To Order

I am honored to be invited to write this Foreword to John Lowe’s book, The Metabolic Treatment of Fibromyalgia, the more so because we have known each other for such a short time. We first met at the University of Texas Health Science Center in Houston, Texas, as co-organizers of a "Congress on Defining a New Paradigm for the Healing Arts, May 28-31, 1998." My colleagues and I were impressed by the account John gave to the Congress of his systematic approach to fibromyalgia research, particularly his practical use of the principles of formal logic, including Mill’s Canons of Induction. This use of formal logic, in my experience, is as rare as it is potentially relevant to clinical research.

In spite of a quite extensive pre-conference e-mail discussion, there was a noticeable lack of consensus amongst participants at the Houston Congress on its purpose. This is not unusual at such gatherings, but amongst a small group of us a sense of purpose emerged quite quickly. We were there to try to characterize an increasingly perceptible paradigm shift in the healing arts of which we, and we felt many others, were becoming aware, and to try to discern and express some of its consequences.

After the conference, I reported to participants and observers that it now seemed clear to me that the nature of the paradigm shift itself had been presented to us—in slightly disguised form—on the very first day. Physicist Elizabeth Rauscher (one of our group) had shown the Congress a cartoon with two near-identical blob-like creatures with the caption "Have you considered the possibility that your reality and my reality are not the same?" The shift itself can be expressed in the following terms: from "implicit acceptance of the view that all human beings have the same perceived reality" (old paradigm) to "explicit recognition that each human being has his or her own unique perceived reality" (new paradigm). The consequences of such a shift are profound and cover all aspects of human existence, including of course, the healing arts.

More recently, Virginia Postrel, in her book The Future and Its Enemies, characterized a static-dynamic, stasist-dynamist polarity in our present day society that reflects, but cuts across, traditional political boundaries. The framework provided by her approach helps us to capture very precisely what is wrong with current, essentially stasist, approaches to clinical practice and how the essentially dynamist approach advocated and illustrated by John Lowe in this book provides a remedy. Ultimately, it all comes down to making it possible for informative feedback to be effective in promoting continual learning in our humanly-created artificial systems, just as it is in natural systems.

One of the consequences of the new paradigm is that we are required to be explicit about things which previously we handled implicitly. This, it seems to me, is literally a change in human consciousness. Frank Lucatelli (one of our group) has pioneered the development of a formal general methodology for making explicit what is implicit in our language of common and technical discourse. It is commonly assumed, for example, that there is just one kind of scientific method; but Lucatelli’s formal general methodology allows at least four types of science—operational, axiomatic, experimental, and exploratory—to be distinguished. At the present time, clinical science seems to be largely an operational science, and this suggests that there may be much to be gained from broadening its scientific base to include the other three types. As the work described in this book demonstrates, John Lowe has made significant progress in this direction.

But when, at the Houston Congress, we attempted to start to apply Lucatelli’s methodology to the language of the healing arts in general, we were almost overwhelmed by the enormity of the task, and many of us were tempted to try to set it aside. The enormity of the task, however, is a pointer to its importance and to the profound consequences of accomplishing it successfully.

Nevertheless, the somewhat harrowing session conducted by Frank Lucatelli at the Congress bore fruit. It led to a realization that maybe one of the things that has been missing is the overt recognition by clinical scientists, that clinical science is, amongst other things, a behavioral science. The study of systems with feedback is, of course, a central preoccupation of behavioral scientists, and it is perhaps no accident that both John Lowe and I were psychologists—behavioral scientists—before we became clinicians.

As a teenager growing up in England in the immediate post WW-II period, I aspired to be a biological chemist. Amongst my heroes were A.J.P. Martin and R.L.M. Synge, who were awarded the Nobel Prize for Chemistry in 1952 "for their invention of partition chromatography." In his presentation speech on behalf of the Nobel Committee, Professor A. Tiselius asked: "How can it happen . . . that something apparently so commonplace as a separation method should be rewarded by a Nobel Prize? The answer is that from the very beginnings of chemistry until our own time, methods for separating substances have occupied a key position in this science. Even today, in Holland, chemistry is called ‘Scheikunde’ or ‘the art of separation’. . . ."

