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TIME--The Weekly Newsmagazine--1994

Jan. 17, 1994 Genetics:The Future Is Now

SCIENCE, Page 54

Riding The DNA Trail


Francis Collins leads an international drive to track down all the genes

and take their measure

By J. Madeleine Nash/Bethesda

Dr. Francis Collins may not have been ready for Saturday Night Live, much

less prime time, but the University of Michigan students screamed with laughter

all the same. As the last class of the semester was ending, the 43-year-old

geneticist slipped an acoustic guitar from its battered case and in a reedy

tenor began warbling lyrics of his own invention to the tune of one of Frank

Sinatra's enduring hits. "So start today," Collins crooned into a microphone.

"Love DNA, and do it ouuuuurrr way." The star of this spoof stood 6 ft. 4 in.

tall. He wore cowboy boots beneath his white lab coat and slung a stethoscope

round his neck like a wayward tie. And as his last note faded, the delighted

audience gave him a standing ovation.

What the students could not have known was how bittersweet this moment

seemed to Collins. It marked the end of a remarkably rewarding and productive

period of his life and the beginning of an expedition into an exciting but

uncertain future. Last year, after months of deliberation, Collins left his

faculty post at the University of Michigan Medical School to lead the Human

Genome Project, an audacious effort to decipher the complete genetic script

contained in human cells. Collins considered it the most important under taking

in the history of biological research. He was moving from classroom gigs to the

big show.

Is Collins up to the role? If not, it is hard to imagine who would be. He

is a natural performer whose stage presence and easy eloquence make him a

persuasive spokesman for the multibillion-dollar genome project on Capitol Hill.

He is a workaholic who logs 100-hour weeks and flies more miles in a month than

most people do in a lifetime. He is an empathetic clinician who agonizes when

delivering a devastating diagnosis.

Above all, he is a relentless hunter of disease genes. Finding a gene

embedded in long, nearly featureless spirals of DNA, he likes to observe, is

harder than locating the proverbial needle in a haystack. "At least a needle

looks different from a haystack," he says, "but a gene is just another piece of

DNA." His love for lab work won't let Collins become merely a bureaucrat. He has

already established his own research center at the National Institutes of Health

so he and colleagues can continue their search for errant genes.

When people describe Collins, they do so in oddly contradictory terms. Thus

he is said to be one of the most compassionate people in the world, and also one

of the most aggressive. He is a skeptical prove-it-to-me scientist but is also

capable of deep religious faith. He is as intent on the impression he is making

as any politician up for re-election. Yet he appears to be utterly

unpretentious, preferring to dress casually in jeans and, when he rides his

Honda Nighthawk 750 motorcycle, a black leather jacket. (On one of his

motorcycle helmets he sticks decals that keep a running tally of every gene he

and his collaborators have tracked down, including the ones responsible for

cystic fibrosis and Huntington's disease.)

The youngest of four brothers, Collins grew up on a small farm in

Virginia's Shenandoah Valley. His father, in addition to raising cows and sheep,

was a serious musician who collected folk songs and taught at a nearby women's

college. His mother, who educated him at home until he was nine, wrote plays,

which were performed at a small theater the couple started in an oak grove on

their farm. "When Francis was seven," his father recalls, "he wrote a full

script for The Wizard of Oz and directed its performance." He played bluegrass

and Bach on the pump organ and guitar, and he would spend hours pondering the

consequences of dividing numbers by zero.

By the time Collins graduated from high school, at 16, he was determined to

become a chemist. Biology, curiously, did not interest him at all. "Somehow," he

muses, ``I had the notion that life was chaotic and that whatever principles

governed it were unpredictable." This prejudice stayed with him through his

undergraduate years at the University of Virginia, where he excelled in the hard

sciences and avoided biology as if it were basket weaving. But as a Yale Ph.D.

candidate in physical chemistry, he took biochemistry, encountering for the

first time DNA and RNA, the molecules that carry the code of life. "I was," he

says, "completely blown away."

Increasingly restless, Collins began to wonder whether he should devote his

days to arcane research that had little immediate impact on other people. So

while completing his doctoral dissertation in physical chemistry, Collins

enrolled in medical school at the University of North Carolina. A three-week

course hooked him on medical genetics, a specialty that let him be both

humanitarian and researcher.

By 1984, when Collins signed on as a junior faculty member at Michigan, he

had been married for 15 years to his high school sweetheart and had two

daughters, ages 14 and 10. Just as important to him, he had become a devout

Christian, focusing on what had previously seemed an irrelevant corner of life.

