Advances in medical research mean we have come to grips with numerous diseases and health conditions over the decades. But, like a game of whack-a-mole, you solve one set of problems to only have other, often more complex problems take their place. There is valid criticism to be had of medicine and its reductionist approach and What Is Health? sees neurobiologist Peter Sterling offer a critique grounded in physiology.
What Is Health?: Allostasis and the Evolution of Human Design, written by Peter Sterling, published by MIT Press in December 2019 (paperback, 257 pages)
Much medical thinking and education, writes Sterling, revolves around homeostasis: self-correcting negative feedback loops, comparable to the thermostat in your house. These allow the body to regulate physiological processes, e.g. blood pressure, without involving the brain. However, he found that many endocrine cells, those that release hormones, do have nerve endings terminating on them. Homeostasis is part of the story, but “error-correcting feedback offers no basis for a full model of human design” (p. xxx*). Together with Joseph Eyer, he coined the term allostasis in the 1980s: the brain is involved by predicting the body’s needs and mobilising resources to meet expected demand, temporarily up- or downregulating processes when an organism’s environment changes. In simple terms, homeostasis corrects, allostasis predicts. This also gives us Sterling’s definition of what health is: “the capacity to respond optimally to fluctuations in demand” (p. 154).
This idea has been criticised from various sides as resulting from too narrow a reading of homeostasis, “a travesty that has taken root in textbooks and is widely taught to students as the only kind of control system“, that is not offering anything “that was not already apparent, or at least readily derivable, from an accurate reading of the original concept of homeostasis“. I am receptive to such criticism. Though I was not trained as a physiologist, my layman biologist understanding of it is that e.g. a healthy blood pressure already falls between a range of values and that what is considered optimal depends on whether you are at rest or exercising. Do we really need allostasis as a separate concept? Especially Carpenter is fierce in his criticism: “there is a need to reassert the unitary nature of homeostasis and the variety of forms it can take, so that we are not obliged to reinvent what was common knowledge even 30 years ago, nor to introduce artificial distinctions and boundaries within a field that is in truth perfectly unified.“
“In simple terms, homeostasis corrects, allostasis predicts. But do we really need a separate concept? I am not sure that disagreements over definitions make much difference to Sterling’s point that modern life can break this physiological control system.”
Having read the rest of this book, however, I am not sure that disagreements over definitions make much difference to Sterling’s argument that modern life can break this physiological control system. Before getting to that discussion, though, he spends the first four chapters on a deep evolutionary history tour to trace the origins of the components of allostasis. This tour encompasses the molecular details of the genetic code, protein functionality, and ATP synthesis and hydrolysis to store and release energy at a cellular level. It encompasses the evolution of multicellularity and what we inherited from our worm-like ancestor in the way of cellular clocks, early brains, and feedback regulation between the different parts. (Side note, this is likely where dopamine was introduced as the brain’s reward signal for useful behaviour, enabling learning.) It encompasses the evolution of endothermy and the respiratory and cardiovascular adaptations enabling it. And, finally, it encompasses the evolution of Homo sapiens when it left Africa some 150,000 years ago. Sterling argues that changes to our brain allowed us to oust our Neanderthal cousins. Summarising from his book Principles of Neural Design, he gives a bird’s-eye-view of how the brain is organised for optimal functioning, what we inherited from our primate ancestors, and what we changed.
