The title for this seminar is derived from the poster that was displayed in the library during Science Week and which now forms an introduction to Darwinian Medicine in this webspace.
That poster was entitled 'Better By Disease' and was meant to be something of an oxymoronic eye-catcher. For me, it was also reminiscent of the time I asked a question at a lecture about the possible benefits of disease in shaping human populations. I was told afterwards that the question had made some people very angry, so I knew I was on to something provocative. Since that lecture, in 1995, I have come to find that I am not alone in this type of thinking and this has, in part, led to the field which I shall endeavour to introduce today.
Darwinian Medicine is a relatively new branch of study involving evolutionary science. For a long time, our understanding of evolution by natural selection has formed an implicit foundation for all biomedical research. There would be no logical justification for the use of laboratory animals in the pursuit of human therapies, for example, if we did not have some organic similarity. This results from having some common evolutionary history. Now, the principles of 'evolution by natural selection' or Darwinism are being used more directly to try to understand the problems of health and disease.
"Darwinian medicine," suggested Randolph Nesse, one of those who first coined the term, "applies the advances that have revolutionized evolutionary biology to the problems of medicine and tries to provide, for each disease, an explanation for why the body isn't better ...",
adding that,
"while natural selection does not shape disease itself, it does shape vulnerability to disease."
A word of caution before going too far, though. Darwinian Medicine, at least in its original or current form, has been primarily concerned with disease. The tacit assumption tends to be that other areas of evolutionary biology have looked at normal (and by implication 'healthy') human biology, but now it is time to look at the converse. There are problems with the terms 'health' and 'disease' as, I hope, will be seen and so for Darwinian Medicine to be couched solely in terms of 'disease,' would, I should like to propose, be inappropriate.
Randolph Nesse has suggested that "an evolutionary approach to disease studies not the evolution of the disease but the design characteristics that make us susceptible to the disease." But he also stated that "if tendencies to anxiety, heart failure, near-sightedness, gout and cancer are somehow associated with increased reproductive success, they will be selected for and we will suffer even as we 'succeed,' in the purely evolutionary sense."
In other words, the effect of susceptibility to certain (what we call) 'diseases' may be greater success in producing offspring. The individual may suffer but more offspring are left as a result.
Here we are beginning to see that disease is not all that it is usually made out to be.
As a field of study, Darwinian Medicine may be said to have originated only in this decade in response to ways of thinking that only began to surface in the 1980s.
In 1980, Paul Ewald's paper, in The Journal of Theoretical Biology, entitled 'Evolutionary biology and the treatment of signs and symptoms of infectious disease,' in many ways marked the beginning of the thinking. Later, in 1991, the paper entitled 'The Dawn of Darwinian Medicine' by George Williams and Randolph Nesse (in The Quarterly Review of Biology) and their book 'Evolution and Healing' published here in 1995 (and in America as 'Why We Get Sick' in 1994) mark the beginning of the use of the term 'Darwinian Medicine.'
This is, therefore, a very new field with all the concomitant attractions and novelty associated with trailblazing - and with all the pitfalls, too.
Nesse and Williams proposed that Darwinian Medicine might have the following branches for study:
Defences
Infection
Novel Environments
Genes
Design Compromises
Evolutionary Legacies
My own interests concern what might be called Non-infectious disease, in particular, diseases due to structure.
This might be thought of in terms of the 'body strategies'. What strategies do bodies, in effect if not consciously, take when constructing themselves as machines out to maximise their chances of passing on their genes and how, in turn, do these 'strategies' affect the experience of health and disease.
What I'm not, personally, interested in, but which has received considerable attention within Darwinian Medicine, is infectious disease. This is often viewed in terms of competition between organisms and incorporates ideas from games theory and is often described in terms of 'arms races' between a host and its pathogen.
For example, why do we sneeze? Is it to our benefit or that of the invading organism? It would appear to be some sort of reflex mechanism whereby the body ejects an invading organism. Then again, our reflex may simply be being used by the invading organism in order to help spread itself. Treatment should take which one it is into consideration. If sneezing primarily benefits us, then treatments that seek to suppress it are unlikely to be beneficial. If, however, sneezing primarily benefits the invading organism, then its suppression may benefit the wider group.
