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Masterminds: Genius, DNA, and the Quest to Rewrite Life
David Ewing Duncan
Combining myth, biography, and wit, this is a highly original depiction of cutting-edge science and its profound implications, told through the scientists who are rewriting life on earth.Throughout history, the scientists’ personalities have astonished us. From Galileo to Jonas Salk, they push and stretch society’s boundaries though their great leaps of imagination and originality, providing us with everything from the wheel to rocket ships and penicillin. Today's masterminds in biotechnology promise lifespans up to 400 years, cures for cancer, and an end to pollution. But they are also capable of causing social upheavals with Frankenstein-like nightmare creations, as well as bioweapons.Award-winning writer David Ewing Duncan has written a startling narrative about science and personality, delving into stem cells, cloning, bioengineering, and genetics by telling the stories of the characters at the fulcrum of the science. He uses a unique method of tying in age-old stories and myths – from Prometheus and Eve to Faustus and Frankenstein – to ask the question: can we trust these scientists?
DAVID EWING DUNCAN
Masterminds
GENIUS, DNA, AND THE QUEST TO REWRITE LIFE
DEDICATION (#ulink_667c9517-d440-54de-bb8f-8121578f69a2)
To my mother and father.
EPIGRAPH (#ulink_3c060591-13fe-5428-8fb7-5e2b3651ecb5)
I’ve had to face up to the
fact that most of our society
thinks of scientists as people
who are likely to do something
bad. Either bad to make
money for themselves, or
to cause trouble in the
Frankensteinian sense.
And the fact is, scientists
that I know are trying to do
good for people.
—Douglas Melton
Harvard embryologist
It is not possible to be a
scientist unless you believe
that the knowledge of
the world, and the power
that this gives, is a thing
which is of intrinsic value
to humanity, and that you
are using it to help in the
spread of knowledge, and
are willing to take the
consequences.
—Robert Oppenheimer
November 1945
CONTENTS
Cover (#ueb3d3cb2-46b6-5ad0-9d81-a7e151fbc894)
Title Page (#u3d2cd4fc-6cd5-5eb0-aeb1-cc9848064f7f)
Dedication (#u478534f5-ddba-556c-be0a-6a70eb50dcbe)
Epigraph (#u9064898a-6ab1-5f47-960a-2aa1838ac56c)
Prelude: The Geneticist Who Played Hoops with My DNA (#ue934411e-a02a-572a-98f1-f4ace3da88a5)
The Language of Biotech: A Genetic Primer (#uf0a8af88-6e7b-5683-be22-fb040004025b)
1. Prometheus • Douglas Melton (#u739b5154-da12-5d66-af09-1c6beba7052a)
2. Eve • Cynthia Kenyon (#uda52b3bc-9c48-5cd5-81ec-b41e12c1700b)
3. Paul • Francis Collins (#u30c75a25-a870-5408-823b-67b8d679681c)
4. Faustus • Craig Venter (#u5af0e89f-19cb-526a-9cdb-e88b6fb6deab)
5. Zeus • James Watson (#u1da5bb40-832d-51c0-8d5e-48d2da5b3b9e)
6. Puck • Sydney Brenner (#ufdd29e56-959b-551b-b0f8-4e7509afdca0)
7. Moses • Paul Berg (#uc75760df-ae74-55d2-a0e3-344e19f3463f)
EPILOGUE: What If Frankenstein’s Monster Had Einstein’s Brain? (#u0218d449-d742-5d49-bfe2-f4166a48749f)
Keep Reading (#uc0a00e7d-afd5-5156-b391-f6628ddbaa90)
P.S. Ideas, Interviews & Features … (#u87ef965c-8968-5e3e-abc6-561607ed9c93)
About the Author (#u1dad702e-a7dc-5396-84a2-3f9d20f9df01)
Q and A with David Ewing Duncan (#u794a846c-04f3-5079-a300-44067c0952a8)
Top Ten Favourite Authors (#u1dae1cb0-673e-5687-a983-d69b54683b76)
Life at a Glance (#u58008da3-672d-5e5d-bdb7-f57d5a2b3125)
A Writing Life (#ue6ae15b1-ab57-5a22-ac95-7ba8f287e5af)
About the Book (#ud06e3ce8-9236-584e-989d-ebcb2de0824a)
The Greatest Story in Human History (#u3d4621ef-fbd2-5b61-8d39-a76ebec5cdb5)
Read On (#u388e5a03-e485-5ef8-aef3-7923991eaf6e)
If You Loved This, You Might Like … (#ue8817e8a-8122-54af-a1d7-5d076e2db07b)
The Web Detective (#u992ac13e-25c1-5dec-bf39-01c5dae7624a)
Index (#u1ceaf1d4-78a0-589b-9a09-762b0ba58bd4)
Acknowledgments (#u6cf1ef23-c162-5dd5-b86e-6348aff41736)
About the Author (#ueb8a7b54-2a8e-59bd-9ffa-423a88032f41)
Notes (#u5eca1a89-7170-5074-b777-8f90ec35448b)
Praise (#u44628911-db4a-54c8-aaef-5bcd6b233c06)
Also by the Author (#udc0ecb1a-3f53-55e9-a55b-bf01d624850a)
Copyright (#u586e88cb-bc42-5b46-8183-9d80281839f9)
About the Publisher (#u00d58c3a-ea32-5597-becc-c73181f6054b)
PRELUDE: The Geneticist who Played Hoops with my DNA (#ulink_9ec605b8-da52-54ae-ae26-d6d8986f05a6)
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.
