A Cure for Cancer?

A recent series of startling discoveries led in last by Professor of Cellular and Developmental Biology Raymond L. Erikson is bringing scientists to the threshold of understanding and possibly controlling one of today's most feared and least understood diseases--cancer.

But while the research is advancing at an unprecedentedly rapid pace, cancer biologists remain divided over its potential to actually provide a cure to cancer. Moreover, competition among researchers has led scientists to withhold information, plaguing the research and slowing down the progress, scientists say.

No one denies, however, that the level of excitement among cancer researchers has reached a new high as scientists come closer to unlocking the mystery of how cancer cells are born. In particular, the interest is aroused by a new theory suggesting that the seeds of cancer are present in virtually all healthy cells.

Frikson recently startled the scientific community by showing that a specific type of abnormal gene--labelled an oncagene (from the Greek word ongus meaning "excessive growth")--corrupts the healthy cell by creating irregular proteins. These proteins then somehow transform the normal cell to a cancer cell.

The discovery has triggered an onslaught of further research focusing primarily on exactly how oncagenes form, how they create abnormal proteins and how these products cause malignancy.

More important, an understanding of how cancer cells form will hopefully lead to a method of stifling the process, scientists say.

"There are several ways to get cancer, but most of what we know of as cancer will be explained in oncagene products," Erikson says. "If we know the pathways we can then think of ways to intervene in the cell growth. Right now, I'm quite optimistic," he adds.

Other top rescarchers, however, are not as optimistic. While most heartily support the continuation of oncagene research, some suggest that the results may not be as fruitful or promising as they may now appear.

"It's hard to see a rational therapy based on oncagene research right now," says Tony Hunter of the Salk Cancer Research Institute in California. "If you're interested in curing cancer, working with oncagenes is a long road and many years away," he adds.

"Even if we find out how it works, we might see that there is nothing we can do about it A real understanding is still a long way away," agrees Larry Rohrschncider of the Hunter Cancer Research in Seattle.

The pessimism, however, is countered by others who explain that somewhere on the path to a full understanding of oncagenes, ideas for treatments or prevention may crop up.

"It's exactly the right direction," says Associate Professor of Biochemistry and Molecular Biology Lewis C. Cantley, adding, "Critics say no treatment may ever come out of it, but a good analysis is polio. Much money was spent on the design of a better iron lung machine, but not on the idea of using a serum. With cancer, much less has been spent on clinical treatment, but we may get the breakthrough from a different line of a research."

Cancer is a condition in which cells multiply without discipline and invade adjoining tissues. Recent research has determined that the oncagenes which are carried in a virus are not really native genes of the virus, but instead are normal genes of animal cells that somehow have been stolen from animal tissues and then incorporated in the virus. It is theorized that in normal cells, these genes have very important developmental functions such as causing cells to multiply when necessary.

That same gene, when incorporated in a virus, can apparently rapidly generate the wild and aberrent growth known as cancer.

In natural circumstances, the initial distortion of cell life that leads to cancer could be caused by a random mutation, man-made chemicals, or any number of still unsuspected causes.

Although there is evidence that such a process occurs in animals, scientists have been unable to prove a similar virus exists in humans.

Nonetheless, the work has produced a wealth of biological insight. One is the idea that one oncagene, by means of a single protein product, can cause a cell to become cancerous.

Working with chickens, Erikson startled the scientific community when he identified the protein produced by the oncagene in one type of virus.

"He really opened up the field of oncagene proteins," Rohrschneider says. "He was able to identify the gene but now must use this to see how it turns a normal cell to a cancerous one."

Erikson made his first headway in the field while at the University of Colorado in the 1970s when he began working with chickens and viruses.

Although he spent most of his youth in the West as an undergraduate at the University of Wisconsin at Madison and as a graduate student at the University of Colorado Medical School, he eventually made his way to Harvard, which is noted for attracting the best cancer researchers from all over the world.

The large number of cancer researchers at Harvard and "the high quality of graduate students here" were enough to lure him East, he says.

According to Erikson, the idea that small changes within a cell could induce oncagenesis eventully allowed him to actually identify the oncagene and the protein it produces.

