Students Expand the Frontiers of Medicine

by Bonnie Gelbwasser & Ruth Trask

"Flashes of Light" Help Breed a New Business

Stem cells are Morey Kraus' passion and profession. Kraus, a doctoral candidate in bioprocess engineering at WPI, has spent much of the last two years working with a class of stem cells known as tHSCs (Totipotent Hematapoietic Stem Cells). The body uses these unspecialized cells, which can be found in the blood and bone marrow and in the peripheral blood in the umbilical cord, to produce a variety of blood cells.

When cancer patients undergo chemotherapy or radiation, healthy stem cells are often destroyed along with the malignant cells targeted by the therapy. Without adequate stem cells, the body may be unable to manufacture enough disease-fighting blood cells to ward off infection. To help the body restore this capacity, doctors can harvest some of the patient's own healthy stem cells and freeze them before treatment begins. After therapy ends, the cells are reinfused into the patient.

But because stem cells make up only a tiny fraction of human blood (fewer than one cell per 10,000 cells in normal blood) and are difficult to grow outside of the body, this procedure can be difficult and expensive. At least that was the case before Kraus came along. As part of his studies, he invented a way to selectively breed tHSCs quickly and efficiently in the laboratory by culturing them in a bioreactor he designed.

Kraus came to WPI in 1988 to continue his education after earning an undergraduate degree in philosophy and running his own construction business in Pennsylvania. For his doctoral qualifying exam, he proposed a reactor that would mimic how stem cells grow in bone marrow. "It took me about six months and a couple of flashes of light to come up with the concept," he says.

Kraus' advisor, Judith Miller, associate professor of biology and biotechnology, immediately recognized the project's potential. "I encouraged Morey to put his ideas into a proposal," she says. "Doctoral committees review a lot of concepts that are interesting in theory. Morey's was the first in a long time that seemed to have recognizable commercial potential and was also the first qualifying proposal ever, in my experience, to eclipse the originally planned doctoral research."

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Jill Friberg and Morey Kraus work on their stem cell breeder at the offices of t.Breeders.

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Kraus put the project aside for a semester, then presented it to Mason "Skip" Irving III, vice president of commercial development for the Massachusetts Biotechnology Research Institute. MBRI, an independent, not-for-profit organization, and its affiliated venture capital firm, Commonwealth BioVentures Inc., have provided capital, laboratory space, equipment, supplies and management guidance to 20 companies since the two were established in 1984. As a result of Kraus' proposal, MBRI funded feasibility testing of the bioreactor and supported further research on Kraus' idea.

"We were impressed not only with Morey's invention, which we believe will have a great deal of commercial value, but with his business acuity and tenacity," says Irving.

In September 1994, Kraus opened his own business, t.Breeders Inc., in a large office at MBRI headquarters in Worcester. He serves as president and treasurer. Jill A. Friberg, t.Breeders' vice president of operations, is also completing a Ph.D. at WPI.

Kraus and Friberg have applied for a patent for the bioreactor, which can grow a variety of cell types, including precursors of T-cells and red blood cells. Because only a small sample of a patient's blood is needed to breed large quantities of stem cells with the reactor, it represents a significant advance over the traditional method of collecting the cells, in which the patient must sit for prolonged periods while a centrifuge-like device extracts the cells from their circulating blood.

t.Breeders' product "significantly reduces patient discomfort and decreases the risk of further compromising their immune defenses, which are at risk because we've removed some of their stem cells," Kraus says. The system is also cost-effective. "We believe that the breeder can ultimately be mass-produced for one-tenth the cost of a separator system," he adds.

But perhaps the most important impact of the new procedure will be on cancer treatment itself, he says. "Our less expensive, more reliable and safer source of cells for replacing or supplementing blood-forming and immune system cells will significantly increase the number of patients that receive cellular therapy and most certainly lead to more aggressive and effective treatments for cancer."

New Forceps Makes Suturing Easier

Two former WPI students, a University of Massachusetts Medical Center physician who graduated from the Institute, and a WPI professor recently patented a new forceps they invented to make suturing simpler and more cost-effective.

"Delicate surgical manipulation requires stability - often involving the use of two instruments," says Dr. Raymond M. Dunn, associate professor of plastic surgery at UMass, who designed the Tissue-Spreading Forceps along with Marc Gomes Casseres '92, Richard Doppler '92 and mechanical engineering Professor Allen H. Hoffman. "By allowing the surgeon to stabilize the wound with the forceps with one hand and suture with the other, the forceps make possible more precise manipulation of tissue and needle placement."

