Book Notes: Why We Get Sick

Back in December I read the book “Why We Get Sick” (1992) by Randolph Nesse and George Williams. While some of the information was outdated due to its age, overall I loved the book as it took a more wholistic, evolutionary approach to explaining sickness.

Given the global pandemic of 2019-nCoV (novel coronavirus) underway and the timely nature of my read, here are my brief notes I took from the book.


Why We Get Sick

Two kinds of explanations for disease:

  1. Proximate explanations — Answer “what” and “how” questions about structure and mechanism. Address how the body works and why some people get a disease and other’s don’t. A proximate explanation describes a trait — its anatomy, physiology, and biochemistry, as well as its development from the genetic instructions provided by DNA.
  2. Evolutionary explanations — Answer “why” questions about origins and functions. Show why humans, in general, are susceptible to some diseases and not to others. (Or why some parts of the body are so prone to failure.) An evolutionary explanation is about why the DNA encodes for one kind of structure and not some other.

Defenses. Mechanisms our body and immune systems designed specifically to combat an issue. A protective response to a problem. Coughing is a defense. The distinction between defenses and defects is important — defects are not preprogrammed responses, they are results of a problem. Skin turning blue from lack of oxygen is a defect.

Causes of disease:

  • Infection. External agents such as bacteria and viruses.
  • Novel environments. Environments our evolved bodies aren’t used to handling. A mismatch between our design and our environment.
  • Genes. Some of our genes are perpetuated despite the fact the cause disease. In the environments we evolved in, they didn’t harm us enough not to be selected out. DNA can also be mutated and create new bad genes.
  • Design compromises. There are costs associated with every major structural change preserved by natural selection.
  • Evolutionary legacies. Evolution is incremental and can’t make major changes quickly. Many of the design choices are not optimal and carry on anyway.

Signs and symptoms of infectious diseases

Symptoms of colds and other sicknesses and diseases can be unpleasant. But most of them are useful. It is an adaptation shaped by natural selection specifically to fight infection.

Fever is an adaptation to raise body temperature enough to assist with fighting infection. Body temperature is carefully regulated even during fever; the thermostat is just set a bit higher. Children who take Acetaminophen take about a day longer to recover from chicken pox. There are costs of a fever, of course. Otherwise the body would just always stay at 103F at all times. It depletes nutrient reserves 20% faster and causes temporary male sterility. Still higher fevers can cause delirium and lasting tissue damage. And because regulatory precision is limited, fever will sometimes rise too much and at other times not enough.

Iron withholding. Bacteria lack the ability to get iron easily. Iron is a crucial and scarce resource for bacteria, and their hosts have evolved a wide variety of mechanisms to keep them from getting it. The same chemical that helps induce fever greatly decreases availability of iron in the blood. In the midst of flu, such iron-rich foods as ham and eggs suddenly become disgusting; we prefer tea and toast. Low iron levels can help fight disease.

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How does a host guard against infection? (Expanding on the above chart.)

  • Hygiene. Avoid exposure to pathogens.
  • Skin. Erect barriers to keep them out of the body and act quickly to defend and repair any breaches.
  • Pain and Malaise. Generalized aches and pains are also adaptive. They encourage inactivity — which favors the effectiveness of immune defenses, repair of damaged tissues, and other host adaptations. Medication that merely makes a sick person feel less sick will interfere with these benefits.
  • Expulsion and Pain. Flag any cells that lack proof of identity and expel them from their entry portal. The body must have openings for breathing, intake of nutrients, expulsion of wastes, and for reproduction. Each of these openings offers pathogens an invasion route, and each is endowed with special defense mechanisms. The defenses at each body opening can be quickly increased if danger threatens. Coughing, spitting, vomiting, nausea, diarrhea.
  • Mechanisms to attack invaders. If all the above defense lines are breached, it can poke holes in the pathogens, poison them, starve them, or do whatever is necessary to kill them. If it can’t kill them, it can also wall them off so they can’t spread. Macrophages constantly wander the body searching for foreign invaders. If they find one, they transfer it to a helper T cell, which then finds and stimulates whichever white blood cells can make an antibody that binds to the foreign protein. This impairs them and labels them for attack by specialized larger cells.
  • Damage and repair. If all the above still doesn’t work and they’ve caused damage, it can repair it or compensate for it in some way.

In order to choose appropriate treatment, we need to know if the cough, or other symptom, benefits the patient or the pathogen. Instead of just relieving symptoms and trying, perhaps ineffectively, to kill the pathogen, we can analyze its strategies, try to oppose each of them, and try to assist the host in its efforts to overcome the pathogen and repair the damage.

