries and dictates how they react to the possibility of miracles, and of disasters. “Science seldom proceeds in the straightforward logical manner imagined by outsiders. Instead, its steps forward (and sometimes backward) are often very human events in which personalities and cultural traditions play major roles.” This comes from James Watson, codiscoverer of the double-helix structure of DNA in 1953 and an obnoxious, dazzling personality himself. The science historian Horace Judson, author of The Eighth Day of Creation, remarks that the personality of scientists “has always been an inseparable part of their styles of inquiry, a potent if unacknowledged factor in their results. Indeed, no art or popular entertainment is so carefully built as is science upon the individual talents, preferences, and habits of its leaders.”

“The whole idea that science is conducted by people working alone in rooms and struggling with the forces of nature is absolutely ridiculous,” says Sydney Brenner, a pioneer of molecular biology famous for talking incessantly with colleagues to tease out ideas. “It is a social activity of the highest sort.”

Why is this important? Because, as the Harvard biochemist Stuart Schreiber once told me over coffee, his eyes magnified through thick wire-rim glasses wrapped around a bald head that looks both thuggish and hip: “There’s a high probability that for Homo sapiens, the process of evolution as we currently think about it, as natural selection, is for all intents and purposes over. It is going to be replaced by our desire and capability to tinker.”

There is the fiery-tempered and temperamental Watson, who in his midseventies still keeps pinups of busty young women in his office close to his Nobel medal. An atheist who believes the double helix proves that God does not exist, Watson has strong views about everything from stem cells to his belief that genetic flaws in behavior as well as disease should be fixed.

There is Craig Venter, a stormy renegade with the gravitas, ego, and devilish brilliance of Faustus, though he also has a cornball sense of humor. In the late nineties, he took on the scientific establishment during the Human Genome Project and succeeded in getting the job done faster and, at least according to Venter himself, better. He ranges about like a junkyard dog snarling and laughing as he brilliantly upsets applecarts. Venter restlessly sails the seas in his yacht, Sorcerer II, collecting microbes from the oceans to sequence genetically, while back in his lab in Maryland he leads a team creating synthetic life-forms.

And then there is Francis Collins, the can-do Boy Scout of molecular biology with a steely resolve and intense competitiveness. Chief of the National Institutes of Health genomics programs, he is a born-again Christian and codiscoverer of the gene for cystic fibrosis, who went head to head with Venter during the race to sequence the human genome. Collins headed up the band of stalwart gene hunters who pursued this nearly $3 billion quest with a religious zeal, proselytizing its benefits and fighting to keep the DNA they sequenced free and publicly available.

Others you will meet in these pages are working to create new life or to extend it, to grow new organs using stem cells, to bioengineer genes—and, in the case of the former Soviet bioweapons expert Ken Alibek, to snuff out the life of his former nation’s enemies when he was working for the secret Union of Soviet Socialist Republics (USSR) bioweapons program in the seventies and eighties.

When I set out to write this book, I experimented with several methods to describe the role of personality in science. In the end, I chose and expanded on a strategy used with delightful effectiveness by Lytton Strachey in his 1918 Lives of Eminent Victorians. Insisting that too much material existed on the recently finished Victorian age to make sense of it in a single book, he picked out four representative figures to profile, among them Florence Nightingale and General Charles Gordon. He described his method as dipping a bucket into the vast ocean of material on his subject, “which will bring up to the light of day some characteristic specimen, from those far depths, to be examined with a careful curiosity.”

I, too, have chosen a few representative people, though in this book I’ve added to Strachey’s idea an element that he would have understood. He chose characters specifically to point up both the grandeur and the flaws of figures whom his parents’ generation had revered and worshiped as heroes and geniuses. He elevates them to godlike status by treating them as standard-bearers of the Victorian era, only to reveal them as all too human. Yet they remain exalted throughout as forceful stories and symbols of the glories and disasters of their time. I have chosen nine scientists with the same emphasis in mind, but with an added element that defines a major difference between our era and Strachey’s. Today, we don’t need to reduce heroes of a former generation to mere humans. In this age of reductionism, that happens as a matter of course. I have taken these very human, and therefore flawed, individuals and assigned them each a mythic status by assigning them a character from myth, fiction, or history—Prometheus, Eve, Zeus. Not because I consider these scientists gods or demigods, but because I believe that to appreciate these figures whose work is so critical to the future of life accurately, it is useful to see them through the lens of stories, myths, and characters that have endured for centuries as devices to understand and absorb the import of major moments in human history.

