A Paradox and Alan Rein: Distinguished Retrovirologist Retires from the HIV DRP

A mutated, cancer-causing protein twisted and bent across the computer screen. As Ruth Nussinov, Ph.D., and her team watched the simulation, two things quickly became evident. First, it was clear how the mutation paved the way for cancers to form. Second, the twisting and bending created a pocket—a gap in the protein’s proverbial armor—no one had seen before. Nussinov’s team at Frederick National Laboratory for Cancer Research has illuminated through computational simulations how mutated versions of that protein, mTOR, contribute to cancer at a molecular level.

Imagine you’re building a dresser. You find all the wood and hardware you need and have the instructions, the right tools, and a team of professionals to help. As you and your team put it together, you realize that while the frame is solid, the drawers don’t open and close correctly. You might be tempted to feel discouraged by the results. But a group of scientists from the National Cancer Institute (NCI), Frederick National Laboratory for Cancer Research (FNL), and other collaborating institutions share a different perspective in their recent work published in PNAS. They weren’t trying to assemble furniture but rather generate a new, better mouse model of the most common kidney cancer, clear cell renal cell carcinoma (ccRCC).

In 1953, a teenaged Alan Rein read about what James Watson and Francis Crick famously called “the secret of life”—the double-helix structure of DNA, which had just been published in Nature. Captivated, Rein decided at that moment that he wanted to be a biochemist. Rein’s biochemistry aspirations shifted to virology during college, leading him to a 60-year career in the field, the last 45 years of which were spent at NCI Frederick, studying how retroviruses like murine leukemia virus and HIV assemble themselves and infect host cells while somehow evading the immune response.

There’s a small, fenced enclosure a stone’s throw from NCI Frederick’s pavilion, just across the street from Building 538. Drawing near to it, you’d see two layers of fence encircling a sapling. If you’re botanically inclined, you might recognize the sharp, five-lobed leaves marking the tree as a Liquidambar styraciflua, a sweetgum—a common species in Maryland. You could be forgiven, then, if you’d think the fences are overkill. Yet this sweetgum is particularly worth protecting.

Researchers from around the world met in October to mark progress their field has made in developing drugs to treat cancers driven by the RAS oncogene, and to map out even more ways they can help cancer patients. “This is a great story about tackling an intractable disease that was said to be an impossible task,” said National Cancer Institute Director W. Kimryn Rathmell, M.D.