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Breaking the Code
A devout Christian, Francis Collins helped discover the genetic roadmap for human life. But can he really see God at work in DNA?
On July 9th, 2009, President Obama nominated Francis Collins to be the head of the NIH. Read this profile of Collins, written by Chris Wilson in June 2007.
The sky was still dark when Francis Collins woke up early on the morning of June 26, 2000, to prepare his remarks for the President. This should have been one of the best days of his life, but he was stricken with grief.
Twelve hours earlier, Collins had been 160 miles southwest of Washington delivering a eulogy at Trinity Church in his hometown of Staunton, Virginia. His sister-in-law Celia, the free-spirited wife of his brother Brandon, had died two days earlier after a three-year battle with breast cancer. In the center of the sanctuary was a papier-mâché ballerina, one of a troupe of marionettes that Celia had created in the last years of her life. She called it her “surprise circus.”
After the funeral, Collins raced back to Washington to attend a reception for some of the world’s leading geneticists. As head of the Human Genome Project at the National Institutes of Health for seven years, Collins had overseen the sequencing of the genetic road map for human life—a breakthrough that promised to save future Celias and millions of others.
For Collins, a scientist who is also a devout Christian, the moment was all the more poignant. How, he wondered, had God allowed Celia to die this way and yet make this achievement possible?
In each of our cells are copies of our DNA’s 3 billion base pairs, the chemical compounds abbreviated as A, T, C, and G. These determine both our individuality and our common humanity. In 1953, biologists James Watson and Francis Crick discovered that DNA molecules take the form of a double helix, like a long ladder of millions of rungs twisted into a spiral. The discovery that these strange molecules formed the blueprints of life revolutionized biology and set scientists on a 50-year quest to piece together a map of the genetic code. At the time, the man who would lead the effort to decode DNA had just learned to count to 100.
“Today Francis is three years old,” Margaret Collins wrote in her journal on April 14, 1953—11 days before the publication of Watson and Crick’s first description of DNA. “He knows the alphabet, all the number combinations on a pair of dice, how to spell 10 or 12 words, how to count to 100 with a bit of prompting in the middle tens.”
Collins had an idyllic childhood in Staunton, then a city of about 20,000. He is the youngest of the four boys born to Margaret and Fletcher Collins Jr., who met in a 17th-century-literature class at Yale. The children came in two pairs, what Margaret calls the “big boys” and the “little boys,” separated by more than a dozen years.
During World War II, Fletcher Collins Jr. had worked as an aviation engineer, first in Pennsylvania and then on Long Island. But when the family moved to Virginia to be with Margaret’s parents, he decided to indulge in his love of the stage, taking a faculty position in the theater department at Mary Baldwin, a women’s college in Staunton. There, among the oak trees on their 95-acre farm, they began a summer theater in 1954 that is still in operation.
The farm had no plumbing, so Margaret took Francis into town once a week for a bath at the Oaks, his grandparents’ three-story Victorian home. She schooled him on the farm until he was ten.
Margaret, 98, still lives at the Oaks with Francis’s brother Brandon. Francis visits her nearly every weekend that he’s not at a conference.
“Mother was a very talented mathematics teacher,” Francis recalls during one visit.
“Before you wanted to make any sense of it, you liked the sound,” she says.
When Collins turned three, his mother wrote: “Francis learns arbitrarily, as a sound, a symbol. By means of the dice, and counting raisins or spoons or cups, he observes that 2+3 or 4+1 or 2+2+1 make 5, and his discovery is to him as new as if no one had lived before him.”
Francis Collins’s life might have taken many different turns in those early days. Brandon thinks he could have been a professional musician—Francis is a pianist and guitarist who rarely passes up a chance to play. As a child he was never far from the stage.
During the summers, students from Mary Baldwin lived at the farmhouse and took roles in the Collinses’ productions. They came in such numbers, Francis recalls, that one summer he and his brother Fletcher slept in the corn crib. By age five, Francis was playing bridge with the college girls. As he grew older, he began acting in the plays, many of which his mother wrote.
In high school Collins encountered John House, a chemistry teacher. House was a charismatic teacher with an odd talent: Ambidextrous, he wrote on the blackboard with both hands at the same time. He held seminars on how to use a slide rule.
“Kids showed up in large numbers—after school,” Collins recalls.
Biology, with its rote memorization and artificial classifications, did not interest Collins. Atoms and molecules, however, adhered to the natural laws and elegant mathematics of the universe. At age 16 he graduated from high school and entered the University of Virginia to study chemistry.
As a senior at Virginia, Collins walked into the first-floor office of chemistry professor Carl Trindle and volunteered to do research. Trindle got him working on mathematical manipulations of the electron cloud that surrounds an atom, which Trindle theorized to be like Silly Putty—you could knead it and twist it gently, but jerk it and it would break.
