Towards a biological perspective on disease

Abstract:

Disease is so familiar that even those concerned with it professionally fail to recognize its conceptual complexity. Many of our perceptions about disease have been adopted uncritically from medicine's long and at times, unscientific, tradition. In recent years, evolutionary ideas – which form the bedrock of modern biological thinking – have come to be applied to disease. However, it has been medical notions of disease to which these ideas have really been applied rather than biological ones. This is potentially problematic; a more accurate biological understanding of this and other medicinal terms is, therefore, necessary. Focusing on the terms 'illness', 'pathology' and 'disease' and their inter-relationships, this paper presents a synopsis of some of the ideas explored while I was a Visiting Fellow at the KLI during the summer of 2005. It is suggested that 'illness' has greater biological significance than is usually realised, especially in terms of individual survival; that the term 'pathology' needs to be distinguished from 'disease', and care be taken to use this term to refer to specific organic characteristics, and that 'disease' be better understood as a label that represents sets of experientially subjective and physiologically objective phenomena that contribute to alterations in the overall biological state of an individual as an organism. Health is mentioned briefly and also envisaged as being a biological state only configured differently to that associated with disease. Some of the consequences of these findings are considered in relation to Darwinian medicine and how they might affect research strategies. Significantly, it is suggested that disease should not be considered in a simplistic, unitary way but as a set of organic responses. Each of these responses should be understood in their own right, in relation to others and in terms of their effect, individually and in combination, on the individual as an organism.

Often at the start of an academic year, I find myself in a meeting where, because we have new colleagues, we have to take turns at saying who we are and what we are interested in. I have, therefore, devised a little statement:

'My research is concerned with exploring the biological and philosophical aspects of the concepts of disease and health and considering the uses and applications of these findings.'

For brevity, the fact that I undertake this within an evolutionary context is left implicit in the word 'biological'. Similarly, this context should also be assumed to be implicit in my title.

Some of this research was carried out here this summer. In the time allowed, this 'Brown Bag' represents a brief synopsis of just some of the ideas upon which I have been working and, I hope, offers some food for thought. There will inevitably be some gaps and some things will be passed over rather briefly.

One of the big problems I encounter with this work is that whenever I tell somebody what I am interested in it seems that they immediately know more about this subject than I do. I'm certainly quite 'Socratic' about these matters, in that I am well aware of my own ignorance, which often seems to grow the more I find out. But my 'betters' in this matter also tend to convey a sense of puzzlement about the need to even address this topic.

For justification, I could call upon Bertrand Russell and suggest that:

'The point of philosophy is to start with something so simple as not to seem worth stating, and to end with something so paradoxical that no one will believe it.'

Or, perhaps Iris Murdoch, that:

'[P]hilosophy is often a matter of finding a suitable context in which to say the obvious.'

More seriously, I could call upon Imre Lakatos and suggest that what I am really doing is standard human biology in a different guise because:

'[I]f we want to learn anything really deep, we have to study it not in its 'normal', regular form, but in its critical state, in fever, in passion. If you want to know the normal healthy body, study it when it is abnormal, when it is ill.'

In this vein, a suggestion from closer to home proposes that:

'Central to the enterprises of both philosophy and medicine are the images and ideas held about what man is and what his existence signifies for himself and the world …

… medicine and biology are two powerful instruments of scrutiny of the image of man. Together with philosophy, they can help contemporary man to understand a little more about what he is'

(Editorial. (Edmund Pellegrino) J. Med. Phil. 1976)

However, rather than simply relying upon these pronouncements, the practical example of this list from an article in the BMJ in 2002, and the ensuing questions, may be more compelling.

Which is, and which is not, a 'disease'?

And why?

The point of opening with these questions is to demonstrate the difficulty in getting definitive views about disease. I could go around the room asking opinions about which on this list is a disease and which is not – and I am sure to get a number of different answers. Not all of these would, in fact, be consistent with each other. Generally, one finds that there are two particularly common underlying assumptions that influence the type of answer given. One is that disease is something 'abnormal' about the body as a whole; the other is that disease is a specific 'malfunction' within an otherwise healthy body. This is not to exclude the influence of other ideas or even superstitions.

This slide has, in effect, already gone around a room and got answers for us.

Here we have 4 groups of people with whom each of us can probably identify in one way or another. The percentage of people in each group who thought that a given named condition on this list was a disease is indicated. Although opinion converges towards the top, we notice that there are differences of opinion within groups and between groups throughout. Deciding that something is or is not a disease is not as easy as one might think.

