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A Biologist’s Mission

Emmitt Jolly targets a neglected tropical disease

By Alexander Gelfand

Associate Professor Emmitt Jolly says that without the influence of his early mentors, the very idea of becoming a scientist might never have occurred to him. Photo by Mike Sands.

Emmitt Jolly, an associate professor in the Department of Biology at Case Western Reserve, studies monsters.

Schistosomes, to be precise: a genus of flatworm, or blood fluke, responsible for the devastating disease known as schistosomiasis—an ailment second only to malaria in the toll it exacts in human suffering throughout the developing world. The worms thrive in environments where sanitation is inadequate and clean water is scarce. As a result, most of the more than 200 million people who are infected live in poor rural communities, and more than 200,000 die each year in sub-Saharan Africa alone.

Scientists like Jolly have long understood what makes schistosomes such a menace. The worms produce eggs whose presence in the human body provokes an immune response that can over time damage the bladder, intestines, liver, kidneys, lungs, heart and nervous system, causing symptoms ranging from pain and fever to infertility and paralysis. In children, among whom schistosomiasis is especially prevalent, the disease causes malnutrition, delayed growth and learning disabilities.

But researchers haven’t yet learned enough to prevent or control the disease. There is no vaccine, and the most effective drug, praziquantel, kills the adult worms but does nothing to their eggs, ensuring a continuous cycle of infection, treatment and reinfection. What’s more, the drug itself makes children in particular so sick to their stomachs that many won’t even swallow it. “They’d rather have schistosomiasis than take the pill,” Jolly says.

Through a mass drug administration program in 2011, these Ugandan children received praziquantel, an anti-schistosomiasis medication. Emmitt Jolly hopes that his research will lead to more effective treatments. ©Schistosomiasis Control Initiative, Imperial College London

Now, using the tools of molecular biology, including DNA analysis and genetic manipulation, Jolly is seeking to understand how these malign creatures grow and change inside us: how particular genes and proteins come in and out of play, are suppressed or kicked into high gear at various times and to varying degrees as the worms mature in our blood. His goal is to gain fresh biological insights that will help the pharmaceutical industry develop more effective treatments.

Jolly chose to investigate the organisms responsible for schistosomiasis out of a desire to improve the lot of others. “I wanted to go into a field where I could have a positive impact,” he says. “And I wanted to affect people who needed it.”

That same desire has also fueled his efforts to advance the cause of underrepresented minorities in science, technology, engineering and mathematics—the STEM fields. As a first-generation African American university student from a family of modest means, Jolly himself had to overcome significant odds to become a tenured faculty member in biology: Black men represent only 3 percent of scientists and engineers in the United States. In fact, Jolly says, if not for the influence of his earliest mentors, the very idea of becoming a scientist might never have occurred to him.

A Web of Supporters

The eldest of four boys, Jolly was born in North Carolina, spent his early childhood in Cleveland and came of age in Alabama. His father, a former Marine who served as an elder in the Jehovah’s Witnesses, earned his living as a janitor and electrician; his mother worked in food service at a Veterans Affairs Medical Center. “We grew up not making much money,” he says. “College wasn’t an option.”

Instead, talk at home focused on jobs and the ministry. From the age of 11, Jolly spent his summers laboring in tobacco and cotton fields. But his strong grades caught the eye of his high school guidance counselor, Mildred White, who asked about his career plans. Jolly figured he would become an electrician like his dad. When White suggested electrical engineering instead, Jolly admitted he didn’t have the money for college. White told him he could apply for scholarships and pointed out the difference in pay between engineers and electricians. “My jaw dropped,” says Jolly, who soon began conducting electrical experiments at home in his spare time.

White also talked Jolly up to James H. M. Henderson, a plant physiologist at nearby Tuskegee University; and Henderson, in turn, invited Jolly to participate in a precollege summer program at the historically black institution. Around the same time, Jolly’s biology teacher lent him a microscope, and he fell in love with genetics.