While living in the campus town of Ann Arbor, Collins and his wife helped start

a Baptist church. The congregation--and his marriage--has since dissolved, but

his faith, which he describes as basically nondenominational, endures.

The search for spiritual fulfillment has led Collins in unexpected

directions. Twice, in the company of his daughter Margaret, a medical student,

he has traveled to Nigeria to treat patients in a small missionary hospital. The

first time, he and his colleagues were closing in on the cystic-fibrosis gene,

and yet at that critical moment Collins risked leaving his laboratory. Once in

Nigeria, he agonized over whether his presence there made any difference at all.

Then a farmer appeared, suffering signs of imminent heart failure. Collins dared

a procedure he had never tried before, plunging a needle deep into the man's

chest to draw off the fluid that was apparently pressing on the heart. "Dr.

Collins," the patient said later after recovering, "I know you're wondering why

you are here. I believe you were sent here just for me, because without you I

would have died."

Medicine, science and religion--in Francis Collins these disparate worlds

daily connect and sometimes collide. Personally Collins is distressed by

abortion, a common outcome of prenatal screening for genetic defects. Yet as a

geneticist he honors a code of professional ethics that demands he hide from

patients his own feelings of right and wrong. As the discoveries of disease

genes move from the lethal maladies of early childhood to the lingering ailments

of advanced adulthood, Collins confesses an increasing level of personal

discomfort. In talks he gives on Huntington's disease, he invariably shows a

slide of the folk singer Woody Guthrie, "one of my heroes." He goes on to

explain that Guthrie died of Huntington's, but he leaves unspoken the terrible

questions: Was Guthrie's life not worth living? If he had been aborted, wouldn't

it have been everyone's loss?

Even as Collins leads the genetic revolution, he refuses to downplay its

dangers. He is worried that private genetic information will be too readily

available to insurance companies and employers. He worries about telling

patients they have the gene for Alzheimer's but then offering them no cure. He

worries about the "slippery slope" that could lead couples to abort fetuses with

merely undesirable characteristics--obesity, for example, or the wrong sex. "The

use of this technology for sex selection," Collins exclaims, "insults the

reasons I went into genetics in the first place. Sex is not a disease but a


Counterbalancing Collins' deep concerns, however, is his passionate

conviction that the new genetic discoveries bode more good than ill and that a

reasonable society will curb abuses. "These are exciting times," he declares,

"and the consequences for clinical medicine will be dramatic." Now that he has

taken on the genome project, Collins can do more than imagine those

consequences. He has an unparalleled opportunity to help shape them.

Copyright (c) TIME Magazine, 1995 TIME Inc. Magazine Company; (c) 1995 Compact Publishing, Inc.

TIME--The Weekly Newsmagazine--1990

Sep. 17, 1990 The Rotting Of The Big Apple


Tracking Down Killer Genes


Francis Collins is finding new ways to trace the origins of disease. But he

agonizes over the implications of this brave new world of medicine.

By J. Madeleine Nash/Ann Arbor and Francis Collins

Q. You just found the gene for neurofibromatosis, often confused with

Elephant Man's disease. A year ago, you were instrumental in finding the gene

that triggers cystic fibrosis. How will such discoveries affect the practice of


A. They will transform medicine in ways we can't even predict. I'm sure

that a hundred years from now, people will look back on this era and shake their

heads in disbelief in the same way that we look back on arsenic treatments for

syphilis in the previous century. But that's in the long run. It's sort of a

paradox. Here we have a field of research that I believe will totally change the

face of medicine. The timetable is going to be slow enough that to the average

person it won't seem like a revolution at all.

Q. But how will it be different?

A. There is going to be a shift away from a therapeutic sort of medicine,

where you treat someone who is already ill, to a medicine where you identify the

risks a particular individual has for developing certain diseases and then try

to prevent that person from ever becoming ill. Ironically, one of the first

consequences of a better understanding of genetics will be an emphasis on

altering the environmental contribution to disease because that's a lot easier

to change. If you know you are at high risk for lung cancer, your motivation to

stop smoking will increase.

Q. You are both a scientist and a physician. Does seeing patients affect

your research?

A. It adds a sense of urgency. The cystic fibrosis gene has been found now

for a year, and in that year 1,000 people have died, including people I knew

personally. That is both troubling and motivating. You can't sit back and treat

what you do as an intellectual exercise when the mere mention of a disease

brings to your mind the faces of people you care about. That's why it's

important to have a certain percentage of people working in this field who are

comfortable with both basic science and clinical medicine. If we don't, we are

going to miss out on opportunities to apply this new information.

