After 60 years, the seminal Williams paper on aging is aging well

After 60 years, the seminal Williams paper on aging is aging well

The paper George Williams published in 1957 about senescence has inspired much of the field of evolutionary medicine.  I never heard about it in medical school, but the evolutionary biologists I was talking with at the University of Michigan in the 1980’s said I should get a copy. Reading it changed my life. If aging has an evolutionary explanation, what about everything else in medicine?  I spent a summer in the library finding and analyzing data on survival curves for animals in the wild.  They showed that senescence greatly decreases fitness for many species in the wild, contradicting the the mutation accumulation theory, and supporting Williams’ idea of antagonistic pleiotropy. That led to publications and a wonderful collaboration with George for the next two decades. 
Now 60 years after its publication, Williams’ article remains fresh. In a new article in Evolution, Laillard and Lemaître offer a review of the paper, and the status of the hypotheses it proposed. I hope it inspires many people to read the original paper that inspired much of the progress in evolutionary medicine. 
Gaillard, J.-M., & Lemaître, J.-F. (2017). The Williams’ legacy: A critical reappraisal of his nine predictions about the evolution of senescence. Evolution.
Abstract:  Williams’ evolutionary theory of senescence based on antagonistic pleiotropy has become a landmark in evolutionary biology, and more recently in biogerontology and evolutionary medicine. In his original article, Williams launched a set of nine “testable deductions” from his theory. Although some of these predictions have been repeatedly discussed, most have been overlooked and no systematic evaluation of the whole set of Williams’ original predictions has been performed. For the sixtieth anniversary of the publication of the Williams’ article, we provide an updated evaluation of all these predictions. We present the pros and cons of each prediction based on recent accumulation of both theoretical and empirical studies performed in the laboratory and in the wild. From our viewpoint, six predictions are mostly supported by our current knowledge at least under some conditions (although Williams’ theory cannot thoroughly explain why for some of them). Three predictions, all involving the timing of senescence, are not supported. Our critical review of Williams’ predictions highlights the importance of William’s contribution and clearly demonstrates that, 60 years after its publication, his article does not show any sign of senescence.
Human Evolution Continues!…Or more exactly: Only two loci in the whole genome influence longevity

Human Evolution Continues!…Or more exactly: Only two loci in the whole genome influence longevity

 Enormous interest is being generated by a new open access article in PLoS Biology: Identifying genetic variants that affect viability in large cohorts, by Mostafavi, H., Berisa, T., Day, F. R., Perry, J. R. B., Przeworski, M., & Pickrell, J. K.  The press release from Columbia was titled “Large-scale Study of Genetic Data Shows Humans Still Evolving.” New Scientist covered it as “Our genomes reveal modern-day evolution.” At The Atlantic the headline was “Huge DNA Databases Reveal the Recent Evolution of Humans.”  What does the article really show?  

Author summary:  Our global understanding of adaptation in humans is limited to indirect statistical inferences from patterns of genetic variation, which are sensitive to past selection pressures. We introduced a method that allowed us to directly observe ongoing selection in humans by identifying genetic variants that affect survival to a given age (i.e., viability selection). We applied our approach to the GERA cohort and parents of the UK Biobank participants. We found viability effects of variants near the APOE and CHRNA3 genes, which are associated with the risk of Alzheimer disease and smoking behavior, respectively. We also tested for the joint effect of sets of genetic variants that influence quantitative traits. We uncovered an association between longer life span and genetic variants that delay puberty timing and age at first birth. We also detected detrimental effects of higher genetically predicted cholesterol levels, body mass index, risk of coronary artery disease (CAD), and risk of asthma on survival. Some of the observed effects differ between males and females, most notably those at the CHRNA3 gene and variants associated with risk of CAD and cholesterol levels. Beyond this application, our analysis shows how large biomedical data sets can be used to study natural selection in humans.

The method is creative.The authors looked at genetic data from more than 60,000+ people in the Kaiser Permanente  system and 150,000+ people in  the U.K. Biobank and asked if certain genetic variations were less common in older people, implying that people with those variations died young. The astounding result is that only two variations popped out. One is APOE ε4, long recognized as a cause of heart disease and Alzheimer’s disease in modern populations.  The other is a variation in CHRNA3 that is associated in higher smoking rates in smokers. 

  • We know that about 25% of the variation in human lifespan results from genetic variations (Brooks-Wilson, 2013) so there should be genetic variations to be found. Why didn’t they show up?
  • Despite having hundreds of thousands of subjects, the study was able to detect only effects from variations present in over 10% of the population. To achieve genome wide significance requires a p<10−8   Perhaps  many more alleles are waiting to be identified;the authors understandably would now like to look at samples of many hundreds of thousands of people. 
  • Both identified alleles may qualify as “genetic quirks” that may cause harm only when interacting with modern environments.  
  • The authors suggest that perhaps all other common variations have been purged by natural selection, perhaps via benefits to kin from long-lived post-reproductive adults. Kin selection is powerful, but is is plausible that it would eliminate all but two common alleles that reduce fitness up at age 75? This is a better starting point than assuming that genetic drift accounts for most disease, however, it seems unlikely. 
  • Environments are so vastly different now from those of our ancestors that many previously neutral variations should now influence age at death. 
  • Mention was made about antagonistic pleiotropy and its role in aging however  genes that are not polymorphic would not have any variation to find. 
Brooks-Wilson, A. R. (2013). Genetics of healthy aging and longevity. Human Genetics, 132(12), 1323–1338.
BMJ recommends against full course of antibiotics–End of a medical mistake?