I agree with Paul Berg that as we move forward with science we must be cautious. Scientists need to be keenly aware of not only potential dangers, but the ethical and social impact of their discoveries. Yet I also believe that many of the discoveries and possibilities will happen regardless of what society thinks. As in splitting the atom, once the knowledge exists, the science will find a way to happen, possibly in secret in countries where neither ethics nor the public’s fears much matter. This makes it even more crucial that this science be allowed to go forward while being closely watched, with appropriate safeguards.

Back in Kari Stefansson’s office, I’m reminded of why I have a personal stake in understanding this Icelandic gene master. We’re sitting in deCode’s new building, a blond wood, brick, and glass palace rising on the edge of Reykjavik like a gigantic piece of Skandia furniture. This in a city of mostly squat, functional, wood-slate buildings that seem hunched over, as if holding their heads down in a storm. Rain does fall here frequently, though the nearby Gulf Stream usually keeps the temperature above freezing, even in the winter.

Inside deCode, three towers containing labs, computers, and offices are connected by a glass-enclosed atrium four stories high, an airy and expansive space crisscrossed by open bridges between the towers. Hanging down from the ceiling, over the lunchroom, a gigantic model of a double helix turns slowly, picking up the dull, gray light from outside like an elongated disco ball. In one tower a supercomputer that can process a person’s entire genetic code in twenty minutes.

Stefansson’s office suite is across a bridge from the spinning DNA model. His large windows overlook the old Reykjavik airport, and the vast sweep of lava fields and mountains. He’s wearing his trademark tight black T-shirt and is preparing to drink two glasses of a Pepto-Bismol-colored drink he says is a protein supplement. I see Yeats’s Ghosts and the NASDAQ Rule Book, among other volumes, in his bookcase. He’s about to tell me the results of one of the tests run on my DNA.

KS: The DNA from you is, of course, a scary substance.

DD: I have friends who would agree.

KS: I’m sure. One of the things we did was that we looked at the genes that confirm a stroke. We have established that you have a series of genetic markers that give you something like a two to seven times greater risk for developing a stroke than if you don’t. You have this entire haplotype [inherited sequences of DNA that cause specific traits] so you probably have three times the risk. If this turns out to be the case in the American population, you are genetically predisposed to stroke.

DD: Oh, hmm. Stroke? But I’ve had no stroke in my family, other than my grandmother when she was eighty-three years old. Doesn’t my own family history weigh in here?

KS: The only thing you have done is to inherit a predisposition. What does that mean eventually? It means that if you stay in a certain environment, or if you are born in a certain environment, you will develop stroke.

DD: This is because most diseases are a combination of mutated genes and the environment—that is, the environment can trigger diseases, or not?

KS: Yes.

DD: But this isn’t good news for me. One day I’ll be watching a movie or walking down the street, and, suddenly, I’ll go limp with a stroke.

KS: Maybe, but here’s the beauty of the genetic profiling. It’s not going to lead to a genetic determinism like that. You are not going to develop stroke, all right? You now know that you have three times the possibility of the average individual to develop stroke. So you have a strong incentive to take measures to prevent stroke. One of them is to make sure that you don’t have high blood pressure; one of them is that you will not smoke. One of them is you will drink alcohol only moderately, because intake of large amounts of alcohol, binges, increases dramatically the probability that you will develop a stroke.

DD: But this genetic profile for stroke has not been tested for Americans. You’ve just tested Icelanders. Right?

KS: Before you can get too excited as an individual, you have to do a clinical trial in the population where you can use it, like in the American population. But this is a fairly interesting example of how genetic profiling is going to impact the delivery of health care.

DD: How common is this stroke gene for Icelanders?

KS: In Iceland, this is a haplotype that you find in about thirty percent of patients with stroke. You find it in about fifteen percent of controls [those without stroke]. And then you say, “Wow, fifteen percent of controls with no stroke.” But this is an inheritable predisposition. We know this from our genealogical data. Of these fifteen percent, a large percentage will eventually develop stroke. But most of these people carrying this haplotype will not develop stroke.

