Dr. Carl Nathan wins David and Beatrix Hamburg Award

(Press-News.org) Dr. Carl F. Nathan, the R.A. Rees Pritchett Professor of Microbiology at Weill Cornell Medicine, has been awarded the David and Beatrix Hamburg Award for Advances in Biomedical Research and Clinical Medicine by the National Academy of Medicine.

Established in 2004, the prestigious award honors innovative biomedical scientists who have advanced global health with an exceptional biomedical research discovery and translation that has fundamentally enriched the scientific community’s understanding of human biology and disease, leading to a significant reduction of disease burden and improvement in human health.

The award recognizes Dr. Nathan’s outstanding contributions that have advanced scientists’ understanding of the building blocks of innate immunity and how the immune system fights infectious diseases, including tuberculosis (TB), and cancer.  He will accept the Hamburg Award Oct. 19 during the National Academy of Medicine Annual Meeting. It includes a medal and $50,000. He plans to contribute part of the funds to BioBus, a program in Harlem that engages schoolchildren in science.

“It’s a distinctive honor to know that a community of physicians who advance the practice of medicine to an exceptional degree find value in what my colleagues and I have contributed to the fields of immunology and microbiology over 50 years,” said Dr. Nathan, who chaired the Department of Microbiology and Immunology from 1998 until last July and is currently senior science advisor to Dr. Robert A. Harrington, the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine.

Dr. Nathan began his research career as a medical student at Harvard University. That time, in 1969-1971, marked the beginning of a transformative era in immunology, when many of the fundamental principles and components of the immune system that society now takes for granted, were discovered. A type of white blood cell in the immune system, called lymphocytes, had only recently been identified to protect people from infection by secreting one product: an antibody.

In pursuit of the question, “How does a living cell kill another living cell?” Dr. Nathan’s research contributed to the discovery that lymphocytes also released a glycoprotein called macrophage-activating factor (MAF), which made macrophages, another type of white blood cell in the immune system’s arsenal, better equipped to kill bacteria and sometimes tumor cells. “The fact that lymphocytes also released something that wasn’t an antibody was a shock,” he said.

After completing an NIH oncology fellowship at Yale University and earning oncology board certification, Dr. Nathan started his first laboratory in 1977 at The Rockefeller University, returning to his glycoprotein research. Dr. Nathan’s discovery that MAF was interferon-gamma (IFN-y), which can drive macrophages to eliminate infected or abnormal cells, provided researchers with a new approach to treating some previously intractable diseases. It also begged the question: What happens if you don’t have IFN-y? “This is where it became clear that susceptibility to TB was high on the list,” he said.

Dr. Nathan’s continued quest focusing on the immune system’s killing machinery also led to defining the role of reactive oxygen intermediates and nitric oxide in enabling macrophages and neutrophils to kill more effectively. Other major milestones include the discovery that the bacterium that causes TB, Mycobacterium tuberculosis (Mtb), contained a proteasome, a complex structure whose protein degradation function is essential for Mtb’s survival during infection in mice. At the time, this was an unexpected finding since bacteria were not known to have proteasomes.

“To find a bacterium that has a proteasome was totally off the charts,” Dr. Nathan said. This finding led to discovery of inhibitors of the Mtb proteasome that kill Mtb. This showed for the first time that interfering with protein breakdown, not just protein synthesis, can kill bacteria and that it is possible to develop proteasome inhibitors for pathogens that spare proteasomes of their human hosts. That finding led to the investigation of pathogen-selective proteasome inhibitors for malaria, Leishmania and a parasitic disease in Africa called “sleeping sickness.” Other highlights of his career include chairing the Open Lab Foundation that works with drug company GSK in Tres Cantos, Spain; working closely with the Bill & Melinda Gates Foundation’s TB Drug Accelerator program; and serving as principal investigator of the NIH-funded Tri-Institutional TB Research Unit. Dr. Nathan was elected to the National Academy of Medicine in 1998 and to the National Academy of Sciences in 2011.

“There is enormous joy in science by following unexpected findings where they point, even if you weren’t pointed that way when you set out on your walk,” Dr. Nathan said. He is most grateful for the people he has worked with over the years, especially students and postdoctoral researchers. “Each person who comes to the lab brings a different way of working and looking at things. You can’t make this kind of progress without listening to them and adding their own walks to the journey,” he said.

Dr. Nathan’s lab is continuing to pursue the study of pathways in host and pathogen that control susceptibility and resistance to TB. “It’s the single leading cause of death worldwide from an infectious disease, except when there’s an emerging viral pandemic,” Dr. Nathan said. “Now, TB is back in front of COVID-19 . It’s what I call a standing pandemic.”

END