Evolutionary arms race

The relationships between hosts and parasites are so competitive, wasteful, and ruthlessly destructive that arms-race terminology offers an entirely appropriate framework for describing them.

Evolution consists entirely of trial-and-error tinkering. The process is slow and unguided — in some ways misguided — by there is no limit to the precision and complexity of adaptation that the Darwinian process can generate.

Bacteria can evolve as much in a day as we can in a 1000 years. We cannot evolve fast enough to escape from microorganisms. Instead, an individual must counter a pathogen’s evolutionary changes by altering the ratios of its various kinds of antibody-producing cells. Fortunately, the number and diversity of these chemical weapons factories are enormous and at least partly compensate for our pathogens’ great evolutionary advantage.

An unsanitary water supply is only one example of what Ewald calls cultural vectors. The history of medicine shows repeatedly that the best place to acquire a fatal disease is not a brothel or a crowded sweatshop but a hospital. In hospitals, large numbers of patients may be admitted with infectious diseases normally transmitted by personal contact.

Natural toxins

Natural toxins are those that are found commonly in our evolutionary environment.

Our best defenses against these toxins are the same as infectious diseases — hygiene, expulsion, avoidance. Many swallowed toxins can be denatured by stomach acid and digestive enzymes. In the liver for example, specialized enzymes will alter some toxic molecules to render them harmless, and bind to others which are then excreted in the bile back into the intestines. For instance, our protection against cyanide depends on an enzyme called rhodanase, which adds a sulfur atom to cyanide.

Many plants make substances that interfere with the nervous system: opioids in poppies, caffeine in coffee beans, cocaine in the coca leaf. Why do the plants contain these toxins? A few coffee beans might give us a pleasant buzz, but imagine the effect of the same does on a mouse. Potatoes contain diazepam (Valium) but in amounts too small to even cause relaxation. Other plants have toxins that cause cancer or genetic damage, sun sensitivity, liver damage — you name it. The plant-herbivore arms race has created weapons and defenses of enormous power and diversity.

If our livers are overloaded with too much toxins, they cannot process them all and excess toxins circulate throughout the body, doing damage wherever they can. Some exposure to toxins can stimulate increased enzyme production in prep for the next challenge. So perhaps with toxins, as with sun exposure, our bodies can adapt to chronic threats but not to occasional ones.

Grazers and browsers limit their consumption of certain plants to avoid overloading any specific toxin. This dietary diversification also helps to provide adequate supplies of vitamins and other trace nutrients. We minimize the damage caused by dietary toxins by this instinctive diversification, as well as with out own special array of detoxification enzymes.

These enzymes are not as potent as those in goats or deers, but are more potent than those of a dog or cat. We could be seriously poisoned if we ate a deer’s diet of leaves and acorns.

Our enzyme systems can apparently cope with low concentrations of tannin, and many of us like its taste in tea and red wine. Small amounts of tannin may even be helpful by stimulating production of the digestive enzyme trypsin.

Human diets expanded after fire was domesticated. Because heat detoxifies many of the most potent plant poisons, cooking makes it possible for us to eat foods that would otherwise poison us.

A new variety of disease-resistant potato was recently introduced that did not need pesticide protection, but it had to be withdrawn from the market when it was found to make people ill. Sure enough, the symptoms were caused by the same natural toxins the Andean farmers had spent centuries breeding out. An evolutionary view suggests that new breeds of disease-resistant plants should be treated as cautiously as artificial pesticides are.

Novel toxins

Novel toxins are a special problem not because artificial pesticides such as DDT are intrinsically more harmful than natural ones, but because they are so different than what we evolved to cope with.

Furthermore, we have no natural inclination to avoid some novel toxins. Evolution equipped us with the ability to smell or taste common natural toxins and the motivation to avoid such smells and tastes. In psychological jargon, the natural toxins tend to be aversive stimuli. But we have no such machinery to protect us from many artificial toxins, like DDT, that are odorless and tasteless.

Tests on rats are of limited reliability as models for human capabilities, and there are many political difficulties that can frustrate public action on environmental hazards.

There is no such thing as a diet without toxins. The diets of all our ancestors, like those of today, were compromises between costs and benefits.

Pregnancy

Embryonic and fetal tissues may be harmed by lower concentrations of toxins than adult tissues are.

Morning sickness is often the first reliable sign of pregnancy. This nausea and its associated lethargy and food aversions are common. For some women they mean many weeks of misery, while others aren’t bothered much.

Nausea and food aversions during pregnancy evolved to impose dietary restrictions on the mother and thereby minimize fetal exposure to toxins. A healthy, well-nourished woman can often afford to eat less. The food she is inclined to eat is usually bland and without the strong odors and flavors provided by toxic compounds. A lamb chop that smells fine to a man may smell putrid and repulsive to his pregnant wife.