At Tuskegee, Henderson arranged for Jolly to work in the lab of geneticist John Williams, studying frog chromosomes. “Am I getting paid for this?” an incredulous Jolly asked when Williams handed him a stack of scientific studies to read. “I’m getting paid to learn?” The following year he worked on a NASA-funded project examining the DNA of tomato seeds that had been in orbit aboard the space shuttle Challenger. This job ultimately landed him in the lab of C. S. Prakash, an internationally recognized plant geneticist with a commitment to training underrepresented minority students and scientists.

From left: Undergraduate biology major Jasmine Lee and doctoral student James Hagerty are members of Emmitt Jolly’s research team. Photo by Mike Sands.

Nurtured by this ever-expanding web of supporters, Jolly enrolled at the university. “I wound up at Tuskegee because I had personal relationships with faculty who cared about me,” he says. They would not be the last. After his sophomore year, Jolly attended a summer program at the University of California, San Francisco (UCSF), where he worked in the lab of biochemist Erin O’Shea. “Emmitt really stood out as being exceptional,” recalls O’Shea, who later moved to Harvard and recently became president of the Howard Hughes Medical Institute. “He was smart, passionate—all the things you want to see in a young person. And he had such clear leadership skills, even at that age.”

Becoming the First

Jolly credits O’Shea with changing the way he thought about genetics. Now, he says, he found himself focusing not on individual bits of DNA, but rather on the big picture: how genes got turned on and off. In his senior year, Jolly’s name appeared alongside O’Shea’s in an article in the journal Science that helped explain how that process occurs in yeast, a model organism that geneticists use to understand biological processes in other creatures, including people.

Jolly returned to UCSF for graduate school, intending to study immunology: His mother had lupus, a chronic autoimmune disease that attacks the body’s own healthy tissues, and he hoped to find a cure. O’Shea advised him to study biochemistry and molecular biology instead, on the grounds that such foundational training would give him the tools to tackle virtually any problem later on. He took her advice and became the first African American in the graduate program in biochemistry and molecular biology.

Going from a historically black, southern university with limited resources to a cutting-edge research institution on the West Coast was not easy. And it wasn’t made any easier by the mixed response that Jolly received. O’Shea, who strongly recommended him to the program, was clearly in Jolly’s corner, as was John Watson, a pioneering African American biochemist who helped found the Coalition for the Advancement of Blacks in Biomedical Sciences. (Jolly met his wife, Stacey, a doctor who investigates health issues affecting Native Americans, in Watson’s lab.) So, too, was the renowned geneticist Ira Herskowitz, who became Jolly’s thesis advisor. But one senior researcher told Jolly that he didn’t deserve to be at UCSF at all and was taking up a space that could have been filled by a more qualified candidate. He was also informed by a faculty member that if he didn’t perform to expectations, he wouldn’t only be the first African American in the program; he would also be the last.

Today, Jolly is philosophical about his experiences. “Racism happens everywhere,” he says. Still, he admits, “Graduate school was rough for me.” To make matters worse, rival labs kept publishing discoveries related to his own before he could do so, delaying his graduation and forcing him to change the direction of his research.

“I was actually surprised that Emmitt stayed in science,” says Frederick Moore, whom Jolly helped recruit to UCSF and who now directs a program at City College of San Francisco designed to increase the number of economically disadvantaged students majoring in STEM fields.

Jolly did in fact seriously consider abandoning academic research for a career in the biotech industry, and came close to taking a job in intellectual property. But he knew that if he announced his intention to do so, his doctoral committee would hold him to a lower standard. “I did not want to be the first African American in the program and graduate that way,” Jolly says. In the end, he prevailed, earning his degree with a dissertation on transcription factors, molecules that activate and inhibit the expression of specific genes. At that point, he decided to pursue a postdoctoral research position.

No longer attracted to immunology, Jolly joined the lab of UCSF parasitologist James McKerrow, who specializes in driving the development of new drugs for neglected tropical diseases. McKerrow hoped that Jolly would work on schistosomes; Jolly, however, had his sights set on the single-celled parasites that cause sleeping sickness, a potentially fatal illness transmitted by tsetse flies in rural sub-Saharan Africa. Known as trypanosomes, these deadly protozoa struck Jolly as an ideal research subject: In addition to afflicting poor people and people of color, they are also genetically tractable, meaning that their DNA is relatively easy to manipulate.

