Dr. Francis S. Collins gave the keynote speechat the 1999 Huntingtion's Disease Society of America convention. Let's hope he is safe on his motorcycle. --Jerry 08/01/99
Scientific American: Profile: February 1998

The combination of world-class scientific researcher, savvy political activist, federal program chief and serious Christian is not often found in one person. Yet that constellation of traits is vigorously expressed in Francis S. Collins.

Collins leads the U.S. Human Genome Project, an ambitious effort to analyze the human genetic inheritance in its ultimate molecular detail. A physician by training, he became a scientific superstar in 1989, when he was a researcher at the University of Michigan. There, together with various collaborators, he employed a new technique called positional cloning to find the human gene that, if mutated, can give rise to cystic fibrosis. That discovery quickly made possible the development of tests for prenatal diagnosis of the disease.

Collins has since co-led successful efforts to identify several other genes implicated in serious illness. His tally of discoveries thus far includes genes that play a role in neurofibromatosis and Huntington's disease as well as the rarer ataxia telangiectasia and multiple endocrine neoplasia type 1. In 1993, after turning down the invitation six months earlier, Collins left Michigan to become director of what is now the National Human Genome Research Institute.

In his office on the campus of the National Institutes of Health in Bethesda, Md., the 47-year-old Collins sits at the center of a vortex of medical hopes and fears that is probably unrivaled. He is widely seen as a strong leader for the genome program, which he reports is on target for sequencing the entire three billion bases of human DNA by 2005. And his influence extends well beyond research. Collins's energetic support for laws to prevent people from losing health insurance because of genetic discoveries is perhaps the best explanation for the limitations on gene-based insurance discrimination in the 1996 Kennedy-Kassebaum bill.

Recently Collins has thrown his political weight behind a new "potentially expensive but very important goal" that he hopes will supplement the genome project's sequencing effort. Collins wants to assemble a public-domain catalogue of subtle human genetic variations known as single nucleotide polymorphisms, written "SNPs" and pronounced "snips." The effort would constitute "a very significant change in the vision of what the genome project might be," Collins says. SNPs are detected by comparing DNA sequences derived from different people.

Unlike positional cloning, analysis of SNPs can readily track down genes that, though collectively influential, individually play only a small role in causing disease. Diabetes, hypertension and some mental illnesses are among the conditions caused by multiple genes. New DNA "chips," small glass plates incorporating microscopic arrays of nucleic acid sequences, can be used to detect mutations in groups of genes simultaneously. By employing this chip technology, researchers should be able to use SNPs for rapid diagnoses.

Collins now spends a quarter of his time building support at NIH for a SNP repository. He bolsters his case by predicting that, absent a public effort on SNPs, private companies will probably survey these molecular flags and patent them. There may be only 200,000 of the most valuable SNPs, so patents could easily deny researchers the use of them except through "a complicated meshwork of license agreements."

Collins the federal official often retains the open-collar, casual style that is de rigueur among scientists, and his preferred mode of transportation (motorcycle) has earned him some notoriety. He is, however, more unassuming than officials or scientists are wont to be. He feels "incredibly fortunate" to be standing at the helm of a project "which I think is going to change everything over the years." Such feelings inspire Collins to musical expression. Last year at the annual North American Cystic Fibrosis Conference, he performed his song "Dare to Dream," accompanying himself on guitar. Yet Collins's easygoing demeanor belies intensity not far below the surface: he estimates that 100-hour workweeks are his norm.

He grew up on a farm in Virginia and graduated with a degree in chemistry from the University of Virginia with highest honors. He followed up with a Ph.D. in physical chemistry at Yale University, then went to the University of North Carolina to study medicine. He was soon active in genetics. As a researcher at Michigan, he was doing "exactly what I wanted to do," which is why he turned down the job of leading the genome program the first time he was offered it. He now admits, however, he is "having a very good time."