Overall, these chapters are well written and full of fascinating information, though I am not sure all of it is necessary to understand allostasis. Also, there are a few minor points I take issue with. I understand that phrases such as “a reptile evolved two new features and came out as a mammal” (p. xxv) and “At the pinnacle of life’s energy-driven complexity, perches—precariously—Homo sapiens” (p. 1) are shorthand. However, they could be mistaken for outdated linear thinking about evolution, even if Sterling’s writing in the rest of the book suggests no such thing. We did not evolve from reptiles. We share a common ancestor with them but they have been on an equally long evolutionary journey. Furthermore, Sterling strongly argues that evolution has produced optimal structures or, where tradeoffs make something seem suboptimal, optimal trade-offs. His endnotes explain that e.g. our appendix and the seemingly backwards design of our retina are actually functional, and he concludes that “[…] clear examples of suboptimality are scarce, if they exist at all” (p. 9). I am not sure I agree. The circuitous loop taken by the recurrent laryngeal nerve or the design of our throat that puts us at constant risk of choking are but two of many examples that Nathan Lents discussed in his book Human Errors. We know that evolution cannot simply start from scratch and that it reuses, repurposes, and rejiggles existing structures for new functions. Furthermore, Daniel S. Milo’s Good Enough criticized adaptationist storytelling and made an interesting argument for the persistence of the mediocre. Perhaps these are just issues of semantics and, seeing they do not really bear on his central argument, I will not dwell on them further.
“the simple pleasures of life were sources of regular small pulses of dopamine. These eroded, first gradually with the advent of agriculture, then rapidly with the Industrial Revolution, leading to our modern, dopamine-deprived lifestyle.”
Having taken the deep evolutionary tour, chapters 5 and 6 are where Sterling finally drops the payload and delivers the goods. The mechanism of allostasis breaks down when demand is excessively high for sustained periods. The body responds by shifting its operating range upwards and what used to be exceptional becomes the new normal. In the example of blood pressure you end up with chronic hypertension. Something similar happens with our reward circuits. We evolved as socially living hunter-gatherers that had regular physical exercise, where children of different ages played together unsupervised, where we learned and perfected skills such as hunting over decades, and where the elderly contributed to care of the young. Call them the simple pleasures of life but that is the whole point, they were sources of regular small pulses of dopamine. Sterling argues that instead we now try to get our dopamine hit from alcohol, nicotine, drugs, food, gambling, pornography, or shopping. And many of these activities deliver greater surges, with allostasis adapting us to take such surges as the new normal, fostering addiction. By his reasoning, the Western epidemic of hypertension, obesity, depression, suicide, alcoholism, and addiction to drugs and gambling are all a consequence of our modern, dopamine-deprived lifestyle. He will even throw in climate change, resulting as it does from excessive consumption of goods, meat, and (air) travel.
There is no shortage of recent books arguing that we are the victim of an evolutionary mismatch with instinctive brain circuits that cause us to e.g. overeat; that we have become unfit for purpose and our hunter-gatherer origins mean that we are poorly adapted to modern life. Sterling puts neurological flesh on the bones of that argument. More importantly, he pleads with us not to blame our evolutionary heritage. This reward circuit “inherited from worms […] works exactly as it is supposed to—just not for what it was intended. This has been termed a “mismatch” […] but that euphemism avoids facing squarely that “how we live now” is intolerable to a large fraction of our population” (p. 138). The tragedy is that medical practitioners try to combat this epidemic of apparently intractable chronic illnesses with pharmacotherapy—a pill here, a beta-blocker there—in a vain attempt to correct specific physiological parameters without recognizing that “the underlying biochemical and neural circuits are not actually broken” (p. 165).
“contrasting our hunter-gatherer lifestyle with “how we live now” raises the question: what of the intervening [time]? […] did we suffer the same epidemic of lifestyle diseases that we see now?”
By and large, I am on board with Sterling’s line of reasoning. We did indeed live as hunter-gatherers for the vast majority of our evolutionary history, and the argument of our current dopamine-deprived lifestyle is attractive.
However.
I am always a bit wary of single-cause, killer hypotheses that seek to explain a wide range of topics with one causative agent. Some claims here do seem rather sweeping, and to write, for example, that “it is sobering to notice that the growth of smartphones and Facebook parallels the growth of mass shootings” (p. 132) risks conflating correlation and causation. But more importantly, contrasting our hunter-gatherer lifestyle with “how we live now” raises the question: what of the intervening ten to fifteen thousand years that Sterling skips over? He limits himself to writing that our drip-feed of regular, small dopamine pulses eroded, first gradually with the advent of agriculture, then rapidly with the Industrial Revolution that “accelerated the process and exaggerated it grotesquely” (p. 131). Archaeology and palaeopathology tell us that the shift from foraging to agriculture was a Faustian bargain that initially took a heavy toll on our health. Our stature diminished and especially our teeth recorded the effects of this dietary change. But did we suffer the same epidemic of lifestyle diseases that we see now? Or was it the Industrial Revolution and especially the Great Acceleration that pushed us over the edge? In the latter case, it would seem there are more ways than the hunter-gatherer lifestyle to live a fulfilling life.
