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In the Company of Excellence
The Making of a Lasker Award Winner

By Christina Stile

On the Front Page...

If you want to learn a new language, some people suggest you spend time in a country where people speak only that language. For instance, living in Germany will help you learn German. But can you apply this same theory to other concepts? If you surround yourself with scientists, for example, are you more likely to learn concepts of science?

Continued...

You might think so if you examined the life of NIH-supported researcher Bertil Hille, who received the 1999 Albert Lasker Award in Basic Medical Research. He has spent his life surrounded by a virtual Who's Who list of scientists that put him on a direct course for scientific excellence. The Lasker award not only commends Hille's extraordinary cellular research, but also honors him as an equal to the great scientists who have long been his mentors.

As a child, Hille's home was alive with science, logic and language. His father, a well-known Yale University mathematician, and mother, the "intellectual wife of a faculty member," entertained an impressive list of intellectuals, including Lars Onsager, winner of the 1968 Nobel Prize in Chemistry, and Edgar J. Boell, a renowned Yale zoologist and embryologist. It seemed only natural, then, for 16-year-old Hille to work in the lab of his family friend Boell, who was then chairman of the zoology department.

1999 Lasker Award winner and NIH grantee Bertil Hille

"Working with [Boell] was like a first-love experience, where everything is fresh and wonderful," Hille said. "He introduced me to science and to research. My involvement with him was certainly a defining moment."

Boell taught Hille the essentials of studying science, like the fun of discovery and respect for the work of others. Hille remained with Boell until 1962, when he graduated from Yale with a zoology degree. Working with Boell stirred Hille's interest in studying cell membranes, the fence-like barriers that determine the boundaries of a cell. At the time, aside from their existence, little else was known about cell membranes. Scientists could only guess at how things moved from one side of a membrane to the other. Membrane permeability would become key to Hille's research career.

Hille continued his graduate studies at Rockefeller University in New York, where he enjoyed the same connection to intellectuals. He met classmates Harvey Lodish, now at MIT's Whitehead Institute for Biomedical Research; David Sabatini, currently chair of the department of cell biology at NYU Medical College; and David Hirsch, now chair of the biochemistry and molecular biophysics department at Columbia University during his first week at Rockefeller. The four became fast and close friends. They shared classes with the likes of: Chuck Stevens, now with the Salk Institute for Biological Studies; Alan Finkelstein, presently at Albert Einstein College of Medicine; and David Baltimore, currently president of California Institute of Technology and winner of the 1975 Nobel Prize for his discovery of reverse transcriptase.

As a graduate fellow, Hille tried to answer the question of how things, specifically ions, move through cell membranes. Ions are molecules that have either gained or lost electrons, giving them an electric charge. Hille found that the cell membranes had pore-like spaces in them, which he called "channels," that allowed ions to pass through. For its day, Hille's discovery was revolutionary. The theory at that time was that any ion could pass through a membrane at any point. Clay Armstrong, who would eventually share the Lasker award and other honors with Hille, was one of the only other researchers at that time to embrace the idea of ion channels. In fact, Hille and Armstrong were among the first to use the word "channel" to describe the pores in the cell membrane. The two were considered "rebels" in the research community.

"We've been interacting since we started in the 1960's," Hille said of his relationship with Armstrong. "It's been wonderful to have a 'sparring partner.' We agreed with each other and didn't try to save our secrets because there were so few of us. We shared as much as we could, which made it enjoyable."

After receiving his Ph.D. in life sciences from Rockefeller in 1967, Hille traveled to the U.K. to do postdoctoral work at Cambridge University. He continued ion channel studies under Sir Alan Hodgkin, who won the 1963 Nobel Prize in Medicine or Physiology for his work with ionic mechanisms and membrane transport. Hille calls Hodgkin "a demanding postdoctoral advisor.

"I was a little afraid of him," Hille admitted, "because by that time he was famous."

In 1968, Hille moved back to the U.S. and accepted a position at the University of Washington School of Medicine. He has been a professor in the department of physiology and biophysics there since 1974. During his first few years there, Hille made another breakthrough when he found that the size of an ion channel was specific to the type of ion the channel allowed to pass through.

Throughout the last 30 years, Hille has made great strides in understanding more about how ion channels behave. His work with blocking agents, materials that prevent nerve impulses from reaching their intended nerve cells, provided a basis for further study in anesthesia. His work also led to a greater understanding of how certain drugs function in the heart to regulate an irregular heart beat, a condition called arrhythmia. In 1984, Hille published Ionic Channels of Excitable Membranes, a standard text for students in biology, physiology, chemistry and biochemistry.

Hille's research focus has also shifted to include ion channel regulation mechanisms. At the suggestion of Robert Steiner, Hille joined the Specialized Cooperative Center in Reproductive Research at UW. Under the directorship of Dr. William Bremner, Hille has been studying the mechanism of action of gonadotropin releasing hormone (GnRH) on a pituitary cell that allows the pituitary glands to "talk" to the gonads, the sex glands. More specifically, GnRH tells the pituitary cells to release other hormones that are essential to the production of eggs, sperm and sex hormones. His task was to determine how the GnRH makes the pituitary release these other hormones.

More recently, Hille's work has addressed questions of male contraception. Since the invention of the condom 200 years ago, Hille said little research has been done on options for male reproductive activity and fertility. He indicates that one approach to male contraception focuses on regulating hormone secretion by altering ion channels on the pituitary gland, which can stop the production of sperm. Another approach, and an additional area of study for Hille, uses ion channels on the sperm themselves to influence the fertility of the sperm.

"I view population as a serious issue for our planet," he explained. "As a basic scientist, it was important to me to find out what options there were for people in terms of reproductive choice. My decision to join the [Specialized Cooperative Center in Reproductive Research] was more of a philosophical choice for me than a scientific choice and I will stick with it for that reason."

October 1999 proved to be an eventful month for Hille. The Lasker award panel, made up of internationally renowned scientists, honored Hille, Clay Armstrong, and Roderick MacKinnon for their remarkable work in clarifying the functional and structural architecture of ion channel proteins. After decades of anonymity, Hille and Armstrong were finally recognized for their discoveries about ion channels in the 1960's.

"The remarkable thing about getting the award is that at one time no one cared about it," Hille said. "In 1964, there were only 10 papers about ion channels; now there are over 5,000 new ones every year. I guess it's 'made it' in terms of being recognized. It's very fulfilling."

Despite his remarkable accomplishments, Hille remains unassuming. When asked if he felt that he, too, had "made it" by winning the Lasker award, his answer was simple.

"I would much rather recognize the accomplishments of others and encourage them than blow my own horn," he said.

Hille is currently on sabbatical from his professorship at UW to finish the third edition of his Ion Channels textbook. He likes teaching and plans to continue "as long as it goes well." With Mt. Rainier practically in his backyard, Hille and his wife enjoy hiking and the outdoors.

"It's actually been rather fun to have new techniques brought in every few years. We get to try something new. The basic question is the same, but the techniques change," he noted. "I am very lucky to get paid for something I love to do."


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