Hiding in Plain Sight: Essays by Joon Yun, MD, Second Edition

By Joon Yun

Collection of essays on investing, healthcare, and life from the unique perspective of Dr. Joon Yun, a renown investor and thinker. Dr. Yun is President of Palo Alto Investors, LLC, a hedge fund founded in 1989 with over $1 billion in assets under management. Dr. Yun has been a healthcare specialist at the firm for 15 years and has been an early investor in companies that develop drugs and devices for unmet medical needs. Dr. Yun is board certified in Radiology and served on the clinical staff at Stanford Hospital from 2000-2006. He received his B.A. from Harvard College in 1990 and his M.D. from Duke Medical School in 1994. He has served on corporate and nonprofit boards and is a founder of Palo Alto Institute, a nonprofit foundation and think tank. Dr. Yun has published numerous patents as well as medical and business articles. His writing covers several topics, including evolution, investing, and the future of healthcare. Dr. Yun is a contributor to Forbes and Evolution: This View of Life.

• Language: English
• Publisher: Lulu.com
• Release date: Sep 5, 2014
• ISBN: 9781312491939

Book preview

Hiding in Plain Sight: Essays by Joon Yun, MD, Second Edition

Hiding in Plain Sight: Essays By Joon Yun, MD

Hiding

In

Plain

Sight

Essays by

Joon Yun, MD

Second Edition

Copyright

This collection of essays is the second publication in a series. Hiding In Plain Sight: Essays By Joon Yun, MD, Second Edition.

Copyright 2014 Anthony Joonkyoo Yun

License Notes

This ebook is licensed for your personal enjoyment only. This ebook may not be re-sold or given away to other people. If you would like to share this book with another person, please purchase an additional copy for each recipient. Thank you for respecting the hard work of this author.

Preface

The essays in this collection were generated over the course of several years. During that time, I have been keenly influenced by the science of evolutionary medicine. The latest evidence shows that the consequences of our evolutionary past are responsible for many of the world’s most common chronic medical conditions, intractable social problems and ubiquitous cognitive biases.

The aim of this book is to apply evolutionary medical analysis to scientific and social challenges that defy conventional analysis. I hope you will find these essays thought provoking and useful.

The Future of Human Evolution

Death, be not proud, though some have called thee Mighty and dreadful, for thou art not so...

― John Donne, Death

Programmed Death

Is senescence (biologic aging and death) a programmed trait? Perhaps no topic in evolutionary biology evokes more controversy.

Senescence was once assumed to be the inevitable result of so-called wear and tear. This view holds that an organism ages and eventually fails as it accumulates defects that are insufficiently corrected. However, the existence of senescence is not a thermodynamic necessity. Although entropy must increase within a closed system, organisms are not closed systems unto themselves. Because it can extract free energy from the environment and reduce its own entropy, an organism typically grows more resilient from seed stage to reproductive maturity. Indeed, life tables for humans suggest that the lowest likelihood of death in females occurs around the age of 14. This coincides with the age, at least in prehistoric times, of reproductive maturity. Organisms appear to be capable of self-repair at times when individual survival is beneficial to the survival of the species. Certain organisms such as Hydra, the tiny and simple freshwater predator, actually exhibit no signs of senescence, providing a counter-example to the notion that senescence is universal and unavoidable.[1]

Most organisms, however, undergo a failure of repair mechanisms and experience an increase in entropy. This heralds post-reproductive-age senescence, despite the fact that these organisms are surrounded by available, free energy. This observation has led some biologists to wonder if senescence occurs merely because the selection pressure against it is insufficient. In his lecture An unsolved problem of biology (published 1952), Peter Medawar suggested that what happens to an organism after it has reached reproductive age is only weakly reflected in natural selection through its effects on younger relatives.[2] Medawar’s view states that traits that affect an organism’s viability after reproductive age tend to have little effect on ultimate fitness since it is a trait that emerges only after that individual's reproductive opportunities have come and gone. Senescence, therefore, is not an adaptive trait since very little selection pressure exists for or against it.

The question of whether or not senescence is an adaptive trait has been considered since the early days of evolutionary theory. This idea that aging and death are examples of adaptive advantage was first promulgated by August Weismann.[3] An early evolutionary theorist, Weismann was building upon the theories of his intellectual predecessor, Charles Darwin. Weismann suggested that senescence might be an important programmed trait, necessary for species’ survival because the older individuals need to make room for the next generation. Weismann saw that turnover that was necessary for the survival of a species. In particular, he claimed that programmed death allowed species to evolve, with new members of the species, perhaps carrying advantageous mutations, replacing older members.