—Stuart Schreiber, Harvard geneticist
I’m playing hoops with Erik the Red on a half-court at the ends of the Earth, and he is toying with me. Also Iceland’s most famous geneticist, he’s dribbling a basketball in a Reykjavik gym on a typically damp, cold day in August near the Arctic Circle. Notorious for being rude, as well as brilliant and filled with an infectious passion, Kari Stefansson, a descendent of Erik—an early Viking explorer and marauder—insisted that I go one on one.
Every day at 2:00 P.M., when he’s not wandering the globe rustling up cash or giving talks, Stefansson drives from his office downtown across this speck of a capital city, home to nearly all of Iceland’s 290,000 people, to a gym that requires a retinal scan to enter (Icelanders love gadgets). Just beyond the gym’s parking lot the city ends and a hardened lava field begins, though this is hardly a landmark in Iceland. Here the black rock everywhere remains raw, hardened in waves and eddies, once lava-hot, covered only by a thin veneer of lime-green moss. Overhead, the sky boils with immense gray-white clouds that turn nearly black above a ridge of distant mountains where active volcanoes still blow off steam. The land looks ripped from a primeval moment in history, when cones spewed ash and fire and Titans roamed the Earth.
It’s a fitting place for Stefansson to be exploring the raw ingredients of life, the nucleotides and other molecules that he first began to study as a medical student at the university here before moving on to the University of Chicago and then to Harvard. There, as a medium-important neurologist, he delved into the mechanics of multiple sclerosis and other maladies of the brain. At first, before new technologies made deoxyribonucleic acid (DNA) easier to work with, he cut open the brains of persons who had died of neurological disorders. Later, he parsed out their DNA, looking for links. But the academic approach was too slow, so in 1996 he returned home to Iceland to start a company.
On the court Stefansson destroys my pathetic game, despite being fifty-six years old to my forty-four, a difference he notes everytime he overpowers me to plant a basket. At six feet, five inches, with close-cropped white hair, a pointed beard, and biceps that bulge out of the tight black designer T-shirts he tends to wear, Stefansson looks as formidable as his wild-eyed Norse forebears in the Icelandic sagas he likes to read, those hairy warriors who sailed in flat-keeled longboats one thousand years ago, snatching women from the British Isles and taking them to this bleak edge of the earth.
I haven’t played basketball in years. When I finally grab the ball he flashes me a glare that Erik might have used before hacking to death an enemy in the tenth century.
Prior to playing, we had been talking about a test that Stefansson’s company, deCode Genetics, had just run on my DNA, a journalist-as-guinea-pig experiment to check my nucleotides for genes associated with disease. Back in the States, I had a lab extract three vials of my blood to ship on dry ice to Reykjavik. deCode’s technicians then plucked out my DNA from the white blood cells and tested it against the company’s database of genetic maladies. Do I have a genetic proclivity for heart disease, Alzheimer’s disease, osteoporosis, anxiety? “We will tell you if you are crazy, or if you might die of a stroke. You will become our first American lab rat,” he had told me a few months earlier, when we met during a biotech conference in New York.
Stefansson had promised to reveal my results when we returned that afternoon to his office, making me one of the first persons ever to reveal publicly so much personal information about a raft of disease markers hidden in everyone’s genes. In a few years, he says, these tests will be routine: a screening like a cholesterol test that will tell us whether we might one day contract a dread disease or die sooner, rather than later. They also might be used to tease out genes that affect behavior, telling us whether we have a predilection for anger, risk taking, happiness, or homicide. Yet I know this sort of predictive genomics is still very much nascent, the information incomplete, the connections between genes and disease or behavior murky, the forecasting power faulty and poorly understood. But I’m willing to listen, and to imagine the possibilities as described by this Armani Viking.
Of more immediate concern to me is how to react if Stefansson tells me that my nucleotides may be harboring an aberration I never suspected, a dread disease ticking inside me like a secret time bomb ready to strike when I’m fifty years old, or seventy. A fatalist, I don’t think much about how I might get sick or die, but I can’t help but feel a small apprehension.
