After Kansas outbreak, UC Berkeley’s tuberculosis researchers stress research and preparedness

May 1, 2025
by Alexander Rony

Earlier this year, the United States experienced its largest tuberculosis outbreak in modern history. For a disease that had largely dropped off Americans’ radar, it was a disturbing reminder of how quickly epidemics can explode into the public consciousness. However, the 153 infections in Kansas were a drop in the bucket compared to the 10.8 million people who contracted the disease globally in 2023.

Tuberculosis is the world’s deadliest infectious disease, killing around 1.25 million people per year according to the World Health Organization. Science, nutrition, hygiene, and sanitation have sharply reduced the toll in most developed nations, yet UC Berkeley’s tuberculosis researchers warn against complacency.

A smiling man wearing glasses, a suit jacket, and a patterned shirt

Professor Jeffery Cox

“People think tuberculosis is cured,” said Jeffery Cox, a professor of molecular & cell biology. “The real problem is in lower to middle-income countries around the world. It's a disease of poverty. Even though we have the antibiotics and drugs to treat and in many cases cure tuberculosis, it continues to be a problem because of infrastructure, financial issues, and the nature of the disease.”

“It's a really hard organism to kill,” emphasized Cox.

As the federal government cuts international programs that combat tuberculosis, Cox predicts that avoidable deaths will increase and the fallout will eventually find its way back to the United States. Uncontained spread can allow pathogens to mutate, growing in severity and virality. Then, when the more powerful strain arrives in the U.S., it is much harder to control.

“These diseases do not respect borders and will come to us,” said Cox. “It's not only short-sighted from the global health point of view, it’s also fiscally irresponsible. Medications cost us hardly anything, but to others, they are phenomenally expensive. In the end, we're going to be spending more money, especially when you see what happened with SARS.”

Berkeley scientists seek answers

These diseases do not respect borders and will come to us.
Jeffery Cox

Cox’s lab aims to understand the basic mechanisms of how tuberculosis causes disease by studying the responsible bacteria, Mycobacterium tuberculosis. The pathogen is particularly insidious. Many people never eliminate their infection, leaving them with a lifelong risk of a deadly flare-up. The disease is difficult to diagnose, particularly in children, and can lead to long-term lung damage even after recovery.

While treatments exist, Cox stressed that they are quite cumbersome. Countries must maintain a substantial monitoring system that can trace outbreaks and reach contacts before they spread the disease. People who test positive can take antibiotics, but those take months — or even years if they have a drug-resistant version of the disease. So many people forget to take their medication or balk at the lengthy treatment time that public health agencies often send workers to patients’ homes to watch them take their medicine.

Headshot of Sarah Stanley, person with short dark hair wearing a dark shirt

Professor Sarah Stanley

Green, blue, black, and magenta shapes indicate biological markers. Magenta (indicating tuberculosis) covers a lot of the image.

An image of Mycobacterium tuberculosis (in magenta) in a lung 25 days after infection (Image credit: Ophelia V. Lee)

A black-and-white photo of a scientist in a lab coat looking at lab equipment

UC Berkeley Ph.D. alum Selman Waksman discovered streptomycin, the first antibiotic effective against tuberculosis. (World Telegram & Sun photo by Roger Higgins retrieved from the Library of Congress)

If we don't do a good job combating tuberculosis, we face the possibility of totally drug-resistant strains, and if those spread, then we are not safe.
Sarah Stanley
A man wearing a blue, buttoned shirt and glasses smiles toward the camera

Professor Russell Vance

Before COVID, tuberculosis was the biggest infectious disease killer of humans. After COVID, that's still true.
Russell Vance

Berkeley immunology professor Sarah Stanley hopes to improve this arduous treatment regime and prevent future infections by discovering how tuberculosis suppresses immune responses. She studies effective immune responses to tuberculosis so scientists can recreate those conditions through medical interventions.

“There are a lot of diseases where it's pretty easy to make a vaccine,” said Stanley. “Most of the COVID-19 vaccines worked fairly well to one degree or another. That's not true for tuberculosis; in fact, we don't even have a sense for how to make an effective vaccine.”

In countries where tuberculosis is more common, infants and small children may receive the Bacille Calmette-Guérin (BCG) vaccine to guard against severe tuberculosis meningitis. However, it doesn’t prevent active tuberculosis, it causes false positives on skin tests, its protection weakens over time, and its effectiveness against adult pulmonary tuberculosis varies. For these reasons, it is rarely administered in the United States.

“For many viruses, it's pretty easy to generate a protective response,” said Stanley. “All you need to do is generate an antibody that blocks its ability to enter cells. Then there are viruses like HIV, where it's hard to elicit an antibody, or diseases like tuberculosis, where antibody responses are not protective. We need a different type of immune response called cellular immunity, and we have no idea how to make vaccines that elicit robust cellular immunity.”

