Into The Breach

Mike Field
Staff Writer

At Hopkins, as in other locales, significant battles have been won; but, with thousands dying daily, research dollars are scarce and many scientists are wondering: Is this any way to wage a war?

On the surface, the numbers look impressive: after 25 years of collaborative research among scientists around the world--much of it sponsored by the National Cancer Institute--the death rates in many cancers have declined. Sometimes precipitously.

Testicular cancer and Hodgkin's disease, for instance, were almost invariably fatal at the time of the signing of the National Cancer Act. Today they are cured most of the time, and overall childhood cancer death rates have been reduced by more than 50 percent. Deaths from colon and rectal cancer are down 17 percent since 1973, and even in the slow-growing, insistently virulent forms of the disease, such as lung and breast cancer, deaths have declined measurably in the past seven years--and most researchers expect the fall to continue.

Yet despite encouraging trends and some notable victories, the underlying numbers tell the story of a tenacious enemy that is far from vanquished.

Most Americans find it intolerable, for instance, that somewhere in the neighborhood of 70 of their fellow citizens are murdered every day. And the onslaught of the human immunodeficiency virus, now responsible for about 110 deaths daily, has led to the description of AIDS as both "epidemic" and "plague" in the popular press.

Yet today, an average of 1,550 Americans will die of cancer. Tomorrow, a similar number will do the same. And so on the next day, and so, too, on the day after that. Slowly, relentlessly, cancer carves a wide swath through American society, leaving scarcely a family untouched in its wake. Current statistics indicate that roughly half the adult males and a third of adult females will experience the disease in their lifetimes; fully one-quarter of the population can expect to die from it. Yet of the current federal budget, only about one-tenth of one cent of every dollar of revenue raised is devoted to cancer research.

Although many have publicly deplored the current rate of cancer research funding, there is one man who gets downright hopping mad about numbers such as these. His name is Donald Coffey, and he has the unusual distinction, at Hopkins or most any other university, of being one of the few triple professors, specializing in urology, oncology, and pharmacology and molecular sciences.

Beginning next week, Coffey will also be president of the American Association for Cancer Research, the largest association of cancer researchers in the world.

"People always ask me, 'When are we going to win this war against cancer?' and I tell them, just as soon as we really start to fight," says the outspoken Coffey, who gladly shares his opinions about the need for increased cancer research funding with anyone who will listen. "Everyone thinks there's been a war when there's only been a skirmish."

He is quick to muster numbers to his defense. "Your danger of dying of this disease is extremely high--about one in four. Yet we will spend 10 times as much money keeping troops in Bosnia--roughly $20 billion--as we will on all types of cancer research combined. We'll put another $14 billion in the space effort, but just slightly over $2 billion into discovering how to prevent and cure this terrible disease."

Part of the difficulty in finding preventive measures and effective treatments for cancer has to do with the great breadth of the disease itself. In reality, the term cancer is something of a shorthand for more than 100 different identified diseases that often manifest themselves in strikingly dissimilar ways. Cancer occurs when cells become abnormal and keep dividing and forming more cells without control or order.

All organs and tissues of the body are made up of cells. In ordinary circumstances, none of these cells is immortal. They live a certain time and then die, and the body disposes of them, primarily by sloughing them off via the bowels or other means. As cells die, others are created through cell division, called mitosis, to replace them. Normally, cells divide to produce more cells only when the body needs them.

If, however, a cell becomes damaged by viral, environmental, hereditary or other means, it may begin to divide when new cells are not needed, and thus form a mass of excess tissue, called a tumor. Not all tumors are life-threatening, but some can invade and damage nearby tissues and organs. These tumors are known as malignant tumors, or cancer. Cancer cells, once they start growing, are not self-limiting; they do not stop on their own accord.

In addition, they have a bad habit of not staying put. Cancer cells that have broken away from a malignant tumor and traveled through the blood or lymphatic system will often form new tumors in other parts of the body. This spread of cancer is called metastasis, and it presents one of the most vexing problems to physicians trying to treat the disease.

Which is why one important avenue of cancer research leads toward prevention of the disease. "Are we going to cure cancer or prevent it?" Coffey asks, and then settles back to consider the answer. "Keep in mind we never "cured" polio. We only prevented it. Right now we are making tremendous strides in how to prevent cancer."

Foremost among the various means of preventing cancer fatalities is one that has been known at least since the signing of the National Cancer Act: elimination of tobacco consumption, especially the cessation of cigarette smoking. Lung cancer remains the largest single cause of cancer death among both men and women, accounting for roughly a third of all cancer mortalities. Much of that number can be directly attributed to cigarette smoking.

"In 1930, lung cancer was not the No. 1 cancer killer--it was not even in the top three," Coffey says. But during World War II, G.I.s received cigarettes as part of their basic rations. Cigarette smoking soared as a result. "After World War II, lung cancer skyrocketed. It went off the scales."

Today, lung cancer mortality rates in America are declining, due largely to reductions in cigarette smoking that have occurred since the 1964 surgeon general's report on smoking and health. Yet it is a prevention battle that is far from over, as the recent upsurge in smoking among high schoolers demonstrates.

"We've put tons of money into environmental protection, mainly because the impact of environment on cancer is foremost in the public mind," Coffey says. "But the biggest one, no doubt, is smoking. If we could prevent smoking we could prevent a lot of cancer. Prevention is one of the mainstreams of cancer research."

One of the more exciting discoveries in the past 25 years has been the linkage between diet and cancer. Just as there is an intuitive relationship between smoking cigarettes and developing tumors of the lung, so the idea that certain foods might help prevent cancers--especially those associated with the digestive tract--has an inherent appeal. But which foods, and why? Demonstrating the scientific validity of common sense propositions is not always an easy matter.

Within the last decade, for instance, studies have shown that a diet high in fiber can lead to a lowered incidence of cancer of the colon and bowel. And human epidemiological studies have repeatedly shown that eating large quantities of fruits and vegetables lowers the risk of developing some types of cancer.

At Hopkins, researchers such as the School of Public Health's Thomas Kensler and the School of Medicine's Paul Talalay, have demonstrated that cruciferous vegetables in particular--broccoli, cabbage, cauliflower and their relatives-- contain compounds that naturally boost the body's cancer-fighting abilities.

News of these discoveries in the early '90s generated considerable media attention, though the extent to which this knowledge will actually change behavior is unclear. It is worth noting, perhaps, there were no stories of broccoli supplies being swept from the shelves at the time, as happened with red wine when a different study posited that a glass or two of vino may reduce the risk of heart attack.

"I think one day there will be a combination of approaches in cancer prevention," says Kensler, a professor of environmental health sciences with joint appointments in pharmacology and oncology. Kensler's research suggests that oltipaz, a synthetic compound originally developed for use in chemotherapy, may, in lower dosages, act as an effective booster of the body's defenses against certain carcinogens.

"For certain members of the population who have a genetic predisposition to cancer, or who are exposed to high levels of carcinogens, a drug-based intervention such as oltipaz may be effective," Kensler says. "But for the general population, who do not face either high or specific risks, we'll probably need a different type of strategy. Then you begin talking about generically enhancing our resistance to cancer through diet."

END PART 1

Next: When prevention fails. Killing cancer without killing you--developing new therapies against a tenacious disease.