Autumn 2008

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“Drug discovery is a very, very specialized area. . . . All the money in the world won’t give people the expertise to discover and develop new drugs. They have to be shown how to do that.” &8212;Dennis Liotta, Samuel Candler Dobbs Professor of Chemistry

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by Patrick Adams 08MPH

In April 2001, at the dedication ceremony for Emory’s Emerson Hall, the late Cherry Logan Emerson 38C 39G boldly declared the $25 million building named in his honor “the best chemistry research laboratory in the world.”

Emerson—chemist, businessman, and benefactor—would have known. The Atlanta native earned his degrees from Emory just as penicillin was being purified for use in the first antibiotics. He had witnessed more than half a century of progress, and he understood, as the founder and longtime chief executive of a company that specialized in compounds for the defense industry, technology’s critical role in research.

Emerson died last year at the age of ninety. But his laboratory lives on, and has come to serve a role Emerson himself might never have imagined. In February, the state-of-the-art space became the principal training ground for the inaugural class of the Emory-Republic of South Africa Drug Discovery Training Program. Founded by Samuel Candler Dobbs Professor of Chemistry Dennis Liotta, the program aims to transfer expertise in drug discovery—namely the identification of candidate compounds for therapeutic efficacy—from the halls of American universities to the areas of the world that need it most.

“Drug discovery is a very, very specialized area,” Liotta said one morning last fall, still jetlagged from his latest journey to Johannesburg. “All the money in the world won’t give people the expertise to discover and develop new drugs. They have to be shown how to do that. So while we love the Gates Foundation and the other great philanthropists of the world, we have an opportunity to do something complementary to that. We don’t have money, but we have something maybe more important.”

For Liotta, who is fifty-nine, the program is the realization of a relationship long in the making, a series of face-to-face meetings that has made the nearly twenty-four-hour trip from Atlanta to Johannesburg almost routine. But that’s a price he is willing to pay. Travel begets trust, and trust is the foundation upon which Liotta has sought to build a partnership of unprecedented aims—a collaboration that he believes could offer South Africa the tools it has long been missing to combat the diseases it has long endured.

“Remember that in Africa, for hundreds of years, people have come in, some well-intentioned, some malicious, and imposed their ‘solutions’ on the people,” he says. “So Africans, I think, tend to be wary of outsiders who are going to tell them how to solve their problems. That’s why you need these relationships. That’s why you have to have trust.”

During his three decades at Emory—as professor of chemistry, department chair, and vice president for research—Liotta has authored more than two hundred publications, served on almost every major campus committee, and been awarded the University’s highest distinctions for both teaching and research. But he is also a problem-solver in practice—a prime example of what President James Wagner has described as Emory’s commitment to courageous inquiry.

Nowhere on campus has that inquiry yielded results more far-reaching, or financially rewarding, than in Liotta’s laboratory. And of the lab’s many medicinal inventions—for everything from cancer and rheumatoid arthritis to hepatitis B and HIV—none has had a greater impact on global health than the drug Emtriva. “One of our little success stories,” Liotta has called it; but the impact of Emtriva, a powerful anti-HIV compound and one of the most prescribed therapies for the disease ever made, was anything but small.

Discovered in 1989 by Liotta, pediatrics professor Raymond Schinazi, and researcher Woo-Baeg Choi, the drug, a nucleoside reverse transcriptase inhibitor, was approved in 2006 for use in the first-ever triple combination therapy. Atripla, as it was called, reduced an HIV-infected person’s pill burden from as many as fifteen a day to just one, marking one of the greatest advances in AIDS treatment to date. Patients with access to the drugs would be less likely to miss a dose, and thus resistance to the drugs would be less likely to develop. Moreover, Atripla was as effective as it was efficiently packaged. As Schinazi put it, the new combination was like having “an H-bomb for HIV—you blow it to smithereens.”

When Emory auctioned off its royalty rights to Emtriva in 2005, it made a bit of higher education history. The deal, which brought in a lump sum payment of around $540 million, was the largest-ever transaction between the pharmaceutical industry and a U.S. university—and with it came a world of new possibilities. “We have an invention here that addresses a real international scourge,” Wagner told Fortune magazine. “And we are now taking these resources and reinvesting them in research and education.”

One year later, Emory established, as part of a new university-wide initiative, the Emory Global Health Institute. Under the direction of the former head of the Centers for Disease Control and Prevention (CDC), Emory Vice President for Global Health Jeffrey Koplan, the institute currently funds more than two dozen health research and training programs worldwide. The Emory-South Africa Drug Discovery Training Program may be one of its most ambitious.

“We went there and we got this idea of developing a student exchange,” Liotta says, describing his first trip to South Africa eight years ago with colleagues from Imperial College in London and Georgia Tech. “In the beginning, it was just collaborative research projects. We would send students to them, and they would send students to us. It quickly became obvious, though, that there were certain gaps in expertise—and one of them was in drug discovery.”

