Kenyan researcher George Njoroge honored as an outstanding chemistry alumnus

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Kenyan researcher George Njoroge honored as an outstanding chemistry alumnus
Njoroge’s daughter, Joyce, followed his example and attended Case Western Reserve, where she graduated from the School of Medicine in 2016. Kenyan researcher George Njoroge honored as an outstanding chemistry alumnus

Early in F. George Njoroge’s career as a pharmaceutical chemist, one of his managers described the Kenyan-born scientist as a true drug hunter—one who was “ready to go the extra mile” to discover new medicines.

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Njoroge (GRS ’83, ’85, chemistry) was humbled by the comment. But it proved true: Njoroge went on to spend more than three decades developing novel therapeutics for cancer and viruses. One of those medicines, Victrelis, was the first drug to directly target the virus that causes hepatitis C, a disease that afflicts more than 70 million people around the world and can lead to severe liver damage and even death.

Last spring, Case Western Reserve’s Department of Chemistry honored Njoroge as its 2021 Outstanding Alumnus. During a virtual ceremony, department chair Gregory Tochtrop noted Njoroge’s singular record of achievement: While holding senior leadership roles at pharmaceutical giants Schering-Plough, Merck and Eli Lilly, Njoroge obtained more than 100 patents and published more than 130 articles in peer-reviewed journals. Among his many awards, he has been named a “Hero of Chemistry” by the American Chemical Society and granted an honorary doctorate in pharmaceutical science from Mount Kenya University.

During his many years as a researcher in the United States, Njoroge always envisioned returning to Kenya someday to put his expertise at the service of his homeland. In 2019, he and his wife, Esther, decided the time had come. They relocated to Nairobi, and Njoroge created a master plan for a multipurpose complex: the Center of Africa’s Life Sciences, or COALS. With this facility, Njoroge hopes to spur local drug development and manufacturing. Just as important, he wants to provide aspiring Kenyan scientists with the kinds of educational and research opportunities that were so scarce in his youth, when his own material circumstances nearly prevented him from pursuing a career in science at all.

Lessons from an Herbalist

Njoroge was born in Kamuchege, a village 25 miles outside of Nairobi, in 1954, during the waning days of British colonial rule. The previous year, his maternal grandfather had been killed by British forces seeking to quash the nationalist Mau Mau uprising.

When Njoroge was 3 years old, his mother, a single parent, got engaged and went to live in a distant village, leaving him in his grandmother’s care. Food was scarce, and he didn’t always have shoes to wear.

“It was a very difficult time,” Njoroge says. “But it formed a good background for me to appreciate my later life.”

Njoroge’s grandmother was a traditional herbalist who seemed to have a cure for almost every ailment. Later, while studying chemistry at the University of Nairobi, Njoroge realized that many of her plant-based treatments actually contained medicinal compounds, and that her methods for concocting them—boiling certain roots and herbs in tea, for instance, and simmering others in oil—made scientific sense.

“She wasn’t a chemist. She never went to school,” Njoroge says. Nonetheless, “she knew how to extract the active agents.” In a 2021 interview with a Kenyan newspaper, he remarked, “The glamour and respect that my grandmother received from our community encouraged me to get an education where I could be in a career similar to hers.”

Njoroge eventually attended Thika High School, a boys-only boarding school founded by British missionaries in a nearby town. Being admitted was a mark of distinction: Thika accepted only one student from Kamuchege, a village of 6,000 inhabitants, each year. Njoroge’s favorite subject was biology, but as a young man from a poor family, he became convinced that a future as a doctor or scientist was out of reach. Instead of taking the advanced courses required for university entrance, he decided to finish school and begin earning money as quickly as possible. But when his British math and biology teachers found out about his plans, they promised to help finance his studies.

“I got a lot of help and motivation from those people,” he says. “I think it contributed a lot to my success.”

During his senior year at Thika High School, Njoroge was presented with a prize in biology by Joseph Mungai, the first African to serve as dean of the medical school at the University of Nairobi. Under the British educational model, students could enter the university and immediately pursue a five-year medical degree without first earning an undergraduate degree, and Mungai assumed Njoroge would enroll as a medical student the following year. But by then, Njoroge had acquired a different ambition: He wanted to become a game warden, like the one he’d met on a school trip to a marine park on the Indian Ocean.

“I told my biology teacher, ‘All I want to do in my life is to become like this man,’” says Njoroge, who was deeply impressed by the fleet of Land Rovers and glass-bottomed boats the warden commanded. Conveniently, achieving that goal would only require three years of undergraduate work in botany, zoology and chemistry.

Once at the university, however, Njoroge became fascinated with organic chemistry. When he learned that most modern medicines were developed through chemical synthesis, the herbalist’s grandson knew he had found his calling.

Capable Tutelage

As it happened, two of Njoroge’s chemistry professors—Shem O. Wendiga (GRS ’72) and Owuor Philip Okinda (GRS ’78, ’80)—had done their graduate work at Case Western Reserve. They were confident that if Njoroge earned a first-class honors degree from the University of Nairobi, he could do the same. With his mentors’ encouragement, Njoroge graduated at the top of his class and earned a scholarship from CWRU.

The transition to his new life wasn’t easy. Winter in Cleveland was tough; he missed Esther, who was his girlfriend at the time; and his first class in quantum chemistry was so difficult he began to wonder why he’d ever left Nairobi.