On the court I’ve got the ball and I’m dribbling toward the basket, making a few clunky moves I remember from years back. I whip around Stefansson; he pushes in close and I feel his hot Viking breath on my face. I zig left; he cuts me off. I zag right, and we crash shoulders as I push to turn a corner around him. He’s behind me, pushing, and I start my leap, holding the ball up, eying the basket when he blurts out, “I have your DNA results.”
“Yeah?” I say, suspended for a moment in the air, feeling that electric rush that says this ball is going to connect, it’s going into the damn basket.
“You are genetically defective.”
I hesitate for all of a split second. He jumps high and grabs the ball, twirls, and races down the court, dribbling and flashing me Erik’s demonic smile.
I’m visiting Kari Stefansson as part of an experiment to unlock the secrets of my own DNA. In due course, I will find out my results. But as I watch him play, his dark green eyes alluring and murderous, I’m struck by a simple revelation. Stefansson in many ways is the early-twenty-first-century equivalent of Erik the Red. He is a marauder and warrior, a larger than life figure who slices through frigid waters in a longboat with an outsized passion to conquer, to achieve glory, and perhaps to get rich, but mostly for the sheer joy of it.
Lest we build him up too much, Kari Stefansson is also just a man. I have seen him tired, and downcast. On one of my visits to Iceland, the stock in his company had dipped down to about two dollars a share, prompting him to fret about an unwanted suitor who might attempt a frontal assault to buy the company out from under him. The Viking was watching his backside—though this Norseman is also a physician who wants to alleviate suffering, if he can. Moody and stormy, he looked depleted after a round of calls to investors and advisors, as if he had been fighting the Furies all day and was still standing, but was exhausted by the effort.
It seems evident that Stefansson’s prickly, infectious personality is crucial to his success in being a scientist and entrepreneur: that peculiar blend of DNA and experience that makes this Viking gene master a genius, bully, and force of nature. As he humbles me by swishing yet another basket, I tease out this idea—that the Stefanssons of this rarified world of scientists and entrepreneurs are driving this era of biological discovery as much as the science itself. This is obvious, though maybe, I think, this is a way to delve into the heart of the matter with genetics: to tease out first what is the crux of the science, and the implications of the discoveries for us humans, by trying to understand its creators—the Prometheuses bringing us fire, the Faustuses taking us to either heaven or hell, the Eves about to bite into another apple on the Tree of Knowledge, and the Erik the Reds blustering about and trying to score big with basketballs and nucleotides.
Here is a man who has glimpsed my most intimate secrets, my DNA, those unique combinations of chemical compounds that make me me: my blue eyes, a crooked left second toe, a tendency to be far more curious than is healthy. I also have this flip in my left eyebrow that my grandmother once called “the lick of God.” All the men in my family for at least five generations have had this upward spike in our left eyebrow that points straight up in the air: My great-grandfather, Harry, had it, my grandfather, my dad, me, and my two sons. Genes are not the only factor; the environment I live in also plays an enormous role: the food I swallow, the gasoline fumes I breathe in when I fill up my gas tank, the ultraviolet rays that permeate the ozone and burn the skin on my nose. But it’s my genes that are the basic ingredients that make me both human and unique—and I’ve just handed them over to Erik the Red.
Stefansson’s aim in Iceland is to unravel genetic secrets from the island’s entire population, looking for patterns in genes that might account for diseases such as stroke and osteoporosis. Thanks to meticulous genealogical records kept for one thousand years in Iceland and collected by deCode into a computerized database they call the Islendingabok, the “Book of Icelanders,” Stefansson can tap into what medical and mortality details exist about the 680,000 people who have lived on the island since the first Vikings arrived here in the ninth century. deCode uses powerful computers to pick out how families inherited disease. The company also has assembled another database containing certain medical details about modern-day patients, with consent, that pertains to diseases deCode is studying. Iceland’s parliament, the Althing, has created an oversight process to protect patient privacy, and to allow patients access to their genetic test results, where it is appropriate. About 110,000 Icelanders so far have willingly handed over their DNA for the program, which asks, for instance, patients with asthma to provide their medical records and their DNA to be tested for nucleotides that are anomalous when compared to the nucleotides of the nonasthmatic population. This provides clues to where the disease-influencing genes might be located. The company has roughly mapped the location of several dozen suspect genes, and has found the exact location of a few major diseases, such as stroke and osteoporosis—news that was important enough that these discoveries landed on the front page of the New York Times when each was announced in 2003.