Around the same time, says Liotta, South Africa President Thabo Mbeki had reportedly paid a visit to Cuba to see firsthand that resource-poor country’s homegrown biotechnology industry. Developed in the face of—and largely in response to—the longstanding U.S. trade embargo, Cuba’s capacity to manufacture its own drugs would surely have appealed to a leader like Mbeki, long a proponent of “African solutions for African problems,” chief among them HIV.

Today Cuba boasts one of the most advanced and efficiently run biotech industries in the developing world, providing a boost to its own economy and serving as a boon to human health worldwide. Among Cuba’s pharmaceutical contributions to date are vaccines for hepatitis B and meningitis, a cholesterol drug derived from sugarcane, and a drug for heart attacks that was found to be both safer and more effective than those marketed by major pharmaceutical companies.

“Mbeki was, we’re told, very impressed with what he saw in Cuba,” says Liotta. “He came back and said this ought to be a priority for the South African government. So they drafted a white paper on it, and we thought, this is a perfect opportunity. We have a lot of folks here like myself who are very experienced in drug discovery. If we could put together a consortium of people, we could transfer that expertise to the next generation of African scientists.”

Benedict Bapela grew up in Sharpeville, a township on the outskirts of Johannesburg. He was raised, alongside four brothers, in the sort of cramped cinderblock house (one kitchen, two bedrooms) that was standard issue for many blacks during apartheid.

“Electricity was installed when I was seven years old,” he recalls in heavily accented English, one of eight languages he speaks fluently. “Before that we were using candles.”

As a kid, Bapela developed a passion for plants and a fascination with their healing properties. “Growing up in Sharpeville, I was raised by my family but also by my neighbor,” he says. “He was a traditional healer. He would take me with him to dig for herbs, and that encouraged me to learn about medicine, about things that heal.”

Bapela, now thirty-six, is a pharmacologist with South Africa’s Medical Research Council, a state-run organization devoted to improving the nation’s health through research. When he came to Emory last March as one of six scientists selected for the pilot run of Liotta’s program, he described how, as a black South African, he got the opportunity to study science in the first place.

“When I finished high school, I wanted to go to Cape Town for college,” he said. “But my parents didn’t have the money. When we went to the banks, we couldn’t get a loan because of where we were coming from. Even if you told them, ‘Look, we have a house,’ it was a house in a township, and they would say, ‘No way.’ ” Undeterred, Bapela went to work for a steel company, hoping to save up enough cash for a bus ticket to the city. “I made the nuts and bolts,” he said. “It was not a job where you think. It was labor. The day they paid me, I left and I never went back. It was a sixteen-hour ride to the Cape.”

Once there, Bapela made his way to the bursar’s office at the University of Cape Town and eventually secured a scholarship to study medicine. After completing a PhD in pharmacology, Bapela joined the Medical Research Council, specializing in African traditional medicine. By testing compounds derived from medicinal plants, he assesses their potential as therapies for malaria, tuberculosis, and HIV, the country’s most devastating diseases and the government’s highest priorities for research. With an estimated twenty-four thousand native plant species, the vast majority of which have never been studied, South Africa, says Bapela, may well be sitting on its own solutions.

“There are chemists with libraries and libraries of compounds from these plants that have never been tested,” he says—despite the fact that thousands of drugs have herbs as their base, including Artemisinin, the most advanced therapy available for malaria. Meanwhile, tuberculosis, once considered to be all but eradicated from the developed world, ravages the country’s poor (and especially the HIV-positive among them) as drug-resistant strains spread like wildfire through overcrowded shantytowns.

“There are some TB drugs in clinical trials,” adds Bapela, whose father was for years bedridden with the disease. “But the drugs that are available today were discovered more than thirty years ago. You have to take them for six to nine months. They taste terrible. And there’s been nothing new since.”

One reason for the glacial pace of TB drug discovery has to do with the nature of the organism itself. Whereas many bacteria can be cultured in a matter of days—providing chemists an assay, or a substance that imitates a biological system, in which to test their compounds for activity—Mycobacterium tuberculosis can take up to six weeks to grow in a laboratory. And because TB is a highly infectious airborne pathogen, experiments with the live organism should always be conducted in a biosafety level 3 facility, a rare commodity even by U.S. standards.

In the eight months since he arrived at Emory, Bapela has been working alongside Daniel Kalman and Melanie Sherman, both assistant professors of pathology, to address the problem by developing an assay for TB using its close relative Mycobacterium marinum. “The advantage with marinum is that it grows much faster,” Bapela explains. “And you can work with it on the table. You don’t have to worry about the aerosols.” If successful—that is, if an assay made of marinum were to behave similarly enough to an assay made of TB—the discovery could make it possible to test thousands of compounds against the disease in the time it currently takes to test dozens.

“TB work is very, very challenging,” says Liotta. “This could have a tremendous impact on the field.”

But for malaria, TB, and HIV, as well as the myriad other diseases that disproportionately affect the developing world, there is an underlying obstacle to drug discovery that science alone cannot overcome.

“Current estimates are $800 million to get a drug developed in the United States,” says Todd Sherer, associate vice president for Emory’s Office of Technology Transfer, the area responsible for taking Emory discoveries to the marketplace. A key player in the historic Emtriva agreement, Sherer knows as well as anyone what it takes to turn a laboratory breakthrough into a patented real-world therapy accessible to patients worldwide.