Selecting just a couple from the list, let us consider these pictures:

A lung taken from somebody with pneumonia; which around 80% of them considered a disease.

However, given these pictures, we might ask, where exactly is or was the disease? We can see quite obvious changes in the configuration of the organs here but organs are made of tissues and doctors often refer to 'diseased tissue'. So perhaps the disease is at tissue level. But tissues are composed of or derived from cells so perhaps that is where the disease really lies. In a few brief sentences, I have, in effect, described a series of changes in medical thinking that occurred within less than a century and a half. Between the mid-eighteenth and late-nineteenth centuries, medicine shifted its disease focus from the patient to his organs, then to his tissues, then to his cells. (And more recently, that focus has again shifted to his genes.)

I can see no real problem in suggesting that these pictures illustrate pathological changes or that we have here illustrations of 'gall bladder pathology' and 'lung pathology'. After all, the word 'pathology', taking its root from the Greek 'pathos' meaning 'to suffer', seems rather apt. However, in medical thinking and usage, the words 'disease' and 'pathology' are frequently used interchangeably. The phrases 'diseased tissue' and 'pathological tissue' have come to mean much the same thing. Fortunately, in bringing about a cure it does not seem to matter. However, it is not medicine – or the medical or related professions – about whom I am really concerned. I want a better biological understanding of such words because, as biologists, we use them too.

Unfortunately, medical usage does have a marked bearing upon my interests. Scientific approaches to disease – as undertaken in Darwinian medicine and in Health Science as an academic discipline – both commit the same error and that is that they both adopt their notions of disease uncritically from medicine where precision in this respect has not been entirely forthcoming. Darwinian medicine seeks to apply evolutionary theory to understanding our vulnerabilities to disease. But if we are going to apply evolutionary theory in this way, we need to stop and ask whether we have the right basic notion of disease in the first place.

Throughout history, there have been two predominant explanations of disease. Each has prevailed at different times but never without the other going away completely. On the one hand, there is the view that disease results from an inherent somatic imbalance within the body of an individual and on the other, there is the view that disease is something added to, or inflicted upon, the body from outside. Even today, our thinking is still influenced in various ways by such ideas. We still speak, for example, of getting or having certain diseases as if they had a separate existence that comes to coincide with our own. We must be careful not to apply advanced biological thinking to outmoded and faulty notions of disease. The results of such a merger are sure to be flawed – if not entirely wrong. Furthermore, theories of disease reflect theories of the organism. For the biologist, adopting erroneous theories of disease may even prove harmful to the science of biology itself.

Much attention has been paid to the notion of disease on its own, but, this summer, I have focussed upon it in conjunction with two other terms: 'pathology' and 'illness'. In so doing, I have tried to gain some understanding of each via the inter-relationships between them.

However, I should note in passing, the word 'sick' (and 'sickness') lest people wonder why it has been excluded. This is a word that gets used in a number of different ways – sometimes synonymously with illness or even disease. However, it does have a fairly definitive technical meaning. The physician Marshall Marinker – who discussed different modes of, what he called, 'unhealth'' summed up sickness as:

'... the external and public mode of unhealth. Sickness is a social role, a status, a negotiated position in the world, a bargain struck between the person henceforward called 'sick', and a society which is prepared to recognise and sustain him.'

An act of societal legitimization is involved here. A 'sick' person gets a 'sick note' from his doctor and adopts the 'sick role' and qualifies for various forms of assistance. Having mentioned this, I should now like to set it aside from further consideration.

Returning to my three terms, of these it is perhaps surprising that the most easily understood and definable is, in fact, 'illness'. I say surprising because the term 'illness' refers to what is after all a subjective experience.

As Marinker points out, illness also has a technically acceptable definition:

'Illness … is a feeling, an experience of unhealth which is entirely personal, interior to the person of the patient.'

It appears that 'illness' is more easily understood and definable precisely because of its very subjectivity. If a doctor were to tell us that we had 'such-and-such disease', most of us would have to take this on trust – remembering, of course, that sometimes such diagnoses can be quite wrong. But if we feel ill, we feel ill and we know it. What's more, it is we who decide when we should go to see a doctor in the first place.

