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Numerical Value

Numerical Value

“I’m not sitting crunching numbers all day. I’m working with people, with teams. I work with physicians, with business people, marketing people.”
—Jovanna Baptista

Not all medical research takes place on animals and in petri dishes. Increasingly, numbers are the raw ingredients of those looking to cure diseases. Jovanna Baptista ’00 and Brian Weiner ’04 address this challenge by tapping into the ability of computers to sort through vast quantities of data in search of information that could hold the secret to the next medical breakthrough.

For almost as long as Jovanna Baptista has loved math, she has found ways to keep the nerd factor from defining her life. In high school it meant becoming captain of the cheerleading squad, while still belonging to the math team. At WPI—where in 2000 she received a BS with high distinction in actuarial mathematics and a minor in management—she relished the chance to work at a London hospital for her IQP, helping design a system for prescribing appropriate wheelchairs for patients with neurological disorders. There, she valued the teamwork with WPI biomedical engineers; the subsequent multimedia presentation back at school led to winning the President’s IQP Award. And now that Baptista is a respected biostatistician for pharmaceuticals, she talks excitedly about the human side of her career.

At her condo in Boston’s Roslindale section, where paintings by her brother Joshua complement the stylish but comfortable furnishings, Baptista says, “I’m not sitting crunching numbers all day. I’m working with people, with teams. I work with physicians, with business people, marketing people. Although I love statistics, it’s very little of what I do. My job is using tools to present the information to nonstatisticians. Doctors are the experts. My job is to understand what they need and work it into a clinical trial."

The ultimate goal, of course, is for a pharmaceutical company to create a drug that will benefit patients, with the fewest adverse effects. Reaching that point, however, involves lengthy and often byzantine processes, both scientific and bureaucratic. In the decade since Baptista graduated from WPI, she has gained insight into virtually every aspect of this vital path, both at a number of pharmaceutical companies and at the Harvard School of Public Health, where she received an MS in biostatistics in 2002.

Whether constructing a clinical trial, or going before the Food and Drug Administration (FDA) to make a case for a drug, Baptista has proved a skilled observer of people. She is sensitive to the suffering of the individuals for whom a future medication might be beneficial, but committed to the highest standards in structuring a trial. She understands physicians’ desires to get a potentially helpful medicine to patients as quickly as possible. And she is able to maintain the diplomacy needed to ensure a study satisfies all involved— from the FDA to the pharmaceutical company—by “not being caught up in the moment.”

A visible record of Baptista’s research shows up in the insert inside the packaging of an approved drug. There, in small print, are the conclusions drawn from the many questions she had to ask along the way. Among the main ones, she says, are, “How do you figure out how many patients you need for a study? What will be a clinical benefit—a meaningful difference? You try to have a study that is clinically meaningful, statistically significant, and cost effective.”

Baptista, who has investigated drugs for cystic fibrosis, cancer, anemia, and other conditions, must focus on the risk versus the benefit of a particular drug in the context of the situation it would treat. A life-threatening disease clearly allows for more potential adverse effects than one addressing a more benign ailment. At Infinity Pharmaceuticals in Cambridge, Mass., where she handled oncology trials, Baptista explains the complexity of figuring out dosing for a protocol. “You don’t know the effective dose,” she says. “You keep bumping it up until you reach dose-limiting toxicities.”

Even though Baptista must weigh negative repercussions in everything she studies, by nature she prefers to focus on positive outcomes. In fact, she decided while at WPI not to become an actuary because it was too downbeat. She did her MQP at John Hancock, assisting on a project to price a disability waiver for the insurance company. She concluded, “Pricing insurance is dry and morbid. You think about how people become disabled and die. You come up with a figure so that the insurance company can make a profit off people becoming disabled.”

The career she chose instead seems full of promise by comparison. She believes biostatistics is “an opportunity, if you’re a person who wants to work in teams of people from different backgrounds. I work in a medical environment. I may not know about disease or the biology of disease, but I go in and start learning. I’m a piece of the puzzle. All these disciplines come together to get a drug approved.”

