I’ve been interested in evolution for as long as I can remember, countless Attenborough programmes probably being the main instigator. However, during university, when really getting into the detail, I was faced with a choice: continue to study evolution, mainly to satisfy my own curiosity and perhaps contribute to general understanding, or specialise in human disease to do something a bit more useful.
I chose cancer because it is essentially evolution within the body, but I should not really have had to make such a choice in the first place. Evolution is linked with every aspect of human physiology, since our DNA is our blueprint – surely understanding how we came to be the way we are and why we do what we do is vital to medical science?
I attended a talk on March 18th given by Prof. Randolph “Randy” Nesse from the University of Michigan:
Making Evolutionary Biology a Basic Science for Medicine – What Will It Take?
He is professor of Psychology and Psychiatry with major research interests in depression and anxiety, has written books on ‘Darwinian Medicine’ (really just sensible medicine that takes evolution into account) and recently co-authored a chapter in the Oxford Textbook of Medicine with Prof. Richard Dawkins.
He kicks off by quoting ‘Zoönomia’ (though I didn’t manage to scribble it down in time) – the 1794 work of Erasmus Darwin (grandfather of Charles) – a physician who, even over 200 years ago, recognised the importance of what would come to be called evolution in human disease
The body is surely a wonder…
Yes, it certainly is. One cannot help but think this frequently when studying biology in any capacity; be it at the molecular/genetic, whole organism or ecosystem level. However, upon any medic’s transfer from text book to clinic, a different view starts to form.
A designer? Seriously? Nesse quips:
“This designer shouldn’t work another day! It’s like the work of someone who’s been drunk for 3 days straight”
There are so many improvements that could (and should, if you’re listening, jeebus) be made to the human body.
Get rid of the wisdom teeth, the blind spot, the appendix (though I remember reading something about it possibly having a function; still, appendicitis kind of negates whatever it may be), give us ladies some kind of zip-function? The list is long.
The thing is, like the eye’s blind spot but no doubt of greater consequence,
“The blind spot in the medical curriculum imposes a limit on understanding”
No medical school in the world currently teaches a full evolutionary biology course. There are some small elements included like infection, phylogeny and genetics, but these are not sufficient.
There are still huge misconceptions in medicine regarding evolution. Nesse recounts some shocking statements he’s heard from the mouths of Nobel laureates regarding evolutionary matters – they don’t even know basic principles that have been established for decades now.
The gap is so wide that any university showing any interest in pioneering this movement would instantly become the world centre. Let’s go, Bart’s & The London!
Proximate vs. Evolutionary
This is a concept, coined by E. Mayr in 1982 in ‘The Growth of Biological Thought’, that many are familiar with in some form but it is not taken into consideration as much as it should be.
Proximate – how does it work? Vs. Evolutionary – why is the mechanism the way it is?
What has been asked is “what are the evolutionary explanations for diseases?” when we should be asking,
“Why has natural selection left the body vulnerable?”
An answer that is given too often, by people who should know better, is “Selection is too weak to correct it!”, which isn’t true.
6 good reasons why diseases exist
Nesse set out the following (and, in parallel, why the current curriculum isn’t up to scratch, but I’ll focus on the science bit):
1. Mismatch with Novel Environments
Selection is a slow process. It took us millions and millions of years to get to this stage, but we are changing our environments and the way we live relatively very quickly. There is a lag between a challenge presenting itself and natural selection’s effects catching up.
One example I remember well from university is that of cholesterol in the body (atherosclerosis being the main clinical interest here). If you look up statistics on statins, cholesterol-lowering drugs, it’s quite alarming how many people are taking them (I won’t go into more detail on that, though). One reason for this is that our bodies just aren’t equipped to deal with the length of time we’re living and the diet we’re living on so suddenly (on an evolutionary timescale).
Also in Nesse’s list are conditions arising from lack of sunlight; breast cancer; allergies; auto-immune diseases; alcoholism; lung cancer and others.
He and colleagues have used the term ‘Genetic Quirks’ to explain the phenomenon of harmless genes in ‘natural’ situations contributing to diseases in combination with our environment – we so often see the ‘Gene for X discovered!‘ where X is the current disease-of-interest because it seems it’s getting more common nowadays, when in fact it just so happens that something ‘new’ in our lifestyle is causing that random mutation to manifest itself in a way we don’t deal with very well.
2. Competition with Pathogens
Pathogens (bacteria & viruses) evolve faster than we do. They have little genomes and immense rates of reproduction (the famous E. coli making a copy of itself every 20 minutes or so), therefore high mutation rates leading to the speedy evolution. This is well-accepted, and the ‘arms-race’ between us and our little nemeses is continuous.
However, one strange and unsettling fact is how Biomedical Journals will almost always prefer to say emergence instead of evolution – Nesse presented a graph to illustrate this striking difference. They’re avoiding the E-word for some unknown reason; further evidence that medicine really needs a good EvoBio injection.
3. Every Trait is a Trade-Off
For every cool function our body has, chances are there’s a downside.
Nesse cites the radius; our arm/wrist connection is brilliantly flexible, allowing us to be good at throwing stuff and performing pretty complex tasks. However, the radius tends to break very easily, almost always in the same place. Very useful but also vulnerable.
