As an assistant professor of biology at Harvard University, I taught physiology in an introductory biology course, Nat. Sci. 5, led by George Wald and pursued research on photoreceptors, the rods and cones of our eyes. In 1969, I chose to join the Biophysics Department at Johns Hopkins, where my research on the rapid diffusion of rhodopsin in photoreceptors led to the Cole award from the Biophysical Society.
In the 1970s, funded by an award from the National Science Foundation based on my undergraduate teaching, I turned my research toward developing methods for contraception that would also protect against sexually transmitted infections, including HIV and genital herpes infections. My colleagues and I developed a vaginal microbicide that had promise both as a contraceptive and a broad-spectrum microbicide for blocking sexually transmitted infection. It succeeded in its contraceptive trials but failed to protect against HIV -- a great disappointment!
My lab has been investigating the role of secreted antibodies for many years. More antibodies are secreted into mucus secretions than into the blood and lymph, but the mechanisms by which antibodies in mucus protect against infections has been little studied. My colleagues and I have now demonstrated that the major protection mechanism involves rapid diffusion of antibodies in mucus secretions, slowed only slightly by weak affinity bonds to the mucus gel. When antibodies accumulate on the surface of a pathogen, they make weak, but numerous, crosslinks to the gel that traps the pathogen in the mucus secretion, preventing the pathogen from reaching its target cells.
Over the past several years, my lab has focused on developing a probiotic method for helping more women to have healthy vaginal microbiota. Most women, worldwide, have polymicrobial vaginal microbiota that markedly increase risks of HIV, and all the other major sexually transmitted infections, as well as increasing risk of preterm births. My colleagues have shown that healthy vaginal lactobacilli can maintain monocultures that acidify the vagina with sufficient lactic acid to fend off all the polymicrobial species that can otherwise inhabit the vagina. The lactic acid also kills the bacteria associated with premature birth and upper tract infections. We have also shown that lactic acid at acidic pH potently inactivates HIV and HSV. So a probiotic approach that enables more women to have healthy vaginal lactobacilli is likely to have a major impact on women’s sexual and reproductive health.