A FIRST EXAMPLE OF WHAT I AM AFTER

On the main page of Site Logic, I outlined my purposes. Science informs medicine, medicine uses science to alleviate illness. Among other matters I am in search of the paths between them. Said more exactly, I am after the mechanisms through which science arises from medicine and how the results of science inform practice. This one disease will suffice, I think, but only if we are willing to study individual examples from it. That is my purpose here.

The picture gives away my general idea. The path is not a labyrinth but a maze. You walk the former pleasurably, there being one path to its center and another back without confusions. You walk the other for it’s wit and for the pleasure of matching it’s wit against your own. It is built as a deception, and the way is anything but obvious.

THE STONE CRYSTALS

I Am Not An Historian

One way to track from science to medicine and back is in retrospect, to read the papers over a century or more and reconstruct what seems to have happened. I like that idea but cannot fulfill it being untrained in history of science or medicine. I also do not believe it is the right way. It will offer a picture from which one may imply what has happened. I prefer otherwise: To look at what we have with a sharp and indifferent eye and ask what it is we have from science in medicine, and in science from medicine, and come up with some scientifically testable hypotheses about how things work.

The Starting Place

It cannot be otherwise than in medicine. Stones are produced by people who present their problem – hard and unwanted objects in the urine – de facto, meaning from the very fact of their existence. How important this is cannot – to me at least – be over trumpeted. Patients produced the stones at the beginning of things, and the troubles they had and have in their passing of them is why the illness came to notice and its causes to such importance as to warrant research. So we enter the maze here, at the fact that some people become ill from the forming and passing of hard objects in their urine.

Being hard, like stones, they naturally took on that name.

It is not in the purview of a patient as such – meaning a patient who is not a scientist – to determine what the hard object is. A patient might be a scientist and try to find out. Likewise a physician as such is not a scientist although some physicians may also be scientists.

This distinction is crucial: the goal of a physician is health in a single patient. The goal of a scientist is to discover how nature does things or how we can do things. Although it is indeed true that one person can be a patient who forms stones, a physician who treats such patients, and a scientist who discovers how stones form and the manner of their prevention, that truth is without meaning here. The roles are different even if subsumed within one life. So it is the roles I emphasize. And the role of first observer of the ‘stones’ is subsumed per force by patients and doctors, whereas the role of those who determine what the ‘stones’ are made of is subsumed per force by scientists.

The Middle Ground

I believe the middle ground is always present.

What stones are made of can be determined only by scientists who discover how nature does things, in this case produce hard objects in human kidneys. The ways of the discovery are those of science, and eventually the problem was solved and the answers given, as I have given them here: Nature produces objects made of crystals, and the crystals make them hard. But the path to discovery is not through science alone. Stones must be provided to scientists who, in their proper roles, neither take them out of patients or from patients but, instead, receive them from those who do.

This brings to the foreground that doctors may be scientists who gather stones from their patients and take them to their own laboratories. But, especially now, we draw a green line between medicine and science. A doctor may not take stones from patients and proceed to analyse their composition without permissions. If in fact the obtaining of such permissions is burdensome and sometimes of questionable value to patients, it demarcates or honors – if one chooses to say so – a powerful philosophical distinction of type.

In the middle ground, stones are provided by doctors or their institutions to scientists who determine how they are made. But, here the word is more important than is often the case, the doctor also provides something unique and easily overlooked: The nature of the people, the patients, who produced the stones.

The laboratory as a place of science and discovery

Everyone knows about this: Equipment, arcane measurements, mathematics, tables of numbers, tracings of unfathomable character to all but the initiated. Out of it come the answers about what the stones are made of.

We know very well that stones are made of crystals. We have come to know how crystals form, how atoms construct crystals, how solutions carry in their supersaturations the power to generate crystals.

Supersaturation is a concept within the field of material science and crystallization research, but can be transferred into medical practice if one knows the crystals patients make and one can obtain the proper samples of urine from patients and make the measurements needed.

We also know that stones contain complex molecules that form a matrix which perhaps holds the crystals together and certainly affects the rates at which crystals form. Unlike the crystals which are well categorized if, perhaps, imperfectly analysed in laboratories which sell such analyses, the matrix is not as yet at all cataloged completely. So although one may say with considerable certainty that this patient, as an example, forms such stone crystals, and that patient other crystals, we cannot at present say the same for the matrix except with considerable uncertainties.

The clinic as a place of science and discovery

By ‘the clinic’ I mean that place where physicians and patients come together that the one might provide for the other relief from illness. It may be a simple room, an operating theater, a hospital setting – that does not matter here.

But what can a physician as a physician ‘discover’? I have already said physicians discover the proper remedy for a given patient. Usually that remedy arises from discovery of the cause of illness, which is called disease, and diseases each have, at any moment in time, their baskets of remedies.

