Fat, Fate, and Disease : Why we are losing the war against obesity and chronic disease (15 page)

Whatever the explanation, variation between individuals and across populations clearly matters a great deal. Consider two people given precisely the same rations to eat day after day—let’s say that they are prisoners in a gaol and are offered a fairly standard set of
foods every day. Depending on their genetic make-up, their developmental history, their upbringing, and the context of where they are they could respond very differently. They might differ in their appetite control, so that one eats more than the other. One might have an allergy to a certain component of the diet, say fish, and avoid eating it. Or they might both eat the same amount but because of their biochemical make-up one is more likely to put on fat than the other. Or they might put on the same amount of fat, but one might deposit it under the skin and the other in the liver. Or one might have a strong family history of heart disease and the other might have parents and grandparents who lived until they were 100. Or one might exercise while the other is an invalid. We could go on … but it is clear that to predict what will happen to the two individuals exposed to the same dietary regime is not easy. We need to understand all these causes of variation, not just the genes of our two prisoners—and our list is by no means complete.

Many doctors will admit that clinical medicine is as much an art as a science. Historically the practice of medicine, growing as it did from the traditions of the barber surgeons and the apothecaries of the 16th century, has not always had a strictly scientific basis. Only 200 years ago, blood-letting by cupping or using leeches was a common practice to relieve certain ‘humours’. However, in the past few decades medical research has exploded. We now know so much more about our biology and the origins of disease, at least in theory. But the diffusion of this new knowledge into medical practice is often much slower. There are many reasons for this. Much biomedical research is highly technical and inaccessible even to doctors. Then the ‘art of medicine’, something they learn from their teachers and acquire through experience during their careers, leaves individual doctors with their biases. These biases may include the use of alternative
medicines such as homeopathy, even when there is no objective evidence that they work and much scientific argument for why they can only have a placebo effect. As one wit put it recently: ‘What do you call an alternative medicine for which there is evidence that it works? Orthodox medicine.’ This is not to dismiss alternative medicine out of hand—after all, many modern medicines are derived from natural products.

So the level of objectivity in a doctor’s choice of what to do may not be as high as is generally thought. This is why one doctor favours one approach to management and is insistent that it is the best approach, while another will vehemently argue for another approach. Often they are both correct—or both wrong—and more often than not the evidence which they need to decide on the course of treatment is missing, not compelling, or hard to access. However, the move towards so-called evidence-based medicine in recent years has been an attempt to systematize what we know and what we do not know, which has gained much support. Large institutes and databases have been established to undertake this type of synthesis. These databases are very useful in describing the general response to a particular therapy, but their limitation is that they treat every individual with the disease as
typical
. And so the new art of medicine is knowing when to apply such averaged approaches to a patient and when not to.

Medicine is in fact a very conservative profession and new knowledge and new paradigms of disease enter its practice very slowly. This contrasts with the rapid development of new technologies such as MRI and CT scanners and the introduction of new drugs. There are inevitable vested interests, which include the influence of drug and equipment companies, insurance companies, hospital administrators, and senior experts in medicine. And increasingly the patient, as an apparently informed determinant of his or her own treatment, influences what the doctor will do; the internet has become empowering in this respect, although most of us are baffled by the sheer amount of information available on any complaint or condition
which we feel we might have. Knowing what weight to put on each of such a plethora of ‘facts’ is where the art lies. That headache, for example—is it a consequence of too much coffee at lunchtime, or is it the first sign of a brain tumour?

The phenomenon of evidence-based medicine has had an important impact. Nowadays young doctors are trained to think in terms of research coming from a range of fields—laboratory investigation, population studies, drug development, and clinical trials. Very often, however, all this evidence does not have an internal consistency and does not provide direct insights into the mechanisms or causes of disease. Rather, what the evidence may do is show that a particular group or subset of the population is more likely to get a particular disease or to respond to a particular treatment. This has been highly successful, for example in establishing the link between smoking and lung cancer, in leading to fluoride being added to the water to prevent to dental caries, and in determining which anti-cancer drug to use for a particular type of tumour.

But even though the evidence from such studies tells us a lot about
when
certain conditions develop, and even perhaps
how
they develop, it does not address the question of
why
they develop. This is a fundamental issue in medicine because it is often difficult to design the most effective treatment if we do not know precisely why the condition has developed. In addition, superficial use of evidence-based approaches implies that all the subjects with a particular disease are similar when, as we have seen with obesity, not everyone is the same.

But how important is the
why
question as opposed to the
when
and
how
questions? Imagine that we are trying to treat people who have high blood pressure. We find something that lowers this pressure—it might be a new drug, it might be a traditional herbal remedy, or it might be a course of yoga or meditation. Does this observation therefore give us the solution for how best to treat high blood pressure in a particular patient? We can see that the answer to this question will be ‘it depends …’ It depends, in fact, on many things.
The use of a drug over a long period may be detrimental, either because it produces side effects or because it is too crude in its action. Alcohol consumption will lower blood pressure for a very short period of time, for example, but we would not prescribe a patient regular shots of vodka. What about meditation? It may calm a patient, and if stress was part of their problem it might help to lower their blood pressure—but wouldn’t they actually be better spending half an hour each day in the gym rather than sitting cross-legged trying to attain another plane of being? We don’t know. And the herbal remedy may work, but how much do we know about its active ingredients? How do such remedies work, and what might be the dangers of sustained use of them? Again, we just don’t know.

