Friday, January 26, 2018

Need a daily dose of dirt?

kw: book reviews, nonfiction, health, colon health, microbiome, therapies

RePOOPulation — What a lovely word! Coined by Dr. Emma Allen-Vercoe of the University of Guelph in Canada, it is one culmination of the research outlined in a new book by Drs. Brett Finlay and Marie-Claire Arrieta: Let Them Eat Dirt: How Microbes Can Make Your Child Healthier. For that matter, this implies that our inner bugs can help or harm us at any stage of life. Dr. Vercoe grows bacterial populations in "fermenters" (they make for a smelly building), for use in helping patients restore a healthy inner "farm" of bacteria and other microbes.

I grew up when a certain proverb was popular: "They can't grow up right without eating a peck of dirt." Considering how dirty and messy kids could get in the 1950's, '40's and earlier, a peck might just be the beginning (it's about 15 pounds, or a 2-gallon volume). Rightly understood, the parallel maxim "Cleanliness is next to Godliness" didn't refer to never getting dirty, but to washing well, particularly before meals.

Let Them Eat Dirt is a book of advice, but so well written that I didn't mind. And while it is about raising children, actually it is about raising a good (meaning virtuous!) crop of the hundreds or thousands of microbes that populate the gut of everyone. Even kids such as the "bubble boy" are not microbe-free, they are just being extremely well protected from pathogenic ones.

For all you germophobes out there: Experiments with germ-free mice (GF mice) show that animals with no internal nor external population of microbes are fatter, shorter-lived, and more prone to all the chronic diseases that seem to characterize our "clean" Western social system, such as asthma and diabetes.
Definition: microbiome. "a community of microorganisms (such as bacteria, fungi, and viruses) that inhabit a particular environment and especially the collection of microorganisms living in or on the human body. Your body is home to about 100 trillion bacteria and other microbes, collectively known as your microbiome." [Merriam-Webster]
The book's chapters take us through all the stages of a child's life, beginning with the various ways a newborn's microbiome is formed, nurtured, and possibly damaged and restored. (Antibiotics effectively carpet-bomb our microbiome. Being nursed at the breast helps build a baby's microbiome, and at least partially restores the microbiome if the baby had to have antibiotics as an infant.) A baby born vaginally ingests its mother's vaginal and fecal microbes. All the cuddling, kissing, and even pre-chewing food a mother does for her baby continually adds to the microbes that colonize her baby's gut. Don't think that is icky! Unless the mother is desperately ill, that is very, very good. Later on, letting a kid play outside, including the inevitable dirty-hand-in-mouth. (The book's cover shows a grinning boy with really dirty hands, but a spotless face. Ironic!)

The book also outlines research that shows the relationship between many diseases that were formerly very rare or unknown but are now common, at least in the "advanced" societies of the industrialized countries. Not only allergies, asthma and type 2 diabetes, but many cases of autism produce a microbiome with a genetic signature that can be detected by analysis of the bugs found in the feces. With what is known now, many chronic diseases can be diagnosed by analyzing a stool sample. Although this presently costs more than more traditional diagnostic methods, that could change very soon. In fact, it may soon be possible to mail off a stool sample and get back a list of the diseases a person either has now or is prone to getting, plus suggestions how to change one's microbiome so as to forestall them. That's probiotics at a whole new level!

Whatever stage of life you may be, whether or not you'll be raising children soon…whatever. This book is well worth the read, and even taking notes for later reference. Enjoy!

