About AIChE

Rakesh K. Jain
University of Delaware

Rakesh K. Jain, the Andrew Werk Cook Professor of Tumor Biology in the Department of Radiation Oncology at Harvard Medical School, began his pioneering work in cancer research by serendipity.

Jain was still undecided about the research topic for his doctoral degree when he accompanied one of his University of Delaware professors, James Wei, now a professor of chemical engineering and Pomeroy and Betty Perry Smith Professor in Engineering at Princeton University, to the National Cancer Institute and met the late Pietro M. Gullino, who was then chief of the tumor pathophysiology laboratory. Gullino, who described his research in tumor biology to Jain and Wei, had developed a unique tumor preparation in rats--an isolated tumor connected to the rat's blood circulation by a single artery and a single vein.

Later, in his quest to find out the possibility of applying chemical engineering principles to the problem of drug delivery to tumors, Jain used Gullino's tumor model to measure drug uptake by tumors. He found that most of the drug, when injected systemically, bypassed a tumor like a beltway around a city and very little was taken up by a tumor. He also developed a mathematical model for drug delivery in tumors.

Jain, who heads the Edwin L. Steele Laboratory for Tumor Biology Department of Radiation Oncology at the Massachusetts General Hospital and serves as affiliated faculty in the Harvard-MIT Division of Health Sciences and Technology at the Massachusetts Institute of Technology in Cambridge, Mass., is regarded as a pioneer in the fields of tumor biology and in vivo imaging and is renowned for integrating bioengineering with tumor pathophysiology. Recently, he has developed a new concept for improving the delivery and efficacy of drugs in tumors and has validated the concepts in cancer patients.

Jain was born in 1950 in Lalitpur, India, where he received his elementary and high school education before he joined the prestigious Indian Institute of Technology in Kanpur. He earned his master's and doctoral degrees from the University of Delaware in 1974 and 1976, respectively.

Jain enjoys spending time with his wife, Jacqueline Samson-Jain, and their 4-year-old twin daughters, Anjali and Natalie. The eldest of 10 children, Jain also enjoys visiting his mother and his siblings, all of whom live in India.

During his career, Jain has received more than two dozen major awards, including the Guggenheim Fellowship, Humboldt Senior Scientist award, an $8.3 million, seven-year Outstanding Investigator Grant from the National Cancer Institute, and the 2005 Academic Scientist of the Year award. He also was elected to the National Academy of Engineering and the Institute of Medicine of the U.S. National Academies.
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Profile
Rakesh K. Jain, '74M, '76PhD, Andrew Werk Cook Professor of Tumor Biology in the Department of Radiation Oncology at Harvard Medical School, began his pioneering work in cancer research by serendipity.

Jain said he was searching for an experimental research topic for his doctoral degree when he accompanied one of his University of Delaware professors, James Wei, now a professor of chemical engineering and Pomeroy and Betty Perry Smith Professor in Engineering at Princeton University, to the National Cancer Institute and met the late Pietro M. Gullino, who was then chief of the tumor pathophysiology laboratory.

"As Dr. Gullino described his research in tumor biology, I was struck by the parallels in our approach. The more we spoke, the more intrigued I became with the possibility of applying chemical engineering principles to the problem of drug delivery to tumors," Jain said. "As an engineer, I wanted to know how systemically injected drugs got into tumors. Dr. Gullino had developed a unique tumor preparation in rats--an isolated tumor connected to the rat's blood circulation by a single artery and a single vein."

Using Gullino's tumor model to measure drug uptake by tumors, Jain found that most of the drug, when injected systemically, bypassed a tumor like a beltway around a city and very little was taken up by a tumor. He also developed a mathematical model for drug delivery in tumors.

"More importantly, working with Dr. Gullino was a turning point in my career and kindled my interest in cancer research," Jain said.

After earning his doctoral degree, Jain started his teaching career as an assistant professor of chemical engineering in 1976 at Columbia University and maintained a keen interest in studying tumors.

