Over twenty years ago, President Nixon announced a federally funded "war on cancer." The defeat of this dreaded disease was confidently predicted. This promise has not been fulfilled. Cancer has not been conquered; in fact, various statistical measures indicate that progress against the disease has essentially ground to a halt.

There is, of course, debate and even argument on this subject. Cancer researchers challenge the numbers, the statistical interpretations, the definitions of progress. They point to new breakthroughs in recent years, particularly applications of biotechnology.

But we've heard all this before. (Remember L-aspariginase?) The excuses are wearing thin. Patients are becoming increasingly feisty, and one hears more and more criticism of the "cancer establishment." Interest in "alternative medicine" approaches to cancer treatment has reached tidal proportions. It can no longer be dismissed as a few pathetic creatures dosing themselves with quack nostrums. Huge numbers of intelligent, educated people are turning to alternative methods, especially acupuncture and herbal medicine. And, following the lead of AIDS activists, patients are beginning to organize their own treatments with novel therapies, using themselves as guinea pigs in the hope of finding a way to survive.

Like other cancer patients, I am immensely excited by some of the new concepts in cancer treatment, such as the recent proposal to use telomerase inhibitors. Unfortunately, any practical application of these promising approaches always seems to recede into the misty future on investigation. When I look at what is actually being brought into clinical practice, the research being done is extraordinarily stodgy.

I have just returned from a meeting of the American Society of Clinical Oncology. Signs were up exhorting attendees to write to Congress in defense of cancer research funding. But--and I speak from the viewpoint of a cancer patient whose life is on the line--it is clear that much, probably most, of the money this country spends on clinical cancer research is being wasted.

With sufficient experience in research management, one comes to understand that every research paradigm eventually becomes sterile. The methods or techniques that previously yielded progress become less and less productive. There comes a point when further improvement of vacuum tubes is not only difficult but futile; one must shift resources to investigation of transistors.

How can researchers know that they have come to the end of the vein they have been mining? By using the well known S-curve technique. Let's look, for instance (see figure) at the history of my own disease, multiple myeloma. Suppose we were to plot the median length of survival as a function of time. We would find a curve having a typical S-shape. At first, progress against the disease was very slow. But with the development of chemotherapeutic methods, the curve began to rise rapidly. Eventually, however, diminishing returns set in, and researchers reached the limit of what can be accomplished with cytotoxic agents.

Looking at this curve, we can see that the research done in the last ten or fifteen years has contributed essentially nothing to the survival of multiple myeloma patients. Moreover, there is excellent reason to believe that current research along the same lines will accomplish nothing more. Researchers may compare alternating regimes of VBAP and the M2 protocol versus VAD. Or they may investigate the value of GM-CSF and G-CSF in combination following BMT. Or they may even try to settle whether alpha-interferon can prolong remission. But in the end, oncologists will still lose half of their myeloma patients every thirty months or so. It's obvious from the S-curve.

It is important to understand that this failure occurs because of the exhaustion of the research paradigm, not because the researchers are stupid. If you're beating your head against a brick wall, it doesn't matter how good are the brains inside it. It is not that the scientists working in the field are not ingenious; the obstacle is that they are applying their ingenuity to the wrong problem.

What is to be done? How can we jump from the plateau of the current cancer research S-curve onto a new S-curve that can take us higher? I would like to suggest that there is something to be learned from alternative medicine. Let me resort to an analogy to point out the basic problem.

Let us suppose that we have a great many automobiles on the road that are not running well, because their fuel-air mixtures are not adjusted properly. And we will assume that there are research mechanics, who are attempting to investigate the problem and find a solution, while fixing as many cars as possible in the meantime. There are two classes of mechanics, whom we will call Miguks and Junguks.

Miguks have some knowledge of how automobile engines function, though they don't know the details. They have correctly deduced that the problem lies in the fuel-air ratio, and they have discovered how to adjust it. Their research paradigm, therefore, is as follows: They take a large sample of automobiles and randomize it into two groups. The cars in the "repair arm" are all adjusted to some particular fuel-air ratio number. The cars in the "placebo arm" are not modified, though the owners are told they have been repaired. The Miguk research mechanics then observe whether the cars in the "repair arm" run better than those in the "placebo arm." By statistical analysis of these results, they try to deduce the proper setting of the fuel-air ratio.