Wednesday, January 17, 2018

It grabs you where you live

kw: book reviews, nonfiction, addictions, technology

When I saw the book Irresistible: The Rise of Addictive Technology and the Business of Keeping Us Hooked, by Adam Alter, the verse 1 Corinthians 16:15 came to mind. It speaks of a certain family that "have addicted themselves to the ministry of the saints". At least, that is how the King James Version and two others translate the word εταξαν, a form of τασσω, which in the First Century meant "to set, appoint or ordain", but has lost that meaning in the centuries since. Becoming curious about the English usage of the King James era (early 1600's), I found that "addiction" referred mainly to fascination and devotion. Thus many English versions of the verse use either "set" or "devoted". The term was neither positive nor negative prior to the mid-1800's

Addiction has a much stronger and more focused meaning today. To be addicted is to be in the grip of a compulsion or obsession that harms one, or may eventually kill. Since the early 1900's or a little earlier, "addiction" has referred to a compulsion to use substances such as cocaine. As author Adam Alter tells us, there was quite a struggle in the later Twentieth Century among psychiatrists and psychologists about whether to recognize "behavioral addictions". But the modern phenomena—from binge-watching of TV episodes to online game playing, online gambling, twelve- to 24-hour FaceBook sessions and even "checking in" so compulsively that people walk into fountains, manholes and lampposts—have convinced nearly all that behavioral addiction is real and can be really, really bad.

Note the phrase above, "…or may eventually kill." I do not mean just the shortening of life due to bad health from being a "couch potato" or "FB zombie". Suicides have resulted, not just from being trolled online, but from despair over falling behind the social media rat race.

In a fascinating busman's tour through history, we find that addictive tendencies are with us for very good reasons: our distant ancestors did not become ancestors by ignoring the siren call of pleasurable experiences. In pre-agricultural days, over most of the Earth, eating everything that tasted good kept you alive, and getting all the sex you had opportunity to obtain gave you a chance at having descendants. Also, our ancestors traveled, and the dopamine-fueled thrill of seeing what is over the next ridge motivated many of them to seek new pastures and far horizons. Those who traveled the farthest may have been subject to extra risks, but the chance to populate a new and empty landscape was a benefit not to be ignored.

Our tendencies to fall prey to obsessions, compulsions, and addictions are a direct result of the tens of thousands, even millions of years, that humans lived with scarcity. Now about half the human race lives with relative abundance. What happens then? We overdo it; we overdo it big time.

The author describes many behavioral hooks that turn a potentially enjoyable experience into a compelling one. Unsteady rewards are a big, big factor. Even as Pavlov learned, once a dog has learned to associate receiving food with the ringing of a bell, it will salivate when the bell rings, whether food is given or not. But if food is given roughly every third time, the dog will salivate more and more. Rats given the chance to push a bar to get a food pellet will do so, of course. But if pushing the bar doesn't always yield a pellet, they will push the bar again and again, gathering pellets far beyond their need to eat them. Uncertainty is a big hook.

The most addicting games are those that you win about 1/3 of the time. If you win every time, you get bored. If you win less than 1/10 of the time, you look for a "better" game. This is just one example. Apparently, the most addicting computer game to come along, at least up to the time the book was written, is World of Warcraft. The second-most is probably League of Legends, which my son plays more than he should…though so far it hasn't affected his work enough to cut into his income. I hope that day doesn't come, but for many others it has come already (Cue a stereotypical video of a jobless Millennial who lives in the parents' basement and plays games all day).

So, can we do anything about this? Friends of ours despaired of even slowing down their daughter's FaceBook addiction. Her grades suffered badly. She almost dropped out of college. Nobody knows quite what happened, but she somehow developed a backbone, and a level of resistance, so that her grades improved, she graduated, and now has a responsible job. I don't know how much she may still read her News Feed on FB but I don't see a lot of posts from her. There are other folks—well, I just shake my head. I wonder how they have time to put one or two or three dozen posts in their News Feed every single day. Maybe we just have to let people outgrow it. Pity those who never do.

At the end of Irresistible the author discusses one "thing" (I can't think of another word) that seems to make positive use of the hooks that draw us in: Gamification. This is adding an element of fun into otherwise mundane, boring or unpleasant tasks. In the modern era, technological hooks can be used to trigger our compulsions, just enough, but breaks or "units" are inserted so we won't binge out. The FitBit is a potential gamification of exercise, but it doesn't have any checks, so some people damage their health trying to achieve ever-increasing goals. It needs some work.