The relation between the experience of illness and our underlying physical state is not always straightforward. As Marinker goes on to point out:

'Often [illness] accompanies disease, but the disease may be undeclared, as in the early stages of cancer or tuberculosis or diabetes. Sometimes illness exists where no disease can be found.'

But everybody has experienced illness and so knows what others are referring to when they use the word. Indeed, I suspect that it is really 'illness' that my 'betters' – those who think they know more about my subject than me – really have in mind.

Illness is certainly not quantifiable. If it could be measured, we would be certain to find that what confines two different people to their beds would differ markedly. That this is the case and that illness is a somewhat subjective phenomenon does not mean that it is without biological significance. However, I do believe that the biological role that illness plays has been overlooked somewhat because we have only thought of it in medical terms. Illness appears to be a feature of an individual's general mechanism of self-awareness and prompts behaviours aimed at remedying some underlying physical condition. In short, it might be described as a means whereby the organism is made to ensure its own individual survival. Although much of evolutionary biology is described in terms of populations and gene frequencies, it must be remembered that, in order for these frequencies to be expressed, genes need organisms – or, as they have sometimes been called, survival machines. By interpreting a body state as (what we call) illness and reacting in a way that ensures survival, an organism increases its opportunities to leave offspring which, in turn, exhibit these same capabilities.

There are numerous animal examples of behavioural and dietary modifications in response to certain underlying physical conditions. Well known, partly because these have been easier to confirm and manipulate experimentally, are responses to infection but responses to non-infectious conditions are not excluded.

I am not, of course, suggesting that animals feel 'ill' in the same way that we do. But what I want to emphasize is the fact that organisms – certainly those above a certain level of organisation – have a means of registering aspects of their biological or systemic state and that this is important in helping them survive and, as a result, reproduce.

Hereafter, I must begin to take issue with Marinker. I concur with his definition of 'illness' (as I did with 'sickness') but of another of his modes of 'unhealth' – 'disease' – I must differ. Of disease, he says:

'Disease ... is a pathological process, most often physical as in throat infection, or cancer of the bronchus, sometimes undetermined in origin, as in schizophrenia ... There is an objectivity about disease which doctors are able to see, touch, measure, smell.'

Here, what we really see is the identification of 'disease' with 'pathology' again. As stated here, the two are synonymous. Many, like Marinker, have sought to provide a concise definition of disease but what statements like this suggest is that a clarification of the relationship between disease and pathology is perhaps more pressing. If we could come to a decision about whether they were really the same or were instead quite separate, then defining disease per se might become easier.

To this end, it is perhaps useful to take a lead from the work of Giovanni Morgagni (1682-1771) and his 'De Sedibus et Causis Morborum per Anatomen Indagatis ' (1761). Morgagni is sometimes described as the father of modern pathology. It was he who set the 'disease focus', to which I referred above, on its course down from the level of the whole individual to that of the cell. 'De Sedibus' was one of the first works to associate the experience of being ill – or more properly, in those days, diseased – with internal lesions. This he did by relating the autopsy findings of many hundreds of patients with their previous medical case histories. Morgagni appears to have seen disease and the associated lesions as being different in kind. These lesions were the 'seats' of disease not their 'sites' – although a few have mistranslated the word sedibus in this way. An internal lesion was not disease incarnate but rather a seat from which disease – in the sense of a 'loss-of-ease' – could be said to emanate.

To put this figuratively, this is a 'seat':

that is, a 'seat of power' – a power which emanates and has it effect (usually malign) throughout a different kind of realm. In organic terms, a body may acquire a 'seat of disease' in some way. This, in turn, will have various effects and consequences throughout the rest of the body. There may be one or more physical lesions as a result plus a variety of physiological changes.

What Marinker believes, ''a doctor can see, touch, measure, smell' etc. is not disease per se but its seat and that seat's effects in terms of the resulting alterations in the structures and/or processes of the body. It is these to which I believe the words 'pathology' and 'pathological' best apply. Furthermore, whereas Marinker saw illness as accompanying disease, since I am arguing that it is the pathological that he is really referring to, then it follows that it is the pathological that illness really accompanies. This is not really surprising given the ways in which the brain can be affected – directly and indirectly – by that which is pathological elsewhere in the body.

Although we tend to think of illness and pathology separately, the two are, in fact, closely linked. Illness is, in effect, the body's recognition of the pathological elevated to the level of awareness. Indeed, there is a case for arguing that what we consider to be pathological gets this title primarily because of the illness – that is, the suffering – associated with it.