“Emory spends about $2 million a year on patent protection around its various inventions,” he says. “We then market those inventions. And we try to find an interested company, whether it’s a pharmaceutical company or a start-up, to develop that technology. So from beginning to end, it takes a huge amount of capital and a lot of talent.”

In business terms, a drug like Emtriva is worth the investment. As part of a combination therapy with an expected global market of nearly $1 billion in 2006, it promised to be a blockbuster for Gilead Sciences, the pharmaceutical company that won Emory’s auction with a staggering $540 million bid.

But home runs like Emtriva are few and far between. “Last year we received 165 new invention disclosures,” Sherer says. “That’s 165 pieces of paper where somebody wrote down, ‘We think we have a new invention here.’ But it’s a big-hit business. Very few of those will ever find their way to the marketplace.”

Speaking at the Rollins School of Public Health this spring, Liotta highlighted the impact research universities have had on drug discovery and noted some recent successes: Tamoxifen, the most widely prescribed breast cancer drug on the market today, discovered at Northwestern; Herceptin, another blockbuster therapy for breast cancer, out of UCLA; and Pemetrexed, a compound first approved for the treatment of asbestos-induced lung cancer, from Princeton.

The 1980 Bayh Dole Act, Liotta said, is the basis for all technology transfer that occurs at universities. “Prior to that,” Liotta said, “universities couldn’t own patents, and therefore they couldn’t sell their technology. So if something important was discovered at a university, there wasn’t anything that could be done with it easily.”

According to news reports, by the mid-1990s, two-thirds of the roughly three thousand drug compounds under development were engineered in biotech labs—either in universities or in small start-up companies, the latter having typically spun out of the former—and, on average, at half the cost of those discovered in pharmaceutical firms. “Big pharma has become a major development engine,” Liotta said, “but because of all the mergers and acquisitions, pharmaceutical companies tend to do very little discovery. And they aren’t so anxious to let people know that; it ruins their image. Academia has a bigger fingerprint than it’s being given credit for.”

Nevertheless, he said, drug discovery for the diseases of the developing world has fallen far short of global need. “We have poverty around the world,” he said. “We have poor health conditions, which lead to high morbidity and mortality. And we have inadequate medications, which lead to tremendous unmet medical needs. And if you think about it,” he added, “even the most sympathetic pharmaceutical company is never really going to be able to address this situation in an adequate fashion. They have an obligation to their shareholders. They’re nice people, and they’d like to do the right thing. But they’re a business, and they have to operate that way.”

What Liotta and his colleagues are proposing for South Africa is a paradigm shift—a bold move that would place critical intellectual resources in the hands of those who stand to benefit most. He envisions the growth of African companies that develop their own therapies for neglected third-world maladies such as TB, HIV, and malaria, staying profitable due to low operating costs and the ability to attract socially conscious investors.

“I believe that we can develop a new business model for companies on the ground in Africa,” he said. “They won’t make the Fortune 500, perhaps, but they’ll make a nice profit. And we want them to make a nice profit so that they can replicate.”

A couple of years ago, Liotta and colleagues started just such a company, a small biotechnology firm called iThemba Pharmaceuticals, in the suburbs of Johannesburg. (iThemba means “hope” in many African languages.) In addition to its own discoveries, iThemba plans to license from major pharmaceutical firms the promising drugs that were never developed because their financial potential was considered too low. “Our hope,” explained Liotta, “is that we can be a sort of broker that partners up big pharma with the right people in the developing world in order to bring those compounds forward through clinical trials.”

Earlier this year, the South African government awarded iThemba start-up capital to the tune of nearly $5 million, a strong show of support for what was, at the time, little more than an idea and an office. But if Cuba is any example, the rewards are well worth the risk. A homegrown biomedical industry would mean not only new medicines for millions of South Africans who need them, but thousands of new jobs as well.

“Part of the reason we started iThemba was to avoid a brain drain,” Liotta explained. “If we were going to train people, we didn’t want them to leave the country, we wanted to give them a viable opportunity within it.”

Steve Sencer, whose father, David Sencer, oversaw the eradication of smallpox as director of the CDC from 1966 to 1977, was recently tapped by Liotta to head up a complementary program at Emory that will train the visiting African scientists in the legal and business issues surrounding international drug discovery.

“The idea is that you really need all three of these components,” says Sencer, Emory’s deputy general counsel. “So when they return to South Africa, they’re not just more advanced in their understanding of the science, but they understand how that fits into raising money from venture capitalists, from foundations, as well as what you need to do to have the basic patent protection so that the work doesn’t go unprotected and so that it remains financially viable.”

What is certain, Sencer says, is that progress will depend on collaboration and trust with colleagues in South Africa—what Liotta has been working for years to build.

“Dennis’s belief, and I think a lot of people share it, is that the only people who are really going to put the energy and resources into finding drugs for these diseases are the people who are most affected by them,” says Sencer. “That means people in Africa and across the developing world.

“Dennis has had great success in his life,” he adds. “He only wants to be involved in something that is truly worthwhile.”

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