When, in the mid 40s, I first became aware of Martin and Synge’s work, I marveled at the power of their separation method. It made me realize—in a way that I had not up to that time—that one can contribute to the solution of a problem not just by solving it, but also by developing a method for solving it. Indeed, the latter may be a more profound way of contributing and may have the most lasting impact, as many other problems beyond the original one may be amenable to the new method. This was already clearly the case with Martin and Synge’s work in 1952. I therefore committed myself to learning not just how to solve problems, but how to develop methodologies for solving problems. From that time on, a project—to get my interest—had to provide opportunities for both.

But I also had an interest in chromatography as such. According to Tiselius, it was invented in 1906, as a technique of chemical separation, by the Russian- Polish scientist Michael Tsvett, although there are earlier examples of similar approaches. So what exactly did Martin and Synge contribute? Tiselius described it as follows: "The novelty in Martin and Synge’s method is thus not the [specific techniques] but rather concerns the fundamental chromatographic process itself. This can now be formulated as the partition of a substance between two liquids . . . . Thus we have a rational basis for the method and enormously larger possibilities for choosing the experimental conditions which will be most suitable in any particular case." This is a clear example of the importance of knowing not only that something works but also why it works.

John Lowe’s work illustrates these same principles. He has conducted systematic clinical research to gather evidence that his fibromyalgia protocol works for many patients, and he has developed a rational scientific explanation for how and why this protocol works when it works. This means that his techniques can be applied and, if necessary, adapted to meet the needs of any individual fibromyalgia patient. By starting from the working assumption that fibromyalgia is a manifestation of some form of "hypometabolism," a search for the underlying metabolic abnormality in any particular case can be conducted, and if it is found, a rational therapy can be instituted. Furthermore, in the context of this approach, the implications of the occurrence of hypometabolic signs and symptoms in various modern chronic conditions, such as chronic fatigue syndrome, silicone breast implant syndrome, and Gulf War Syndrome, can be seen.

In his Nobel presentation speech, Professor Tiselius described a common application—paper chromatography—of Martin and Synge’s method as follows: "A drop of a liquid containing the substance to be investigated is allowed to fall onto a strip of paper, where it forms a little spot. This paper is then caused to draw up some suitable mixture of liquids . . . by capillary action. The spot begins to move, and one can see how it then gradually segregates into several spots, some of which follow the liquid which has been drawn up, while others lag behind. There thus results a resolution of the mixture into its component parts, a resolution which in the last analysis depends on the different partition of the substances between [the liquids in the mixture]."

To me, the most obvious thing about this account is that it describes a "behavioral" science. The components of the substance being investigated are separated because they behave differently in the liquid environment in which the spot is placed. One can imagine photographing the paper at regular intervals to show successive positions of the spot. This record would allow construction of a behavioral trajectory of the spot. Its final photograph—when the spot has come to rest—would correspond to the paper chromatograph as normally understood. In John Lowe’s fibromyalgia protocol, the results of examinations (photographs) at intervals of various aspects of the status (spot positions) of the patient are recorded graphically to show the "behavioral trajectory" of the status of the patient, as she responds or fails to respond to therapy.

This kind of behavioral trajectory was pictured in my mind when I later became a behavioral scientist and started looking for opportunities to return the chemists’ compliment and develop a "behavioral chromatography." There was no shortage of leads. Maze learning tasks—if the details of the learner’s behavior in successive traverses of the maze are recorded, and this is a purely technical problem—can be regarded as generating a series of behavioral chromatographs. In 1966, my coworkers and I reported the application of a method based on this principle to the study of brain failure in elderly patients. We were later able to show that it yielded results of considerable predictive value in the management of the rehabilitation of patients with brain damage. It was found, for example, that irrespective of their performance on such a maze learning task on the day following admission to a rehabilitation unit, patients who had achieved an error- free performance by their third weekly re-test had a high likelihood of eventually making a good functional recovery. The task performance seemed to be reflecting not so much the patients’ initial status as their ability to respond to the rehabilitation program. Back then there were technological barriers to the widespread use of this method. But nowadays an up-to-date version of the method could easily be made available as a computer game—downloadable over the Internet—and might well have a future role in the management of the metabolic rehabilitation of patients with fibromyalgia by allowing the regular monitoring of behavioral markers of hypometabolism.