(I must acknowledge here that there are, indeed, instances of illness being experienced without obvious organic basis and instances where lesions develop without giving rise to discernable illness. However, I don't think that such examples fundamentally alter the position I have just outlined. I shall be returning to this again below.)

I have referred to the pathological as that which brings about suffering. Pathological changes are essentially alterations in anatomy and physiology and affect a number of different discernable parameters. Each of these exhibit operating ranges where suffering is and is not experienced. This may be represented figuratively by a series of linear variables which constitute a group I shall refer to simply as 'Anatomy & Physiology' in the following way.

Earlier, I also suggested that illness appears to be a feature of an individual's general mechanism of self-awareness. As part of self-awareness, we may consider a similar series of parameters, again represented linearly, that refer to such experiences as nausea, headache, pain etc. This group I shall refer to simply as 'Self-Awareness' in the following way.

These too may be expected to have ranges where illness is and is not experienced.

Together, all these variables contribute to an organism's 'overall biological state'.

This we may think of as an overall quality of the system that, although contributed to by some objectively measurable components is, when considered as a whole, not itself measurable in the usual sense.

This 'overall biological state' may also be easier to understand figuratively. The blob below has the overall quality of being (I shall say, being colour-blind) 'orange'. But the computer produces this using RGB values. In computer terms, these numbers have some objective meaning in relation to redness, greenness and blueness. The blob, however, has the overall quality of 'orange-ness' for which the computer has no separate, objective measure.

As a consequence, I would like to suggest that disease can be better understood as being one, or more probably a range of 'overall biological states' that an organism may have. Such a state can result from what I shall simply refer to as a 'disturbance' of some sort impinging upon both the material aspect of the body – that which I have referred to merely as 'Anatomy & Physiology' – and the existential aspect – that which I have referred to merely as 'Self-Awareness'.

I would like to suggest further that when one uses a specific disease term – such as 'pneumonia' – one is really using a convenient label to refer to certain arrangements of the variables within the 'Anatomy & Physiology' and 'Self-awareness' sets.

Thus, disease is not just a set of pathological features; nor is it just an experience of illness – it is a combination of both. And if one or other is absent, then the individual's state, I suggest, is not strictly one of disease.

At this point, it is perhaps worth adding a brief note about the concept of 'health'. If disease is, as I have just said, 'a convenient label [that] refer[s] to certain arrangements of the variables' in the two sets that contribute to 'overall biological state', then health too is a label, only applied to a different arrangement of the same variables. Disease and health are different versions of what I have called 'overall biological state'.

The difference between what we might call, a 'disease set' and a 'health set' is, at least, threefold. Firstly, there are differences in the status of the component variables of each set; secondly, there is a qualitative difference in the 'overall biological state' of the organism as a whole; and thirdly, there are lived consequences of these first two.

As the WHO would have it, health should not be seen as merely the absence of disease. Indeed, many others have expressed similar aspirations. I think that that perspective is evident here as a matter of course rather than desire. What I have suggested does not see health as an absence. A 'health set' is as full as a 'disease set'. What differs is the condition of the components of each set and the resultant biological state of the organism.

As noted above, disease is not just the pathological; nor is it just illness – it is a combination of both; if one or other is absent, then the individual's state, I suggested, was not strictly one of disease. By the same token, health is not just undisturbed anatomy and physiology; nor is it just undisturbed self-awareness – it is both. If one or other of these is otherwise, then the individual's state is not strictly one of health.

As noted earlier, there are instances of illness being experienced without obvious organic reason and instances where lesions develop without giving rise to discernable illness. In the model proposed here, neither of these situations conforms to either a state of disease or of health. We now have a position in between the two. Rather than being a problem, this seems to conform more accurately to reality where intermediate positions between disease and health exist and need to be accommodated.

In the literature, the idea that there are shades of health or shades of disease seems to have gone largely unexplored – even though a number of writers have described disease and health as being part of a continuum. No two people that one might label as 'healthy' are 'healthy' in exactly the same way. Likewise, no two people that can be labelled as having the same disease will have exactly the same condition or experience thereof. Thus, taking my coloured blob metaphor further – and hopefully not stretching it too far – these blobs all look the same but they are 'the same' in slightly different and virtually indistinguishable ways: they are all slightly different shades of orange because the underlying RGB values differ slightly. In the same way, the components of a 'disease set' or a 'health set' are also sure to differ slightly.