When we have a fever as a result of an infection, is it simply the concomitant result of foreign organisms getting into the system or is it the body's way of turning up the heat to a level that impedes the action of these organisms and leads, in various ways, to their death? In this case, the latter is strongly suspected. However, fever suppression is often practised. There is now some evidence to suggest that treatment to reduce fever can prolong the period of illness.
This, perhaps, typifies much of our approach to disease - we look at what ails us and try to remedy it. This might be nick-named the 'Anadin approach'. The advert used to state, "Tense, nervous headache? Take Anadin!" It described how tension at the back of the neck led to pressure at the top of the head and pain in the forehead. Anadin, however, relieved the pain, which reduced the pressure and thence lessened the tension in the back of the neck. Even as a boy, I puzzled why Anadin worked backwards. The logical approach is to knock out the cause and the rest will go too.
When one is suffering from an infection, iron levels are generally found to be reduced. This, to most clinicians, is a state of anaemia and should be corrected. It is, however, only an apparent lack of iron. During infection, the body locks away free iron as a form of defence so that invading organisms cannot use it themselves and make the infection worse.
The first time I read 'Evolution and Healing', I started a cold and took a multivitamin tablet with iron to pep myself up a bit as I was keenly reading this interesting new book - I promptly ended up needing antibiotics. Perhaps I fed the infection just what it needed? I do not know for sure - but it serves to illustrate a point and since this is, again, not my area, I shall leave infection at this point.
For some women, morning sickness is a particularly unpleasant feature of early pregnancy. It has gained notoriety because of what happened when thalidomide was used to alleviate its effects. It is now postulated that morning sickness may, however, have its benefits. It appears that morning sickness occurs at about the same time that the developing embryo is most vulnerable to toxins contained in the maternal diet. It has been suggested that nausea and sickness are the means whereby they are limited or expelled before they can cause too much harm.
Recently, one of the election campaigns was described, in derogatory terms, as having a compass but no map. In the old days, the lack of a map was all that was needed for some intrepid explorer to set off in order to fill in the blanks. This is what Darwinian Medicine feels a bit like at the moment.
Churchill said that we knew more about Alfred the Great than we did about Garibaldi. It was not that we had more information about Alfred - we have a great deal more about Garibaldi. The trouble is fitting so much, sometimes inconsistent, even contradictory, detail together accurately.
In suggesting that Darwinian Medicine should be concerned with health and disease, one is confronted with a fairly fundamental problem that is generally overlooked. On the Science Week poster, I had a section entitled 'The Conundrum of Health and Disease'.
I have found that while it was possible to do courses that describe what happens in various disease processes - for which all one needs to do is crib from a few pathology books and try to sound knowledgeable - there is very little by way of more meaningful understanding of these terms - certainly not in biological terms.
Finding a concise and accurate definition of 'health' has long proved illusive. Taking the term 'disease' and trying to define it - and by implication 'health' as its antithesis - is just as problematic.
Govan and colleagues suggest that disease might be considered using a form of equation:
The point of balance in any mathematical equation is the '=' sign. The left and right are, in effect, the same although expressed differently. This equation, however, hinges on the Body's Response. The Agent of Damage receives its distinction as such only if the Body's Response is one that conforms to a previously constructed concept of Disease.
And so we seem to be no further on.
This approach does highlight some important points though. Our diseases are the way they are, and we experience them the way we do, because of the way we are.
As bodies differ, then so must any definition of 'health' or 'disease' (just assuming such a definition is possible).
One approach open to the biological scientist may be to disregard the terms 'health' and 'disease' altogether as being simply too emotive and to concentrate instead upon the range of body responses characteristic of human life in all its forms. Sadly, the offending terms are too entrenched and layered with meaning to be ignored entirely.
However, Darwinian Medicine can be used to begin to try to do this, viewing 'health' and 'disease,' when the terms are used, as part of a single biological continuum.
As adults, we may be asked questions about our medical history. We may talk of having had the 'usual' or perhaps the 'normal' 'childhood illnesses'. This is partly because we can only just remember having had some red spotty disease but more generally we are referring to a normal biological manifestation of human living.
Darwinian Medicine asks why this should be our normal experience.
