Pursuing Premier Public Health

Georgia’s research universities are on the forefront of breakthroughs to improve treatments and reduce barriers to healthcare.
Georgia Trend November 2022 Research Univ Plemper Cover p20
Advancing Better Drugs: Richard Plemper, director of Georgia State University’s Center for Translational Antiviral Research Photo: Ben Rollins

COVID showed us just how vulnerable we are to emerging infectious diseases – not to mention health inequities and underlying conditions that made infected people sicker. But the pandemic also showed us how collaboration could fuel a quick and innovative response. That could be an area where Georgia leads in the future.

As the home of prominent research universities, medical schools and the Centers for Disease Control and Prevention, the state is uniquely positioned to be a leader in public health – not just for the U.S. but around the world. Bolstered by the Georgia Research Alliance (GRA), whose mission is to bring government, business and academia together to expand and further university research, the state is able to recruit the scientists who are making breakthroughs in major health issues. These include forecasting the next pandemic, developing new antibiotics and tackling chronic health problems like high blood pressure, among many other efforts.

“If you look at the GRA’s focus in this area, over 70% of our investments are in some way related to human and animal health,” says Susan Shows, president of the GRA. “And the startup companies we are grooming out of the venture development program [have similar numbers]. Our universities, via the intellectual capital and the physical infrastructure, are just wired to create intellectual property and discoveries, and to improve therapies and treatments.”

Meanwhile, organizations and health leaders are working to reduce the barriers to healthcare, so everyone can benefit more equally from these new discoveries. In Georgia, making public health paramount is good for everyone.

Better Pandemic Response

John Drake, Regents’ Professor in the Odum School of Ecology and founding director of the Center for the Ecology of Infectious Diseases at the University of Georgia (UGA), calls it “infectious-disease intelligence” – models that can provide real-time information and interpretation of outbreaks anywhere in the world, similar to the way meteorologists use models of atmospheric conditions to predict the weather.

With a $1 million grant from the National Science Foundation (NSF), Drake’s team at UGA is developing algorithms to forecast epidemics – taking information from lots of disparate sources and developing a coherent picture of what’s going on amid the chaos of an outbreak that should help us respond better, he says. And beyond that, the team aims to provide tools for making crucial decisions by showing what would happen, for example, if restaurants and bars were closed to prevent a virus from spreading – or if they were kept open. “We develop therapeutics, diagnostics and vaccines and we distribute them well … we’d like to be able to estimate that effectiveness,” Drake says.

With the NSF grant, Drake’s team has 18 months to work on six “demonstration projects,” ranging from creating a reasoning engine – a type of artificial intelligence that can infer consequences from a set of facts – to producing an explainable AI model for infectious disease (“explainable” means the AI can explain to humans why it made certain predictions).

Another project is in an area Drake has studied for a long time: tipping points in epidemics. But while the usual tipping points he and other experts consider are things like the point at which vaccine hesitancy increases transmission of childhood diseases, this project will model social tipping points. “We saw in COVID-19 how influential certain thought leaders were,” says Drake. “Our project is to develop a new model that looks at the transmission of opinions and how that can be sensitive to public policies. … I don’t believe any of this theory has been developed before.”

One of the issues with creating predictive models for different uses is that they “don’t talk to each other very well,” he says. That’s a weakness when addressing pandemics. So Drake also aims to bring all the projects together using an engineering paradigm called systems of systems. “We need a way to integrate across different models, from private individuals to households to communities to the country to the world,” he says. If the team succeeds, the next step would be a bigger project to show how this approach could be deployed in real-time.

Drug Discovery Dream Team

Scientists are sure of one thing: The next pandemic is coming. And although we don’t know where it will come from or what it will be, Richard Plemper, director of Georgia State University’s Center for Translational Antiviral Research, believes we will be ready with treatments.

That treatment may well come from the Antiviral Countermeasures Development Center – AC/DC for short – at Emory University and Georgia State. Plemper is co-directing the AC/DC alongside his collaborator for more than a decade, George Painter, CEO of the Drug Innovation Ventures at Emory (DRIVE) and executive director of the Emory Institute for Drug Development. Their history of working together on antiviral drugs includes developing molnupiravir, one of the first antiviral pills used to treat COVID.

Funded with a $52 million, three-year grant from the National Institute of Allergy and Infectious Diseases, the AC/DC is one of nine Antiviral Drug Discovery (AViDD) Centers around the country. With the established partnership between Emory and Georgia State – “and specifically between George’s lab and my lab,” says Plemper – as the nucleus for the new center, the co-directors set about assembling a national team of experts to find new antiviral drugs. “Drug development takes a village,” says Plemper. “AC/DC is truly a nationwide center, so we have collaborators from New York to Texas to Colorado to Seattle.”

