At the Stowers Institute, insect genetics has the potential for relieving human suffering – or increasing it.

Weird Science 

At the Stowers Institute, insect genetics has the potential for relieving human suffering – or increasing it.

This is the part of science people rarely get to see.

A dozen or so casually attired scientists sit around a long conference table in the Stowers Institute for Medical Research on Volker Boulevard east of the Plaza, eating lunch and watching a digital slide presentation that documents a string of recent failures.

The slides show bright color bursts and black-and-white bands that look like stripes on a fuzzy sweater, the results when a quarter-million-dollar microscope catches the cells of fruit flies in midreproduction.

These images document the futile attempts by Wei Cui, a research associate at the institute, to extract a particular protein from the fly cells. The protein, dubbed "NOD" by scientists, plays a remarkable role. The substance somehow makes sure chromosomes in fruit-fly cells line up correctly when the gene-replicating phase of reproduction happens.

NOD, in other words, keeps fruit-fly birth defects from happening, and Cui's boss, Scott Hawley, who first discovered NOD's crucial role, wants to extract the substance to learn more about how it works. But, as the slides show, NOD is stubborn. Cui has tried all kinds of chemicals to tease out the protein, but it simply won't pull free.

Hawley, at 50 a large man with graying blond hair and an unintimidating presence, squints at the screen, focusing on a broken black stripe on one of the slides. "It looks like you're getting some NOD up there," he says, pointing. "But it's all chewed up."

He suggests adding other chemicals to Cui's trials. By the sound of them, they aren't the sort of compounds one finds under the kitchen sink. Each will be pricy, but they might stop whatever it is that's gnawing on the NOD. "If there's not enough," he says, "order more."

Hawley says this with the conviction of a man who knows that money is not an issue.

As one of the premier research facilities in the nation, the Stowers Institute operates with a $1.3 billion endowment. With that kind of cash behind them, Hawley and his colleagues spend less time applying for grants and more time doing the grunt work of science -- the hidden efforts that usually mean lots of little failures before the breakthroughs that lead to big discoveries, and to nationwide headlines and news reports that make science seem so easy.

Not that biologists who study the lowly fruit fly normally expect that kind of attention and acclaim. But after nearly thirty years studying the genetic secrets of drosophila melanogaster, Hawley is used to quizzical looks when he explains what he does for a living.

Once, on a flight after a scientific conference during his graduate-student days, Hawley was asked by a fellow passenger what he and a colleague had been talking about. When he explained that they were scientists who studied flies, the woman, who was returning from the funeral of a loved one who had died of cancer, became dismayed.

"Why do you work on fruit flies?" she asked. "Why don't you work on cancer?"

Back then, in the mid-1970s, Hawley found it a difficult question to answer. Studying the genetics of flies held out the promise of future breakthroughs in understanding the human genetic code -- but such an outcome seemed light-years away.

Over the past decade, though, genetic research has advanced much faster than Hawley or any of his colleagues ever imagined it would. Now he can see that his work will have an impact on human biology not in decades but within the next couple of years.

Yet with these developments, Hawley harbors new concerns. Although breakthroughs in genetic science carry the potential to help humans in ways few thought possible, they also demand a level of responsibility that Hawley fears society is not quite ready for.

"We're able to predict all kinds of things," he says. "We're able to make predictions of how a child is going to live their life. And we're getting better and better at predicting things like: What are they likely to die of? What are they likely to become sick from? What personality traits might they exhibit?"

He pauses for a moment, considering.

"How in heaven's name are we going to cope with this?" he asks. "The answer, I think, is: We don't have any bloody idea."

In 1990, Hawley discovered that NOD ensures that chromosomes go to the right place during egg production in female flies. It was a career-making breakthrough that helped him land a full professor position at the University of California-Davis in 1991.

Still, it wasn't fully satisfying. Despite his love of science, Hawley couldn't shake the guilty feeling he'd get after spending hours in the lab. Growing up, his father had often told him, "You only have one obligation in life, and that's to leave the planet a better place than when you came into it."