Women who have no pregnancy nausea are more likely to miscarry or to bear children with birth defects.

Pregnant women should be extremely wary of all drugs, both therapeutic and recreational. Do not succumb to the urgings of others to eat what you are inclined to avoid.

Certain kinds of clay, as mentioned in the discussion about acorns, tightly bind soluble organic molecules, including many toxins. In other words, they may relieve symptoms in the best way possible — by removing the harmful cause.

Polaroid, Apple’s spiritual successor

I just finished 2 books on the history of Polaroid 🌈*. A remarkable tech company with enormous success in consumer and industrial applications for decades. It’s also remarkable just how much Apple was influenced by Polaroid.

A brief history

As a child Edwin Land found a copy of the 1911 edition of Physical Optics, a textbook by the physicist Robert W. Wood. He obsessed over its contents, lingering on one chapter in particular: the polarization of light.

In 1928, Ed Land was 19 when he invented the first thin-sheet polarizer. He cofounded Land-Wheelwright Labs with a friend in 1932 after dropping out of Harvard. Their first products were polarized versions of headlights, sunglasses, etc.

They grew slowly with mostly small industrial contracts for 6 years, then reincorporated as Polaroid Corporation. During the war sales grew an order of magnitude, 80% of which went to the military for products like polarized goggles.

In 1943 Land came up with the idea for a film camera that can process right away instead of in a lab. R&D started immediately, but it wasn’t until 1948 their first camera, the Model 95, was released. It went on to sell 900k units in 5 years.

The 95 was a classic disruptive innovation: worse quality than traditional film cams, dismissed as not “real” photography, but appealing to a new market of customers. And profitable: camera for $90, film packages with 60% gross margins.

With all the new cash flow, they could plow it back into R&D. To Land, they had “. . . created an environment where a man was expected to sit and think for two years.”

Polaroid’s growth lasted decades longer, peaking in the ’80s right when, ironically, they won an historic years-long lawsuit against Kodak for patent infringement.

Apple, the spiritual successor

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Back to the Apple comparison. The similarities are clear: from values, to marketing, to org structure, to product launches and demos.

Just like Jobs, Land was at the top of every invisible organizational chart. An anonymous former colleague: “Don’t kid yourself, Polaroid is a one-man company.”

When faced with scientific illiteracy or lack of imagination, Land resorted to a restrained bit of showbiz. As it turned out, he was strikingly good at explaining his work to people, and powerfully persuasive.

Ed Land was one of Jobs’ childhood heroes. Jobs met with him later and connected when when Land said his products have always existed, they were just invisible: waiting to be discovered. Apple exemplified Land’s motto “Don’t do anything that someone else can do.

Polaroid’s downfall started long before the digital apocalypse with their sidelining of Land in the ’80s. His final mistake was giving little thought to his own succession and the future of the company in the new generation. When they all but kicked Land out, Jobs met with and scolded management, saying Polaroid would turn into “a vanilla corporation”.

And it did. Jobs would take this lesson to heart many years later with his own succession plan.

Snapshot

Evan Spiegel is also heavily influenced by Land and Polaroid. But alas, Snap is not a camera company—they’re a communication company. And I think they’d do better in the future remembering that.

Inspiration, not imitation.

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Polaroid Variable Day Glasses; Snap Glasses.

I’ll finish with a Land quote from 1970: “We are still a long way from the… camera that would be, oh, like the telephone: something that you use all day long … a camera that you would use as often as your pencil or your eyeglasses.”

 


* “Instant: The Story of Polaroid” by Christopher Bonanos (2012).
Land’s Polaroid: A company and the man who invented it” by Peter Wensberg (1987)

Books: 2017 Reading List

Competing Against Luck — finally a full writeup on “Jobs Theory”, and required reading for anyone involved in product strategy & UX design (i.e. all startups).

The Change Function — good, simple model to think about how valuable a new innovation is (all about UX, or if (perceived crisis > cost of adoption)).

Marketing High Technology — best book on distribution you can find, for technology or otherwise.

Shoe Dog — Great story; wish he would have spent more time in the later years of Nike’s growth.

Doing the Impossible — too dense overall, but I loved hearing the story of the moon mission from the inside, especially from such a talented project manager that made it happen.

Scale — not as good as hoped, but a good “skim” with lots of interesting ideas around a theme.

21 Irrefutable Laws of Leadership — great leadership advice + stories to go along with, Dale Carnegie style (but could have been much shorter).