“The work we’re doing is laying the foundation for good things to come: diagnostics, new drugs, new vaccines.”
—Brian Weiner

Strength in Numbers

It’s a disease that has been identified in an ancient Egyptian mummy and that still plagues a third of the planet’s six billion residents as a dormant threat. Every year the microbe that causes tuberculosis infiltrates the lungs of many, killing two million individuals and destroying the well-being of countless others in the process. For Brian Weiner '04 those statistics represent a challenge, which he is addressing with his own arsenal of computations. Working at the Broad Institute of MIT and Harvard, he wrestles vast quantities of data into revealing some of the secrets of what he calls “this horrible bacterium.” As he sits at his desk on the seventh floor of the Broad’s 7 Cambridge Center building, overlooking the technological hub of Kendall Square in Cambridge, he appears hopeful and his bright eyes shine: “The work we’re doing is laying the foundation for good things to come: diagnostics, new drugs, new vaccines.”

The battle between Weiner’s team and the disease requires weapons so potent and sophisticated they could not have existed a mere decade ago. Central to his strategy—and to the field of bioinformatics—is an ability to understand and manipulate genomic data. On twin computer monitors, a colorful array of graphs and charts depicts the strengths and potential vulnerabilities of tuberculosis DNA. Weiner admits that his two Dell desktops are nothing exceptional, however.  “They’re standard,” he says. “You could go to Best Buy and pick them up.”

What lends power to Weiner’s quest lies on a different floor of the bright and ultramodern Broad building, which opened only four years ago. Behind a secure door, row upon row of towering steel-gray machines punctuated by blue lights hum with activity. This load-sharing facility—“the farm” to Weiner and his colleagues—can analyze sequenced DNA at dazzling speeds, enabling scientists to discern the location of mutations in the microbe. By comparing drugsensitive TB, multidrug-resistant TB, and, the most worrisome, extensively drug-resistant TB, the researchers are hoping to pave the way for more targeted treatments.

To explain complicated concepts such as gene expression and the transcription network in an organism,Weiner clutches his arm. The area he grabs represents a protein called the transcription factor, which “sits down on the DNA” and activates it. The graphs on his computer screens, with their sharp peaks, “allow us to see where they’re sitting down, where they’re located, which genes they’re controlling,” he says.

In the whirlwind decade that has included the decoding of the human genome and invention of the Illumina DNAsequencing machine, Weiner has gone from a high school student in Brookfield, Conn., to an associate computational biologist with a BS with distinction in biotechnology from WPI and an MS in bioinformatics from Boston University. WPI’s Odyssey of the Mind—a team-oriented science competition for schoolchildren—left a lasting impression on him as a talented young scientist, who would be growing bacteria, running DNA gels, and taking a biotechnology elective before graduating from high school. When it came time for college, Weiner wanted a school that took a similar team approach to creative problem solving.

Investigating bone biology at the University of Massachusetts Medical School for his MQP confirmed Weiner’s passion for biology—but with the computational slant that had just begun to be offered as a concentration at WPI. He wanted to “analyze data and get to the bigger picture,” he says. Biology’s links to the human condition made the field particularly appealing to Weiner; adding math to the mix only enhanced what he perceived as the long-term potential of his efforts.

First at the nearby Whitehead Institute, and since 2006 at the Broad, Weiner has found exactly the sort of environment he was seeking. While he has been assembling such databases as the one for mutations associated with drug-resistant TB, he has been able to look around him and witness astounding work on other gene-related problems. Modest about his own accomplishments, Weiner is quick to praise the achievements of others, who are training their genomic sights on HIV, cancer, diabetes, malaria, and other global maladies. “Working at a place like the Broad, you feel like you’re in school. You’re continually learning while you’re doing professional science,” he says. “The Broad, as a model, is a gigantic institute structure where all collaborate.” Weiner gives a shout-out to the Bill and Melinda Gates Foundation for funding a grant for the TB database, and to Eli and Edythe Broad for recently doubling their contribution to their eponymous institute after being impressed by the research being done there.

For Weiner, ultimately it’s not about the numbers. In the Broad lobby—where a mini-museum houses a luminous interactive display of ongoing enterprises at the organization—he takes an iPod-style clicker and flashes onto the TB section. There, in vivid hues, charts and maps and photographs tell the stories of people ravaged by disease. Weiner’s research numbers—untold millions and millions of them—will add up when the pictures in the display become obsolete.

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Last modified: September 02, 2010 16:25:53