"As elegant and innovative as Dr. Gullino's tumor preparation was, it did not allow me to look at what was going on inside a tumor at a cellular or sub-cellular level," Jain recalled. "During my literature searches, I found that as early as the 1920s-30s, biologists had implanted glass windows in rabbits' ears to see the growth of blood vessels. In the 1930s, these rabbit windows were being used to study tumor growth. I was determined to create these windows and then use them to study drug delivery in tumors."

Jain learned that such a window was being used in the laboratory of Shu Chien, then a professor of physiology at Columbia University Medical School. Jain immediately started collaborating with Chien, but did not have an opportunity at Columbia to study tumor growth using such windows.

Jain accepted a job as an assistant professor of chemical engineering at Carnegie-Mellon University in Pittsburgh, after his wish to implement his own rabbit and rat animal facility in the Chemical Engineering Department was granted and subsequently funded.

"My career took a wonderful turn," he said of his work at Carnegie-Mellon, where he worked for 13 years, including two year-long sabbaticals, before moving to Massachusetts General Hospital (MGH) and Harvard in Boston." The past 15 years have been the most rewarding period of my life."

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. 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 cells.

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 aren’t evenly distributed, causing a lack of flow to certain areas and specifically 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 cell.

Shortly after his move to Boston and Massachusetts General Hospital in 1991, he began to investigate the mechanistic underpinnings of this high pressure in tumors. To this end, he formed a multi-disciplinary team of scientists, engineers, physicians and surgeons, and developed a number of sophisticated animal models and innovative imaging methods. Today, his laboratory is considered a world leader in quantitative tumor pathophysiology and drug delivery.

"I am very proud of the molecular, cellular, anatomical and physiological insight our work has provided into the inner workings of solid tumors, and how we have taken this insight from the lab bench to bedside and back.”

In 2001, Jain proposed that drugs that are supposed to kill blood vessels of tumors, when used in right doses and schedule, could make the tumor vessels "better" functionally and structurally, a process he referred to as vessel "normalization."

"My coworkers and I tested this concept first in tumors growing in mice and then confirmed our findings in cancer patients. We then went to reveal the mechanisms and consequences of vascular normalization," he said. "This work has changed the thinking about how to combine and schedule different drugs for cancer treatment, and has led to a number of clinical trials at MGH-Harvard."

Jain said his most enjoyable time is with his wife, Jacqueline Samson-Jain, and their 4-year-old twin daughters, Anjali and Natalie. The eldest of 10 children, Jain also enjoys visiting his mother and his siblings, all of whom live in India. He has fond memories of Lalitpur, the town in India where he was born 55 years ago, his elementary and high school education there, and the prestigious Indian Institute of Technology in Kanpur, India, where he earned his bachelor's degree in chemical engineering.

Influenced by one of his chemical engineering professors at IIT who received his doctoral degree from the University of Delaware, Jain applied to UD for his graduate education and studied pollution control in the Delaware River with Morton M. Denn, now the Albert Einstein Professor and Director of the Levich Institute for Physico-Chemical Hydrodynamics and professor of chemical engineering and physics at the City College of the City University of New York.

"At the University of Delaware, I developed close friendships with my mentors and colleagues," Jain said. "I will be eternally grateful to Dr. Arthur B. Metzner, who, as chairperson, offered me a fellowship to come to Delaware to do my graduate work. He was the one who arranged to pay my first month's salary in advance on my arrival at Delaware--I had left India with only $50 in my pocket!"

Jain attributes his trailblazing success to the support from and friendship with inspiring teachers, mentors, friends, and colleagues at UD, the National Cancer Institute, Columbia University, Carnegie-Mellon University, the Pittsburgh Cancer Institute, as well as MIT, MGH and Harvard.

"At MGH and Harvard, I have the unyielding support of my former and current department heads, and I have had the pleasure of working with more than 100 former and current graduate and post-doctoral students, as well as collaborating with a large number of wonderful clinicians and basic scientists at Harvard, MIT, and elsewhere."

Jain said the most significant milestone in the future would be the discoveries taking place at the interface of chemical engineering and life sciences that will improve the quality of life.

"My concern is whether all citizens of this planet will be able to afford the benefits of this revolution because of the cost considerations.”

Rakesh K. Jain University of Delaware

Rakesh K. Jain
University of Delaware