Hawley initially planned on becoming a lawyer, a career choice inspired by his relationships as a young man with people with disabilities.

In junior high school, Hawley was diagnosed with epilepsy. The malady wasn't much of a problem for him; he just took his medicine, and the seizures stopped occurring. But because of his condition, the state of California forced him to enroll in a class called "Modified P.E."

"The students called it much uglier names," Hawley says.

The kids in the class had problems large and small -- one student was normal save for a missing big toe; others struggled with severe mental and physical disabilities. "We were all labeled," Hawley says. "We were all clearly misfits. We were not people, but for this experience, who would have spent a lot of time together. But we bonded together because we spent an hour together every day."

One of his classmates stands out in his memory: Earl, who had Down syndrome. In most cases, this disorder impedes intellectual development. It can also distort facial features. Earl was the butt of a lot of jokes.

"I'll never forget walking down the hallway, and one of our big deals on campus stuck his foot out and tripped him," Hawley says. "He fell flat on his face and started to bleed. I think what was really hard for him was to understand why people thought this was funny."

Witnessing this and other cruelties, Hawley longed to sue school districts that stigmatized people with disabilities by banishing them to "special" classes.

For reasons he can't remember today, he asked his father to take him to a conference on birth defects sponsored by the March of Dimes. There, he listened to a lecture about chromosomes and how these microscopic carriers of genetic code, when moved in the wrong direction when cells divide, can create disorders like Down syndrome.

"I just got so excited," he says. "I was jazzed."

In college, a counselor suggested that he try researching the genetic causes of birth defects.

"When I took my first genetics course in college," he says, "the purity of the analysis -- just the beauty of genetic analysis -- excited me so much. The intellectual power. I loved it."

But Hawley felt selfish studying science. "Science was something I did for me, because it was so much fun," he explains. "And there were other people out there being doctors and lawyers and public advocates, out there making a difference."

Studying fruit flies only added to this feeling.

So he found other ways to get involved. As a grad student, he volunteered for a suicide-prevention center, answering a phone in the early morning hours and talking to people who were struggling to find reasons to live. He began working with organizations that help people with birth defects, which he continues to do. And at UC-Davis, he took under his wing a grad student named Kara Koehler, whose lab work would have a profound impact on his career and his desire to help people.

It didn't seem that way at first, though.

Hawley asked Koehler to run a series of experiments on the earliest stages of fruit-fly reproduction. Specifically, he had her look at meiosis, the process in which drosophila cells split to form eggs. Sometimes during this process, chromosomes carrying DNA -- the genetic material that carries information to create all the working cells in an organism -- don't go where they are supposed to. Hawley wanted Koehler to map the histories of chromosomes that failed to go the right way.

"It was one of the most arcane, off-the-wall, drosophila-genetics-for-the-pure-joy-of-doing-drosophila-genetics projects that you could imagine," Hawley says. "And I told Kara, 'This is going to be a very nice piece of work. It's going to prove that you really know your craft. But, you know, when we're done, I think five people are going to read this paper.'"

When Koehler was still in the early stages of preparing her paper, Hawley attended the Gordon Conference on Meiosis in New Hampshire, one of the most important annual meetings in his field. "I wasn't even going to mention Kara's work in my talk," he says. "It was so drosophila-centric."

Then he sat in on a lecture by Terry Hassold, a professor of human genetics at Case Western Reserve University in Cleveland. The subject of Hassold's talk was his research on human chromosomes that don't go where they're supposed to go during the early stages of egg production in females.

"And every experiment he starts to talk about," Hawley recalls, "I know the answer to because we've done the experiment in flies. And I just know the answer. And it's, Bing! Bing! Bing! Bing! Bing! And it's just, Oh, my God! These systems are really not just similar, they're strikingly similar!"

Hawley and Hassold stayed up most of the night talking about their discoveries. At some point, Hawley asked Hassold what he was doing about publishing his findings. Hassold told him he had already submitted a paper to the journal Nature Genetics and that it was being reviewed.

"But you know," Hassold said, "if you guys are ready to publish, the coolest thing that I could think of would be for the two papers to come out back-to-back."