Why physicians per se are not scientists though they discover

But the discoveries of physicians, howsoever important, are not scientific; they do not give insight into how nature does things, nor into how we can do things we cannot do now. The diseases they know to discover – diagnose – in their patients have already been discovered by science and are provided to physicians in their textbooks, or reviews, or courses, or whatever means are used to enable them to practice. Likewise for the remedies for a particular disease.

In the present example, physicians can provide to scientists the stones from a patient, or from many patients they have seen. Likewise, they can provide other information about these patients, like their urine supersaturations, or even facts about their general medical conditions. But in so providing they are not performing science, they are performing a service to the furthering of science.

Science concerned with how nature does things arises from an idea, about – in our example – what makes stones hard; and such science progresses as the ideas are tested against reality. The test demands some deduction from the idea to a prediction about what will be found in the real world when looked for in a specific way. So the stones and other information physicians might provide to scientists will be materials used to perform the test.

Science concerned with how we can do things also arises from an idea – in our example, perhaps, how to facilitate stone passage or removal. The test is more obvious than in the prior instance: The way works or not. Here, physicians perform the test, for who else can manage stone passage or removal but a physician? But that is not necessarily to do science. It is to test a prediction that has arisen in others – of course once again I am concerned with roles not people who may be both physicians and scientists.

The physicians who do the test are scientists only if whether it works or not has been organized scientifically, for example as a clinical trial, and they have an intellectual and scientific role. To do the test is to be a technician, in a laboratory or a clinic, an agent of science but not a scientist. To design and analyse a trial is to be a scientist. That is why the myriads and bevies of physicians who find patients for a trial, even when they help to collate and organize the data, are usually not scientists.

Why physicians who are also scientists are so important

Physicians who also perform science have direct access to the information about patients that arises in the course of practice and also know how to conduct scientific research. They are closer to the reality of stones in people – using our example here, see them in a fresher state, observe stone passage first hand. Their passion for discovery arises, or may arise, from not only curiosity but also a sense of necessity as they face the reality of what stones do. They have – to borrow metaphor from a sport I do not much favor – a ringside seat.

Likewise they are more likely to envision a better way to facilitate stone removal, or even passage, being so accustomed to the reality of these situations. And, once envisioned, they are the very people who can carry out the test.

Why scientists who are not also physicians are so important

Although physicians may indeed run laboratories of even a highly technical character, one human life permits only so much range, so in general the time and energy needed to become a physician and remain a good physician leave less than enough to permit sustained performance in highly technical measurements. This is not an absolute rule; the world teems with exceptions. But even so, much of the time, novel and difficult measurements – on stones in this case – will need scientists who devote their careers to the difficulties of the techniques involved and join their results with those from the clinic to make up the final scientific product.

What happened to the stone crystals?

I am afraid like some careless electrician I have left out a crucial wire and the circuit is undone: No current flows, the lights do not go on. We began with an implied history – how things had to have happened, and have achieved one part of that necessity. Stones arise in people, and when their nature was unknown scientists had to find it out. But what then?

It is this: The names of the crystal become – became in fact – the names of the stone diseases. Think about that. Calcium oxalate, hydroxyapatite, brushite, uric acid, cystine, struvite, and the rare. Patients who pass hard objects and have proper names, and genders, become – in their care – the names of the crystals they form.

If you like words like ‘phenotype’ – which I hardly do, the word having been coined only very recently and lacking therefore any historical resonance, lacking even an atom more than the meaning of its Greek constituents – the stone crystal becomes the first name: Calcium oxalate stone former, for example.

What happened to the marriage?

This is how it can work – it being the marriage of science and medicine. Depending upon the importance of a distinction which arises from scientific measurement, the distinction becomes part of that patient phenotype within which physicians intuit and scientists prove other distinctions that make up the causal nexus and the suitable treatments, empirical or mechanistic, of that organized body of information we refer to as a disease and its remedies.

I cannot write my entire book here, in this little space, but consider. Calcium oxalate stones and a high urine calcium excretion sans other obvious disease – we have the idiopathic calcium oxalate stone former with that hypercalciuria which has gradually become understood as genetic, systemic, and an apparent cause of bone fractures as well as stone formation.

The crystals of the stones are linked to the patients who produce them. The causes of the stones in those who have formed them are linked to the persons and their stones. One by one and layer by layer – how the urine calcium comes to be high; how crystals form in the kidneys – the phenotype of a particular kind of patient comes into its existence and gathers about it its web of remedies.

The crystals are discovered in the laboratory using stones from the clinic. The causes are defined in the patients using blood and urine and perhaps other materials from the clinic. Each new element proven in patients can become a minor or major part of the final phenotype.