“He picked that up as quickly as he picked up anything else, which is phenomenally fast,” Trindle recalls. The pair eventually published their work, Collins’s first academic paper.
After graduation Collins went to Yale to continue studying physical chemistry. He whipped through, finishing his PhD coursework in three years. About that time, researchers in California learned how to cut and paste strands of DNA from different species, a technique known as recombinant DNA that revolutionized genetics and bioengineering. Such breakthroughs meant Collins could no longer avoid biology, and he enrolled in a biochemistry class at Yale.
Things were changing for him. He had married his high-school sweetheart at 19 and become a father at 20; his daughter was now three. He began to question the prospect of a life in the ivory tower.
Learning about DNA and the theoretically graceful mechanics of the genome appealed to him. “I was finding this new field of molecular biology unexpectedly and overwhelmingly exciting,” he says. “I had missed out on recognizing that much was going on there until rather later in my educational career.”
Collins decided to go to medical school.
“I wasn’t absolutely sure this wasn’t an infatuation,” Trindle says. He told Collins to finish his PhD and get a postdoc in a biology lab, where he could pursue his new interest. Collins considered his mentor’s advice—and ignored it. He began medical school at the University of North Carolina, finishing up his dissertation on weekends.
During his residency in his third year in medical school, Collins met many patients with severe illnesses and was struck by their religious faith and comfort in an ultimate grace. Collins recalls one particular patient, in great pain from a severe case of angina, who pressed him on what he believed.
Collins had no answer for her. As a child, Collins saw God as a moral pawnbroker with whom one could bargain for meteorological favors such as, “If tonight’s performance isn’t rained out, I’ll never smoke.” By the time he was a graduate student, he says he was an “obnoxious atheist.”
But challenged by his patients, Collins investigated his faith. A pastor gave him a copy of C.S. Lewis’s Mere Christianity, which makes a rational case for the existence of God. Collins tried out a menu of world religions and examined the evidence, as he puts it, for and against the existence of God.
The new information challenged old prejudices. Lewis’s arguments appealed to the scientist in Collins. The British scholar and author saw humankind’s universal sense of morality as evidence, unexplainable to him by other means, of God’s presence in the universe.
By the time Collins finished medical school, at age 27, he was on his way to becoming a believer. A year later, while hiking in the Cascade Mountains of Washington state, he says he was struck by the sublime beauty of creation. The next morning, kneeling in the dewy grass, he became a Christian.
After graduating, Collins stayed at UNC for his internship and residency before returning to Yale and then migrating to a lab at the University of Michigan. He joined the hunt for the genetic cause of cystic fibrosis. That hunt had begun in earnest in 1985, when a Canadian scientist, Lap-Chee Tsui, had narrowed the search to the “long arm” of chromosome 7. (Each of the 24 chromosomes is shaped like a ribbon tied into a bow, with one end of the bow longer than the other).
Collins compared the search to looking for a burned-out light bulb by going house to house throughout the United States. He eventually joined forces with Tsui. Using points on the genome that had already been identified and mapped out, Collins used a method he had developed with the help of his postdoctoral adviser at Yale, Sherman Weissman, that allowed them to speed the search by “jumping” along the chromosome from one reference point to the next.
Thanks to this new method, Collins uncovered the cause of the disease. Three missing base pairs from the DNA’s 3 billion were to blame for one of the worst scourges of people of northern European descent. It was a recessive disease, which meant the deadly accumulation of fluid in the lungs and pancreas was the byproduct of a tiny fault in the genes of both parents.
The discovery vaulted Collins to stardom. It also proved “that this method could succeed for other diseases,” he says.
Progress in science occurs in spurts, with moments of great inspiration accompanied by long stretches of frustration. One can see an analogy in the genome itself, in which the productive parts, genes, are divided by much longer expanses of noncoding letters.
“Science is pretty tough going if you’re working on interesting problems,” Collins says. “Most of your experiments fail, most of your hypotheses are wrong, and most of your days you’re knocking your head against the wall. But once in a while you’re given this incredible glimpse of truth. And that’s what keeps you going year after year, hoping for another one as soon as possible.”
Four years later, Collins was invited to head NIH’s Human Genome Project after its first director, James Watson, the mercurial and combative discoverer of DNA, stepped down over a personality conflict with NIH director Bernadine Healy.
Craig Venter, another researcher, had left NIH for a privately financed lab and eventually helped start Rockville’s Celera Genomics as a rival to the government effort.
Collins and Venter have been portrayed as alter egos. Though Collins rides a motorcycle and plays guitar, he describes himself as a nerd and is better known among colleagues for his good humor and honesty than for his rock ’n’ roll. Sherman Weissman, Collins’s adviser at Yale, says, “A very striking aspect of Francis was his ability to get people to work for him.” Weissman recalls that the secretary in their department had joined a union and taken to leaving the office at the stroke of 5 o’clock—unless Collins asked her to help. And then she would even deliver pizza to them on Saturday.