The picture of chromatography that I have painted above led me to an interest in analogous processes of many kinds. Stimulated by my own Cornish ancestry, I developed an interest in the history of tin mining—until quite late in the 19^th century Cornwall was the world’s leading producer of tin. I was particularly intrigued by the mechanical separation processes that had been developed to concentrate the relatively low grade cassiterite (SnO₂) ore found in Cornwall to a smeltable level. The processes involved mixing the pulverized ore with water to form a slurry which was then fed through a series of devices, including vibrating tables, which separated the cassiterite particles "behaviorally"—according to their relative density. Interestingly enough, mining engineers call these devices "classifiers." But I was initially mystified by the fact that the flow charts of the separation plants for different mines, while constructed of similar components, were quite different from each other. This turned out to be a reflection of the fact that while the cassiterite from different mines was quite similar, the other minerals from which the cassiterite had to be separated were characteristic of the specific mine from which the ore came. And so a unique process, adapted to the context of the cassiterite ore, had to be designed, implemented, and managed—using informative feedback—to maximize yield. The individualized nature of the metabolic treatment of fibromyalgia patients parallels the mining situation. John Lowe’s protocol can be "adapted to the context" (to the variability of symptoms in patients with inadequate thyroid hormone regulation of transcription) by "using informative feedback—to maximize yield."

When, nowadays, we speak metaphorically of "data mining," we are acknowledging similarities between the mining engineer’s physical processes and our own data processing techniques. We recognize both the extent to which our software processes model mining processes and the extent to which mining processes may be thought of as embodying a form of computation—witness the mining engineer’s use of the term "classifier."

An account of a seminal experience which, to the best of my recollection, took place in the spring of 1965, will lead us to a discussion of the relevance of these considerations to the metabolic rehabilitation of fibromyalgia patients. In the fall of the previous year, I had been appointed to the faculty of the University of Cambridge, England, and had set up a Unit for Research on Medical Applications of Psychology (URMAP) under the joint auspices of the Departments of Medicine and Experimental Psychology. The general aim of the URMAP program was to develop a model of a behaviorally-oriented clinical science, while its specific focus was research on traumatic brain injury (TBI) rehabilitation. This implied taking a careful and thorough look at the nature of rehabilitation and rehabilitation research in general. We started by noting that people seemed quite prepared to discuss re-habilitation without first discussing habilitation. It raised the question, "Can one understand how to re-do something without first understanding how to do it?" In view of the fact that I ended up with an approach which placed regular clinical practice in a rehabilitation context, rather than the (traditional) reverse, I find it particularly significant that John Lowe has chosen the title "metabolic rehabilitation" for his approach.

At that time, I held an appropriate British National Health Service honorary (adjunct) appointment in the Department of Neurological Surgery at the university hospital (Addenbrooke’s Hospital, Cambridge). This department was headed by a well-known neurological surgeon who had worked in Oxford during WW-II and had helped to pioneer modern surgical methods of treating traumatic brain injury.

Most weeks my URMAP colleagues and I attended the Department of Neurological Surgery rounds at Addenbrooke’s Hospital. On the occasion in question, the director of the Department was out-of-town and his deputy officiated in his place. We reached the bedside of an unconscious young women who had been admitted some days previously. The deputy director went up to her and conducted a neurological examination, relaying his findings to the rest of us as he did so. On completion of his examination, he confessed that he was stymied; he could not recall having previously seen anything like the clinical picture the woman presented. Neither could anyone else present. The deputy director decided that the only thing to do was to maintain the necessary life support and wait until the director was back in town.

The following week the director was back in town. When the round reached the bedside of the unconscious woman, the deputy director summarized the situation for the director, who then conducted his own neurological examination. When he had finished, he stepped back from the bedside and said to the assembled company that he had seen a case like this when he was at Oxford in the fall of 1939 (over 25 years previously). The patient had died and on post- mortem examination it had been found that a small blood vessel had burst and bled into a mid-brain nucleus. He suggested, therefore, that in the present situation a radiological examination that would visualize the region of the woman’s brain where the bleed had occurred in the previous case should be carried out. This type of procedure had not been available in 1939, though in 1965, there were still many advances to come before reaching the days of modern radiological visualization techniques.

The radiological examination suggested by the director was carried out, and it revealed not a burst blood vessel but a tumor causing pressure on the same region of the midbrain nucleus that had been damaged in the earlier case.

The events described in this story had a profound effect on the direction of both the general and the specific URMAP program. The points to which it drew attention were as follows:

Consideration of these three points makes it clear that the value of precedent cases in deciding what to do for a current case does not depend on there being exact matches between corresponding parts of the precedent case and the current case. It depends, rather, on there being what we might call a "sufficient connection" between corresponding parts.