Why the terms disease and health are used as they are is a question that continues to tax many engaged in the philosophy of medicine. It is, in effect, one of the questions I posed before I started:

Which, from the BMJ list above, is, and which is not, a 'disease'? And why?

I have avoided the 'Why?' question and am not going to try to give a concise answer to it today. Neither has what I have suggested so far sought to answer that question directly. However, I raise the 'why' question now because I do believe that what I have suggested does change the way in which we go about asking this question. Previously, we had a list of named conditions each of which, I suspect, we thought of in a rather distinct and circumscribed way. One of the corollaries of what I have suggested is that now we must think of different diseases as being continuous with each other in some way. When we considered gall stones and pneumonia earlier we saw, I suspect, two distinct conditions and only noticed the differences between them. There certainly are differences but there are also similarities in tissue response, in systemic response and in how the individual is affected as an entity.

In medicine, were the aim is to effect a cure, a disease label is convenient in managing a patient's condition. Sometimes this may be the wrong label but this does not matter so long as you get better (or you get your patient better) – and if that is achieved, who is to know that the label was wrong anyway? Biologists are not concerned with cures. For a biological understanding of what is going on within the organism and its significance for that organism, and, indeed, its significance for the species as a whole, medical type labelling is inadequate.

As a label, one can still, I think, use the notion of disease in a unitary way – much as before – but now, that unity, it must be recognised, results from thinking of disease in terms of a set of component responses, not as an independent entity. But whereas for the clinician a few signs and symptoms may be sufficient to make a diagnosis and effect a cure, the biologist must now ask exactly what constitutes a given 'disease set' and what the individual roles of each of these components might be. More than that, consider this as a set depicting just four ways in which the body can change in response to different stimuli.

A given stimulus 'X' results in a certain response, whereas a given stimulus 'Y' results in another response.

Then, the following questions arise:

· Why these particular responses? (Or lack thereof)

· Why the differences?

· Why the similarities?

· What are the consequences for the organism?

In effect, the final question does already exist in Darwinian medicine. However, I believe it to be limited somewhat to a consideration of some of the better known signs and symptoms already familiar to clinical medicine. There may be effects, yet to be described, where the biological significance is greater than the clinical.

Having mentioned Darwinian medicine above, I should return to it before closing and note how what I have suggested relates to what is probably Darwinian medicine's most fundamental statement (given by Randolph Nesse), that

'Darwinian medicine is the enterprise of trying to find evolutionary explanations for vulnerabilities to disease.'

If, as I have suggested, disease is better understood as a quality or state of the whole organism – the result of changes in component parameters due to what I called a 'disturbance' – what does that do to this statement? I tend to think that this statement fits better with the 'disease as an entity in its own right' school of thought which tends to see all disease in terms of the infectious disease model. In my view, a 'Man vs Disease' mentality, where the former is a victim of the latter, is not an appropriate biological stance to adopt.

In at least one place, Nesse adds:

'… Disease, [is] not … a product of [natural] selection.'

If my suggestion is correct, might not at least some of the phenomena associated with a 'disease set' be open to, or the product of, natural selection? I rather suspect that they are.

My aim here has been to try to provide suggestions as to how we might tidy up the biological use and understanding of certain words imported from medicine. My aim has not, therefore, been to try to analyse why the medical profession – or anybody else for that matter – uses these words in the way they do. As a result, I have, quite deliberately, not attempted to concern myself with any notion of seriousness or severity when it comes to illness, pathology or disease.

I am not sure exactly where the following quotation comes from – or whether, as given, it is entirely accurate – but I should like to close with this thought from Wittgenstein, that

'The meaning of a word is its use.'

And in using this phrase, I shall use it so that it has the meaning I want it to have.

The words I have discussed are used in different contexts – I have mentioned only the medical and the biological – and it is not inappropriate for these words to have certain differences in use and, therefore, meaning. However, while biological meanings should not differ fundamentally from those found in medicine – which is, after all, the prime user of these words – it does not necessarily follow that biological insights should not result in achieving more accurate and precise meanings for these words. Medical words and the way they are used are not the sole preserve of the medical profession; biology – certainly where focused on the human – should stake at least an equal claim. But while medicine seeks to cure, biology seeks to understand and in understanding has to express this, largely through words about which it should be clear.

To this end, I believe that the suggestions I have offered, at least, help us to make a start.