But even without FitBit and its kin, overdoing it is a risk. I used to exercise a lot, including certain body-mass strengthening routines, and began keeping records. As it happens, that might have been a mistake. Or, at least, I ought to have obtained a buddy or coach to help me keep track and not ramp up my routines too fast. One day I did too many dips and pulled a muscle in my chest. It took five months to heal (I was about 40; were I younger it might have taken only a month or two). By then, the cycle was broken, and since then I primarily walk. There was no FitBit involved, nor have I ever owned one.

I am also reminded of Zooniverse, with more than 70 somewhat gamified "citizen science" projects. There aren't even any bells and whistles, just accumulating numbers of tiny projects completed, but that is enough that millions of people (myself included) enjoy sorting galaxies, counting penguins, or transcribing hand-written museum labels. Without a few little hooks in the projects, it is actually deadly dull work!

I consider the matter unfinished. We don't yet know how to cope with behavioral addictions. As the author writes, we are in the foothills of addictive technology. But not everyone is equally prone to addiction, whether to substances or behaviors. Perhaps Darwinism will run its course, and a future generation will consist mostly of people who are largely immune to the allure of the Like button.

Wednesday, January 10, 2018

Is evidence-based medicine dead?

kw: book reviews, nonfiction, medicine, medical research, critiques

Research incentives are messed up, big time. So much so that Sturgeon's Law of fiction writing applies, doubled: when someone protested to him about the presentations at a science fiction convention, that 90% of it was crud, he replied, "90% of everything is crud!" When people's careers are on the line, when jobs, promotion, tenure and salary all depend on "Publish or Perish", virtue vanishes. Young, idealistic researchers become jaded, cynical cheaters. One medical author has written that as much as 99% of published medical research is valueless or even damaging. Another wrote,
"One must not underestimate the ingenuity of humans to invent new ways to deceive themselves."
This quote is found on page 192 of Rigor Mortis: How Sloppy Science Creates Worthless Cures, Crushes Hope, and Wastes Billions by Richard Harris. Author Harris admits that his title is a bit tongue-in-cheek, because rigor mortis literally means the stiffness of a corpse, while "rigor" also means strictness in carrying out a procedure. While it might be more accurate to title the book Mortis Rigoris (the death of rigor) or Mortuus est Rigor (rigor has died), it wouldn't resonate with doctors and others of us who know Latin.

More accurately, however, while experimental rigor is neglected more than adhered to, and may be on the ropes, it isn't quite dead yet. The ten chapters in Rigor Mortis illustrate and document every major aspect of medical research, from experimental design (The "gold standard" of the double-blind trial is nearly always compromised to save expenses, and frequently foregone entirely) to animal studies (Suppose you were told that a certain medicine was tested exclusively on women pregnant in their first trimester, of ages between 22 and 25, all from a specific ethnic group in Scandinavia? That's the analogy to a typical mouse study) to statistical analysis (The p-test is dramatically misleading, and we'll get into that one anon).

Have you ever heard of the "desk drawer file"? It is a lot like a Roach Motel; experiments with "negative results" check in, and are never checked out. Some of the few honest researchers left in the field are agitating for a requirement that every study funded with tax dollars be published, no matter what the outcome. The good news: transparency. The bad news: a ten- to 100-fold increase in the number of papers published. There is already an overwhelming deluge of publication! Gack!!

We need look no further than this to validate Sturgeon's Law. Consider the much-overused p-test, or p-value. You take a bunch of numbers, grind the formula (found in every statistical software package out there, including Excel), and out pops a number. Is it smaller than 0.05? Publish! That number gets inverted into "95% statistical probability that the result shown is not due to chance." Hmm. But what is it due to? Sunspots? Batch effects (perform run 1, clean equipment, perform run 2; do they differ because of the cleaning?)? Something you would never think of in your wildest dreams (all too frequently, yes)? But just suppose all those "95% chance it's right, 5% it's wrong" papers actually do have the "correct" cause and effect. How many experiments went to the "desk drawer" since the last time you published? 5, 10, 20, 100? The average is (wait for it) about 20! So, ignoring the desk drawer, five out of 100 publications must be reporting a chance association or correlation. Add the desk drawer factor of 20, and now at least half of them are reporting a correlation due to chance. Just by the way, it is amazing that the vast majority of studies that report a p-value have a number just under 0.05: "Dig around until you get a p-value you like, then stop looking."