This dream team, as Plemper calls it, will join the other AViDD centers in building a pipeline of drugs that target SARS-CoV-2, the virus that causes COVID, as well as other viruses that could set off the next pandemic. Plemper himself is directing one project aimed at advancing better drugs that inhibit coronaviruses like the one that causes COVID. “We need more weapons in our arsenal to really leave this pandemic behind,” he says.

They’re looking for drugs that can work against families of viruses and that people can take at home, in pill form. “We have to have broad-spectrum drugs to be sure we have something, even if the next challenge comes from an unforeseen corner, that is still able to control it,” Plemper says. “We have to have drugs on the shelf, ready to use.”

The nine AViDD centers will drive the antiviral drug development pipeline over the next decade, Plemper believes. “I’m very confident these centers will deliver,” he says, noting that they’re designed to try different approaches. “There is enormous breadth. That is our best hope to truly improve pandemic preparedness.”

The Social Lives of Bacteria

Usually, compounds that might one day be drugs are first evaluated in test tubes. When it comes to antibiotics, though, the problem is that bacteria don’t always act the same in test tubes as they do in bodies.

With antibiotic resistance growing, there’s a real need for new drugs. At Georgia Tech, where he holds the Bennie H. and Nelson D. Abell chair in molecular and cellular biology, Marvin Whiteley believes his research into how bacteria react to each other and their environment – their social behaviors – can point the way to new treatments. The Georgia Research Alliance Eminent Scholar says it turns out that bacteria are highly social organisms.

“A lot of microbes are not really disease-causing unless they’re in the proper community context,” Whiteley says. “They don’t really cause a significant infection unless there are other microbes there that they sense and start to interact with.”

After studying this behavior in the lab at the University of Texas in Austin, Whiteley was drawn to Georgia Tech because of a partnership with Emory that would allow him to see how it worked in humans. “[With] some of the bacteria we work on, their susceptibility to antibiotics is totally dictated by the environment,” he says. Grown in one condition, they are extremely vulnerable to a particular antibiotic; grown in another, the same antibiotic doesn’t work very well. “So the question really becomes, what’s it like to live in humans?” Whiteley says.

His research should help in the search for new therapeutics in two ways: First, his team has developed test-tube models that are very “humanlike,” as he describes them, which allows for better testing of potential new antibiotics. And second, understanding bacteria’s social behaviors in humans may help researchers interrupt those behaviors. “Can you make [bacteria] not know who’s there – or make them not able to perceive the environment around them?” is the way Whiteley puts it.

“People think bacteria are bags of enzymes, so they think, I’m just going to find something that kills them,” he says. “But they are these social and intricate organisms that change their behavior very quickly based on the environment. And these changes can have tremendous impacts on whether they live or die with antimicrobials.”

Whiteley’s decades-long research in cystic fibrosis – he is co-director of the Emory + Children’s CF Center of Excellence – is focused on a bacterium that persists in the lungs of people with CF and can lead to a faster decline in lung function. Why do these germs remain even after treatment with antibiotics? Whiteley’s team is trying to answer that question from a variety of approaches; one is by developing test-tube models that mimic the lungs of a person with CF.

Being able to work at a “top-flight engineering school” while partnering with a “top-flight medical school” at Emory is what drew Whiteley to Georgia. “It’s a terrific partnership that doesn’t exist in a lot of places,” he says.

Studying Salt’s Effects

High blood pressure, or hypertension, is called the silent killer because it doesn’t usually have symptoms. But it can trigger stroke and heart disease, the leading cause of death for men and women in the U.S. and especially in the South, where hypertension is particularly prevalent from Texas to the Carolinas, says David Mattson, a GRA Eminent Scholar and chair of the physiology department at the Medical College of Georgia (MCG) at Augusta University.

Mattson studies salt-sensitive hypertension, which can be more difficult to treat and to live with than “typical” high blood pressure. People with hypertension that is made worse by a high-salt diet (which most Americans eat) are more likely to have heart attacks and strokes, as well as organ damage like kidney failure. Doctors aren’t sure how many people fit this category, but it could account for anywhere from one-third to two-thirds of cases of high blood pressure – so it’s a big public health problem. And it tends to affect African Americans more than people of European ancestry.

