By MITZI BAKER

Eugene Butcher, MD, has just won a $500,000 prize that he didn’t even know he was nominated for. When the pathology professor answered his ringing phone last Tuesday – something he said he rarely does – a voice on the other end informed him that the Royal Swedish Academy of Sciences, the same group that delivers the Nobel Prize, had selected him to receive the Crafoord Prize.

“It was pretty amazing,” said Butcher, who also directs the serology and immunology section at the Veterans Affairs Palo Alto Health Care System. “I didn’t know much about this prize because it is not often given in medicine. I didn’t even know how to pronounce it; the man on the phone said it could be pronounced like ‘Crawford.’ In mathematics and astronomy, it’s a well -known award. My brother is an astronomer so he was excited about it.” He said he still has no idea who nominated him.

Eugene Butcher, shown in his office at the VA, has been named the co-winner of the $500,000 Crafoord Prize for his research on how white blood cells migrate to the locations where they are needed. Sweden's King Carl XVI Gustaf will present Butcher with the Crafoord Prize in Stockholm on Sept. 22. Photo: Mitzi Baker

Butcher received the prize for his immunology work and its application to understanding arthritis. He will split the prize with Harvard biologist Timothy Springer, PhD, who Butcher said has been following a parallel path to his own. They have sometimes collaborated and sometimes competed and even had a business together for a few years. The work that earned the duo the prize was “their studies of the molecular mechanisms involved in migration of white blood cells in health and disease,” according to the Crafoord Prize announcement.

The prize is earmarked for fields not covered by the Nobel Prize: mathematics, geoscience, astronomy and basic biosciences, especially ecology and evolution. One award is given annually, with the category changing each year. In addition to the main fields honored, every third year the prize can be given instead to recognize a finding in the field of arthritis that is advanced enough to suggest concrete medical applications. Although the prize was established more than 20 years ago, the only other time it has been given to researchers studying arthritis was in 2000.

Butcher studies the carefully choreographed series of events that direct the response of the white blood cells, the body’s immune defense team that responds to an injury or infection. The ability of immune cells to cross through the blood vessels is crucial to the launch of an effective attack.

On the other hand, having an overactive immune system, such as one seen in autoimmune diseases like rheumatoid arthritis, can cause tissue damage and illness, so understanding the migration patterns of white blood cells and the molecular interactions that lead them to their target could suggest techniques to halt the response.

Butcher identified molecules that selectively pull out the correct types of white blood cells that the body needs. There are about a dozen main white cell players and a hundred or so variations, each with its own special migratory program that determines when they go where.

Early on, he determined that one type of molecule called a selectin provided the initial interaction between the blood vessel wall and a white blood cell floating by in the blood. He later determined that this one signal was not enough to differentiate between all the various cells and went on to discover a series of molecular steps a cell had to take to be coaxed out of the blood.

His early findings are now considered classic. “The proposal was that this multi-step process is like a universal mechanism for providing the specificity of white blood cells migration from the blood. This has become kind of dogma now even though there are a lot of aspects of it that really haven’t been proven yet,” he said.

“It’s interesting when you propose something and then 10 years later it is so widely accepted that people don’t even think you need to test it any more. “

Butcher continues to look at the interplay of the different stages of trafficking, with an eye toward how to alter the signals. “I am interested in how the cells are programmed to traffic so we can start to manipulate the good and bad actors in the immune world to change the nature of the immune response for the better,” he said.

A direct offshoot of Butcher’s groundbreaking studies are some clinical trials now under way. These studies are attempting to block the overactive immune response of autoimmune conditions such as inflammatory bowel disease and multiple sclerosis by inhibiting recruitment of white blood cells.

“We’re hopeful that some of this stuff is going to lead to some real applications, although that’s not why we do it,” said Butcher. “We do it because it’s fun.”