Messenger - Vol. 4, No. 2, Page 4
Tackling tumor research with engineering tools

     When Rakesh A. Jain, Delaware '74M, '75PhD, was growing up in
India, his dream was to become a jet fighter pilot. Poor vision kept
him from flying, but good judgment gave him a different enemy to
     As the head of Massachusetts General Hospital's tumor biology
laboratory, Jain fights that enemy daily as he and his colleagues try
to find a way to help anti-cancer drugs penetrate solid tumors more
     His work in tumor biology also has led to joint appointments as
the Andrew Werk Cook Professor of Tumor Biology at Harvard University
Medical School and as a professor in the Harvard University-M.I.T.
division of health sciences and technology.
     As part of his doctoral work in chemical engineering at Delaware,
Jain worked at the National Cancer Institute with Pietro M. Gullino,
who was measuring the consumption of nutrients by malignant tumors in
     The more Jain worked with Gullino, the more he began to suspect
that something in the physiology, or physical makeup, of a tumor might
be blocking the spread of blood-borne drugs to all of the cancer
cells. "I began to think that my engineering background, including my
understanding of fluid and molecular transport, could aid in exploring
that possibility," Jain wrote in an article last July in Scientific
     Scientists have had success in developing drugs that kill cancer
cells, but those drugs are far more effective in liquid cancers such
as leukemia and lymphoma than in solid tumors of the breast, lung and
brain, Jain explains. In most cases, the drugs shrink, but do not
completely destroy, the solid tumor.
     Jain looked into the physiology of tumors to identify the path a
drug takes through the blood stream to cancer cells. Because this area
of cancer research was not in vogue at the time and Jain's engineering
credentials were not typical, his first six grant requests were turned
down. Ultimately, he and his team were able to show that several
characteristics of a tumor can impede the flow of drugs to the cancer
     First, a tumor is composed of only about 50 percent cancer cells.
Forty percent is composed of the area between the cells made up of a
collagen-rich matrix called the interstitium. Ten percent is the blood
supply system, or the vasculature, which brings nutrients and drugs to
the tumor and removes waste. For a drug to reach the cancer cells, it
must leave the blood vessel and travel through the interstitium. The
interstitium in a tumor is more extensive than in healthy tissue, so
it takes drugs much longer to arrive at the cell through the
interstitial matrix.
     Jain and his colleagues found that not only did high pressure in
the interstitium interfere with the transfer of drug molecules to
cancer cells, but that blood vessels in a tumor are not evenly
distributed, causing a lack of flow to certain areas and to the cancer
cells in those areas.
     In 1987, Jain began to test his theory that interstitial pressure
in a tumor is unusually high, equal to the pressure within the
capillary network from which the drug must flow to reach the cancer
     Shortly after his move to Boston and Massachusetts General
Hospital in 1991, he published a paper in the journal, Cancer
Research, detailing the results of a study using seven women who had
cervical cancer. The team used small doses of radiation to lower
interstitial pressure in the women's tumors, along with the
application of therapeutic drugs. In four of the seven women, the
tumors were completely eradicated.
     Those results have led to a larger study. Jain and his team have
now tested 30 patients with cervical cancer. "We looked at the six-
month survival rate, and we're now looking at the two-year rate. We
will probably publish at the end of that period, in a year or so,"
Jain says.
     Jain will only say that the results are "very interesting"; he is
determined not to overstate the significance of his work.
     Jain, the person, like Jain, the scientist, doesn't overstate the
facts of his life, either. For example, when he was a boy in India and
he wanted to drop biology to study Sanskrit, he had to make up three
years of Sanskrit to take the course, and he did. And, despite his
aversion to the study of biology and the fact that he has never taken
a course in either biology or physiology, Jain read and absorbed in
one week the classic human physiology book given to him by his
doctoral professor at Delaware, James Wei, now dean of the School of
Engineering and Applied Science at Princeton University.
     Jain has received numerous honors, including a Research Career
Development Award in 1980 from the National Institutes of Health, a
Guggenheim Fellowship and a Humboldt Senior Scientist Award. Most
recently, he was awarded an $8.3 million, seven-year Outstanding
Investigator Grant from the National Cancer Institute.
     Despite his overload schedule at Massachusetts General, Harvard
and M.I.T., Jain manages to swim twice a week, listen to music,
indulge in fine dining and admire art. His tastes are eclectic. "I
could listen to Maria Callas for hours, but I also like the Grateful
     He met his wife, Janet, in Pittsburgh while he was attending
theatre in the round. He spoke to her during intermission, and they
discovered they shared a love of cities and other cultures. Janet
teaches smoking cessation classes for the American Cancer Society.
     Jain speaks in superlatives of his time at the University of
Delaware. He came to the U.S. to study with UD chemical engineering
Prof. Morton M. Denn, now at the University of California-Berkeley,
the author of five textbooks, one of which Jain had read.
     He arrived in the United States with "only $50 in my pocket. One
of my professors helped me get my first month's stipend at the
beginning, rather than the end of the month, so I was able to survive.
I have very fond memories of Delaware," Jain recalls.
     When asked how he managed to continue his research even when most
of the medical community had no faith in it, he responds: "Hope-the
hope of finding a better way to deliver cancer-fighting drugs, of
building a bridge between the test tube and the patient, the lab bench
and the bedside."
                                                     -Barbara Garrison