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"It's difficult for many people to grasp just how dreadful this type of cancer is. It is cancer in the organ that makes us human," says John Henson, executive director of the Brain Tumor Center at Massachusetts General Hospital. "[Gliobastoma] tumors take the lives of patients in one year, on average. And despite very aggressive research efforts over 25 years . . . the improvement in median survival is about a couple months."
Michael E. Berens grew up in Phoenix, the son of a BNI surgeon. Berens says his father would take him along on house calls to visit recently discharged patients.
"I'd pick grapefruit in the trees and he'd pick out stitches," Berens says. "That was how I grew up."
After receiving degrees from Arizona State University and the University of Arizona, Berens completed his postdoctoral training in oncology at the University of Zurich. In 1990, he was working as a research biologist at the University of California-San Francisco when he was recruited by Barrow Neurological Institute, a division of St. Joseph's Hospital.
"I was sure that I was going to find some things that would make a difference," he says.
Not just any difference, a major difference. Most cancer studies prove our limitations, but Berens wanted to "swing for the fence," and he thought he knew how to do it.
Cancer researchers needed a large-animal model for studying the most deadly form of brain tumor, a gliobastoma. Berens had performed tumor studies in mice, but mouse brains are about a fifth the size of a thimble. Beagle brains are about the size of a small child's, and beagles have a high incidence of naturally occurring brain tumors. But how can you make an animal sprout a gliobastoma tumor on command?
The answer hit Berens while driving down a freeway: He could teach the animal's immune system to accept a tumor, then transplant it into its brain.
The way he figured it, a fetal animal's immune system is the same as its mother's. It accepts her system as its own. Berens thought if he injected cancer cells into a beagle early enough, the developing immune system would not fight the cancer and would allow it to grow -- thus becoming a perfect model for testing new therapies.
It was a clever idea, and Berens was optimistic. He arranged some private funding and, later, was awarded a grant from the National Institutes of Health. He ordered some pregnant beagles (at $2,000 each) from Marshal Farms in New York, a breeder of "purpose-bred animals." He also had a talk with his wife.
"I said, 'Patty, I have this idea, and it involves some animal research, and I'm sure that people will have a hard time with it.' And so she asked, 'Why us? Why can't somebody else do it?'"
There was a real cause for concern. Berens' grant manager at the National Institutes of Health, Dr. Tom Jacobs, says many researchers are reluctant to develop large-animal models. They worry about protesters and the increased level of peer-review scrutiny. One reason the NIH agreed to fund Berens in 1998, despite his history of trouble with this project, was the study's inherent technical and political difficulty -- and inherent promise.
"He's considered a pioneer by his peers and by us," says Jacobs. "He has taken on a formidable challenge of developing an animal model that, until this time, has been extremely difficult and has hampered our understanding of brain tumors."
From the start, there was another issue as well: Berens' protocol is undeniably grim. ASU says the study is at least three on the standardized one-to-four pain scale for animal research.
Though the pregnant dogs can be adopted out, their puppies are another matter.
The puppies that don't get cancer are euthanized.
The puppies that do get cancer are given large doses of chemotherapy and radiation -- then euthanized.
It is not fair to an adopting family, researchers say, if their pet later develops a brain tumor because of the fetal surgery. Also, once an animal is adopted, Berens is not allowed to examine it again. It is now a pet, and researchers, perhaps out of psychological necessity, draw a fine distinction between research animals and pets. To Berens, he is not killing Snoopy.
"Snoopy is a pet," Berens says. "It should be cuddled and loved and played with on the floor with rolled-up socks and those kinds of things. It's a very sensitive thing. Nobody in the United States for the past 15 years does research on pets. The decision was made decades ago that there is such a thing as a pet population and there's such a thing called a 'purpose-bred animal population.' Every animal that we've worked on has been a purpose-bred research animal. They were never bred for purposes of being Snoopy. Is that different? That's hugely different. We're not dealing with the emotionally charged issue of pets."
Less emotionally charged for Berens, perhaps, but certainly not for animal lovers. A dog is a dog. And a dog does not know why it was bred.
Yes, Berens himself has pets. A Shetland sheepdog, but no beagles.