Russell Vance — another Berkeley immunology professor — tackles a similar challenge as Stanley from the opposite angle. He is trying to figure out why some individuals make the wrong immune response to Mycobacterium tuberculosis — fighting the bacterial infection as if it were a virus. His lab has shown that this inappropriate antiviral response can actually increase susceptibility to tuberculosis. Vance’s goal is to determine how to make more appropriate and effective immune responses to tuberculosis. He hopes that his lab’s insights into tuberculosis may also be relevant to other diseases, including cancer.

Cox, Stanley, and Vance perform fundamental (or basic) research to understand the underlying mechanisms that explain how things work. Basic research is a necessary first step toward real-world applications. Basic research led to CRISPR cures, carbon dating, and cancer immunotherapy — all Nobel Prize-winning discoveries with Berkeley connections. In fact, it was a Berkeley Ph.D. — Selman Waksman — who won a Nobel Prize for discovering streptomycin, the first antibiotic effective against tuberculosis.

“Anyone working on tuberculosis always has in the back of their mind the idea that something we discover about this disease could be helpful,” said Vance. “Even if we are not the ones to actually develop the drugs, we're still hoping that what we discover will be important for people who do drug development.”

Pharmaceutical companies conduct their own research, of course, but they focus on turning profits. They rarely do basic science, instead translating foundational knowledge into commercially viable medical treatments. Since tuberculosis mainly affects people living in developing nations, private companies deprioritize the disease. Entities like the Gates Foundation try to bridge the gap between academia and private industry, but researchers say investment is still insufficient for the need.

An alliance against infectious disease

Stanley also serves as faculty director for the Alliance for Global Health and Science. The program’s goal is to strengthen the public health research capacity of low- and middle-income countries. For instance, Stanley trains students and faculty at Uganda’s Makerere University to do independent research on tuberculosis and other diseases. The alliance team also helped Makerere University become a certified clinical diagnostic center, strengthening local capacity to test residents for COVID-19, Ebola virus, and tuberculosis.

“We're focused on East Africa because we believe that the way to a healthier planet is to empower people locally to work on the diseases that affect them,” said Stanley. “In the U.S., a 70-person tuberculosis outbreak is a big deal. Whereas, in Uganda, that's just one day in one town’s clinic.”

The Alliance’s mission is becoming more critical as the U.S. cuts global health programs, including those that deliver life-saving tuberculosis medicine.

“Part of the reason why it's important to invest in global health is because diseases travel,” said Stanley. “If we don't do a good job combating tuberculosis, we face the possibility of totally drug-resistant strains, and if those spread, then we are not safe.”

Funding changes fuel concern

Private donors support the Alliance for Global Health and Science’s entire budget, but affiliated faculty members’ labs depend on federal and state funding for their research.

Cox is Berkeley’s principal investigator on an NIH-funded Tuberculosis Research Advancement Center. Cox distributes small pilot grants through the program to encourage other researchers to work on tuberculosis projects. For instance, the funding enabled a test of chemistry professor Matt Francis’s encapsulation technology’s potential for a tuberculosis vaccine formulation.

“This is one of the things that NIH does really well,” said Cox. “They fund these kinds of activities that are hard to get funding for. The number one global funder of tuberculosis research, by far, is the NIH, and that's for fundamental research.”

Some federal programs, such as the SMART4TB research consortium, have been eliminated in the past few weeks. Even if the federal government continues to fund tuberculosis research, cuts to other health programs may prevent scientists from discovering the key that unlocks improved tuberculosis treatments or even vaccines. Many tuberculosis researchers investigate other diseases for clues. Cox’s lab, for instance, studies Mycobacterium avium, a close relative of Mycobacterium tuberculosis that is a growing public health concern. Vance works closely with cancer researchers through Berkeley’s Immunotherapeutics and Vaccine Research Initiative to determine whether they can apply new findings to different diseases.

Another fear is that a reduction in federal funding will threaten the operation of Berkeley’s critical labs. Infectious disease research requires considerable safeguards. The federal government classifies Mycobacterium tuberculosis as a Biosafety Level 3 organism, a designation for lethal and airborne pathogens that requires the second-highest level of lab security.

“Maintenance of these facilities is extremely challenging,” said Stanley. “We operate them at the highest standards, and that means they're expensive. We are constantly on the edge of these facilities failing and becoming unavailable to researchers because we don't have sufficient funds to keep them going.”

Vance agreed.

“These laboratories take years to build,” said Vance. “You can't just build them when there's an outbreak — so it's really important to maintain this infrastructure.”

Biosafety Level 3 facilities enabled UC Berkeley to quickly shift gears during the COVID-19 pandemic. Researchers were able to study the virus because these secure labs already existed. If those facilities are allowed to close, fewer resources will be available during future pandemics.

While the World Health Organization declared the end of the COVID-19 pandemic in May 2023, the tuberculosis epidemic continues to rage across much of the world. It’s a maddening constant for researchers who feel the disease is severely under-resourced, given its unacceptable toll.

“Before COVID, tuberculosis was the biggest infectious disease killer of humans,” said Vance. “After COVID, that's still true.”

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