So I am hardly alone in being tested by Stefansson’s labs and computers, though what sets me apart is that I’m the first healthy person with no family predisposition to be tested by deCode and to have my results announced publicly. I’m also not the first person to take tests for specific genetic diseases. More and more, tests are offered that identify genes linked to Alzheimer’s disease, Huntington’s chorea, breast cancer, and other maladies. Except for Huntington’s, which has a 100 percent “penetrance”—the certainty of which people who have a mutation will get the disease—most of these tests offer only the possibility that a person will get the disease. For instance, testing positive for the apo-e4 gene, which is associated with Alzheimer’s, a person has a two-and-a-half times to ten times greater chance of getting the disease than a normal person. So this is not necessarily deterministic information but, rather, offers up probabilities that you or I will get a disease.
These genetic tests fall under the rubric of “personalized medicine”—which offers not only tests for genetic predispositions to disease, but also the possibility of customized treatments. So drugs could be targeted to your specific malady and genetic makeup rather than the one-size-fits-all medications of today. Yet this is only the bare beginning of what scientists are offering up as future possibilities in this nascent age of genetics. You and I and our children may soon be living in a world where damaged hearts and shattered spines are routinely regenerated or spare ones are regrown using stem cells; where a human egg containing a person’s DNA can be engineered by adding and subtracting genes; where genetic fixes or perhaps a pill can be popped to extend life span and keep one young, fit, and lean up to age 150, or 300, or longer. The possibilities are thrilling in some cases and frightening in others, particularly since the collective knowledge of genetics and the impact of mucking with the basic recipes of life remain fantastically complex and largely unknown.
This creative fire in biotechnology is occurring after a half-century of biological discoveries and more recent technological breakthroughs, combined with an unprecedented surge of funding from government and the private sector, and supported by a society that loves the gadgets, the medical miracles, and the standard of living afforded by modern science, even if the pace of change sometimes makes us feel uneasy. The outcome of this explosive moment in genetics is anybody’s guess: a brilliant future or, if something goes terribly wrong, a nightmare. Or both. We will cure cancer; vanquish AIDS, malaria, and tuberculosis; increase life span to three hundred years; eliminate pollution; and feed everyone on the planet. Or we will create a monster, either inadvertently or deliberately. Maybe we’ll do it all. I believe this is the greatest story of our time, perhaps of all time. A species is developing the tools to redesign itself, to self-evolve in a way Charles Darwin never imagined.
Experiments are under way to create new forms of life. The geneticist J. Craig Venter, cosequencer of the human genome, is creating at his nonprofit Institute for Biological Alternatives the first synthetic life-form. Working in Rockville, Maryland, with the Nobel laureate Hamilton O. Smith and funded in part by $12 million in grants from the U.S. Department of Energy, Venter wants to create a simple microbe designed to munch up carbon dioxide pollutants in power plants and to release harmless hydrogen. This sounds wonderful, though this technology could also be used in the wrong hands to create organisms for more nefarious purposes such as bioterrorism. Or one of these critters might be released into the ecosystem for a useful purpose, only to mutate or evolve into something deadly. As a nonscientist enthusiastic about science, I am properly awed by the possibilities. I also wonder, at times, whether I should be afraid. I lean more toward amazement than not, but I am skeptical, too, strongly believing that nonscientists need to do their homework to understand the new science, to be informed enough to be impressed, cautious, or afraid. Most of all we need to stop being mystified, to learn enough to question intelligently and to push our high priests of science to explain what they’re up to.
Lest we forget, periods of explosive scientific achievement and technological breakthroughs have always created the potential for both miracles and horrors. DDT rid the West of malaria-bearing mosquitoes and other pests but poisoned birds and other animals, including humans; electricity lights our cities and powers our factories, but touch a live wire, and zap!; fossil fuels have provided us with fuel to zip about in the air, and on the land and sea, but befoul skies and cause global warming. The list goes on in the pluses and minuses of television that educates and enervates, drugs that cure and cause side effects, cars and airplanes that convey us places but also turn lethal if they crash and burn. The most classic example of all occurred when the physicists of the early twentieth century found their dazzling theories turn into not only the transistor and spaceflight, but also the bomb. The Manhattan Project chief Robert Oppenheimer, for one, spent the rest of his life after Hiroshima and Nagasaki trying to reconcile his conscience for his role as a scientist in creating this awesomely deadly weapon. “It is not possible to be a scientist unless you believe that the knowledge of the world, and the power that this gives, is a thing which is of intrinsic value to humanity, and that you are using it to help in the spread of knowledge,” he said in the autumn of 1945, three months after the bombs erupted over Japan, in what could be considered a classic statement of a modern scientist justifying his work. Yet he added an important caveat: “and are willing to take the consequences.”
The last century contains many other examples of science’s running amok: the sick experiments of Josef Mengele at Auschwitz; the program at Tuskegee, Alabama, in which black sharecroppers who had syphilis were denied treatment for forty years by researchers who were studying the effects of the disease; and the bioengineering of super-virulent smallpox variants by Soviet virologists working for the secret Soviet bioweapons program during the sixties, seventies, and eighties.