Mattson’s team is investigating a complicated relationship between food, bacteria in the gut, the immune system, the kidneys and hypertension. In some people, a high-salt diet can cause their kidneys to have trouble filtering out fluid, which builds up and increases blood pressure. In animal experiments, Mattson’s team has found that the kidneys of rats with salt-sensitive hypertension are filled with immune cells “doing all kinds of things that are deleterious,” he says. The resulting inflammation makes high blood pressure worse and can cause kidney failure.

But it doesn’t stop – or start – with the kidneys. “It turns out there’s a relationship between the food we eat and this activation of the immune cells [because] the food we eat actually changes the bacteria – we call them the microbiome – that live in our gut,” Mattson says. The bacteria release molecules (called metabolites) that affect the immune system. Thanks to an unintended consequence of switching rats to a cheaper diet, Mattson and his colleagues discovered that changing the kind of protein they ate changed the bacteria and metabolites, which made the rats less salt-sensitive.

In working with clinical researchers at MCG, Mattson’s team is finding that the same changes in gut bacteria that are linked to hypertension in rats are also present in humans. “Maybe there’s something we can develop where you could take a pill or a supplement – or change your diet – that would simply cure it or at least [reduce] the deleterious effects,” he says.

Addressing Health Equity

Health equity is key to fighting any pandemic, because the population is only as protected as its most vulnerable members. With its concentration of public health organizations and research efforts, Atlanta has the opportunity to address some of the most challenging questions about access to vaccines and treatments.

Improving health outcomes for everyone is at the heart of the Center for Global Health and Innovation (CGHI), a nonprofit working to foster collaboration across the global health, health technology and life sciences areas. “We’re really here to help accelerate innovation opportunities [around] global health problems,” says Maria Thacker-Goethe, CEO of CGHI and president of Georgia Bio. “Big problems can’t be solved alone and our public health partners and community organizations on the ground … are really good at identifying problems and knowing what communities are dealing with on a day-to-day basis.”

The center, launched in 2020 as the COVID pandemic was beginning, is developing a health innovation hub in Midtown, with a 200,000-square-foot innovation center, collaborative office and wet-lab space, plus conference space. “Our mission is all about advancing global health equity by promoting and facilitating collaboration to drive impactful innovation,” Thacker-Goethe says. The new space is designed to do just that. She says it’s the first to “intentionally place global health entities next to private sector partners in life sciences and digital health [to] allow for that necessary cooperation and intentional as well as accidental partnerships.”

In addition to its role in bringing other organizations together, CGHI also administers some programs. Its Vaccine Access and Training (VAT) initiative, funded by a $9.8 million federal grant, has deployed community health workers in seven states to build trust in COVID vaccines among underserved communities.

Stephanie Adams, managing director for health equity and crisis coordination at CGHI, says the VAT program has hired 115 community health workers who have reached more than 200,000 people. “It’s one-on-one outreach,” she says, noting that workers connect with people at everything from football games to church to community group meetings. That’s the kind of approach needed to build trust in vaccines – and in a larger sense, in public health itself, she says.

“I think we even have some high school young people [working as community health workers] who really just want to do good and help their neighbors and the communities they live in,” Thacker-Goethe says. “As organizations and policy leaders and private sector leaders, we need to be willing to trust and empower them to do that because they are the strongest messengers.”

The goal of the Satcher Health Leadership Institute (SHLI) at Morehouse School of Medicine is to advance health equity, and its health equity tracker, launched in the midst of the pandemic, immediately became a valuable tool for researchers, public policymakers and citizens. It tracks COVID-19 data across race and ethnicity, sex and age, by state and county. It also tracks behavioral health issues and chronic conditions including COPD and diabetes, along with social and political determinants of health such as uninsured and poverty rates. And in August, SHLI partnered with pharmaceutical company Gilead Sciences and Xavier University of Louisiana on a project to improve testing, care and treatment for people living with HIV in Black communities.

Funded by Gilead over three years, the project will address inequities in care through a focus on three areas, according to Maisha Standifer, director of health policy at SHLI. Those include gaps in the continuum of care to identify “what’s missing, what are some barriers?” Standifer says. “What are some challenges, particularly in the South … we’re really looking at the stigma in the Southern rural population as well.” The project will include training for community stakeholders and clinicians in providing culturally appropriate care and reducing stigma. The other areas are policy issues and data equity and analysis.

It’s a badly needed project, says Standifer, who notes that there is a much higher rate of HIV among the Black population than the White population. In 2019, Black Georgians were more than eight times more likely to be diagnosed with HIV than White Georgians.

Reducing and eliminating those disparities is why SHLI was founded – “to make sure we are training and educating and employing all we can in public health to eliminate health disparities and to promote health equity,” Standifer says. With a growing number of public health organizations, Georgia may be an ideal place to make progress.

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