When Hawley got back to California, he asked Koehler, "What are you doing this weekend?"

They canceled plans and spent their Fourth of July holiday completing Koehler's paper in just five days. The marathon session paid off when the paper ran alongside Hassold's research in Nature Genetics.

That's when things started to move quickly.

After Hawley and Hassold discovered the similarities between chromosomes in flies and humans during the earliest stages of reproduction, scientists working on other life forms began to find more connections.

They first found a protein that behaved just like NOD in toads. Then they found it in mice. Then, finally, they found it in humans.

"And it was just, Oh, my God! There's a human protein that looks like NOD!" Hawley says. "All of this is starting to make sense. It was all beginning to fall together. We started to see that it wasn't years to get to humans. It was months."

Hawley's NOD research elevated him to the top of his field. He became the perfect candidate for position as a principal investigator at Kansas City's Stowers Institute, which, since its founding in 1994, had begun to emerge as one of the top facilities for exactly Hawley's kind of research.

The idea for the institute was born out of misfortune. In the late 1980s, James Stowers, whose Twentieth Century mutual fund company (now American Century) had made him a very rich man, was diagnosed with prostate cancer. In 1987, he and his wife, Virginia, launched a foundation to help men get free prostate-cancer screenings and to train doctors in urologic oncology.

In 1993, Virginia was diagnosed with breast cancer. The following year, the couple founded the institute for medical research. They began contributing so much of their fortune to the institute's endowment that, in 1998, American Benefactor magazine ranked them as the seventh most generous Americans -- ahead of Bill Gates and Ted Turner.

Through subsequent additions and investments, the institute's endowment grew to more than $1.6 billion before the stock market turned south. Today the endowment stands at a little more than $1.3 billion, according to the institute's most recent annual report. The Stowerses hope that, once the economy rebounds, it will grow to more than $30 billion.

(Late last month, the institute was in the news because scientists there made a breakthrough in understanding how blood is formed in the bones of mice, a puzzle that has stymied researchers worldwide for a quarter-century. This discovery will in turn be applied to the study of human blood-cell production and may help people who suffer from anemia.)

Hawley wasn't looking for a new job when Stowers came calling.

"My initial response was, 'No, I'm not moving to Kansas,'" he says. "Kansas is a fly-over state. No. Not going to happen."

But he wasn't happy at UC-Davis, either.

In order to run a lab at a state university, Hawley had to keep three to four major research grants going at the same time. Typically, it took three to twelve weeks to write a proposal for each one. And not all proposals win grants. Hawley had a "pretty good" success rate, about 80 percent to 90 percent. But he still had to write proposals constantly.

Then there were all the meetings. Too many of his responsibilities, he says, dealt with the "mechanics of the university."

He would arrive at work at eight in the morning, go home at five and, after dinner, return to the lab to work again until ten or eleven. These late-evening hours were usually the only time he could devote to science.

Before he left for home, he would complain to his secretary, "I haven't done a single thing all day."

"What do you mean?" she would say. "You taught two classes. You went to this meeting, took care of this and that. You wrote these letters of recommendation."

"Yeah," he'd reply. "I haven't done any work all day. I haven't done a single bit of science."

The Stowers recruiters offered Hawley an opportunity to abandon the busy work. The institute's massive endowment would relieve the pressure to win grants. Hawley would have to teach only if he wanted to. And, best of all, he'd have to attend only one administrative meeting a month.

So he visited Kansas City, still skeptical about moving to the Midwest.

"It was literally love at first sight," he says. "We visited a school in Overland Park, the one my daughter attends now. And as we were walking out, my wife said, 'I don't know if this is the best thing for our careers or not. But this is the best thing we can possibly do for our kids.' And she's been absolutely right about that."

Once it became known that Hawley was considering a move, he began fielding generous offers from other universities and research facilities. UC-Davis fought hard to keep him as well. But they couldn't beat Kansas City and Stowers.

"The facilities -- I've never seen a place like this," he says. "I got a doctorate in 1979, so I've been in this business for almost 25 years. And I've never seen a facility like this.

