Washington State Magazine

Fall 2005

Fall 2005

In This Issue...


Where Have You Gone, Edward R. Murrow? :: Edward R. Murrow '30 broadcasted reports from a London rooftop during the Blitz. He confronted Joseph McCarthy on national television. And he admitted "an abiding fear regarding what...[radio and TV] are doing to our society, and our heritage."

{ WEB EXCLUSIVE—Interview: The Battle Against Ignorance : An Interview with Bob Edwards }

Diabetes: It's Still Up to You :: Although Mary Ellen Harvey '58 knew about her type 2 diabetes for nearly 20 years, she wasn't managing it very well on her own. That changed when she joined thousands of other diabetics across the country in a diabetes management trial.

{ WEB EXCLUSIVE—Recipe: Tortilla soup for diabetics }

How Coug Are You? :: Would you paint your airplane crimson and gray? Or drive hundreds of miles to wave the Cougar flag at a non-Coug game? Or keep a concrete cougar in your yard? Well, how Coug are you?

WSM Special Report :: Drinking on Campus

How WSU is helping to change the culture of alcohol

More Thinking, Less Drinking :: "Everybody knows this place as a party school," says a student about WSU. But what everyone knows is starting to change. by Hope Tinney

Our Drink :: Toren Volkmann and his mother, Chris Volkmann '70 have co-authored a book about their family's experience with Toren's alcoholism. What they learned through direct experience dovetails with what counselors and researchers are discovering at WSU and beyond. by Hope Tinney

Two chapters from Our Drink: Detoxing the Perfect Family, by Chris Volkmann '70 and Toren Volkmann. (PDF: Requires Adobe Acrobat Reader or another PDF reader.)


{ WEB EXCLUSIVE—Gallery: Bringing couture to campus: A gallery from the 22nd Annual Mom's Weekend Fashion Show }

{ WEB EXCLUSIVE—Gallery: If clothes could talk...but they do! What WSU students are wearing on campus. }


:: FOOD AND FORAGE: The spice of life

:: PERSPECTIVE: Thinking about Washington State

:: A SENSE OF PLACE: Bounty on the bluff

:: SEASONS|SPORTS: I never said thank you.

:: SEASONS|SPORTS: Legends of the Palouse

{ WEB EXCLUSIVE—Story and video: An affair of the heart :: In his documentary film, Legends of the Palouse, Jeff McQuarrie '98 seeks to answer the question, "What is this love affair we have with our school?" Includes an exclusive video excerpt of Junior Tupuola and Rod Retherford from the film. }


{ WEB EXCLUSIVE—Story: Elegy: May 18, 1980 :: In memory of a friend and the geologic event that marked her passing. by Bill Morelock '77 }

Cover: Edward R. Murrow '30. Photography from Manuscripts, Archives, and Special Collections.

'What we're trying to do is evolution in a test tube,' say molecular biologist Margaret Black (right), here with assistant Karina Villa-Romero.

'What we're trying to do is evolution in a test tube,' say molecular biologist Margaret Black (right), here with assistant Karina Villa-Romero. Shelly Hanks

Molecular Mata Hari

by | © Washington State University

Margaret Black designs weapons that make their targets self-destruct. She's not a military strategist or explosives expert, though, but a molecular biologist working to perfect a way to trick cancer cells into killing themselves.

Her approach is called suicide gene therapy. It works by a sneaky route that even a fabled spy like Mata Hari could appreciate. In conventional chemotherapy, the patient is given a drug that kills any cells in the body that are replicating their DNA. Suicide gene therapy works by infiltrating cancer cells and getting them to make the drug that will do them in.

Best of all, says Black, suicide gene therapy can minimize the nasty side effects commonly suffered by patients on chemotherapy.

A patient on suicide gene therapy receives two substances: a prodrug, which by itself has little effect; and a suicide gene that codes for an enzyme that converts the prodrug into a toxic form of the drug.

Black, who is an associate professor in the Department of Pharmaceutical Sciences, says most gene therapists are working on how to target cancer cells specifically, so the suicide gene doesn't end up in normal cells. Her research focuses on what happens once the gene and prodrug get into the cell. She's trying to make a form of the gene that is more deadly for cancer cells and that produces less spillover of toxin from cancer cells to normal cells.

She does that by making mutations in the natural form of the enzyme's gene and then screening for mutant enzymes that can work with just a tiny amount of prodrug.

"What we're trying to do is evolution in a test tube," says Black. "Evolution is generally something that happens one step at a time, one mutant at a time. What we're trying to do is make leaps at a time by introducing many mutations simultaneously."

One approach is to hit the gene with random mutations. That works, but it's inefficient. Black prefers to target areas of the gene she thinks might shift the enzyme's activity without destroying it altogether. Then she puts the mutant genes into bacterial cells and uses a two-step screening process to find the mutants that are most likely to succeed as suicide genes. First she identifies the mutants that still have a functional enzyme.

The second test is a bit tricky. The mutants she wants -those best able to turn the harmless prodrug into the deadly drug-will die during the test. Black keeps samples of each mutant alive and healthy in other containers until the test is completed. Those whose brethren die when fed the prodrug move on to more detailed analysis of their mutant enzyme.

The screening process looks reasonable on a diagram. Then you see the numbers she's dealing with. In one series of experiments, Black and her students screened more than a million mutants. They found two that were good candidates as therapeutic agents.

"It's a numbers game," she shrugs. "There's a point where you can go crazy doing this. My students will tell you that, because they're in the process of screening a lot."

In work recently reported in Science Magazine, Black and several colleagues at the Fred Hutchinson Cancer Research Center and the University of Washington described a new method to streamline the process. They used a special computer program to predict the effects of mutations at various points in the enzyme, and came up with a triple mutant that looked promising. Black is now testing the new weapon for its ability to kill cells from a rat brain tumor.

Black didn't start out as an espionage agent in the cancer wars. Her main interest has been the enzymes involved in DNA synthesis-how they work, and how their structure relates to their function. The cancer connection came about in 1992, when she read a paper describing the use of one of her subject enzymes as a suicide gene. "I immediately took my mutants and said, 'We can do better with these.' It totally shifted in two minutes what I was doing already. It was just a little bit of an extension, and it made a big difference."

Categories: Biological sciences | Tags: Cancer, Gene therapy

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