Now, if the population of automobiles were essentially homogeneous in their basic characteristics, this methodology would work well. If, for instance, all automobiles were 1989 Honda Civics, the Miguk mechanics could quickly define the best fuel-air setting for that particular engine type. But, unfortunately, this is not the case. The automobiles present a wide variety of brands and model years, with all sorts of engines--four-cylinder, six-cylinder, V-8--each of which has its own optimum fuel-air ratio. What is good for one, is bad for another. As a result, the Miguk research mechanics eventually find themselves stymied.

The Junguk research mechanics have an entirely different approach. They do not at all understand how automobile engines function and are fundamentally ignorant of what is going on. In fact, they believe in a totally wrong theory in which magical squirrels inside the engine provide the driving force. However, the Junguks have very extensive experience with automobile problems and a long tradition of empirical observation based on trial and error.

The Junguk approach is to regard each automobile as a unique individual. They carefully note its model, its age, how it has been driven, and every other characteristic they can find out about it. Then, based on centuries of tradition, they try various remedies. Sometimes they hit upon exactly the necessary adjustment; on many other occasions, especially when they are trying to satisfy the magical squirrels, their efforts are ineffectual.

The analogy to cancer research should be clear. The "Miguks"--Western medicine--have gradually worked themselves into a situation in which they have assigned themselves an impossible task. It is like trying to find the optimum conditions for growing apples and oranges in the same orchard. No progress is being made, because no solution exists to be found.

Is this a fair characterization? In fact, the importance of biochemical individuality of patients is coming up increasingly in the literature. In my own disease, for instance, there is a developing debate over whether alpha-interferon may actually stimulate progression of multiple myeloma in some cases. A recent study of low-dose IL-2 found that some myeloma patients benefited; some did not; and in some patients the disease was apparently stimulated. In a study of cell lines from leukemia patients, it was found that some were inhibited by ascorbate, but others were stimulated.

Alternative practitioners, or at least those varieties of them based on Oriental models--the "Junguks"--have at least recognized the crucial importance of biochemical individuality. But they face their own handicap. Eastern medicine lacks the foundation in anatomy and biochemistry that Western medicine developed from dissection and laboratory studies. Thus a disease such as cancer does not even have a distinct conceptual position in Oriental medicine. Instead there are vague and unproductive concepts such as "yin and yang" or "meridian lines" or "ki."

This leaves Eastern medicine with no effective theoretical basis to guide its efforts. Its empirical insights can be fruitful. Particularly to be commended is the emphasis, in herbal medicine, on synergistic effects of drug combinations. But to the extent that "alternative medicine" truly perceives itself as "alternative"--ie, in opposition to scientific medicine--it can never reach its potential. Research on curing cancer by massage-induced "energy flows" is just as futile as double-blind trials of Yet Another Cytotoxic Drug.

The time has come for cancer research to look beyond the paradigm of double-blind placebo-controlled trials. As I have pointed out above, the fundamental assumption of a biochemically homogeneous patient population is simply incorrect, so that it is very difficult to get valid information from trials of this sort. In any case, the era of the placebo-controlled trial is coming to an end. Already there is visible and increasing resistance from patients, who are not attracted by the prospect of being randomized into the placebo arm and left to die. In five or ten years it will no longer be possible to recruit subjects for a placebo-controlled trial for a fatal disease.

If research progress is to continue, scientist-physicians must begin to treat their experimental subjects as individuals--from both a scientific and a medical point of view. This will mean a greatly reduced utilization of statistical studies. This is no bad thing. As Nobelist Ernest Rutherford said, if you need statistics to interpret your experimental results, that indicates that your experiment is badly designed. Correlation of the biochemical characteristics of the individual patient to experimental results will allow clear conclusions to be drawn without massive double-blind studies. At the same time, clinical effectiveness and patient cooperation will be improved.