The situation in legal reasoning is similar. In his Introduction to Legal Reasoning, Edward H. Levi wrote: "The basic pattern of legal reasoning is reasoning by example. It is reasoning from case to case. It is a three step process . . . similarity is seen between cases; next the rule of law inherent in the first case is announced; then the rule of law is made applicable to the second case." The judge’s initial task is to determine similarity or difference between cases, deciding when it will be "just to treat different cases as though they were the same" and so allow a rule derived from consideration of a first case to be justly applied to a second case.

John Lowe started his work by studying the literature to find conditions that "matched" the symptoms of fibromyalgia. It appeared that rheumatologists had failed to recognize—or even to look for—known conditions that had a "sufficient connection" with fibromyalgia. So, like the deputy director of the Department of Neurological Surgery in the story above who had to wait for the director to come back to town to "recognize" the problem, clinicians have had to wait for someone to recognize fibromyalgia as hypometabolism. And this is what John Lowe has done. He saw the connection between inadequate thyroid hormone regulation of transcription and fibromyalgia signs and symptoms. He studied the literature further to see if most characteristics of both conditions "fit" together. And in Section III of this book, he shows that he has established a foundation for making such a "sufficient connection" a working hypothesis in individual cases.

Much of clinical practice is based on reasoning from case to case, and like the judge, the clinician’s initial task is to determine similarity or difference between cases. If a clinician learns the science and follows the protocol in this book, he will be able to recognize fibromyalgia as a hypometabolic disorder and discern how to help fibromyalgia patients, even though they may vary from each other in the specific pattern of symptoms they exhibit (which is, in itself, evidence of a pathophysiology that can manifest with variable tissue responses). John Lowe has developed guidelines for determining when it is "just to treat different cases as though they were the same," so that fibromyalgia patients can be treated as hypometabolic by reason of either thyroid hormone deficiency or peripheral resistance to thyroid hormone. When he treated fibromyalgia patients this way, most of them recovered. The protocol chapter (Chapter 5.2) describes a set of rules derived from consideration of a set of "first cases" which can be justly applied to a "second case."

The story of the "out-of-town director" also raised the question of what would have happened if the director of the Department of Neurological Surgery had not seen a similar case previously, or if he had been out- of-town indefinitely, or if the patient had been admitted to a different hospital, and so on. The whole process of relying on the recalled personal experience of the individuals who happened to be on duty, or on call, seemed too haphazard and inefficient. It suggested a role for the then-emerging electronic information handling technology in health care—to store the experience gained by clinicians in handling each case in such a way that it could be retrieved to assist the same, or other, clinicians in handling a similar case at a later date.

A little reflection will show that pursuit of these seemingly modest goals will sooner or later raise all the key questions and drive a long-term R&D program. And that has certainly been the case up to the present time. One not immediately obvious consequence is that a patient might well benefit from the investigation of another patient seen later by the same, or another, physician. To see something of the implications of this, just consider how the early history of AIDS or the Gulf War illnesses might have been different if such a system had been in place 20 years ago.

The above example introduces what is, essentially, a librarian-library model of clinical research. One can imagine a case library, each volume containing a clinical description, with a shelf-mark based on its contents. With each new case, baffling or not, an appropriate shelf-mark is determined using standard classificatory rules, and adjacent volumes on the shelf are examined for helpful suggestions on how best to help the new case. Easier said than done, but a very worthwhile goal nevertheless.

Nowadays, of course, the librarian-library metaphor is ubiquitous; it is the underlying metaphor of the Internet and the World Wide Web, with the Universal Resource Locator (URL) as the shelf mark. We can conceive of patient records being a part of such a library and accessible by the same means as any other document on the Web. Leaving aside issues of security and privacy—which may be best handled by infomediary agents buffering transactions—the main outstanding problem is how to address documents by content. The method used must determine similarity or difference between cases, allow a decision as to when it will be "just to treat different cases as though they were the same," and so allow a rule derived from consideration of a first case to be justly applied to a second case.