DD: Those odds still make me want to go and have a drink.

KS: You cannot drink anymore.

DD: Did you find out anything else about my DNA? Or do I want to know?

KS: We tested your ancestry to see if the population data from Iceland is relevant to you. You told us your ancestors came from Scotland. In the Icelandic Sagas, they said that Iceland was settled by Norwegian Vikings who stopped in the British Isles and picked up slaves and women, in Ireland and maybe Scotland. And we decided to test you by looking at your mitochondrial polymorphisms [mitochondrial DNA exists in each cell, separate from the double helix of human DNA; polymorphisms are DNA in an individual that are different from the norm]. Remember, mitochondria is passed from mother to offspring. Then we looked at your Y chromosome—these both are fairly good measures of paternal and maternal lineage. When we looked at this, it turns out that when we compare it to all of Europe, about seventy percent of Icelandic mitochondria are Celtic.

DD: The Celts being Irish and British, among others.

KS: Yeah, and about seventy percent of Icelandic Y chromosomes are Norwegian. So it looks like Iceland was settled by Norwegian boys who grabbed British girls. This is important when it comes to your mitochondrial DNA, because if we look at the mitochondrial sequence number one, that people look at mostly for ancestry, we find out that you have a haplotype that is characteristic for Europeans. However, when we look at region two, there is this very rare haplotype found only in Iceland and the north coast of the British Isles. We found this haplotype in you.

DD: Uh-oh, then this stroke gene is relevant to me.

[Stefansson calls someone on the phone.]

KS: [Into the phone] I’m out of coffee and I’m in a desperate need because I’m talking to a very boring fellow. [To me] My eighteen-year-old daughter would have said, “boring dude.”

That night, I meet Stefansson for drinks at an Italian restaurant that served, among the usual pasta and veal, horse meat, apparently an Icelandic specialty. After drinking enough red wine to give me a stroke for sure, we walk up the main drag of Reykjavik—there is only one, though the bars, clubs, and restaurants are as sophisticated as any in the world. Icelanders travel incessantly and take back music, art, dancing—and genetics—from elsewhere, integrating with their own sensibility.

In one bar heads turn when Stefansson walks in. He’s a rock star here, the second most famous Icelander after the pop singer Björk. He towers over most people and is known by everyone. I step over to the bar to order beers, and two Icelandic women say hello. One of them says she is in love with Stefansson, the other is annoyed with him, because, as many Icelanders did, she bought deCode stock and watched it tumble when biotech stocks took a nose dive in 2001–2003. Stefansson comes over and is sullen—he’s had a long day, but we drink until 3:00 A.M. As he says good night—and it’s still light out—Stefansson tells me that drinking tonight will kill me, that I’ll have a stroke for sure by morning. I walk home through the eerie lightness, with the streets slick with dampness in the air, and the distant volcanoes black and steaming. I wonder whether I should believe him and ponder the bioluminaries I am talking to about bioengineering humans, extending life, and regenerating hearts and brains, wondering, Can they be trusted?

Emerson wrote that every age has its geniuses, its masterminds who propel humanity in a new direction, for good or evil—though he also said you need circumstances to bring them out. I believe that the time is now. The circumstances are here. The masterminds are in place. The Prometheuses are bringing in the fire, the Florentines are carving Davids, Faustus is talking to the devil, and the Los Alamos boys are building the bomb.

(#ulink_7f884180-ccd9-503e-9e85-86fd1d2f20cc)See pages 145–46.

THE LANGUAGE OF BIOTECH: A Genetic Primer (#ulink_c13bb965-808d-5d91-930e-a092b622168f)

Science has given us the means to create utopia and dystopia, incinerate and mutate ourselves, build elevators into space, and tinker with the Lego blocks of life. Yet most people blanche when they see terms such as deoxyribonucleic acid—better known as DNA. Stare at your left hand and, if you could see them, you would glimpse billions of deoxyribonucleic acid molecules tucked just inside the cells that make up your hand. The eyes you are using to stare at your pinky contain deoxyribonucleic acid. Your eyes were made according to instructions stored in you in those nucleotides, and they continue to see thanks to eyeball maintenance programs stowed in your DNA.