Q. Many people find the notion of genetic testing scary. Should they?

A. When you go to your doctor and have your cholesterol measured, what's

really being measured is your genes. We as a society seem quite comfortable with

screening for cholesterol and then using that information to alter behavior. No

one would argue that testing for cholesterol is opening a Pandora's box. So we

have already started down this path. Like it or not, we have opened the door and

walked through.

Q. Surely you must have some concerns?

A. Here we are, poised on the threshold of widespread genetic screening

that should be beneficial to people. Yet we are talking about carrying this out

on a population that is largely uninformed about genetics. Those of us involved

in genetic counseling are appalled by the scale of the problem.

Q. What kinds of things might go wrong?

A. We have the disturbing example of sickle-cell anemia to prove to us that

if we don't include explanations and education and counseling in a screening

program, we will end up doing more harm than good. An awful lot of people were

found to be sickle-cell carriers, with no significant risk to their own health,

but they wound up believing that eventually they would become ill. Insurers

canceled policies. It is terrifying to look back on this experience, and a good

reason to go slow on screening for cystic fibrosis.

Q. Couldn't genetic screening also be misused by affluent individuals to

create superior children, thereby increasing social inequalities?

A. The notion of yuppie couples' picking the child with the highest IQ out

of the 10 or 12 possibilities they might be able to generate through, say, in

vitro fertilization is not worth spending a lot of time on. Intelligence is very

complex. We can't even define it. It is not at all clear to me that a real grasp

of the genes responsible for intelligence is going to come about, certainly not

during the next hundred years. Athletic ability? That's even worse. Are we

talking physical strength or height or quickness, and what do those traits mean?

We should be focusing on scenarios that are closer to home.

Q. Such as?

A. It is important to make a distinction between a life-threatening disease

and a trait. In our society, prenatal diagnosis followed by pregnancy

termination has been deemed acceptable when the consequences to the unborn child

are devastating disease and early death. But now we come to sex selection. Sex

is not a disease. Yet it is possible, using simple diagnostic techniques, to

determine the sex of an unborn child well before the time when pregnancy

termination is no longer allowable. There are certainly instances in genetics

clinics where couples come in with just that idea in mind. Legally there is

nothing criminal about what these couples are proposing. But to me, and I

suspect to the majority of the American population, this is troubling, even

repugnant. It affronts me.

Q. What about diseases that may not strike until late in life, or that vary

in severity?

A. This is where it gets muddy, and everyone is going to draw the line

differently. Consider the situation with manic-depressive illness, a reasonably

common disorder. It is clearly genetically influenced, though not in a simple

way. Now, manic-depressive illness can be a terrible cross to bear. The swings

into depression are awful, and the highs can be very destructive. Yet a

substantial number of highly creative people have suffered from this disease.

Suppose we find the gene responsible for manic depression. If every couple has a

prenatal test to determine if a fetus is at risk for manic depression, and if

every time the answer is yes that fetus is done away with, then we will have

done something troubling, something with large consequences. Is this what we

want to do?

Q. Where do you draw the line?

A. Because of my own religious background [Baptist], I will be on one end

of the spectrum arguing against the use of this information too broadly for

fetal selection. And that really highlights that we're not talking about a

scientific issue. Scientists have the capacity to understand and explain what it

is possible to do. But they are not in a unique position to be saying what is

proper, moral and ethical to do. We are in an awkward situation right now

because those who have the most experience in philosophical and religious

spheres are not well informed about the scientific facts. We need to get

ourselves together and teach each other something.

Q. Personally you do not approve of abortion. How do you handle this in a

clinical setting?

A. It is a sacred and unbreakable rule that genetic counselors avoid

imposing their own value systems. If a patient struggling with a terrible

decision asks me, what would I do, I don't answer. I must not answer. The

consequence of taking that rather hard-line view is that I can tell you of

situations where couples have taken information I have helped them get, and then

done with that information things that horrify me.

Q. When will gene therapy start providing couples with better options?

A. It's conceivable that we'll have effective treatments for some of these

diseases in the next 10 to 15 years, but I couldn't swear to it. The problem is,

we're just starting down this path, feeling our way in the dark. We have a small

lantern in the form of a gene, but the lantern doesn't penetrate more than a

couple of hundred feet. We don't know whether we're going to encounter chasms,

rock walls or mountain ranges along the way. We don't even know how long the

path is.

Copyright (c) TIME Magazine, 1995 TIME Inc. Magazine Company; (c) 1995 Compact Publishing, Inc.