One interpretation may be that we are more able to cope with such diseases as children than as adults. Notice that this is not couched in terms of children being more susceptible than adults or vice versa. This may well be so but to talk in such terms is to focus on disease made manifest. Darwinian Medicine starts by thinking in terms of the benefits that may be gained by having such diseases in childhood rather than at any other time.
Diseases like chicken pox, for example, seem to be more severe in adulthood and may even be life-threatening. To have it as a child and gain the acquired immunity is not only to have it in a more palatable form but, in effect, to reduce the number of risks of death in adulthood.
To explain how such a situation may have arisen, suppose we take a population where there are just two types of people - those who get a disease, like chickenpox, more easily as children and get over it quickly, gaining acquired immunity, and those who get it as adults and show a higher incidence of mortality. These characterisitics are also inherited.
One would find that those in the latter group - who die before producing as many offspring as they could have - accordingly leave fewer offspring than the former group.
After a number of generations, the proportions of each group in a descendent population will have shifted to show a higher proportion of childhood disease-getters.
Another problem of the terms 'Health' and 'Disease' is whose 'health' and whose 'disease?'
The problem for any teacher of disease to a non-specialist audience is what are the diseases to which one confines oneself? To confine oneself to those important to the British or to the industrialized west has a quasi-racist element as not all diseases are experienced in the same way by all ethnic groups. If one chooses diseases commonly experienced by adults, there is a quasi-ageist element; a quasi-sexist element enters if one over-emphasises the diseases of one or other sex and there is a quasi-temporalist element if one focuses only on modern day experience. It is arguable that as far as the experience of health and disease is concerned, the twentieth century has been the least typical of any in human history.
An example of the way in which one can easily become blinkered into industrialized, Western adult thinking concerns the differences in the ability of humans to drink milk. All mammals have the ability to utilize milk as a food source as babies - that is what lies at the heart of the definition of being a mammal. In mammals, this ability is lost with age and may even form a biological mechanism whereby the ties between mother and child are broken so that she can go on and have more offspring and the child can go and have offspring of its own. When I talk about the ability to utilize milk, what I am referring to is the possession of sufficient quantities of an enzyme called lactase. This breaks the milk sugar lactose into its two component monosaccharides. These can be readily absorbed whereas lactose cannot. If not broken down and so not absorbed, lactose can get into the large intestine where the normal population of bacteria digest it, producing large quantities of gas. The osmotic relationship is also changed, causing water to be drawn into the large intestine. The sufferer becomes bloated, gets abdominal cramps and diarrhoea. (To simulate the effects, try a high colonic lavage with some gold top.) But, you may be thinking, I've had milk on my cornflakes, milk in my tea - we have a whole dairy industry! Westerners are mutants. It has been calculated that about 20,000 years ago, a mutation arose in humans which brought about the ability to produce sufficient lactase into and throughout adult life. This established itself in populations that have gone on to populate large parts of the globe. Nearly 100% of Europeans are lactose-tolerant - they can drink milk throughout life, whereas nearly 100% of Chinese and Japanese are lactose-intolerant. (When did you last see Ken Hom or - my favourite - Nancy Lam put cow's milk - as opposed to coconut milk - into a wok?) In Africa, the picture is more mixed; some tribal groups are lactose-tolerant, some are not.
Consider now what form food aid frequently takes: milk powder. The Westerner's perception is that you cannot beat milk - "drinka pinta milka day" was the advertising slogan. But for many non-Westerners, it is just the wrong stuff to get. In some places where milk powder has been received, it has been used to whitewash houses (important in order to stay cool) and, tellingly, as a laxative.
A corollary to this story is the reliance by lots of hip-Americans and similarly trendy Europeans on the macrobiotic diet. I do not know whether or not it has benefits so I am not really knocking it but for some, it does have a certain cult status. However, what is interesting is that this is a diet which excludes all dairy products and was devised by a man of Japanese extraction - where lactose-intolerance is commonplace.
At some stage in our evolutionary past, when salty and fatty foods were not as readily available as they are now, a physiological mechanism became established which produced a craving for these substances such that they were consumed whenever possible. It had clear advantageous effects in ensuring the maintenance of necessary physiological stores. These mechanisms have not been lost though.