The situation soon improved, however. For one thing, Esther joined him. (The two were married in 1987; their daughter, Joyce [MED ‘16], is a cardiology fellow at the University of California, San Francisco, and their son, Jesse, is a pharmacist in Virginia.) For another, Njoroge quickly adapted to the academic environment, falling under the capable tutelage of faculty members such as Anthony Pearson, now the Rudolph and Susan Rense Professor Emeritus of Chemistry, and the late Lawrence Sayre. With his advisor, the late Eric Nordlander, he co-authored several papers that eventually helped him secure employment in the pharmaceutical industry. And once he earned his master’s degree, Njoroge completed his doctoral research in less than two years, thanks in part to the materials and equipment available to him at Case Western Reserve.

Njoroge knew his PhD would secure him a job as a professor back at the University of Nairobi. But he also knew that opportunities to discover new medicines in Kenya would be severely limited. So, he became a postdoctoral fellow at the Institute of Pathology at University Hospitals in Cleveland—where, he says, he acquired “a wealth of knowledge about research opportunities in medical areas.” Then he landed a job with the Schering-Plough Research Institute in New Jersey.

His first major project was in the field of cancer therapeutics. Seeking a way to prevent metastasis, or the spreading of cancer to new areas of the body, Njoroge focused on a protein, Ras p21, that plays an important role in the proliferation of cancer cells. Ras p21 attaches itself to the membrane of a cell and triggers a cascade of biochemical events that cause the cell to multiply. An enzyme located on the membrane provides an opening: A portion of Ras p21 fits into a binding site on the enzyme like a key in a lock. Njoroge set about developing a small molecule that could slip into the enzyme’s binding site instead, preventing Ras p21 from fastening to the membrane in the first place.

By modifying a molecule that Schering-Plough had previously synthesized for use as an antihistamine, Njoroge developed a new drug, lonafarnib, that showed early promise in treating cancer patients but failed to make it through phase III clinical trials. Several years later, however, doctors at Boston Children’s Hospital discovered that lonafarnib reduced the risk of death among patients with progeria, a genetic disease that leads to extreme premature aging. (Most people with the condition die in their teens from heart attack or stroke.) The drug, which is marketed under the name Sarasar, received FDA approval in 2020 and remains the only medication that can improve life expectancy in children with the disease.

For his next project, Njoroge was asked to work on a treatment for hepatitis C. At the time, the only drugs available were general-purpose antivirals with relatively low cure rates. Given the devastating global impact of the disease, there was an urgent need for more effective therapies that were custom-tailored to target the virus.

As he confronted this challenge, Njoroge’s experience in cancer research served him well. Like cancer cells, hepatitis C replicates with the help of an enzyme—a protease that binds to long chains of viral proteins and chews them into smaller pieces. These pieces are then assembled into new viral particles. As with lonafarnib, Njoroge’s strategy was to synthesize a molecule that would interfere with this process from the start.

Ideally, such a molecule would fit snugly into a deep binding site on the enzyme’s surface. When he examined the structure of the protease, however, Njoroge discovered that it was unusually smooth and featureless. In the parlance of chemists, it had “shallow pockets”—though Njoroge prefers an analogy closer to his African roots.

“It was like the Kalahari Desert,” he says, laughing.

It took Njoroge 15 years to develop a molecule that could find purchase in that barren wasteland, resulting in the first FDA-approved oral protease inhibitor for the treatment of hepatitis C. Victrelis, whose generic name is Boceprevir, quickly became part of the standard of care for the disease and paved the way for even more effective therapies—including Narlaprevir, another protease inhibitor that Njoroge subsequently developed for Schering-Plough.

In a speech he gave to graduates of Mount Kenya University in 2017, Njoroge cast the discovery of Victrelis, which ultimately saved thousands of patients who would have otherwise died from hepatitis C, as “the greatest thing that ever happened in my life.”

Building a Legacy

By the time he discovered Narlaprevir, Njoroge had been promoted to director of medicinal chemistry and was leading a team of 20 fellow chemists. After Schering-Plough was acquired by the pharmaceutical company Merck in 2009, he retained that title for two more years and then took a position as a senior researcher at Eli Lilly, where he spent nearly a decade developing cancer drugs before he and Esther moved to Nairobi.

Though Njoroge had visited over the years and still had family and friends in Kenya, resettling there was still a challenge: The process of translating basic research into new medicines was foreign to his Kenyan colleagues, and the country lacked the financial resources and technical capacity he had grown accustomed to in the United States. But he soon found that his knowledge and skills were in high demand. Njoroge joined the board of the Kenya Medical Research Institute (KEMRI), the Kenyan equivalent of the National Institutes of Health, and became chief scientific advisor at Kenyatta University Teaching, Referral & Research Hospital, one of the country’s top-tier medical institutions.

His primary focus, however, is on making COALS a reality. Situated on 400 acres in the Great Rift Valley, the complex will include a life sciences university, research laboratories, incubators for African biotechnology firms and a manufacturing plant that will produce much-needed, affordable generic drugs for Kenya and other parts of the continent. In addition, Njoroge’s plan calls for an international conference center where Kenyan scientists and university students can interact with top scientists from around the world.

Njoroge started thinking about COALS some 30 years ago. “As I became more involved in drug discovery,” he says, “the idea started to become more clear and convincing to me.” He especially wants the center to help recruit, train and mentor young Kenyans so they will pursue research careers. He envisions them spending at least some time studying and working overseas, and then bearing the fruits of their experience back to their homeland.

“If I leave something to my mother country, that will be it,” Njoroge says. “That will be my legacy.”

Alexander Gelfand is a freelance writer in New York City.

BY ALEXANDER GELFAND

Source-https://artsci.case.edu/

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