The issue of whether people should be treated as fundamentally all the same or as fundamentally all different has already been raised, and it has been suggested that the latter presumption underlies the emerging new healing arts paradigm. In practice, however, it comes down to a matter of finding an appropriate "resolution level" for the situation we are trying to deal with. At one extreme everyone is unique; at the other extreme everyone is the same. But for most problems, particularly clinical problems, we need a resolution level that will give us a picture between these extremes. This is the resolution level that will maximize the informative feedback needed for learning by both physician and patient. The following example brings out some of the relevant issues.

Imagine a black and white graphics display screen showing a 64 by 64 checkerboard. Overall there are equal numbers of black and white pixels, but they are distributed over the screen in such a way that the individual checkerboard squares appear as lighter and darker shades of gray. When we view this checkerboard from the right distance, we recognize a portrait of Abraham Lincoln. Now imagine what will happen if we progressively simplify the picture by merging adjacent pairs of rows and columns, replacing each 2 by 2 block of 4 squares by a single block which displays the average of their grayscale values. The number of squares in the picture will decrease from 4096 to 1024 to 256 to 64 to 16 to 4 to 1. At some point we will fail to recognize the President, and at some point we will fail to recognize a human head, until, with the portrait collapsed into a single gray square, we will have a picture of nothing.

If I ask the question, "This is a portrait of Abraham Lincoln—True or False?", the answer will obviously depend on the resolution level of the display. If I ask the more general question, "This is a portrait of a man —True or False?", it will usually be answerable at a relatively coarse minimum resolution level, while a more specific question, "This is a portrait of Abraham Lincoln wearing his double-breasted coat—True or False?" will usually require a relatively fine minimum resolution level.

But now imagine the 64 by 64 checkerboard resolved downward to the penultimate level, where it becomes a 2 by 2 picture containing just 4 squares. We cannot answer any of the questions about Abraham Lincoln simply by looking at such a picture using our unaided human senses. But we may be able to answer most, if not all of them—or at least narrow the possibilities—by using a technology of "pattern matching." Each of the four squares represents a shade, or value, of gray. If we reduce "reference" portraits of all American Presidents to such 2 by 2 pictures, the likelihood of any two portraits containing identical gray scale values for each of the four squares is small.

If we now similarly reduce an unknown portrait to the same 2 by 2 level, we can almost certainly identify it (or demonstrate that it does not belong to the reference set) by comparing it with each of the reference portraits until we find (or fail to find) a match. If we find multiple matches, we can resolve the uncertainty by moving to the next highest resolution level. If we find no matches, we can reasonably conclude that the unknown portrait does not belong to the reference set. This kind of pattern matching is possible because, in any set of portraits created under uniform conditions, even small patterns of gray scale ratios drawn at low (and therefore economical) resolution levels are likely to be unique for each individual portrait.

This use of a "portrait library" to identify an unknown portrait is an example of what, nowadays, is called "collaborative filtering." The "filtering" portion of the name refers to the pattern matching that sorts, or "filters," or classifies, the unknown portraits. The "collaborative" portion refers to the fact that the people who contribute portraits to the library collaborate to produce the result. We may apply collaborative filtering to clinical practice (and thus lift it beyond "anecdotal evidence," which is the rough equivalent of trying to recognize the 2 by 2 square portrait of Lincoln by unaided senses alone) by producing, electronically, "clinical portraits" based on such clinical data as patient and family histories, symptom profiles, standard laboratory blood test results, and so on. And in the future, this data will be augmented with relatively easily obtained "personality profiles," "behavioral chromatographs," and "biofield characterizations"of various kinds.

Such clinical portraits provide us with the informative feedback we need to manage the metabolic rehabilitation process. In this book John Lowe describes manual ways of doing this by plotting charts (behavioral chromatographs) of patients’ progress based on changes in their symptoms. Our goal for the future is to develop and provide easy-to-use computer based aids that will bring this process electronically within the reach of all physicians treating fibromyalgia with this protocol.

I suggest that an important element in our description of the "new healing arts paradigm" is the idea that for each "clinical problem" there is a "clinical portrait" at an appropriate resolution level. This ensures that the informative feedback the physician uses is relevant and appropriate and so maximizes the opportunity for learning. A corollary is that many current problems result from adoption of inappropriate resolution levels, sometimes because the very concept of appropriate resolution level is itself unacknowledged. If, for example, the indications for a particular drug therapy are defined at too coarse a resolution level, the success rate at clinical trial could turn out to be less than that needed for the drug to become an accepted treatment. If the indications had been defined at a higher resolution level, it is likely that fewer patients would have met the criteria for the therapy but the success rate in those who did qualify would have been higher. One can even imagine a situation in which there are, say, 10 drugs which, when given to a random selection of the patients for whom they are indicated on the basis of a low resolution level clinical picture, each work in 10% of the patients treated—not an impressive outcome. But this situation is entirely compatible with the same 10 drugs being given to (random selections from) subsets of patients defined in terms of a higher resolution level clinical picture and working in 100% of the patients so selected, and together covering all patients, a 100% overall success rate.