Are there solutions? Fortunately, Sterling does not advocate we head back to the caves and draws attention to the, I think, underappreciated argument that history has acted as a ratchet: “higher population densities gradually disallowed any return to the wild” (p. 128). One option is to work with the body’s mechanism of allostasis, not against it, through what he dubs “system therapy”, which is basically what rehab is for drug addicts. It is hard and slow, but the only way to resensitize our body’s reward circuit to more modest dopamine pulses. Preventative strategies would involve changes to modern life to restore physical and mental challenges, lifelong learning, and social relationships between the generations. These suggestions are, to my taste, rather generic and I would have loved for him to develop this part of the book fuller.
Given that neurobiology can be a technical topic, Sterling writes accessibly and makes good use of numerous illustrations to clarify principles further. I found the detour into deep evolutionary history particularly interesting, even if not all of it was relevant to the central argument. Though I am on the fence regarding some of the material here, What Is Health? is overall a cogently argued book that provides both reason for concern and food for thought.
* Have I forgotten to insert a page number here? No, this quote is taken from the first 32 Roman-numeral-numbered pages of prefatory material.
Disclosure: The publisher provided a review copy of this book. The opinion expressed here is my own, however.
Other recommended books mentioned in this review:
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Sleep, or rather a lack thereof, has either caused, or greatly increases the risk of this rather arbitrary and short list. Many more unpleasant things can be added to it. Neuroscientist Matthew Walker is a man on a mission: to impress upon you the importance of sufficient sleep. Why We Sleep is a book that is sure to make you lose some sleep, seeing that it is both fascinating and extremely well-written, but also deeply disturbing in showing the damage we inflict upon ourselves by cutting short our sleep. And, hopefully, it then proceeds to be a book that will make you get more sleep. This is the most important and influential book I have read this year.
“Why We Sleep: The New Science of Sleep and Dreams”, written by Matthew Walker, published in Europe by Allen Lane in October 2017 (hardback, 360 pages)
Why We Sleep is divided into four parts, two parts dedicated to explaining what sleep is, how it is generated, why we do it and how and why we dream. The other two parts show the benefits of sleep, and the effects of sleep deprivation on brain, body, and society at large, and how we might change things for the better.
The last twenty years have brought many insights into the biology of sleep, and the first part of the book is absolutely fascinating. There are many things I could talk about here, so I will pick two findings Walker explains that were completely new to me.
Most of us will have heard of melatonin and how it rises and falls over 24 hours as a function of exposure to light and darkness (and how jetlag plays havoc with this). But melatonin is only part of the story. Say hello to adenosine, which normally works in lockstep with your circadian rhythm to regulate sleep and wakefulness. Adenosine accumulates in the brain while awake and builds up sleep pressure. It is only broken down during sleep, and the build-up of a normal 16-hour day takes about 8 hours to break down. The nasty thing about adenosine is it’s cumulative. Sleep too little, and you will not have broken all of it down. As you wake up, the build-up starts again, but now reaches higher levels than before. This is how you build up a sleep deficit during a regular workweek, even by sleeping an hour less than you should, and start feeling really tired by the end of the week.
Or what about the finding that the brain has a system equivalent to the body’s lymphatic system, called the glymphatic system, which drains metabolic waste products? At night, the glia cells that make up this system have been found to shrink by some 60%, allowing the brain’s cerebrospinal fluid to flush out metabolic debris. This includes beta-amyloid that forms the plaques in the brain responsible for Alzheimer’s disease, raising the distinct possibility that a lack of sleep could enhance the risk of developing Alzheimer’s.
“Our body may be asleep at night, but make no mistake, our brain is hard at work doing vital maintenance.”
