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 Developing diagnostic tests for Alzheimer's hasn't been quite the burial grounds that developing therapeutics for the disease has been. That's mostly because there has been even less progress on basic science underlying diagnostic testing than that on the therapeutic one.

I don't know if much of the electorate appreciates that while there is much work taking place on Alzheimer's disease, particularly therapeutics, a significant portion of that work is based around one hypothesis for the etiology of the disease—amyloid. For 30 years, advocates of the amyloid hypothesis have pushed for research funding (perhaps more than 30, I know just the past 30) into that particularly line of thought. Other areas haven't received quite as much funding even as the amyloid hypothesis work hasn't been able to show much progress on the therapeutic front. Perhaps that will change if there is a diagnostic test for an earlier stage of disease when more neuronal pathways presumably remain intact.

A similar focus was made in the national War on Cancer. The research hypothesis then was viruses, and because the Nixon and Ford Administrations were convinced that scientists outside the government (and even most of those in it) were people who were wasting precious government funds proceeding in an organized manner, those administrations issued contracts for research mostly into a viral etiology. Perhaps there is a viral etiology to cancer; the research conducted certainly didn't find it, and the bureaucrats in the White House who directed the NCI to contract this research at academic medical centers and contract research organizations (think RAND, Batelle, and so on) were insistent that this be the singular focus of the NCI. (BTW, funding to develop stealth technology was originally declined by the White House because it was too "fanciful"—the term used by the analysts in the Office of Management and Budget and work on the Internet (then known as the Arpanet) almost met the same fate except that it was sheltered in the ARPA budget; the assertion by the White House then was that if the ARPAnet really had any value, it would developed by private industry, not the government.)

Not much progress was made on either the etiological or therapeutic fronts (in contrast to heart disease, where the research program of the government, spearheaded by the NIH) rested on a variety of etiological and treatment hypotheses) with cancer. Indeed, for thirty years, the major achievements of the War on Cancer was the reduction in the incidence of lung cancer. That result was achieved principally through smoking cessation programs (the culmination of research at the NSF as well as the NIH—some from the heart institute, some the cancer one), not the contracted basic science work. With lung cancer incidence in decline, the NCI decided to roll the dice with other prevention programs, principally diet and supplements. The basis for such an approach was not nearly as developed as for smoking cessation (for which the epidemiologic base was solid), and it has not been nearly as productive.

The knowledge on viruses was useful, just not for cancer. Peter Ducker notes that this research was still valuable for discerning that viruses were not the etiological approach to be further pursued (at least not then) and that the information gleaned in the course of that research was nearly as valuable as if the research had been successful. The response to the AIDS epidemic, when research funds were finally made available, was greatly facilitated by having that knowledge base about viral etiologies of disease available. And in that respect, it's probably one of the reasons AZT, originally developed as a treatment for cancer before work with it was discontinued, found its way into the treatment regimens for the disease. It took some time to develop a sufficient basic science basis for the develop therapeutics for HIV infection, and we still lack a cure (and for all the hoopla about how those with HIV live almost as long as those without it, the reality is that resistance is developing to the available medications so the need to develop new medicines is still present).

One of the lessons of the success of the smoking cessation programs compared with the other approaches to cancer was that the basic science work needed for those programs—from epidemiology and behavioral science—was established by the time the cessation programs were developed. (The same can be said for high blood pressure control and stroke.)

The problem with the moon shot approach to biomedical research is two-fold: 1. It needs to be coordinated by the government (and as NCI demonstrated, picking the winners in such research isn't something the government does well—better to take the ideas from the medical community and pursue the leads meeting with increasing success) and 2. (as Peter Drucker has noted on many cases) in the absence of an established research base, such efforts are doomed to failure. For both Manhattan Project and Apollo, the scientific base was established before the "moon shot programs" developed.

Don't be surprised if the current moon shot approach to cancer meets with the same fate as the viral etiology one.

As for Alzheimer's, maybe this diagnostic test will mark the beginning of a different approach to the etiology and treatment of the disease.


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