BMJ recommends against full course of antibiotics–End of a medical mistake?

This week’s British Medical Journal has an article “The antibiotic course has had its day,” by Llewelyn et al., that recommends against taking antibiotics for a full standard course. It goes further to challenge the WHO advice to take antibiotics “exactly as prescribed,” and suggests that cessation of symptoms is a better indicator of when to stop. This is welcome, and about time. However the bad advice doctors have given their patients for decades results from ignorance about evolutionary biology. The BMJ article does not use the word “evolution” or the phrase “natural selection.” It does not cite the work of evolutionary biologists who have analyzed this problem for years. Instead, it relies on brute empiricism. When will medicine incorporate sophisticated evolutionary biology so it can avoid making such mistakes?

The article is behind a paywall, but here are choice bits.   “in materials supporting Antibiotic Awareness Week 2016 WHO advised patients to “always complete the full prescription, even if you feel better, because stopping treatment early promotes the growth of drug-resistant bacteria.”  However the article goes on to say, “the idea that stopping antibiotic treatment early encourages antibiotic resistance is not supported by evidence, while taking antibiotics for longer than necessary increases the risk of resistance.” “Outside hospital, where repeated testing may not be feasible, patients might be best advised to stop treatment when they feel better, in direct contradiction of WHO advice. Of note, a recent clinical trial found that using fever resolution to guide stopping antibiotics in community acquired pneumonia halved the average duration of antibiotic treatment without affecting clinical success.”

“The fallacious belief that antibiotic courses should always be completed to minimise resistance is likely to be an important barrier to reducing unnecessary antibiotic use in clinical practice and to developing evidence to guide optimal antibiotic use. The idea is deeply embedded, and both doctors and patients currently regard failure to complete a course of antibiotics as irresponsible behaviour.”

Llewelyn, M. J., Fitzpatrick, J. M., Darwin, E., SarahTonkin-Crine, Gorton, C., Paul, J., … Walker, A. S. (2017). The antibiotic course has had its day. BMJ, 358, j3418.
In Memory of Jeremy Taylor, Associate Editor

In Memory of Jeremy Taylor, Associate Editor

Jerry Taylor passed away July 17, 2017, at age 70 from pancreatic cancer.  He was an enormous force for good in the field of evolutionary medicine, and a wonderfully creative, critical, and energetic Associate Editor for the Evolution & Medicine Review. He is survived by his son Linus, and his wife, the actress Barbara Flynn. 

I first met him at evolution and medicine meeting in the UK in 2010, but was only when the University of Chicago sent me proofs of his book, Body by Darwin, that I recognized that the field had a new champion. His background was as a producer for BBC television, where he created many films for the Horizon series, and many more for other science channels, but his writing and scientific acumen were unparalleled.No one else has tackled multiple big topics including cancer, Alzheimer’s disease and autoimmune disease by mastering the relevant science, getting personal interviews with the scientists, and even finding patients who talked eloquently about how an evolutionary perspective changed their view of their disease, and sometimes even its treatment. This required not only industry and intelligence, but extraordinary social and organizational skills that are equaled by few.  If you have not read his book yet, get a copy now and prepare to enjoy yourself 

After the book came out, to wide appreciation, Jeremy and I talked about his possible contributions to the EMR. I thought he might write an occasional article, but soon he was writing eloquent essays twice a week, bringing new insights to the entire community. Readership rose sharply. He wielded his critical faculties firmly but gently.  He was a consummate editor.  I asked him if  he would like to become the Editor. In typical modest fashion, he said no, he thought it was better if he just continued as the Associate Editor. However, he kept coming up with great ideas for how The Evolution & Medicine Review could become more interesting and more useful to its readers. In my last Skype with him just a few weeks ago. he was full of new ideas and eager to write more for the Review despite knowing his prognosis was grim. He loved the Evolution & Medicine Review, and it joined with his intelligence to infuse his many posts. 

Some people you just plain like and admire and enjoy spending time with. Jeremy was one of those. His curiosity and wide range of knowledge and good humor made him someone everyone wanted to be with, and someone who will be missed very much by all who know him, and even by many who know him only through his prose.

For those in London, here will be a celebration and cremation  on Monday 7th August at 2pm prompt at St Marylebone Crematorium.  Donations  made in his name to the UCL Hospitals Charity. fund. will go straight to the lab of Professor Charles Swanton (The Crick Institute and UCLH) whose team is focusing on the cancer that killed Jerry.

Ashley Montague on Anthropology and Medicine

Thanks to Holly Smith who provided a copy of a lovely little 1947 article in The Interne, by Ashley  Montague titled, Anthropology in Medicine.
Some quotes offer crucial historical perspective, such as: “Any suggestion that another course should be added to the already overcrowded medical curriculum will justly be viewed with alarm” He goes on to suggest that an anthropological perspective is crucial for physicians to have a view of the whole person in context, and to recognize individual variation as intrinsic to science and medicine.  Click here for the full pdf.

Montague 1947Montague titled,