Venter cuts a swashbuckling figure. A Vietnam veteran whose defiance of commanding officers had landed him in the brig, Venter bragged that his company could map the human genome better and faster than the government. Collins and NIH, he said, might as well study the DNA of a mouse.
Without either man, decoding a draft of the human genome by the year 2000—well ahead of schedule—wouldn’t have happened. Venter had his own system for sequencing large stretches of DNA. Instead of jumping along the genome as Collins did, Venter used a strategy known as shotgun sequencing, in which several copies of a long stretch of DNA were shattered into short, manageable pieces and reassembled with the use of complex software.
In 1998 this method was unproven as a means of sequencing for large genomes. Venter put much doubt to rest with his sequencing of the fruit fly, which he completed in 2000.
The race for the human genome was on.
Equations aren’t the usual medium for high drama. The formula for universal gravitation may be an exception.
It begins with a capital G, known as the gravitational constant, a fixed figure that allows the calculation of the gravitational pull among all things. (Every mass in the universe attracts every other, though you feel it only with large masses, such as the planet.)
Here’s the catch: If that number were off by the tiniest sliver of a percentage, scientists generally agree, the expansion of the universe after the Big Bang would not have happened in a way that made life possible.
There are several universal constants with precise values that determined our fate. Change any of those values by an infinitesimal fraction, and matter would not have coalesced. There would be no stars, no planets, no people.
The circumstances that created our universe suggest it is uniquely well tuned for life—a theory known as the Anthropic Principle. A rich variety of theories tries to explain this, most of which don’t envision a God. Perhaps there are countless universes, some propose, each one slightly different; ours just happens to be one of the few capable of harboring life. Call that the natural selection theory of universes.
Collins sees the Anthropic Principle as a ratification of the presence of a higher power. He enunciated this in a book, The Language of God, published last year. It makes a case for “theistic evolution”—a worldview that embraces both Darwinism (evolution set in motion, but not actively managed, by a higher power) and theism, the existence of a God actively engaged in human affairs.
The book also makes the case that our concern and care for others is evidence of God. Of the many mysteries of human behavior, our sense of altruism—our caring for those we do not know and do not depend on—is perhaps the greatest. The desire to help others seems antithetical to survival of the fittest, Collins argues.
Many scientists—particularly evolutionary biologists intent upon finding an empirical explanation—have postulated that caring for others was, at some point in the evolutionary trajectory of Homo sapiens, beneficial to survival. Collins and others argue that, given the central role of competition in biological advancement, evolution cannot account for human caring.
Our sense of good and evil—or moral law, the nearly universal sense that some behavior is right and some is wrong—defies both cultural and genetic explanations, Collins argues. “To some extent, it would not surprise me if some elements of the noble human impulses that we describe as altruism have some evolutionary roots,” he says. “I don’t believe [evolutionary biologists] have solved it, and I think it’s unlikely that they will. If they do, would my faith be shaken? No. Certainly for me, though, in my phase of examining whether there were in fact plausible arguments for God, this one came across as a pretty compelling one. And it remains so, some 28 years after I became a believer.”
Since his conversion, Collins has spoken about his faith clearly and unapologetically. His book gave him a broader audience and made him a spokesman for a middle-of-the-road viewpoint in the battle depicted on the cover of Time last year as “God vs. Science.”
As he talked about the book, Collins was challenged often. How could he be driven by a quest to decode the human genome and also by a quest to understand God?
To him, the quests are similar. “In those moments of discovery, where you do glimpse something grand, where you have this insight into how things work and a sense, maybe, that nobody else had that insight before—you cannot go through that experience without having it affect you in some fairly substantial core reaction,” he says. “I think it is akin to the kind of reaction one has in a moment of spiritual enlightenment.”
Over the years, many scholars, scientists, and theologians have described evolution as incompatible with scripture. Collins calls himself an evangelical yet denounces the theory of intelligent design. A defender of evolution and a believer in God, he is staking out a position that might bring a little peace to the fight.
“I think he’s a master teacher,” says Dr. James Childress, a professor of bioethics and religion at the University of Virginia who served on President Clinton’s National Bioethics Advisory Commission. “He has a knack for presenting very complex scientific and technical material in a clear and compelling way. At the same time, he’s able to address the larger philosophical, religious, and ethical questions.”
Collins feels a sense of stewardship over how his discovery is used. It’s an old dilemma: Are Robert Oppenheimer and the other scientists at Los Alamos responsible for how the atomic bomb was used?
