Using tools no more complicated than a microscope, a calculator and some common sense, cancer researchers at Harvard Medical School have pinpointed a vital step in the growth of malignant tumors in the human body.

Led by Assistant Professor of Pathology Donald Ingber and Professor of Anatomy and Cellular Biology M. Judah Folkman, the theoretical part of the research resolves a longstanding clinical question in the study of tumors: rather than being "born" with the capacity to cripple their host, bodily tumors acquire that ability sometime in the early stage of their development.

In other words, the researchers found, bodily tumors are harmless until they undergo a deadly transformation which pumps them full of nutrients and changes them from underfed weaklings into potent centers of cancerous activity.

This theoretical research is important in its own right: the New England Journal of Medicine gave these findings top billing in its January 3 issue. But the work holds even more promise now that another group of Harvard scientists has stumbled across a drug which prevents this transformation in the first place.

The proposed treatment, a synthetic version of an uncommon fungus known as fumagillin, has already shown evidence of halting cancerous lumps before they can send fatal offshoots to nearby lymph nodes or other vital organs. Laboratory animals subjected to this drug suffered from no harmful side effects associated with most common cancer treatments such as radiation therapy.

Together, these two discoveries, which came within months of each other at the end of last year, may change the direction of the entire cancer research industry, medical experts say.

"We hope this paper will stimulate others into looking into this," says Noel Weidner, a surgical pathologist at Brigham and Women's Hospital and a co-author of the New England Journal paper. Weidner's group is the only one at Harvard--and one of only a few in the world--currently studying angiogenesis, the sudden and dangerous transformation of benign tumors into malignant beasts.

The Medical School research has already gone beyond academic circles and penetrated the ranks of corporate cancer laboratories, Ingber says, as many companies are beginning to focus their anti-cancer divisions on the tumor-repressing approach.

"It opens up a whole new frontier in cancer therapy," says Ingber, who co-authored a December paper in Nature which identified the fumagillin fungus as an anti-tumor agent.

Besides helping the fight against cancer, the researchers say, the work may also potentially have applications to combatting other diseases, such as arthritis.

Nipping Tumors in the Bud

The fundamental scientific concept underlying the research is wonderously simple: tumors cannot grow unless they are well-fed with blood. In most cases, a normal cell which has somehow turned cancerous can multiply and divide about a million times before it "suffocates," unable to survive on the nutrients supplied to the original cell.

Folkman likens this tumor expansion process to the construction of an apartment complex on the spot where a lone house once stood. The plumbing and electricity--meaning the cell's blood--must be improved dramatically, since the apartment's residents cannot survive on the much fewer resources of the old house.

If the tumor manages to coax nearby blood vessels to come to its aid, it can continue on its growth pattern past the "apartment complex" stage, ballooning up from the size of a pinprick to that of a golf-ball or even larger.

"That's very dangerous," Folkman says. "That's when the tumor can grow exponentially." Even more importantly, he says, the newly-recruited blood vessels allow the tumor to send out offshoots known as metastases, which travel through the circulatory system until they lodge in vital organs such as lymph nodes, the lungs, brain or sexual organs.