Our body may be asleep at night, but make no mistake, our brain is hard at work doing vital maintenance. Walker shows himself to be a master communicator here, summarising results from many clinical and neurological studies. Not only does he explain things very well, his use of repetition and analogies make this topic easy to comprehend and accessible to a wide audience.
This, then, brings us to the effects of sleep deprivation. In short, large numbers of carefully controlled and conducted clinical studies show that there is no aspect of our health and well-being that is not affected by a lack of sleep: learning and memory formation, risk of injury during physical exercise, concentration (which so strongly shows in the link between drowsy driving and car crashes), emotional stability, the cardiovascular system (with sleep loss causing increased risk of heart attacks and permanently increased blood pressure), metabolism (sleep loss is implicated in diabetes and weight gain by upsetting the hormone balance that controls appetite), reproduction, the risk of developing Alzheimer’s and cancer later in life. Even DNA expression and telomere integrity are negatively affected (telomeres are like end caps on your chromosomes, keeping them from unravelling).
The worst part is, “catching up” on sleep is not going to negate the damage that a lack of sleep causes. You may feel better by reducing sleep pressure, and regain emotional stability, but your brain is not a bank where you can lend sleep and pay it off later. Sleep too little, and for quite a few things the damage is done. Systematically sleeping too little slowly deteriorates your health, often irreversibly. Sleeping pills and stimulants such as caffeine only add fuel to the fire, causing more damage. Caffeine keeps you awake by masking the effect of adenosine (which continues to build as you stay awake) and takes a very long time to be decomposed, resulting in more sleep deprivation and cycles of addiction. Sleeping pills, too, are harmful. No sleeping pill on the market actually induces natural sleep, instead bringing on a state of sedation much like alcohol does, which is not the same. In this state, the brain will not experience the benefits of deep sleep, with all the consequences described above.
“[…] your brain is not a bank where you can lend sleep and pay it off later”
Another fiendish aspect of sleep deprivation is that you can’t accurately judge just how sleep-deprived you are. Go without sleep for 22 hours and you are as impaired in your actions and judgments as someone who meets the legal definition of being drunk. Now remember that many doctors and nurses, people who make life-and-death decisions, regularly work extremely long shifts. Unnerving, no? The same goes for emergency workers and soldiers carrying firearms. Or what about children, who we often force to start school days early (this is especially true in the US, according to Walker), right when they are in a stage of their life where their circadian rhythm is naturally shifted forward in time and they need sufficient sleep for proper psychological development? We inflict years of sleep deprivation on them, all the while expecting them to actually learn things and absorb information.
Once Walker gets around to sketching how our industrialised Western society, with its 24/7, hurry-up mentality is literally depriving billions of people of the health benefits of normal sleep, I had a sinking feeling in my stomach. A public health crisis of enormous proportions has been slowly building for decades. Already many speak of epidemics of all sorts of afflictions in our society (obesity, depression, cancer etc.). But how many of us actually implicate a lack of sleep in this?
Walker is down to earth and honest. We don’t have all the answers yet, but there is overwhelming evidence to implicate insufficient sleep as a contributing factor to many health problems, more likely an important cause. The tide is changing, however slowly. The WHO has started recognising the effects of shift work on sleep as probably carcinogenic. Forward-thinking companies are allowing people to start working according to their chronotype (i.e. whether you’re a proverbial night owl or lark), and school times are being changed. But we need many changes, on all levels of society. Many institutions and companies are stuck in their old habits, and many still scoff at the spectre of sleep deprivation. We need to remove the stigma from wanting and requiring sufficient sleep. This has nothing to do with being lazy. The roadmap Walker offers in the last chapter is helpful in this regard.
As we all need sleep and most of us don’t get enough, this book is deserving of the widest possible audience. Luckily, Walker is more than up for the task and has written an engrossing book. Why We Sleep is one of the most important books I have read. If you read just one book this year, please make it this one, it’s almost guaranteed to improve your life.
Disclosure: The publisher provided a review copy of this book. The opinion expressed here is my own, however.