Add in other factors, all detailed in Rigor Mortis, and there is little chance that more than a tiny fraction of published research results will stand the test of time. And that is a problem. A little time? That is OK. If a lot of further research and even development and marketing are based on a faulty result, and it takes "medical science" 5, 10, 20 years or more to find and correct the mistake, how many people die or suffer needlessly?

Is there a way out of it? Only partially. Transparency is part of the answer. But bureaucrats are lazy, so even with a law on the books that all studies funded by NIH must publish all results, for example, it is poorly enforced. There are a lot of partial answers out there. Here is my answer: We must live with what we have now, while things are possibly getting better, but today is today. When I must choose a new doctor or specialist, I inspect the waiting room, and later the visitation room. How many drug company trinkets can I find (pens, calendars, note pads, posters, and many more)? The fewer the better. My current doctor's rooms don't have anything with a logo on it. That's a great start; it means the doctor has better-than-usual resistance to high-pressure sales. Such a doctor is more likely to make a decision on medical grounds. Secondly, who do I actually see? Curiously, I prefer to be seen by a PA or NP, rather than a DO or MD. They haven't had all their good sense educated out of them yet. In my experience they are also a lot more willing to answer questions and do so more meaningfully. Also, I do ask a lot of questions, because a brusque doctor is likely to be impatient in the operating room also. In medicine, patience isn't just a virtue, it is a necessity! There is more, but if you aren't doing these things, start there.

What else can you or I do? Educate yourself. Not from medical journals, but from summary materials on things that are known to work. WebMD and Healthline are just the beginning. Don't limit your reading to a single source. When offered a "new" drug, always ask, "Is there an older one that works well enough, perhaps with fewer side effects?" There are always side effects. Some you can live with, some you can't. Do avoid, desperately, a drug that needs another drug to deal with side effects. My wife takes a statin drug for high cholesterol. She was originally prescribed the strongest one, and even taking a tiny dose, had troubling side effects. Her "undrugged" total cholesterol is 240, but that drug is best used for folks in the 400+ range. She demanded a weaker one, and even then, splits the pill in thirds. She has no noticeable side effects, and her "drugged" total cholesterol is about 160. Good enough!

I've learned to tell a doctor, "I am not a patient. I am a customer. You and I will collaborate. I will never cede my right to make decisions, except during anesthesia that we have agreed upon together." Call it an intelligence test. For the doctor. Occasionally a doctor fails it, and then I get another doctor. When needed, I make a doctor aware how skeptical I am of the "evidence" presented in modern journals.

Rigor Mortis is scary. Is it right? Sadly, yes, it is more right than the average published medical study. But don't let that drive you to the amorphous world of "alternative medicine", at least not wholesale. Allopathic medicine has produced amazing health in most Americans and others in the First World. For a generation or so medical research has gone astray. Will it return? Maybe. Until it does, we must be our own best doctors.

Thursday, January 04, 2018

Sleep, beautiful sleep

kw: book reviews, nonfiction, sleep

What a way to start the year! with a book about sleep. Michael McGirr, a former Jesuit priest, and a victim of sleep apnea, writes about sleep and sleeplessness from a few unique perspectives in his book Snooze: The Lost Art of Sleep. I read the book hoping to re-connect with this lost art, but found instead a travelogue, a book of "what" but not "how".