"I used to say that what science is all about is, you get a big room, you put really smart people in it and keep them busy with lots of really cool toys, and good stuff happens," he continues. "In this place, the toys are incredible. Absolutely unbelievable."

Hawley and his colleagues now devote much of their lab's resources toward the challenge of extracting NOD. Once Cui's months of trial and error bear fruit, it'll take just weeks to answer the questions that drove the experiments in the beginning. They're working with another lab in Germany that has a system to test their NOD model. Those results will in turn be applied to further tests on "KID," the counterpart protein in human cells.

"The main thing we can hope to do in the future is give couples more information about what their level of risk is, and people will make good choices," he says. "Will we be able to do something about it and reduce their risk? Maybe. But that's more Buck Rogers stuff."

But even though Hawley is thrilled by the prospect of giving people power through scientific information, he also worries that his research could be used for nefarious ends.

He is especially concerned that the first ones in line to make use of the information he pries out of cellular biology will be profit-hungry insurance companies.

"How do insurance companies work?" he says. "They look at our driving records, determine how many tickets [we get] and what area we live in. And then they set higher prices. Now they're pulling our credit ratings. These companies live for information. So how long do you think it is before they want info about what [diseases] you're susceptible to?"

A few years ago, Hawley took out a life-insurance policy. During the application process, administrators for the insurance company told him they wanted to draw some of his blood.

"Why are you drawing blood?" he asked them. "I'm obviously healthy. I don't fall into risk groups."

"We can detect the presence of antidepressants in your system for the last four or five months," they replied.

"That kind of stuff is child's play compared to what we're going to be able to do in the next three to five years," Hawley says.

He warns that we're on the brink of being able to predict just about any malady imaginable, from a predisposition for cancer and heart disease to depression and personality disorders.

Insurance companies, he says, are salivating for this kind of information. He fears the result will be just the kind of discrimination that he first set out to defeat.

A few years back, Hawley asked a classroom of nonscience majors which human traits, if found in the genetic code of a fetus, would merit the termination of a pregnancy.

Among the inherited conditions he named was one that causes wine-colored birthmarks on the face.

More than half of the students in the large class raised their hands. They wouldn't tolerate such an anomaly on their children's faces.

Later that afternoon, Hawley received a distraught phone call from the mother of one of the students in his class.

Her daughter, the woman informed him, had the disorder.

"This student was crushed," Hawley recalls. "Basically, the way she felt about it was, half of her classmates felt she didn't deserve to live."

Hawley uses the episode to illustrate the ethical quandaries that scientists can't help but find themselves in as their research takes them into uncharted territory.

"We need to lobby politicians, educate the populace and policy makers, and be involved in decision making," he says.

Hawley is active in the Genetics Society of America, which in turn is part of the Joint Steering Committee for Public Policy in Genetics, which monitors legislation and federal funding of research. Nearly all of the legislative alerts archived on the committee's Web site, for instance, urge members to contact Congress regarding budget issues. Others address the recent debate over the use of human stem cells in research.

But none of the alerts refers to bills being considered by Congress that would prohibit insurance companies from using genetic information to deny coverage or increase rates, an issue that concerns Hawley. Six years ago, Congress passed the Genetic Privacy and Nondiscrimination Act of 1997. But the law has so many loopholes that less than a third of the population is covered by it, according to Rep. Robert E. Andrews, a New Jersey Democrat who is cosponsoring a bill in the House that would toughen the 1997 standards.

Over the past seven years, members of Congress have introduced new bills, but they have languished as insurance companies have increased their lobbying efforts and contributed enormous amounts to campaign funds. In 1997 and 1998, when new and improved bills were first being introduced, House Majority Leader Tom DeLay, a Texas Republican, received $51,499 from the insurance industry. As majority leader, DeLay sets the agenda for the House. He has not yet scheduled hearings on the bill.

"The insurance industry is a major contributor and supporter of the Republican Party, and Tom DeLay wants to keep his contribution," Andrews told a New Jersey newspaper in June.