Not very likely perhaps, but clinical trials of drugs and other therapies could be aimed at learning how to move closer and closer to such an outcome. By comparison, the current approach is enormously wasteful and ineffective.

One of our Houston Congress colleagues referred, in a nice turn of phrase, to "the much-worshiped double-blind study." In the present context, "taking the double-blind study seriously" is a convenient way of introducing some key issues of practical importance. We will conclude that the role of the double-blind study in the new healing arts paradigm will be a much more restricted one than is generally accepted at present, as it is possible to sketch the outlines of a plausible successor. The value of examining this issue in some detail is that it exposes the weaknesses of the current paradigm and leads to an appreciation of the strengths of possible successors.

Imagine the following situation. We have a pure chemical substance, PCS, and we have good a priori reason to believe that PCS, administered to patients according to a well-defined PCS protocol, could be an effective therapy for some, but not all, patients in a general diagnostic category known as CDC (Chronic Debilitating Condition), for which there is no known effective treatment. In the present context, it is acceptable to substitute "thyroid hormone" for PCS and "fibromyalgia" for CDC, and to note that the PCS example provides a model for understanding what John Lowe actually achieved with a mental inference engine in his early clinical trials and later double-blind studies.

We conduct a clinical study of PCS therapy by, initially, offering the treatment to ALL patients who meet the standards for diagnosing CDC. After a pre- specified time, appropriate to the natural history of CDC, we evaluate each patient’s response to the therapy and decide whether they are "better," "worse," or "neither" (this is, of course, a nontrivial task, but with computer aids it can be done with internal consistency). As soon as we have some patients who have been evaluated in this way, we build the first version of an inference engine that, given the data on which the original diagnosis of CDC was made, infers whether the outcome of PCS treatment will be better, worse, or neither.

We use this inference engine to predict the outcome in all patients who have started, or are about to start, PCS treatment but have not yet been evaluated. As each patient is evaluated, her data is added to the database and a new version of the inference engine is built and applied to patients whose responses to PCS therapy have not yet been evaluated. Let us suppose that, after a time, the inference engine is predicting, with a consistently high level of performance, the outcome of PCS therapy in patients who have not been evaluated. Let us say, for illustrative purposes, that the engine is indistinguishable from 100% effective. We might now make a decision to offer PCS treatment only to patients for whom the inference engine predicted a "better" response, or perhaps, a "not-worse" response, depending on how cautious we want to be. An advantage of the latter would be that it would allow a more effective fine-tuning of the inference engine’s discrimination of the boundary between "better" and "not-better."

The overall result of this approach is that the inference engine has allowed us to refine our diagnostic criteria to the point that PCS treatment is, for all practical purposes, 100% effective. A smaller proportion of CDC patients will be getting PCS treatment than originally, but those that do get it may be, with near certainty, expected to benefit. And the search for equally effective alternative therapies for those who do not qualify for PCS will be accelerated.

At this point a skeptic might ask, "OK, you have evolved this augmented PCS treatment protocol that is 100% effective, but how do you know that the pure chemical substance, as such, has anything to do with it?" Responses to such a question might take many forms, some best left to the imagination. But if PCS was a low cost, readily available, nutritional supplement with no known harmful effects, and given that CDC is what its name implies, a chronic debilitating condition for which there is no known treatment, we might be tempted to answer, "We don’t, and it doesn’t matter to us or to our patients; they are only too happy to be better, whatever the mechanism." (Such arguments are often put forward by practitioners of Traditional Chinese Medicine—"This therapy has worked for 4,000 years; who are we to question it?").

