Professor Cone inspires biophysics and beyond

Richard Cone, a Hopkins professor in the Biophysics Department, is a man of many quirks. He would rather roll up his black jeans and risk arriving late to class on a bike than leisurely drive up in a car. Cone prepares for a class by scribbling notes on a sheet resembling an unfolded napkin, and rather than lecturing about the laws of thermodynamics and molecular binding, he explains nearly every biological phenomenon using the laws of diffusion. His white chinstrap beard appears a shadow for the smile that always adorns his face.

But under what the casual observer may see as a collection of quirks, lies an altruist. In his research, his teaching, and even in the way he gets to school every day, Cone tries to make positive strides on as large a scale as he can.

Cone carries with him a deep, personal motivation that drives his work, along with a unique set of skills that have allowed him to have a career as a scientist. But there was a time nearly 50 years ago that Cone, a high school student in St. Paul, Minnesota, only knew a few things: he was good at math, interested in science, and wanted to study physics in college. During his undergraduate career at the Massachusetts Institute of Technology and half of his graduate career at The University of Chicago, he did just that.

Yet when it came time to decide which research group to join, Cone found himself at a fork in the road. He looked up on the walls of the physics buildings, each filled with posters representing ten or even fifteen years of work in quantum electrodynamics or solid state matter culminating in an obtuse theory that would only affect or even be read by a miniscule portion of the population.

Finding himself uninterested in these pursuits, Cone teamed up with a professor to study photoreceptors in the eye, a more biology-related project than what was normally pursued in Chicago’s Physics Department. He was hired by the Hopkins Biophysics Department to study the same thing: rods and cones, the photoreceptors that together allow humans to see.

Armed with the new title “a Cone that studies rods,” bestowed by his new colleagues, and an ample set of skills he had developed while studying at Chicago, Cone began his own research project. He focused on rhodopsin, a pigment in photoreceptor cell membranes that initiates the perception of light in the eyes.

At the time, scientists believed that cell membranes, the protective outer layer of the cell, were solid and held membrane proteins like rhodopsin in place. The lab’s research showed that rhodopsin undergoes rotational diffusion, meaning that spins around and floats through the membrane. This result suggested that cell membranes were in fact fluid, resembling bubbles more than balloons.

Patrick Fleming, also a biophysicist at Hopkins, explained his reaction to Cone’s initial work: “I was interested in membrane diffusion in general and the fluidity of biological membranes, and his work was a beautiful example of applying clean thinking and simple tests to a controversial problem.”

Cone was also able to uncover the reason that humans can’t recognize polarized light while insects can. Skylight is weakly polarized and insects are able to see this effect while humans are not because of fundamental differences in their rhodopsin proteins. While human rhodopsin is constantly rotationally diffusing through the cell membrane, insects lock their rhodopsin into place, allowing their eyes to detect the angle of polarization with great sensitivity and thus determine the sun’s location even when only a small portion of sky is visible.

The photoreceptor research was a successful and well-funded project over a long period of time, but despite this, Cone still felt unfulfilled. Cone thought the work was a good introductory research project, but he wanted to study something that would have the chance to directly affect a wide range of people.

One of the scientists Cone looks up to most is Abel Wolman, a former Hopkins professor and pioneer in the field of sanitary engineering. Wolman mandated filtration of water supplies and worked to make tap water potable across the world. Cone admires Wolman’s accomplishment because of the way he was able to affect health and the quality of life for millions of people.

Cone set out to find a similar calling himself. “From physics you learn a lot about orders of magnitude or scale…How big is it? What’s the scale? How big a problem is it? So I started thinking about, well what are the really big problems out there?”

Cone’s inspiration, as it happened, came in the classroom. Teaching a large physiology class at Hopkins in the 1970s, Cone gave a series of lectures on all of the different systems of the body. During a lecture on the reproductive system, he found that students held misconceptions about contraceptives and sexual health.

At this time, birth control pills had recently been released and were taking over as the primary contraceptive. While the birth control pill represented a major hurdle in contraceptive advances, the public’s perception of it as a “miracle pill” was unrealistic; its effectiveness was overvalued and using it in place of condoms could lead to higher chances of passing along sexually transmitted diseases. By creating an improved alternative to birth control that also protected against STDs, Cone would decrease the spread of disease, while also slowing down the growth rate of the human population and subsequently human-caused problems

While continuing his research into photoreceptors, Cone began to seek out funding and students for his new project. He aimed to unify the efforts to prevent conception and the spread of STDs, by creating a more effective contraceptive that could fight both “sperm and germs.” The project struggled to get off the ground though. The NIH wanted to fund research into “contraceptive vaccines” that could temporarily make men infertile, while Cone’s primary interest was in creating a prevention-focused barrier method. He planned to utilize mucus, the viscous secretion that lines the interior of the vagina, as the protective barrier between the body and sperm or infection.

For nearly 20 years, Cone struggled to receive funding for this project from any source. He had to continue researching photoreceptors and leave contraceptives as a side project until 1992 when he claims, “The NIH discovered the vagina.” It was in 1992 that the NIH first hired a woman to head the departments responsible for funding STD and contraceptive research. They sent out invitations for research proposals targeting vaginal infections and barrier contraceptive technologies, and Cone sent them an extensive and successful proposal. Since then, he has been well-funded and has focused all of his labs’ resources on the project utilizing mucus as a contraceptive.

Now well into his new research project, Cone is using natural products of the body to stop sperm and germs in their tracks. When a couple is infertile, one of their bodies secretes anti-sperm antibodies, which trap sperm in the mucus. The human body also secretes anti-STD antibodies, which do the same with germs. By creating a method that lines the vagina with antibody-filled mucus, Cone hopes to create a brand new, marketable contraceptive.

“Having a motivation is what orders your curiosity and energizes you,” Cone said. The scientist has spent the majority of his professional life searching for his motivation, but if his jovial gait and attitude are any indication, he has found his passion. He has found it in his teaching, in his research, and in learning.

While his career has given him expert-level qualifications, he most enjoys taking on the attitude of a child. His favorite question to ask is “why?” Cone implores students to constantly question the status quo and go searching for answers the same way a child asks their mother “Why is the sky blue?” And while he has been in the field for 50 years, his effervescent smile shows that he has yet to stop wondering himself.