Large-scale human DNA sequencing was not initiated until 1996, after preliminary mapping had been accomplished. So far only 2 percent of the total human genome has been sequenced. The only cloud on the horizon that Collins foresees is reducing the cost enough to fit the entire project into the budget, $3 billion over 15 years.

Sequencing now costs 50 cents per base pair. Collins needs to get that figure down to 20 cents. If he could reach 10 cents, the gene sequencers could tackle the mouse as well, something Collins wants to do because comparisons would shed light on how the genome is organized. Cutting against that, however, is the need to ensure reproducibility. This year Collins has enacted cross-laboratory checks to ensure that sequence accuracy stays over 99.99 percent.

Collins notes with satisfaction that today there are people alive who would have died without genetic tests that alerted physicians to problems. Patients with certain types of hereditary colon cancer, which can be treated by surgery, are the most obvious examples. Testing for genes predisposing to multiple endocrine neoplasia type 1 and, possibly, breast and ovarian cancer may in time save lives, Collins judges.

Congress funded the Genome project hoping it would lead to cures. But for most of the diseases to which Collins has made important contributions, the only intervention at present is abortion of an affected fetus. Although normally fluent, Collins is halting on this subject, saying he is personally "intensely uncomfortable with abortion as a solution to anything." He does not advocate changing the law and says he is "very careful" to ensure that his personal feelings do not affect his political stance.

He volunteers that his views stem from his belief in "a personal God." Humans have an innate sense of right and wrong that "doesn't arise particularly well" from evolutionary theory, he argues. And he admits his own "inability, scientifically, to be able to perceive a precise moment at which life begins other than the moment of conception." Together these ideas lead to his having "some concerns" about whether genetic testing and abortion will be used to prevent conditions that are less than disastrous, such as a predisposition to obesity.

The recent movie Gattaca thrust before the public eye the prospect that genetic research will in the near future allow the engineering of specific desirable traits into babies. Collins thinks it is "premature to start wringing our hands" about the prospect of genetic enhancement. But he states, "I personally think that it is a path we should not go down, not now and maybe not for a very long time, if ever."

Researchers and academics familiar with Collins's work agree that he has separated his private religious views from his professional life. Paul Root Wolpe, a sociologist at the University of Pennsylvania, states that "[Collins's] history has shown no influence of religious beliefs on his work other than a generalized sensitivity to ethics issues in genetics." Leon E. Rosenberg of Bristol-Myers Squibb, a former mentor, says that "the fact that he wears his Christianity on his sleeve is the best safeguard against any potential conflict."

Despite the general approbation, Collins is not entirely without critics. John C. Fletcher, former director of the Center for Biomedical Ethics of the University of Virginia and an Episcopalian minister before he left the church, faults Collins for not pushing to remove the current ban on using federal funds for human embryo research. Research on early embryos could lead to better treatments for pediatric cancers, Fletcher argues.

In 1996 Collins endured what he calls "the most painful experience of my professional career." A "very impressive" graduate student of his falsified experimental results relating to leukemia that had been published in five papers with Collins and others as co-authors. After Collins confronted him with a dossier of evidence, the student made a full confession. But Collins thinks his feelings of astonishment and betrayal "will never fade."

The fraud was detected by an eagle-eyed reviewer, who noticed that some photographs of electrophoresis gels that appeared in a manuscript were copied. As a result, Collins says that when someone displays a film at a meeting, "instinctively now I am surveying it to see if there is a hint that something has been manipulated." Collins remarks that since the fraud became public, a "daunting" number of scientists have contacted him to describe similar experiences of their own.

Collins still runs his own laboratory, and he continues to press a "very sharp" policy agenda. These involvements keep him busy, but he will soon spend a month with his daughter Margaret, a physician, in a missionary hospital in Nigeria. During his last visit, almost 10 years ago, he saved a man's life in a dramatic do-or-die surgery conducted with only the most basic instruments. These expeditions, to Collins, are an expression of his faith. But they are something else as well, he adds: "It seemed like it would be a wonderful thing to do with your kid."