But mindful of the value of learning more about how such a successful therapy works we might be tempted, in our response to the skeptic, to add, "If you can provide us with a good enough reason for wanting to know the answer to this question (one that will make sense to us and our patients), and if you are willing to cover the cost, we will conduct a double-blind study for you." The study will be conducted as follows: Starting from a certain date, we will explain to each new patient meeting the requirements for being offered the augmented PCS treatment protocol, that we are conducting a study to determine what contribution the pure chemical substance in the PCS treatment protocol makes to its 100% effectiveness. We explain that if the patient agrees to volunteer to enter the study, she will have a 50% chance of having the pure chemical substance in her PCS treatment protocol, and neither she nor we, her doctors, will know whether she did or did not until after the evaluation of the treatment’s effectiveness.

It should be noted at this point that whether or not the patient volunteers, the very introduction of this choice opportunity into the situation changes the doctor-patient relationship irrevocably. The doctor has revealed him or herself to be someone who is willing to put the patient in the position—potentially stressful— of having to decide whether to volunteer or not. If the doctor decides beforehand which patients to offer the choice to, he or she may later be accused of biasing the results of the study by manipulating the patient selection. I am not suggesting that putting the patient in this situation can never be justified; I am just making the point that such a step cannot be taken without consequences that may affect the outcome, one way or another.

If, for the moment, we assume that a double-blind study can be justified and that we have sufficient volunteers, the advantage of the approach I have outlined is that since all the volunteers are qualified under the augmented PCS treatment protocol, the expected success rate if treated is 100%. So if the pure chemical substance is indeed essential, the effects of its absence will show up quickly and definitely, and so a statistically significant result can be obtained with a small sample. Under the most favorable circumstances, this might mean that the placebo patients start on the genuine PCS treatment protocol after a modest delay, the research having been completed.

The key point is that to use the double-blind approach legitimately, the treatment protocol must have already been optimized. The double-blind method can then be used to detect differences in alternative approaches to the part of the therapy for which double- blind substitution is possible (such as PCS versus a lower cost alternative).

As I mentioned above, John Lowe’s therapeutic research followed this model quite closely. In his double-blind studies, the "pure chemical substance" was indeed essential, and the effects of its absence in placebo phases showed up quickly and definitely. So a statistically significant result was obtained with small samples of patients. John’s treatment was not quite 100% effective, but almost! His experience, however, raised an additional issue: If, in a double-blind study of the above kind, the treatment works, the patient, the doctor, or both will tend to change their a priori expectations as to efficacy and outcome while the study is still in progress. It is clear that this happened in John’s studies because the treatment was so effective. So in this extreme case the double-blind may be of limited duration.

So what, in a nutshell, is the message of this Foreword? There is a phrase in American political discourse that originates from the 1992 Presidential campaign. The ultimately victorious Democratic party campaign manager had a slogan over his desk to remind him of what it was all about, lest he be tempted to wander off target. The slogan was, "The economy, stupid!" I shall count my writing of this Foreword a success if just one reader makes him or herself a sign, physically or metaphorically, that says, "The feedback, stupid!" Let me, in conclusion, put this statement in a broader perspective.

One of my most persistent memories of the pathology course I took as an undergraduate at Cambridge in 1952—the year prior to the publication of James D. Watson and Francis H.C. Crick’s paper on the "double helix" structure of DNA in the journal Nature—was Professor H.R. (Daddy) Dean’s unstinting praise of Oswald T. Avery’s work, published in 1944, which identified DNA as the purveyor of genetic information. This primed me to read, upon its publication in 1976 (nearly a quarter of a century after my course), Rene J. Dubos’ fascinating book, The Professor, The Institute, and DNA: Oswald T. Avery, His Life and Scientific Achievements. In Chapter 5, "Avery’s Life in the Laboratory," the book contained an account of a normal day. I was astonished to learn that, typically, research was conducted on a 24-hour cycle. I had not appreciated until then, that in this kind of laboratory research (because, in this case, of the relatively short incubation times needed to grow microorganisms) new hypotheses could be formulated and tested, and the resulting feedback digested and assimilated, in less than 24 hours. At that time, all my own research experience (apart from computer software development) had been in the human behavioral sciences, much of it in clinical research on possible therapies for Alzheimer’s Disease, and the research was conducted on a minimal time cycle of months, if not years. No wonder progress was slow! Since this realization I have become increasingly interested in the whole question of how the minimum possible informative feedback cycle time affects the nature of research.

