AIDS TREATMENT NEWS Issue #206, September 2, 1994
John S. James

The Problem

The recent Yokohama conference was badly reported in the press. Behind the gloom and doom on AIDS treatments, much valuable science was overlooked. AIDS Research is improving, and good work is finally being done; but drug development, a very different process by different people, is still a disaster. Why?

If you ask scientists, most will say that the lack of treatment progress results from the biological difficulty of the problem, of controlling the HIV virus. This is true -- but not the whole story. The lack of progress also results from systematic human mistakes. Yes, if the biology of stopping HIV were easy, even the crippled effort we have today would have already been successful. A hard problem means that we have to do better to succeed.

But there are political reasons why it has been difficult or impossible to successfully raise the alarm. And the same political obstacles are stopping progress today.

Medical Research Progress -- Where It Comes From

Almost all medical advance in the past, and still today, comes not from rational calculation or design, but from the unexpected, the unpredictable, the unknown. And the unknown first comes into view without a major corporate, professional, or political constituency behind it. But today, the process of mainstream drug development creates such high barriers and obstacles -- regulatory, financial, legal, and other -- that only the largest companies, with a major corporate commitment, can progress over them.

This means that the new ideas and information that come to doctors, scientists, and others through accident and chance observation -- the very ideas and information that feed medical progress -- usually cannot go anywhere. No matter what their intrinsic merit, they cannot move at all to build the credibility required to crank up the very expensive processes required today before the first human test. There is no path which leads over the barriers. So they are stuck forever.

Hundreds of entirely reputable ideas wait like this, frozen on display in peer-reviewed journals, or out of public sight in a scientist's or doctor's mind or in unpublished work. Eventually, a tiny handful may be picked up by a well- financed corporate development project. But because of the great role of the unexpected in medical research, there is no reason to think that these lucky few are the cream of the crop. Instead, they are essentially selected at random, based more on patents, contracts, deals, and personalities than on perceived merit (however unreliable even the latter is).

As a result, the world has appallingly few shots at a significant treatment improvement. What is needed is a rational development path for the hundreds of other good ideas and proposals, so that they can begin the process of establishing their credibility, if they merit it. Many different possibilities would then have a chance at development. Eventually, the best of them could move into formal clinical trials.

AIDS Politics: The Unholy Alliance

It's no accident that this reform was not accomplished long ago.

Start with a big picture, beyond AIDS, beyond medicine. In any public-policy arena where regulation is involved, there is usually an ongoing battle between two superpowers, big business and consumer protection. And public policy is determined by where the battle line between them ends up. This battle is the normal and usual process by which we as a society balance different risks and different benefits against each other.

In drug development, for AIDS or for other diseases, this battle proceeds, as elsewhere. But unfortunately, there is one key place in drug development where the battle does not work as it should, and instead produces pathological results. And this key place is the unexpected, the creative, the chance observations, the new ideas -- which proceed from the unknown, and form the river which feeds most of the potential for advances in treatment development, as discussed above.

In this one key area (which is unimportant for the present, but centrally important for the future) big business and consumer protection are not in conflict, but instead work together -- an unholy alliance against new ideas. For very different reasons, both of these superpowers want the barriers and obstacles, which any forward movement must cross, to be set as high as possible. Consumer protectionists want high barriers to protect the public against dangerous products and unscrupulous companies; big business wants high barriers to protect itself against competition by small business. Big business can pay almost any price; and later, with a monopoly of an essential drug, raise prices as high as necessary to get the money back and more.

Whether a potential advance is a major corporate development project with tens of millions of dollars behind it, or an accidental observation with no constituency yet, doesn't matter -- both are treated equally. But the multimillion dollar corporate effort can (with sufficient merit) overcome the barriers and prevail, while the new idea which has had no chance yet to build a constituency or financial support is stopped cold, usually forever.

This problem has not been solved because both consumer protection and big business have such a pervasive influence throughout the AIDS research and service communities. Almost everybody who is professionally involved worships at one or both of these altars. Big business funds thousands of projects by scientists, doctors, and service organizations -- as it should (and small business, incidentally, funds almost nothing in comparison). Meanwhile, consumer protectionists dominate policy almost everywhere in AIDS, from our friends in Congress, to the FDA of course, to AIDS Action Council and the large service organizations -- which, despite ongoing pressure from their major donors, have usually refused to become seriously involved with treatment development. To do so could jeopardize important relationships that they must maintain in order to accomplish their service missions.

The end result is that treatment progress is seldom allowed to happen outside of big-business control. And big business had no interest in AIDS until AZT made money, and is losing interest now as ddI, ddC, and d4T are unlikely to ever repay their development costs. The result? Near-guaranteed stagnation, which is what we have today, and have had since the beginning of the epidemic. This is why there has been so little progress in finding better treatments for HIV, and why so little relief is in sight.

HIV RNA: New Viral Tests and Their Importance

New viral blood tests, much more accurate than the ones used before, have recently become available to physicians. These may provide a partial escape from the bleak drug-development and political landscapes above. [For background on these tests, see "HIV RNA: New Blood Test for Individualized Therapy and Faster Trials," AIDS Treatment News #204, August 5, 1994.]

These tests are important because they can indicate quickly (within a month, and possibly within days) whether a particular antiviral treatment is working for a particular patient. It doesn't matter if the treatment is mainstream, such as ddI, or "alternative," such as Chinese herbs; if the virus in the blood is reduced, the tests will show that.

This means that certain new treatments -- those in actual use by people with HIV, or which can be prescribed by physicians or otherwise obtained -- now will have a path to begin to build credibility. Probably the great majority of "alternative" treatments will be found not to work, and be largely discarded. But if one patient benefits dramatically from a treatment (as seen by reduction of virus in the blood), and then a second, third, and fourth also show a dramatic reduction, then there will probably be enough interest to get that treatment into a formal trial, either through a community-based research organization, or by finding a corporate sponsor. The potential new treatment will then be on a development path, instead of left waiting forever.

This almost never happened before the new tests were available, since it has been necessary to crank up an expensive and cumbersome trial before there was any credible data suggesting measurable benefit in people. Now, the credible data can start with one person's decision to use an unproven treatment, not for research but for their own medical care. If the early data is negative -- the usual case -- the patient can drop the treatment quickly, and perhaps try another. And if the data is promising enough, formal research can follow.

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