For Collins, the scientist’s first responsibility is to be a messenger of facts in a debate. “There is a great deal of time to be wasted as honest people try to come up with solutions for a problem that isn’t really a serious problem,” he says. “It seems to me that scientists, while they ought not to put themselves forward as being on a higher moral plane—they are not—do have information,” he says. “They do therefore have a responsibility to be deeply engaged in these discussions so that, in fact, when people are trying to figure out what’s possible and what is not, there is a well-grounded, reality-based answer.”
Collins was due at the White House at 9 in the morning on June 26, 2000, to celebrate an achievement that, technically speaking, had yet to be achieved. The sequencing of the human genome to a reliable degree of certainty takes many drafts, and the version that both Collins’s team and Venter’s had separately compiled was not completely vetted. That would take several more years.
The celebration was the culmination of a frantic year of sequencing for both Collins and Venter, who shared the invitation to the White House. The dueling efforts bore a close resemblance to the sprint to the finish line 47 years earlier, when Watson and Crick had narrowly beaten out the American chemist Linus Pauling for the honors of discovering the structure of DNA.
After arriving at the White House, Collins was taken to the Blue Room to wait for the ceremony. Clinton eventually showed up, Diet Coke in hand. What happened next was an embarrassing moment for a man who grew up in the theater.
“Various people had been quite clear about the stage directions—that when they start playing the music you should walk out into the hall and walk down to the East Room,” he says. “So the music starts playing—‘Hail to the Chief’—and there I am with the President, so I start heading out into the hall. And I feel this hand on my shoulder. And it’s the President, and he says, ‘No, I go first.’ And I’m thinking, ‘Oh yeah, “Hail to the Chief.” ’ ”
The title of Collins’s book comes from Clinton’s address that morning. “Today we are learning the language in which God created life,” Clinton said. “We are gaining ever more awe for the complexity, the beauty, the wonder of God’s most divine and sacred gift. With this profound new knowledge, humankind is on the verge of gaining immense, new power to heal.”
After Clinton and British prime minister Tony Blair concluded their remarks—the latter by telecast from Britain—Collins spoke:
“So there is much to celebrate. But I have to tell you that this morning is also a bittersweet moment for me personally. Less than 24 hours ago, I attended the funeral of my beloved sister-in-law, a wonderful marionette artist who brought magic and joy to thousands of children with her art. She died much too soon of breast cancer. The hope and promise of understanding all of the genes in the genome and applying this knowledge to the development of powerful new tools came just too late for her.”
Toward the end of dinner one night, Collins paused and said, “Some people ask me, ‘Aren’t you kind of disappointed now that the genome project is over?’ I’m like, ‘Are you kidding me? This is the part I’ve been waiting for my whole life. And most of this I didn’t think would happen during my lifetime.’ ”
A week earlier Collins had attended the first meeting of one of his team’s newest ventures, the Cancer Genome Atlas. “No one would say we really understand all of the glitches that occur at the DNA level that causes cells to grow out of control,” he says. “And cancer is a disease of the genome. It comes about because of mistakes in vulnerable places in genes that are involved in cell-cycle control. We have a menu of such genes, but it’s a very incomplete one.
“Whatever it is that killed my sister-in-law was some combination of a very badly behaved set of DNA misspellings that caused those cells to grow rapidly and spread to other parts of her body. And we desperately need to know the encyclopedia, not just a page or two, of what it is that causes cancer at the genome level.”
The cancer project, Collins says, is equal in magnitude to thousands of human-genome projects—an unthinkable quest even a few years ago. But in the past several months, Weissman says, a major breakthrough in the technology to sequence genes has been achieved through a strategy known as massively parallel DNA sequencing, which may dramatically cut the time required for decoding genetic stretches.
“It’s happening week by week in an exhilarating way,” Collins says. “I want it to go faster, and I feel this great responsibility as someone who commands a lot of resources as the director of the genome institute at NIH to be sure that they’re used wisely and nothing is wasted. And at the same time, I know we have to try things that are high-risk, and high-risk means some of those things are going to fail. Having to balance all those things is a daily challenge, especially when budgets are very tight, as they are right now. But I can’t imagine another job in all of science that would carry the kind of impact that this does at this moment in history.”
The ethical concerns that the field of genetics has uncovered are matched only by those of nuclear energy. As that conversation proceeds, Collins will be at the forefront.
“I protest against some statements that people glibly make that science will eventually do everything that it wants to, and the idea that you can limit science in any way is ultimately hopeless,” he says. “We have not blown ourselves up yet. We may yet, but we have not, after many decades of having the opportunity to do so.”
If there is one true point of intersection in everything Collins says, it is an underlying awe for the majesty of the genetic code and its nearly unimaginable complexity. At this intersection, faith in science and evidence of God become intertwined. Having helped the world to understand the code, Collins now is on a mission to protect it.
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