The father of the science of evolutionary medicine, Randolph (Randy) Nesse, has a favorite aphorism: “Medicine without evolution is like engineering without physics.” In the same way that it would be impossible to imagine building the Rosetta spacecraft, sending it 300 million miles to rendezvous with Comet 67P, and successfully deploying the Philae lander, chock-full with sampling instruments, without physics and specifically Newtonian mechanics, it proves similarly impossible, for instance, to get to the root of the horrifying scourge of Alzheimer's disease unless we ask deep and fundamental questions, informed by evolution, about what the alleged poisonous plaques of beta-amyloid protein are doing in the brain in the first place. Is amyloid pure pathology or does it have an vital evolved function in the brain? In this sense, Nesse has frequently claimed that the value of evolution to medicine is that it while it may lead directly to changes in medical practice or indeed to new therapies, more fundamentally its value lies in explaining why things are as they are. That is why Nesse argues that evolutionary biology should be the foundation and cornerstone for medicine as it should be for all biology. This book is an attempt to put yet more flesh on the bones of Nesse’s idea that evolution is the “physics” of medicine. I describe the evolutionary background to seven areas of human disease that are causing deep contemporary medical concern to explain why they exist in the first place—why things are how they are - and how evolution might help us to combat them. I hope it will leave readers with a new respect for evolution as the prime mover for the structure and function of human bodies, even if it does, on occasions, cause them to break down and drives us into ER!

Each chapter is built around the sometimes harrowing but always inspiring personal stories of people trapped in the disease process in question. Each chapter provides an evolutionary explanation for why the disease has come about, and each chapter shows how medical researchers, using powerful insights gained from thinking about disease in an evolution-informed way, are charting our way out of it.

How a modern version of the hygiene hypothesis - called the "old friends" hypothesis - explains why the Western world is riddled with allergic and autoimmune diseases, and what we can do about it.
How evolutionary theory explains why the battle between the different selfish genetic interests of mothers, fathers, and fetuses causes low fertility and can lead to diseases of pregnancy like recurrent pregnancy loss, preeclampsia and gestational diabetes.
What is the relationship between the fact that we have evolved to walk upright - our bipedalism - and a range of orthopedic illnesses?
Creationists have always used the example of the "irreducible complexity" of the human eye as the bedrock of their argument that God designed the human body, not evolution. Modern developmental biology, however, not only strongly rebuts creationism but explains the astonishing secret of how the recipe for eyes actually unfolds from within the developing eye itself, not from external influences, and is leading to cures for eye diseases like retinitis pigmentosa and macular degeneration.
How does cancer evolve so remorselessly towards malignancy that it is proving almost impossible to cure? Cancer evolution can be so extreme and drastic it is forcing us to re-write the rules of evolution by resuscitating a heresy from the 1940s.
Why are coronary arteries evolution's answer to feeding our powerful, muscular hearts with the food and oxygen they need and how has this led to the continuing pandemic of coronary heart disease?
Research into curing Alzheimer's disease has become hopelessly bogged down and billions of dollars have been wasted trying to turn the "amyloid hypothesis" into therapy. Can we use evolutionary thought to better explain why dementia comes about in a way that might lead to fresh hope for a cure?


Monday, 27 July 2015

Scientists find first drug that appears to slow Alzheimer's disease

This piece in The Guardian 5 days ago is typical of the hype and hoopla that attended the unveiling of solanezumab's apparent positive affect on patients suffering from mild cognitive decline in an Alzheimer's disease study. Despite the fact that the medical scientists running the Eli Lilly trial admitted that the arrest in cognitive decline was so subtle that friends and relatives of any person concerned would not have noticed it, the result, found by recognizing a sub-group of mild decline patients among pooled data that showed no statistical relevance, is being hailed as a breakthrough because all previous trials of solanezumab have proved negative - as have trials of all drugs for Alzheimer's that have been produced to either interfere with the enzymatic chain by which beta amyloid is produced in the brain, or remove beta amyloid from the brain. This excited hype is typified by a quote in the Guardian article: “This is the first evidence of something genuinely modifying the disease process,” said Dr Eric Karran, director of research at Alzheimer’s Research UK. “It’s a breakthrough in my mind. The history of medicine suggests that once you get through that door you can explore further therapeutic opportunities much more aggressively. It makes us less helpless.”

Well, in reality, it falls far short of a breakthrough. The very subtle apparent effect was found by massaging the trial statistics, has not been subjected to peer review in a learned journal, and is yet to be bolstered by a dedicated trial of solanezumab on mild cognitive decline patients. The hoopla ignores several very important points:

1. Its postulated effect is by removing soluble molecules of beta amyloid from the brain, whereas the main postulated toxic form of beta amyloid are oligomers of a number of molecules.
2. A great many people die in their 70s, 80s and later and are found, on autopsy, to have substantial deposits of both beta amyloid plaque and neurofibrillary tangles of tau protein in their brains yet died with pin-sharp cognition for their age.
3. All the drugs, including solanezumab, that have been produced, tested, and found wanting so far have targeted the genes that produce amyloid in people with the familial type of the disease - the type that is passed down generations. Yet this accounts for only 1% of people who eventually develop Alzheimer's.
4. The three big GWAS (genome wide association studies) conducted so far to find subtle associations between genes and disease, on Alzheimer's disease, found no significance for the genes implicated in familial Alzheimer's disease. They simply did not feature.
5. The one gene that will demonstrably greatly increase your risk of contracting Alzheimer's is APOE epsilon 4, which is involved in lipid (fats) metabolism in the brain, not the production or clearance of beta amyloid.

It remains to be seen whether further science backs up these very tenuous results. In the meantime we would be very advised to reach for the salt cellar and remember that beta amyloid is not always the villain - it has, in appropriate concentrations, important roles to play in the brain either fighting pathogens or regulating transmission of nerve impulses across synapses between our billions of neurons. To my mind the balance of evidence so far suggests strongly that Alzheimer's is a disease of neurons rather than amyloid and amyloid may well be simply the rubble left behind after the disease process has taken hold and countless neurons have been destroyed.  

Other, sensible commentators have made the point that it may be too much to expect ANY drug to cure Alzheimer's when administered to individuals in whom the disease is already advanced. Too much irreversible damage has been done to their brains. This is why two big trials are presently testing the so-called amyloid hypothesis to destruction by identifying populations of individuals known to be at enlarged risk of early-onset Alzheimer's (perhaps because they harbour significant mutations to one or other of the genes controlling steps in the pathway that produces amyloid) and treating individuals from a young age before any cognitive tests or brain scans reveal deficits to see if they can stave Alzheimer's off.

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