According to the World Health Organization, “schistosomiasis is prevalent in tropical and subtropical areas, especially in poor communities without access to safe drinking water and adequate sanitation. It is estimated that at least 90% of those requiring treatment for schistosomiasis live in Africa.” Map courtesy of World Health Organization.

This is a trait that schistosomes do not share. Indeed, their life cycle is so tortuous that it is difficult to work with them at all. The worms initially live in freshwater snails that inhabit lakes and rivers, but they soon change shape and begin to search for human hosts, burrowing through the skin of their victims. Once inside a warm body, they travel through various tissues and organs before settling in the veins of the liver and bladder. Maturing to adulthood, they undergo further transformations before mating and laying their eggs. While a majority of the eggs remain in the body, wreaking havoc, the rest are passed through elimination back into freshwater, where they hatch and reinfect the snails from whence they came.

Deciding which of these developmental stages to target, much less which genes to analyze, is itself a puzzle. Moreover, while successive generations of adult worms can continue to reproduce inside a human host for decades, feeding on red blood cells and thoroughly stymieing the immune system, they will not mate in the lab.

“I had no interest in working on this stupid worm,” Jolly says, laughing.

McKerrow evidently knew Jolly a little too well, however. When a graduate student from the Dominican Republic arrived in the lab to do schistosomiasis research, McKerrow asked Jolly to teach her how to clone genes. “He got me when he said that there was a minority student who needed to be trained,” says Jolly, who was unable to resist helping a fellow traveler. Once Jolly learned how little was known about schistosomes, the die was cast.

Jolly had always seized the opportunity to mentor others, in part because he appreciated how important his own mentors had been to him. Soon he would establish an entire organization designed to extend that kind of support.

A Community of Scientists

As a graduate student and postdoc, Jolly received funding from the United Negro College Fund (UNCF)/Merck Science Initiative, which aims to increase the number of minority students in science and engineering. While attending a gathering of UNCF/Merck Fellows in 2007, Jolly and his friend Matthew Walker III, now an associate professor of biomedical engineering at Vanderbilt University, founded the Association of Underrepresented Minority Fellows (AUMF) in order to keep the community of scientists fostered by the UNCF/Merck initiative alive should the program itself ever lose funding.

The AUMF was initially conceived as a peer-mentoring network that would allow the fellows to continue to benefit from each other’s counsel and companionship. “Sometimes, you just want to talk to somebody,” Jolly explains—especially when that somebody understands the challenges confronting minorities in the sciences. But the organization’s mission gradually expanded, and its 650 members are now intent on patching the infamously leaky pipeline for underrepresented minorities in STEM fields. Since 2012, the AUMF has been formally hosted by Case Western Reserve—a relationship that Marilyn S. Mobley, vice president for inclusion, diversity and equal opportunity, says furthers the university’s diversity-enhancement efforts.

In 2014, the AUMF and the university jointly hosted a national symposium on minorities in the biomedical sciences that drew 125 minority researchers to campus from institutions like Harvard, Stanford and Duke and highlighted CWRU’s commitment to increasing the participation of people of color in STEM fields. Several AUMF members have given seminars on campus, and Jolly played an important role in bringing Tuskegee University into a $3.7 million project led by Case Western Reserve and funded by the National Science Foundation that seeks to increase underrepresented minority preparation, participation and success in STEM graduate programs. He is also helping to renew a long-standing partnership between CWRU and Fisk University, another historically black institution. “The partnership has tremendous potential,” says Mobley. “I believe that the best is yet to come.”

The same might be said of Jolly’s work on schistosomiasis. Having identified some of the key genes and proteins responsible for regulating the development of schistosomes once they are in our blood, Jolly has begun investigating the molecular mechanisms that lead the worms to invade our bodies in the first place. In addition, he is trying to adapt a powerful gene-editing tool called CRISPR-Cas9, which has in recent years allowed researchers to genetically engineer a number of other seemingly intractable organisms, for use on the parasite. “I think it’s doable,” he says. “But there are real serious challenges in terms of getting it to work.”

Fortunately, that is precisely the sort of challenge that Emmitt Jolly specializes in overcoming.

Alexander Gelfand is a freelance writer in New York City.

Page last modified: February 9, 2017