Hard Drive — 3rd reading of the best bio of Bill Gates & Microsoft’s early years.

The Elements of Computing Systems — I never had formal CS education so this was a great practical explainer, from translating binary to assembly, to how an OS works.

A Mind at Play — always been a huge fan of Claude Shannon’s work, mind, and humility.

Turing’s Cathedral — a little long in places, but great overall history of computing & early people who shaped it.

Softwar — Reading now. Interesting insights about early Oracle, also gives me new appreciation for Ellison. [Update: I would not recommend this book. First part is good but last half rambles on, fawning over Ellison with random stories. “The Difference Between God and Larry Ellison” is much better.]

Book Notes: Benjamin Graham

As with my other book notes, some passages are direct quotes and others are my own paraphrasing/summaries. Any footnotes or [brackets] are my personal comments.

The Intelligent Investor (1973) + Security Analysis (1934), by Benjamin Graham

Benjamin GrahamTo invest intelligently in securities one should be forearmed with an adequate knowledge of how the various types of bonds and stocks have actually behaved under varying conditions—some of which, at least, one is likely to meet again in one’s own experience.

An investment operation is one which, upon thorough analysis promises safety of principle and an adequate return. Operations not meeting these requirements are speculative. An investment operation is one that can be justified on both qualitative and quantitative grounds.

We speak of an investment operation rather than an issue or a purchase, for several reasons. An investment might be justified in a group of issues, which would not be sufficiently safe if made in any one of them singly. In our view it is also proper to consider as investment operations certain types of arbitrage and hedging commitments which involve the sale of one security against the purchase of another. The safety sought in investment is not absolute or complete; the word means, rather, protection against loss under all normal or reasonably likely conditions or variations. A safe stock is one which holds every prospect of being worth the price paid except under quite unlikely contingencies.

Outright speculation is neither illegal, immoral, nor (for most people) fattening to the pocketbook. There is intelligent speculation as there is intelligent investing. But there are many ways in which speculation may be unintelligent. Of these the foremost are: (1) speculating when you think you are investing; (2) speculating seriously instead of as a pastime, when you lack proper knowledge and skill for it; and (3) risking more money in speculation than you can afford to lose.

The defensive (or passive) investor will place his chief emphasis on the avoidance of serious mistakes or losses. His second aim will be freedom from effort, annoyance, and the need for making frequent decisions. The determining trait of the enterprising (or active, aggressive) investor is his willingness to devote time and care to the selection of securities that are both sound and more attractive than average.

Obvious prospects for physical growth in a business do not translate into obvious profits for investors. The future of security prices is never predictable.

In his endeavor to select the most promising stocks wither for the near term or the longer future, the investor faces obstacles of two kinds—the first stemming from human fallibility and the second from the nature of his competition. He may be wrong in his estimate of the future; or even if he is right, the current market price may already fully reflect what he is anticipating. In the area of near-term selectivity, the current year’s results of the company are generally common property on Wall Street; the next year’s results, to the extent they are predictable, are already being carefully considered. Hence the investor who selects issues chiefly on the basis of this year’s superior results, or on what he is told he may expect for next year, is likely to find that others have done the same thing for the same reason. To enjoy a reasonable chance for continued better than average results, the investor must follow policies which are (1) inherently sound and promising, and (2) not popular on Wall Street. Continue reading “Book Notes: Benjamin Graham”

Book Notes: Innovation and Entrepreneurship

As with my other book notes, some passages are direct quotes and others are my own paraphrasing/summaries. Any footnotes or [brackets] are my personal comments.

Innovation & Entrepreneurship (1985), by Peter Drucker

Innovation and Entrepreneurship“The entrepreneur,” said the French economist J. B. Say around 1800, “shifts economic resources out of an area of lower and into an area of higher productivity and greater yield.”

All new small businesses have many factors in common. But to be entrepreneurial, an enterprise has to have special characteristics over and above being new and small. Indeed, entrepreneurs are a minority among new businesses. They create something new, something different; they change or transmute values. An enterprise also does not need to be small and new to be an entrepreneur. Indeed, entrepreneurship is being practiced by large and often old enterprises.

The entrepreneur upsets and disorganizes. As Joseph Schumpeter formulated it, his task is “creative destruction.” They see change as the norm and as healthy. Usually, they do not bring about the change themselves. But—and this defines entrepreneurship—the entrepreneur always searches for change, responds to it, and exploits it as an opportunity.

When shifting resources to a more productive area, there is a risk the entrepreneur may not succeed. But if they are even moderately successful, the returns should be more than adequate to offset whatever risk there might be. One should thus expect entrepreneurship to be considerably less risky than optimization. Indeed, nothing could be as risky as optimizing resources in areas where the proper and profitable course is innovation, that is, where the opportunities for innovation already exist. Theoretically, entrepreneurship should be the least risky rather than the most risky course. [There are “hidden” risks of not being an entrepreneur.]