The patented forceps (pictured below) has two gripping members (which resemble pairs of tweezers) that are pivoted at the end and secured to each other by a spring. When the surgeon applies pressure to the spring, it causes the grippers to close and hold tissue at two locations. Additional pressure makes the forceps spread apart in relation to each other, thereby spreading the tissue. "More sophisticated and delicate surgical procedures are routinely being developed," says Dunn. "Many of these require the redesign of traditional instrumentation and the development of new ones."

Dunn, who received his bachelor's degree in chemistry from WPI in 1978 and now directs the medical center's Plastic Surgery Research Laboratories, saw a need for an improved forceps and identified prototypes that could be used to make those improvements. Gomes Casseres and Doppler were WPI seniors in 1991 when they began working with Dunn to develop the new device as part of their Major Qualifying Project. Hoffman, the students' advisor, helped them focus on their task and refine the product. WPI and UMMC funded the cost of securing the patent, which was assigned to both institutions.

"The factors that were considered in the design of the forceps were ease of manipulation, complexity of the closing and spreading mechanism, and cost to manufacture," says Gomes Casseres. "The Tissue-Spreading Forceps will enable the surgeon to concentrate on the complicated techniques involved in surgery, rather than on the mechanics of the instrument."

After earning their bachelor's degrees in mechanical engineering with biomedical interest, Doppler and Gomes Casseres went on to earn master's degrees in mechanical engineering at WPI. Doppler is now vice president of operations at Reed & Prince Manufacturing Corp. in Worcester. Gomes Casseres is a mechanical engineer at Lockheed Sanders Inc. in Nashua, N.H.

Model Predicts Boston Marathon's Medical Needs

The 100th running of the Boston Marathon on April 15 was an exciting and memorable spectacle. But with nearly 40,000 runners participating - four times the number who typically compete and the largest field for any marathon in history - the race represented a huge challenge for its planners and organizers. Thanks to a computer simulation developed by WPI juniors Kevin Ciszewski, Timothy Caldwell and Joseph Danubio, those harried men and women were able to confidently plan for the medical needs of the runners.

"The students' work provided the cornerstone for the medical care plan for the 100th Boston Marathon," says Dr. Marvin Adner, medical director for the race. Adner, chief of hematology at MetroWest Medical Center in Framingham, Mass., was responsible for planning all of the medical support for the race. Last spring, he approached WPI's Management Department with a request for a computer simulation study to help prepare for the centennial.

"The finish line for the marathon is like a funnel and is not conducive to easy disbursement of the finishers," says Francis Noonan, associate professor of management, who served as the students' faculty advisor. "This marathon historically incurs higher casualty rates than other marathons - either because of the nature of the course or the fact that many runners elevate the status of Boston to a higher level than other races and are thus more likely to push themselves beyond their physical capabilities."

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Sylvia Mehl of Minnesota, one of the 1,400 casualties of the 100th running of the Boston Marathon, rests in a medical tent at the finish line.

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For their computer model, the students input data based on assumptions about the total number of runners across a discrete range of finish times; staffing levels for the various categories of the race (including the number of available medical support personnel); weather conditions; and casualty rates for each type of injury.

"The resulting model predicted that up to 1,000 cots had to be available in the three medical tents and that the medical team needed to stock about 850 intravenous lines," says Noonan. "We also provided information to Dr. Adner on the number of medical support volunteers he needed to call upon to assist finishers who required medical attention."

Ciszewski and Caldwell, chemical engineering majors, and Danubio, a civil engineering major, were present on race day to see how well their model predicted the actual medical needs. They found that some of their assumptions were a bit conservative; for example, only 2,000 "bandit" runners (runners not officially registered) joined the race (they had predicted 5,000) and it took 28 minutes for all the runners to clear the starting line (they'd estimated 40 to 45). In addition, the cool weather held down the number of heat-related medical problems. As a result, there were 1,400 casualties at the finish line, vs. the 2,100 the model had predicted, and the population in the medical tents never got beyond 350, while the model suggested it might hit 500.

"Being overprepared is better than being underprepared," Noonan says, "and the medical staff was most grateful for the early planning work from these students."