And so, as in that marriage upon which rests the renewal of the human world, this more minor but nevertheless essential marriage of science and medicine creates the very substance of medicine itself – the diagnostic categories, or diagnoses, towards which all clinical practice tends and from which all treatments take their starting points. And these diagnostic categories are nothing more nor less than the phenotypes, or archetypes of disease.

The marriage partnership

The crystals are discovered by professional scientists in the course of their natural work. The causes of the crystals are discovered in patients by professional scientists in the course of their natural work. Physicians use the results to practice. In their practices physicians often observe what needs to be explained by science, and often observe that what science has provided lacks reliability or general application. They are not passive. Physicians are to science like engineers to physics, or skilled carpenters to their blueprints – practical users inpatient with results that do not work well in practice, that do not reliably produce remedy of illness.

New ideas about how the causes produce the stone crystals, how the causes themselves come to be – for example that idiopathic hypercalciuria might be genetic – or how stones might be prevented or removed may well arise in the minds of those physicians who are also scientists, or perhaps in the minds of scientists having an interest in the problem, or – perhaps – in the minds of physicians who are not trained in science but able to collaborate with scientists who can convert their ideas into experiment.

But to convert new ideas into science requires scientists – who are or are not physicians – both because of the complexities of measurements and because the scientific process of hypothesis, deduction, and proof by experiment is an intellectual activity that takes a lot of practice to use correctly.

The essential materials to test the idea are gathered by physicians who are scientists or guided by scientists, and by scientists themselves. Measurements are made in laboratories, whether set up in a clinic or in some other place. The marriage occurs in the collaboration, and is celebrated publicly in the pages of journals.

The Ending Place

What do we have when the marriage is done?

We have the kind of knowledge I presented very briefly and incompletely in my posts about kinds of stones. Who makes uric acid or cystine or struvite stones, for example, compared to calcium oxalate stones. What are the characteristics of each type of patient; for example their urine supersaturations. That kind of information. My posts about the lexicon of stones, and about what stones are made of hardly hint at all we can say about the matter. But they illustrate the value of the marriages, for there had to have been many, as is evident from the various kinds of stones and their causes.

How do physicians come to know the answers?

What are the answers?

They are the kinds of stones in terms of their crystals, the kinds – phenotypes if you want to be fancy – of patients, which goes with which, and the implications of the stone types for remedy of stones in a particular patient.

It would be silly to say physicians learn all this by reading the original papers; that is not practical. Likewise, although I have edited and even written papers, reviews and even whole medical textbooks about stones, I have no illusions that physicians in the main have the time to study in them. They learn as physicians always learn, from other physicians, from their practice with patients, from such glances at books or articles as is practical – from the world of medical practice, which is large and hard to characterize precisely.

They also learn from summary texts – reviews, and perhaps blogs and sites like this one. It is indeed likely that the more common kinds of persons who write reviews, and blogs even, will be physicians who are also scientists – as I am.

They learn from guidelines, when there are any, and I have already expressed my lack of happiness with this process.

Of what value are the answers?

In this one example, the type of crystals linked to the types of patients who form a particular type of crystal, they learn which diseases – for that is what they have contributed – give rise to which crystals. In itself that knowledge does not directly lead to remedy. It leads to another cycle in which scientists must discover how a particular kind of patient with some specific kind(s) of disease form the crystals. This takes two parts: The factors that create such crystals and which of those factors arise from the diseases in patients. In other words, the problem is solved by scientists and then progressed in the middle ground.

As an example, it is supersaturation that drives crystal formation, so scientists must contrive means for measurements of supersaturations in the urine of those patients who form a specific kind of stone and determine if the supersaturations are, perhaps, increased by some abnormality in the patients. All this is within science itself because such measurements, though made using patients as subjects, are not part of their care but arise from research.

Physicians in the course of their own work discover what might contribute to higher or lower supersaturations in their patients, low urine volume because of occupation, for instance, and in so doing marry the reality of a patient’s life to the higher supersaturation that would cause crystals to form. At the ending place the life of a patient is translated through supersaturation into one pathway of treatment.

THE STONE MATRIX

As if provided for my thesis by a good fairy, this is a perfect example of a starting place. It is almost a void of knowledge. Right now technology is offering a way to progress knowledge in the laboratory, and perhaps soon one will have enough to proceed into the middle ground. A few papers I have quoted present matrix analysis from individual stones but none have approached a marriage between matrix, crystals, and patients who formed the stones.

How fortunate as a writer to be here now.

Perhaps in the life of this very site we will observe the opening of the middle ground, and see first hand how things go forward –  see what is there.

Regards, Fred Coe

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