Sam Miller: Focusing on bacteria's survival strategies

Sam Miller Photo by Jordan Rehm

With an extensive background working with patients, as well as in basic science research, Dr. Sam Miller is trying to learn a few of the tricks disease-causing bacteria use to survive and prosper, so that humans have a better chance of staying one step ahead.

“It's clear now that, in spite of our discovery of antibiotics, infectious disease is not going away,” Miller says. “The discovery of penicillin was in some ways a lucky break for medicine. Now, as organisms become resistant to antibiotics, I think we need to rely on a better understanding of how bacteria function so that we can design the next generation of antibiotics.”

Miller, associate professor of medicine and microbiology, received the 1997 Squibb Award from the Infectious Disease Society of America for his outstanding contributions to understanding infectious diseases. The award is given every year to someone under the age of 45. In previous years, both Dr. King K. Holmes, professor of medicine and head of the Center for Research on AIDS and STD, and Dr. Walter Stamm, head of the Department of Medicine's Division of Allergy and Infectious Disease, have won the award.

Miller's research has focused on the Salmonella genus of bacteria. Many of these cause the familiar diarrheal illness, but others are far more lethal. Salmonella typhi causes typhoid fever, now rare in the United States but still common in other parts of the world.

While he was at Harvard before moving to the UW in 1995, Miller developed a new salmonella vaccine for typhoid fever based on eliminating virulence factors from the bacteria. In human trials, the vaccine has now been proved effective and safe.

He is now engaged in work to develop salmonella vaccines that will induce immunity to other diseases, such as cholera. Better vaccines against bacterial diseases, and multi-valent vaccines to protect against many diseases at once, are at least as important as new antibiotics in the struggle with disease.

Miller's progress in understanding how to counter bacteria has come from a sustained focus on the interactions between bacteria and host at the molecular level. Exactly what elements make some related bacteria lethal and others benign? How do bacteria change their surface proteins in contact with a host tissue and how does the host respond? How can the bacteria's virulence genes be mutated to make an effective vaccine?

One of the reasons Miller found the UW an attractive place to work, he said, was the collaborative opportunities here. For example, Dr. Maynard Olson's laboratory in the Department of Molecular Biotechnology has recently completed sequencing of the entire genome of the bacteria Pseudomonas, a boon to other bacteria researchers.

Miller earned his bachelor's degree at Johns Hopkins University in Baltimore and his M.D. from Baylor College of Medicine in Houston. After a year as a research fellow at Baylor, he took up an internship and residency in internal medicine at Massachusetts General Hospital (MGH) in Boston. He was also a clinical and research fellow in the Infectious Disease Unit at MGH, a research fellow in tropical public health at Harvard School of Public Health, and a fellow of the Medical Foundation at Harvard Medical School.

He joined the Harvard faculty in 1986 and became an associate professor of medicine in microbiology and molecular genetics before moving to the UW.

His extensive clinical experience and knowledge of worldwide health threats drive his research into better prevention and treatment for bacterial diseases. While he is now a consulting physician at UW Medical Center, his primary focus is his research laboratory and training graduate students and postdoctoral fellows.

“By the time I moved to Seattle,” Miller said, “I realized that it's just not possible to be both an active clinician and an active basic science researcher at the same time—especially if you want to have a personal life, too. For now, I'm concentrating on the basic science.”

Miller has received numerous other honors, including a National Research Service Award from the National Institutes of Health, a Rockefeller Foundation scholarship and a Physician Scientist Award from NIH. He has been a member of several NIH and Food and Drug Administration panels and in 1996 chaired the NIH Special Study Section on Host Susceptibility to Bacterial Infection.

He has written several book chapters on infectious disease and Salmonella, and since 1996 has been associate editor of the Journal of Infectious Disease. ¶
Claire Dietz