“Innovation,” then, is an economic or social rather than a technical term. It can be defined the way Say defined it, as changing the yield of resources. Or, as modern economists would tend to do, it can be defined in demand terms rather than in supply terms: changing the value and satisfaction obtained from resources by the consumer. Continue reading “Book Notes: Innovation and Entrepreneurship”

How to separate luck and skill

These are some of my notes from the book “The Success Equation” by Michael Mauboussin. This book was spotted on Warren Buffett’s desk in this tour of his office. There’s lots more interesting stuff in the book, but these notes in particular answer the question “How do you separate luck and skill?” We’ll start off with some definitions:

Luck is a chance occurrence that affects a person or a group (e.g., a sports team or a company). Luck can be good or bad. Furthermore, if it is reasonable to assume that another outcome was possible, then a certain amount of luck is involved. In this sense, luck is out of one’s control and unpredictable. Randomness and luck are related, but there is a useful distinction between the two. You can think of randomness as operating at the level of a system and luck operating at the level of the individual. Luck is a residual: it’s what is left over after you’ve subtracted skill from an outcome.

The definition of skill depends on how much luck there is in the activity. In activities allowing little luck, you acquire skill through practice of physical or cognitive tasks. In activities incorporating a large dose of luck, skill is best defined as a process of making decisions. Here, a good process will have a good outcome but only over time. Patience, persistence, and resilience are all elements of skill.

Separating luck and skill

Luck-Skill Continuum
At the heart of making this distinction lays the issue of feedback. On the skill side, feedback is clear and accurate, because there is a close relationship between cause and effect. Feedback on the luck side is often misleading because cause and effect are poorly correlated in the short run.

In most cases, characterizing what’s going on at the extremes is not too hard. As an example, you can’t predict the outcome of a specific fair coin toss or payoff from a slot machine. They are entirely dependent on chance. On the other hand, the fastest swimmer will almost always win the race. The outcome is determined by skill, with luck playing only a vanishingly small role.

Continue reading “How to separate luck and skill”

Book Notes: The Visible Hand

The Visible Hand: The Managerial Revolution in American Business was written by Alfred Chandler and released in 1977. It’s a great history and study on business and why it exists the way it does today. For some books I read, I transcribe and summarize my highlights/notes in order to better learn the material and for future reference. Below you’ll find my (very long) summary of The Visible Hand. Some passages are direct quotes and others are my own paraphrasing/summaries. So if you’re interested in this sort of topic, send this baby to Instapaper, plop down on the couch, and enjoy.

The Visible Hand

Modern business enterprise is easily defined, having two specific characteristics: (1) it contains many distinct operating units and (2) it is managed by a hierarchy of salaried executives. Each unit has its own administrative office, set of books and accounts. Each could theoretically operate as an independent business enterprise. Such enterprises did not exist in the U.S. in 1840. By World War I this type of firm had become the dominant business institution. It was the institutional response to the rapid pace of technological innovation and increasing consumer demand.

This study is a history, moving chronologically. Before entering the historical experience, here is a list of general propositions to make more precise the primary concerns of the study:

The initial appearance of modern business enterprise:

  1. Modern multiunit business enterprise replaced small traditional enterprise when administrative coordination permitted greater productivity, lower costs, and higher profits than coordination by marker mechanisms. [This was due to both corporate efficiency and economies of scale.]
  2. The advantages of internalizing the activities of many business units within a single enterprise could not be realized until a managerial hierarchy had been created. An enterprise without such managers remains little more than a federation of autonomous offices.
  3. Modern business enterprise appeared for the first time in history when the volume of economic activities reached a level that made administrative coordination more efficient and more profitable than market coordination. It came with new technology and expanding markets.

Growth of the modern business enterprise:

  1. The hierarchy itself became a source of permanence, power, and continued growth.
  2. The careers of the salaried managers who directed these hierarchies became increasingly technical and professional. Training became longer and more formalized.
  3. The management of the enterprise became separated from its ownership. Stockholders didn’t have the influence, knowledge, experience, or commitment to take part in the high command.
  4. Career managers preferred policies that favored the long-term stability and growth of their enterprises to those that maximized current profits. For salaried managers the continuing existence of their enterprises was essential to their lifetime careers.
  5. As the large enterprises grew and dominated major sectors of the economy, they altered the basic structure of these sectors and of the economy as a whole.

Continue reading “Book Notes: The Visible Hand”