Also there’s Bilirubin, a product of the metabolism of Heme (the complex molecule in blood cells that carries oxygen around). Bilirubin is toxic and it has been common practice for doctors to try to reduce its levels in babies kept in hospitals by putting them under lights. However, it seems that bilirubin is also an anti-oxidant, protecting tissues from damage, essential for cell survival – children with high bilirubin levels actually do better (if someone can find the paper(s), do let me know; I’m still getting used to clinical articles).
Ageing is a hot topic – what genes cause us to age? Can we mess with them a bit and live longer? Well, possibly not, since genes that are beneficial in youth but have negative effects in old age will be selected for a lot more strongly than against. Playing with genes that affect us in our dotage may end up having deleterious effects on youth, and that’s no good. For example, when genes are silenced in flies and worms giving the result of a doubled lifespan, the creatures seem to just live in a kind of suspended animation. Not what we’d be going for.
Alzheimer’s disease is no doubt a huge challenge to medical science still. We know this beta-amyloid protein is partly responsible, but is it really just defective, a by-product causing such immense damage? Again, probably not, as with the ambiguous nature of Lewy Bodies in Parkinson’s disease, which may actually be the result of cells trying to protect themselves from messed-up proteins. It seems that beta-amyloid is an incredibly effective pan-antibiotic, according to a paper out this year.
Then Nesse makes a point that really shows the value of experts in preventing the spread of nonsense – claims were published that high glucose prevents tissue damage upon freezing, so Type I diabetes is a result of selection for high blood glucose during the ice age. Nesse recommended sending these crazy claims to some EvoBiologists, but they didn’t bother and printed it anyway. ‘We asked the diabetes experts and they said it was very plausible!’ – well that’s not really good enough, is it?
Having looked at where these claims were published, one place is in this book by Sharon Moalem – looks like it might have a multitude of crazy claims in there…
4. Constraints on Natural Selection
Selection can’t just start over. We can’t ever rewind time and hope for some better mutations to occur; we’re stuck with what we got.
Genome-wide association studies (GWAS for short) have been performed a lot lately, trying to find a few genes that are solely or mostly responsible for major diseases or traits we’re interested in by looking at the patterns of thousands of genes’ activity at once.
A good example is height; what causes all the differences? Well, a GWAS found 20 significant loci (gene locations) that explained 3% of height variation. So, to explain 100% of it there would be 14-15,000 genes. That’s pretty much as many genes as we have. So it’s just not useful in this type of case.
This is because that isn’t how the genome works – we have to think about its evolution; genes that, when present, definitely or very likely cause something horrible to happen will be strongly selected against! The reasons will be be more subtle than that.
5. Organisms are not only shaped for health
Proportionately, men have a 50-400% increased risk of death, depending on what age range you look at, compared to women. That’s worldwide, across the cultures, and there are many reasons for this. Nesse and Kurger’s paper on this.
It could be said that health isn’t the primary output of natural selection; the ‘goal’ is that genes are passed on and living to be very old and/or always very healthy isn’t always necessary for that. Looking at mayflies, for example, they only live for a few days.
6. Defences and Suffering; Defence or Defect?
Many problems humans face are in fact protective e.g. fever, coughing, moods, pain.
Why do we experience so much suffering?
If the immediate and direct purpose of our life is not suffering then our existence is the most ill-adapted to its purpose in the world
– Schopenhauer, 1851
Nesse explains the ‘smoke detector’ idea using panic attacks as an example. 999/1000 are unnecessary but normal, if you do some maths (that is beyond me) involving how many calories you risk wasting in a fight-or-flight situation by running unnecessarily vs. not running and, say, being eaten by a lion. Much of what doctors have to deal with are unnecessary but totally normal responses to possibly non-existent stimuli that have evolved because not having them would be even more costly. This needs to be taken into consideration in the clinic.
For example, with flu, some people die from their fever rather than the virus itself. The fever is a protective mechanism but sometimes the excessive inflammatory response kills, so in understanding this evolutionary cost/benefit concept, we can better assess who should receive the drugs that suppress inflammation and who would do better left with their natural defences to combat the disease.
The big questions in getting EvoBio into medicine are:
Who will pay? Who will advocate it?
I agree with Nesse in that it’s important that it happens, since it
– can improve clinical methods
– is superior to the archaic ‘the body is a machine’ way of thinking
– acts as a framework to organise the >10,000 facts medics have to memorise
– gives a feeling for the organism and diseases that afflict it; what better context than evolutionary history??
One more bridge between EvoBio and Medicine is forming;
asking evolutionary questions about diseases.
After the talk I asked Nesse whether he thought the somewhat unique position of evolutionary biology among the sciences, being under routine question and scrutiny (read: due to religious nutbaggery), might be a problem.
He replied that they are
… worth no more heed than people who don’t think genes exist.
I’m not sure I agree; whilst of course I do not find such questioning of evolutionary biology valid or useful, it can be surprising how much influence religion still holds in government and where it holds sway in government, it can affect science. Look at the USA, now just recovering from the Bush administration since Obama has appointed some real scientists in positions that will get some good things done.
He recommended some books, including Adaptation & Natural Selection; Evolution of Infectious Disease and of course his own publication, Why We Get Sick: The New Science of Darwinian Medicine.
And finally some of Nesse’s articles: Making Evolutionary Biology a Basic Science for Medicine; Evolution in Health and Medicine
This article also looks to be saying similar things.
As a lover of genetics and working in the biochemistry/genetics of human disease, I emplore the medical schools of the world to expand future med students’ knowledge of the history of our genome.