How do we ever get out of this wood? Are we saying that we can never treat a condition unless we know how the treatment works? Well, almost. This is because the best treatments work through rectifying the problem at its very root, not by just relieving the symptoms. We can stop a patient complaining about the pain from a broken collar bone by giving them morphine, but in the long term it is better to set the fracture. The smartest drugs which we can use to treat the patient with high blood pressure will strike at the cause of the problem by blocking the action of hormones that cause the blood pressure to rise or by preventing the structural changes in blood vessels which make them more rigid. The snag is that to develop such drugs we need to know the causal pathways to the disease in the first place. So we see that knowing why a treatment works is closely bound up with knowing how a disease develops.

Why
questions can be answered at two levels. The first is at the proximate level—that is the immediate cause question.
Why
does a particular individual have high blood pressure? The proximate answer would be because their blood vessels have been hardened with age
and if the heart is pumping a certain amount of blood, the pressure in rigid blood vessels will be higher than it would be if they were flexible. But
why
are the person’s blood vessels stiffer? Because most of the elastic tissue in them has been laid down in their early development, before they were born and in infancy, and this tissue becomes less elastic as time goes on. In addition, deposits of calcified fibrous tissue accumulate in the blood vessels throughout life, particularly in response to the inflammatory processes triggered by fats and certain hormones in the bloodstream. But this is still a proximate level answer.

So
why
can be asked again and the answer would be: because it would appear that the human body (and that of many other animals too) has been ‘designed’ to keep blood pressure and cardiovascular function within a healthy range in the period at least up to the point when a person reproduces, even though this has to be traded off against the decline in function (seen here as arterial stiffness) which in all probability will happen later in life.

This game can become very tedious or annoying, but we can see that we have shifted now to a different level of question—what we can call the ultimate level. Why have the processes of evolution allowed the disease process to exist and why did natural selection not select characteristics which allow us to avoid developing high blood pressure or diabetes? This takes us a long way (and over a long time historically) from modern evidence-based medicine. But it is a journey worth taking.

The ultimate
why
question brings us to the fundamental principles of a very new field—evolutionary medicine—one we have written about in other books. The processes involved in evolution ultimately operate towards only a single goal—successful reproduction. When the complexities of evolution are peeled away, genetic features which
favour successful reproduction are more likely to be passed on to the next generation than those that do not. So over time, in a lineage, the genetic make-up of individuals is increasingly reflected in features that enhance reproduction. In time an equilibrium is reached where the features of the organism are matched well to the environment, provided of course that the environment has not changed.

But when we say ‘matched well’ we need to interpret this solely in terms of its direct effects on reproduction. A cheetah’s coat gives it camouflage in the savannah, its skeletal and muscular structure allow it to run at high speeds, and its sharp teeth and claws allow it to kill its prey. But the reason it is
matched well
is because these are features that allow it to hunt successfully, and better nutrition supports reproduction in the female and gives strength to the male, ensuring reproductive success. Reproductive success plays out in terms of the number of offspring that survive to reproduce themselves.

All of what we have just said is standard evolutionary biology. But the point which is often not recognized is that the drivers of evolution, which protect and enhance effective reproduction, are not always the same ones which might ensure longevity or health. Some species, such as the antichinus family of mouse-like marsupials in Australia, or for that matter the salmon, only reproduce in one season. The male marsupial goes into a mating frenzy and then dies from exhaustion; the male salmon fertilizes thousands of eggs, then also dies. But both have, in their ecological system, maximized their reproductive success and produced lots of offspring. The male praying mantis may even get eaten by his mate as they are in the process of copulation—this changes the meaning of enjoying sex. Health and survival are important for reaching reproductive age, but in general, once reproduction has been completed, there is little advantage—in purely evolutionary terms—in continuing to live. The exception to this rule is in some long-lived but slowly reproducing mammals such as the elephant, or indeed the human. In these there is an advantage in living long enough to ensure that offspring survive to adulthood and themselves reproduce.

Because we usually reproduce before we reach middle age, evolutionary processes operate to maximize survival up to the time of reproduction and are much less concerned with longevity beyond the reproductive period. This has caused the trade-off of biological processes which are designed to favour successful development to reproduction rather than investment in cellular repair and protection mechanisms in later life. This is not an absolute rule, as there is some evidence of a fitness benefit from longevity: for example, the presence of a child’s maternal grandmother aids its survival. This ‘grandmother effect’ may be the origin of the human menopause in that there may be greater evolutionary advantage to a woman assisting her own child to raise children than continuing to reproduce herself, but this is speculative. This effect is relatively weak compared to the selective pressures acting in earlier life, although it might have its echo in women having on average a longer lifespan than men. But in general we have less capacity to cope with challenges to our biology that occur later in life.

It is hard to understand how much modern medicine has changed our perceptions of what to expect of our lives. When Sir William Beveridge set the retirement age for men at 65 in the UK in 1942, their average life expectancy was 62, so less than half of all men would need a pension. At that time much medical care was aimed at addressing the relatively fast decline and demise in adult life—whether from infection or from diseases such as heart disease or cancer, which carried off their victims fairly quickly by today’s standards. Treating chronic disease and the demand for a healthy life into the eighth decade or beyond was not then a major focus of attention for most doctors.

We do not know precisely what life expectancy was in our evolutionary past. It is probable that most people had died by the end of the fourth decade of life and relatively few lived to the sixth or seventh decade. Death was largely due to trauma, childbirth, or infection. Reproduction was over by that age so what happened later was of little evolutionary consequence. But now we live on average much
longer lives and so disease associated with the failure of repair and maintenance has become more common.