In her recent book, Molecules of Emotion: The Science Behind Mind-Body Medicine, Candace Pert made the very same points about feedback in describing what she found most effective in the conduct of her own laboratory research. She wrote: "This concept of the rapid feedback loop . . . explains the way I have done my science over the years. Most of the success my team and I have had resulted from a shortened feedback loop between performing an experiment and then using the results to make immediate changes or adjustments. In our AIDS research [my partner] and I cracked the mystery of the peptide that fit the AIDS virus receptors by initiating a new experimental question each morning, getting the results in the afternoon, and then pouring over the data every night for changes to be made the next day." This approach was part of her legacy from Solomon H. Snyder, in whose laboratory she did her Ph.D. research. She wrote of "[Snyder’s] philosophy of the rapid, one-day turnaround, what he called the ‘speedy flier.’"

The above quotation comes from a section, in Chapter 12 of her book, in which she described a visit and consultation with an "information doctor," a California physician, Dr. Robert Gottesman. Dr. Gottesman approvingly quoted Gregory Bateson’s definition of information as "the difference that makes a difference" and went on to say to her: "‘. . . I use the rapid feedback loop concept when treating patients. As you yourself have experienced during our consultation, I ask lots of questions to get my patients to pay attention to what’s going on with them, to self monitor. It takes time, which most doctors won’t spend, but I do it because I want my patients to become aware of the difference that makes a difference to them. Those who are able to respond in this way, to do their own self- monitoring, get well faster because they have more intelligence at work in their systems, more information to bring about changes that bring about improvement. So I think ultimately it saves time.’"

Dr. Gottesman is helping his patients to become co-researchers of their own health problems. But why do most of us regard this as new? Have not good physicians always done this? Yes, I think they have, but what may be new is that we now have the concepts of information science available to us to help us to describe and discuss, in behavioral terms, what may be going on in such doctor-patient relationships. It seems to have taken an inordinately long time for this to come about. When, in 1953, I was a beginning psychology student at Cambridge, there was incessant talk about "information theory" and the promise it offered for the development of a truly scientific psychology. Similar discussions were going on amongst students of other biological sciences, including the future molecular biologists. Information theory inspired the work described by British psychiatrist W. Ross Ashby in his well-known book Design for a Brain. This, and similar publications, formed our staple diet. When, in 1954, I arrived at University College Hospital Medical School, London, as a clinical student, one of my classmates, Oxford graduate Hugh B.G. Thomas had already made substantial progress in developing a quantitative information theoretic approach to the study of human behavior that could be applied to a wide range of clinical research problems. Later he was one of the earliest clinical researcher users of the computer time-sharing services that became available in the early 60s.

While I can think of quite a few possible reasons for this 50-year delay in adopting an information theoretic approach to clinical science, I suspect that the reasons are quite complex, a reflection of the static- dynamic, stasist-dynamist polarity described by Virginia Postrel (referenced above), and will need careful historical research to sort out. Such research would be very useful because it would help us, at this millennial moment, to better understand our present situation and future opportunities. Nevertheless, we already know enough to conjecture that the minimum informative feedback cycle time for clinical research can be lowered to close to the time it takes for a therapy to produce reportable change in individual patients. The technology of the Internet makes this possible by allowing cases that previously had to be studied sequentially to be studied in parallel. Instead of one physician studying 16 patients, 16 physicians—using an agreed upon protocol—can study one patient each. The results can be analyzed as they become available, and the information so obtained can be used, as necessary, to modify the protocol for the next cycle—a clinical "speedy flier." The development and promulgation of such a collaborative, parallel approach to clinical research are important aims of the new Academy for the Helping Professions. John Lowe, our colleagues, and I are currently working to bring the Academy into operational existence.

In this book John Lowe describes what appears to be a remarkably successful therapeutic approach to fibromyalgia, which is generally considered an "incurable" and largely "untreatable" condition. It is an approach based on well-tried principles that have, in times past, found expression in a wide variety of human endeavors, from jurisprudence to tin mining. These principles—as I have tried to show above—allow past experience to be justly brought to bear on new situations, even when those new situations are perceived to be unique. Taking the message of this book seriously is the first step in providing meaningful help, and a well-founded hope of recovery, to fibromyalgia patients. The book does not offer a "cure" for fibromyalgia, or give, or even try to give, all the "answers." But it asks and begins to answer the right questions—questions that change the underlying paradigm upon which fibromyalgia research is based, and thus help steer this research in a more promising direction.