Shortly thereafter, J. Michael Bishop and his colleagues at the University of California at San Francisco found a virtually identical set of genes in cells of vertebrates including humans. And, in each case, a similar protein to Erikson's was produced.

Since then about 20 different oncagenes have been isolated from viruses that cause leukemia and other forms of cancer in animals such as chickens, mice, cats and monkeys. And once an oncagene is identified, researchers are able to discover its products within a few weeks, Frikson says.

In the past few years a second line of attack has also uncovered oncagenes as scientists have found genes in various tumor cells that can transform them into cancer cells. Presumably, each oncagene was instrumental in generating the tumor from which it was isolated.

"Right now, we may be nearing the end of identifying oncagenes," Erikson says. "This is the first step. Next we must understand how oncagene products change the way a normal cell behaves."

In particular, Erikson is focusing not only on the functions of oncagenes but on identifying the areas of a cell that they attack.

"Until we understand these pathways, we won't understand cancer," he says.

Once oncagenes are understood, the final step will be to design a drug that inhibits the protein formation process. This, however, may be the most difficult part of the puzzle, Cantley says, since all cells have these proteins, and if they are attacked and destroyed, normal body cells may fall victim to the drugs as well.

Other scientists in the meantime have ade a number of advances in understanding the protein's functions. Most commonly, the protein within a cell adds a phosphorous atom to another protein known as amino acid tyrosine. This seemingly minor action, however, has intriguing effects on living tissues and is somehow related to normal growth in skin cells.

Moreover, scientists have also discovered that the proteins act on the chemical adenosine triphosphate usually known as ATP. This is the key energy chemical in all animal and human cells, and by impinging on this substance, the proteins are in an extremely powerful position to change a cell.

Further research has shown that some cells cannot produce oncagenes. But, they still may be able to induce tumor growth by somehow instructing another cell to produce oncagenes and cause cancer.

Stemming from Erikson's identification of oncagenes in chickens, scientists have jumped rapidly into various related areas of research, leading to a further series of discoveries pushing the field closer to its ultimate goal.

Despite the progress, however, scientists critical links of information are missing Moreover, not all the obstacles are scientific as competition and sluggish cooperation among researchers has plagued the work.

An a field where the scientific stakes are as high as the personal ones, researchers often withhold information from each other as government funding is limited. The need to show significant advancement to attain the necessary support to continue research prevents scientists from cooperating with each other, scientists say.

"Some people talk to each other and some don't, but relations are far from ideal," says Geoffrey M. Cooper, associate professor of pathology at the Medical School. "But its like crime on the streets. How do you get rid of it?" he adds.

Others, however, downplay the damage. "It's competetive, but it dosn't hinder the science," Hunter says. "There maybe is some duplication of work, but you always find out what's going on within two or three months. It's amazing how scientists worry about precedent when it dosn't really make a difference in the long run," he adds.

Despite the more than $1 billion received annually from various sources that is poured into cancer research, only a small percentage has gone to oncagene research. The trend, however, is shifting, says. Director of the Dana Farber Cancer Institutre Emil Frei.

"Priorities are constantly shifting in terms of how money is spent, but oncagene research is establishing itself as a priority," he says.

Approximately 80 percent of the cancer research funds come from government sourees, namely the National Institutes of Health (NIH) and the American Cancer Society. Industry and other private sources provide the remainder of the funds.

While cancer resarch remains a high priority item, scientists say there is no telling how much more support will be necessary before cancer is brought under control.

"It's not like most areas. For example, with the space shuttle the government said they'd put in a certain amount of money and they will get a certain result. Cancer is different No one can tell us how much it will take to get us there," Cooper says.

Although cancer biologists are betting heavily on oncagene research to provide some clues, there is also strong sentiment that time and money be directed to other avenues of cancer resarch.

"Great advances have been made inreducing cancer deaths without oncagene research," Erikson says. "For example, many forms of leukemia are treatable now even though we don't understand it."

But he adds that there are also a vast number of currently untreatable forms of cancer which provide an impetus for oncagene research. "Without an understanding of the biochemical system, chances for survival in these cases will remain low."