Instead, compared with the pace of biological evolution, there has been a rapid transition to a society where such foods are now in abundance. An excess of these dietary components and a body that does not have a regulator that effectively limits intake are now implicated in a number of modern health problems.
To use the technical terminology, the environment in which the salt and fat craving mechanisms established themselves is referred to as an Environment of Evolutionary Adaptedness (EEA). We have, however, relatively little understanding of our Environment of Evolutionary Adaptedness - but least of all from the stance of treating modern disease.
Until now, emphasis has been placed on what are called 'proximate' causes of disease with very little emphasis on determining what humans are literally 'designed' for.
In looking for proximate causes of disease, one is seeking to answer questions of the 'what is going on [now]'-type; it focuses on too much fat in the diet; it describes the mechanisms involved in how this affects the individual.
Looking for evolutionary causes of disease, one is asking 'why'-type questions; such as why excess dietary salt or fat is so palatable and seeks understanding of human beings in terms of their 'design'.
Another example is polyarticular osteo-arthritis (OA).
This condition shows a particular pattern of joint involvement. Some joints, such as that between the base of the big toe and mid-part of the foot are commonly affected, whereas others such as the shoulder are rarely affected. A quick and simple - proximate - explanation for this pattern is that heavy mechanical forces due to walking cause the damage whereas the lighter forces act elsewhere to spare other joints i.e. it is simply a matter of physics acting on the body.
OA has been shown to preferentially involve the first carpometacarpal joint; first metatarsophalangeal joint; the distal interphalangeal joints and apophyseal joints of the spine. Also, the knee and the hip are commonly involved. Wrist, elbow, shoulder, ankle and 'hind foot' joints are rarely affected, though.
An evolutionary hypothesis for the pattern lies in a detailed understanding of the way in which the function of these joints has changed from moving from a quadrupedal to a bipedal form of locomotion - via a less clear intermediate form. In mechanical terms, the risk of OA developing in any given joint is related to the functional reserve in that joint.
All machines have a certain built-in functional reserve, whether designed-in by humans or by natural selection in the case of biological machines. One may think in terms of a car engine which has always been driven within its rev. limit and one that has not. The latter breaks down first.
The same argument may be applied to OA. Limb joints first evolved to suit quadrupedal locomotion. The move to bipedalism has been relatively rapid and has meant a redistribution of forces. This, in turn, means that the functional reserves of each joint have changed.
Those joints in which OA tends to develop more frequently are those joints with lower reserve capacities whereas those where it develops infrequently are those joints with plenty of reserve capacity. The upper limb in humans is no longer a weight-bearing structure and so has excess capacity in relation to the demands placed upon it, whereas most of the body's weight is now transmitted through the legs and much of the spine, for which reserve capacity is less.
An evolutionary approach to the structure of organs provides insight into why the form might be as it is and how this may then influence normal and abnormal function.
One common feature of organs such as the lungs, kidneys, and other glands (also the muscles - even perhaps the brain?) is that they are composed of numerous sub-units. These sub-units are repeated structures, each undertaking, by and large, the same function as the organ as a whole. The kidneys, as a whole, produce urine because each one of the thousands of functional sub-units, or nephrons, produces urine which contributes to the total. There appears to be a certain strategy behind this sort of structural arrangement - that of 'safety in numbers'. Such organs are not dependent upon the successful or healthy operation of one single component. The whole organ does not break down, should one sub-unit go wrong. Composite organs are, therefore, quite robust. The odd damaged nephron is not noticed.
In addition, these organs also have a common mechanism for coping with damage in these sub-units, as and when it occurs. They simply shut them down using fibrosis - a process of tissue deposition that may be triggered by a range of adverse stimuli. The loss of one sub-unit amongst thousands does not affect overall function.
Darwinian Medicine is, in effect, 'applied evolutionary theory.'
As a witty description, it could be described as:
Because of this focus on conceptualisation, Darwinian Medicine should have the added attraction of being a science without the necessity for mathematics. One could say -
That is not to say that mathematics will not become part of it, as it has done in mainstream evolutionary biology, but this remains to be developed.
This has been a very potted account. I think it is correct to say that more has been left out than included and I feel that I am still very new to the field.