According to Wikipedia, Weismann’s hypothesis suffers from the following incongruities: (1) the hypothesis fails to explain how an individual might acquire the genes that make them get old and die; (2) it does not explain why individuals who possess genes for aging would be more successful than other individuals who lack those genes; and (3) the hypothesis offers a teleological explanation but does not provide a mechanism.[4] Weismann himself appears to have disavowed his own theory later in life.

Weismann’s hypothesis, however, has recently regained its momentum.[5] The word phenoptosis has entered the lexicon to describe the phenomenon of programmed death in organisms.[6] The scientific community has recently treated as heresy the idea of phenoptosis, in much the same way it treated the idea of cells undergoing programmed death when that concept was raised several decades ago. The programmed death of cells, called apoptosis, has become a generally accepted concept among biologists, however. The programmed death of organisms may soon approach a similar level of scientific acceptance.

Wikipedia catalogues some of the circumstantial evidence that supports the theory of programmed senescence: (1) Progeria syndrome and Werner syndrome are both single-gene diseases that can cause accelerated senescence, suggesting that a common mechanism is responsible for the disparate manifestations of aging; (2) lifespan varies greatly, even among very similar species, suggesting relatively minor changes to genotype could cause major differences in lifespan; (3) mammalian lifespan varies tremendously, but the symptomatic manifestations of aging remain very similar across species, suggesting a common mechanism; (4) genes responsible for controlling aging, yet possessing no other function, have been discovered; (5) caloric restriction increases the lifespan of many organisms under experimental conditions, once again suggesting a common mechanism for senescence and delayed senescence; (6) acutely programmed death seems to have been observed in certain animals such as the octopus, salmon and Australian marsupial mice.[7]

Again from Wikipedia, the argument against programmed senescence goes something like this: individuals who carry genes for programmed senescence would be displaced by individuals who were not in possession of those genes.[8] That is, non-aging individuals would produce more offspring during their longer lifespan, and they could promote the survival of those offspring by providing more extended parental support.

To the notion that longer survivorship might potentially allow individuals to produce more offspring and provide more support for descendants, we counter that individuals who reproduce during dotage may compete with the efforts of their own offspring in seeking opportunities to mate. For example, fathers may be competing with their sons, displacing the available fecund females. Aging individuals might also compete for other survival resources against their own offspring, possibly in a way that more than offsets their support of descendants.

As for the contention that Weismann’s hypothesis is invalid because it does not offer a plausible mechanism, a number of theories on the mechanism of aging (mutation accumulation, antagonistic pleiotropy, disposable soma, etc.) have been advanced and debated elsewhere.[9] None, however, has been widely accepted.[10]

It has been proposed that autonomic dysfunction is a unifying theory that describes the mechanism of diseases of aging.[11] Specifically, the autonomic neuroendocrine system begins by augmenting survivorship during early life but later becomes dysfunctional and biases towards sympathetic (the mechanism responsible for the fight or flight response) predominance in later life. This produces a myriad of conditions referred to as the various diseases of aging.

Increasing scientific specialization has led to the atomization of human ailments into an ever-lengthening laundry list of newly-named diseases, but it seems highly unlikely that as we age, so many different things could go wrong through so many disparate mechanisms. Interestingly, several disparate human ailments are manifest through a rather small set of symptoms (namely nausea, rash, dizziness, etc.). Each of these symptoms is, at least partially, driven by the autonomic nervous system. In Cellular Automata, Stephen Wolfram argues that apparent complexity may be the result of simple rules, applied recursively.[12][13] As Sir Isaac Newton pronounced, we are to admit no more causes of natural things than such as are both true and sufficient to explain their appearances. Therefore, to the same natural effects we must, so far as possible, assign the same causes.[14] Autonomic dysfunction may be that single cause, and may therefore be the key to understanding the panoply of diseases associated with aging.

In several ways, the autonomic nervous system is an obvious suspect for the mechanism of programmed death. After all, one effective way to kill a system is to disrupt a single, critical regulatory network. The autonomic nervous system can be seen as the fundamental regulatory network in the body that maintains homeostasis.

During juvenile phase, our autonomic nervous system is effective at maintaining homeostasis. During adult phase, we can tell from many everyday circumstances that our autonomic homeostasis becomes increasingly defective. For instance, when we are young, we come out of a somersault or a roller-coaster ride without much dizziness. When we are old, such upheaval invariably produces dizziness. When we are young, we can accommodate to cold weather and not feel too cold. When we are adults, the same weather can feel too cold. When we are young, we can rebound from a bad night’s sleep quickly. When