Last month, the Senate passed its bill with the backing of President Bush. (The House is still considering it.) But this willingness came into play only after certain concessions were made. If passed, the law would prohibit insurance companies from using genetic information to discriminate, but they would still be able to obtain it.

This disturbs Hawley. "One of the real issues is who can have information and who cannot," he says. "Once the information is out there, it's hard to get it back."

Dressed in his standard uniform -- a button-down shirt, casual slacks and a sweater vest -- Hawley sits at a desk in the front of a classroom at the University of Kansas' Edwards Campus in Overland Park.

"Here's where this class is different from genetics classes taught at other universities," he tells the dozen students seated before him and the dozen more whose image is piped from a classroom in Lawrence to a monitor in the back of the room. "Typically, beginning genetics classes focus on simple organisms -- fruit flies, yeast, stuff that's really easy to work with. Sometimes it's hard for students to maintain interest in those classes because they're interested not in fruit flies, yeast and bacteria but in the only organism we all deeply care about: us."

Before Hawley agreed to come to the Stowers Institute, he asked for assurance that he would be able to continue teaching. He considers teaching more important for ensuring that his work is ultimately put to good use than writing senators or serving on scientific boards that influence public policy. This is especially true, he says, when he teaches genetics to nonscientists.

"It's fine to go preach to the choir," he says. "It's another thing to go out there and talk to the people who are going to become lawyers, businesspeople. They're the ones who have as large a part in decisions as scientists do."

In every course, he includes at least one lecture on the American eugenics movement of the early twentieth century. Armed with a tiny fraction of what is now known about genetics, scientists suggested that, in order to keep the human species strong, certain strains deemed to be inferior had to be weeded out.

These efforts reached appalling heights. Legislators in 34 states made it illegal for people of different races to marry. In 1907, Indiana passed the first law mandating sterilization for people the state labeled undesirable, clearing the way to wipe out, in the words of a brochure touting the movement, "idiocy, insanity [and] epilepsy" to create "a race of human thoroughbreds such as the world has never seen."

In 1922, the U.S. Supreme Court approved these efforts in a decision led by Oliver Wendell Holmes, whom history books regard as a noble proponent of social reform. "If we are willing to ask the best of us that they lay down their lives in the defense of their country," the court ruled, "why can not we ask from the weakest of us to voluntarily deprive themselves of the right to reproduce children?" An estimated 30,000 to 35,000 were forced to become sterilized in the United States between the 1920s and 1940s.

Hawley is constantly reminded that these sentiments haven't disappeared.

In his book The Human Genome: A User's Guide, Hawley writes that new acquaintances often ask him if intelligence is inherited. In return, he offers a typical scientific answer, long on words but short on definitives. Intelligence, he explains, is partly hereditary but also the result of myriad environmental influences, such as the quality of schooling, financial conditions and the strength of family structures.

His new friends "don't like that answer," he writes. "They don't like it one bit."

What they really want, he believes, is scientific justification for whatever prejudices they might harbor.

All around him is evidence of this mindset -- from a class in California where most of the students said they'd terminate a pregnancy if they knew the child had a high likelihood of becoming overweight to the way genetic discoveries are simplified in the media. Reporters are often impatient with Hawley because he won't reduce science to facile absolutes.

"I've been working for the past few months with a reporter for 60 Minutes II," he says. "She talks to all these people, and she'll call me and ask, 'Who's right?' And she gets frustrated when I tell her it's not a matter of who's right. It's complicated."

But he doesn't blame the media or the undergrads in his classes or the people he chats with at parties for these misconceptions. He blames scientists like himself.

"I think it's the failure of scientists to talk about what they do in a way that other people can understand," he says.

But he has faith that, when he and his colleagues succeed at this, his work will fulfill the good he intends.

"The more information we can give people, the better decisions they'll make," he says.

In the meantime, on any given day, fruit-fly cells are splitting at the laboratory on the fifth floor of the Stowers Institute as Hawley and his team seek the elusive NOD protein. When they finally isolate it, they'll publish their findings. Other scientists who study the genetics of mice and men will apply Hawley's discoveries to their work.

But that's no guarantee the world will become a better place.

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