There is no table of contents and I didn't count as I went, but I reckon there are upwards of a dozen chapters. Each is titled by a time and a year (or a few related years), thusly:



in which chapter he writes of his diagnosis of sleep apnea and the invention of the CPAP machine, and about his marriage to Jenny who loved him anyway (this after he left the Jesuit order), or



riffing on Jacob son of Isaac, one of history's celebrated sleepers, he of the dream of angels on a ladder, but one who nonetheless complained to his father-in-law,
… by day the heat consumed me, and the cold by night, and my sleep fled from my eyes.
He writes of Edison, who was too busy inventing to sleep; of Florence Nightingale, who slept little but spent some 3/4 of her life directing matters worldwide from her bed; and of coffee and its use to ward off sleep, so much so that Balzac, who fueled his amazing literary output with sixty cups of coffee daily, died of caffeine poisoning at age 51. Balzac might have lived a lot longer on half the coffee, and while writing less daily, his total production might have been even greater.

I am reminded of Alfréd Rényi, who said, "A mathematician is a machine for turning coffee into theorems," a quote usually attributed to Paul Erdős, and tangentially of Leonardo da Vinci, who is said to have kept to a regimen of three hours and 40 minutes of work followed by a 20-minute nap, day in and day out (that comes to two hours in each 24-hour period). I read about one man who tried working on this schedule and did so for a few years, but then gave it up because he ran out of things to keep him busy. I guess to keep Leonardo's schedule you have to have Leonardo's creativity. I wish McGirr had included these also in his travelogue of sleep and its variations, but he did not.

Regardless, his own studies of sleep, restful or not, led him in many directions, including into those antonyms of caffeine, the various sleep-inducing drugs, from Benadryl® to Ambien® and beyond. During a hospital stay, a nurse gave me two Benadryl®, which worked well. My father used a prescription sleep aid that turned out to be a double dose of diphenhydramine in one pill; the exact equivalent of taking two Benadryl®, but a lot more costly. But the more recent drugs induce sleep by messing with the normal sleep cycle, which can put you into a deep sleep without the total sleep paralysis needed to keep you from acting out your dreams. Lots of sleepwalking (and sleep driving, etc.) incidents are known, some with fatal results.

In the last chapter, he writes that reading in bed can help us drowse, but only if we are reading off of printed paper. The reflected light from a page with dark ink does not inhibit melatonin production. The light from a computer of phone screen has a different quality, and does so interfere.

Overstress is a primary enemy of sleep. We need a certain amount of stress to keep life interesting, but overwhelming, chronic stress just burns us out. Some folks respond with depression and may take to their beds, sleeping much or most of the day. Most of us have trouble getting to sleep, wake too early, and feel tired much of the time. While a few chapters of Snooze address chronic insomnia, a broader affliction is that many of us get some sleep each night, but never seem to get enough. Many, many of us have an experience like mine.

During the last ten or so years of employment at DuPont, I seldom slept more than four hours nightly. For some of that time, I was also on one or another medication to address my bipolarity, but they didn't do much so I learned to cope with it unmedicated. During those medicated periods, I usually napped up to two hours daily, so you could say I had six hours of sleep, but not in one installment. However, without medication with a sleep-promoting side effect, four hours was it. No naps. I had work I enjoyed a lot, a congenial boss (the last 8 of the 10 years), and even told my boss I might work until I was 75. But when the company declared a retirement incentive, I retired at age 66.

After retirement, two important things happened. Within a few weeks, I was sleeping 6-7 hours nightly, and over about half that first year I lost 15 pounds. I remember looking back one day, and saying to myself, "I didn't realize the level of stress I was under!" I had also been using a lot of "cold caffeine" (Pepsi Max), up to a liter daily.

Now that four more years have passed and I am over 70, I get 5-7 hours of sleep, and if I wake early I simply get up, read my Bible a while, have breakfast, then have a morning nap for another hour or two. There aren't a lot of conclusions to draw from that. I am thankful that, though I snore some nights (not all), I don't have apnea; I have part time work that keeps some structure in my life, but is incredibly less stressful than any job I had before; I practically eliminated caffeine, using caffeinated cola only for driving alertness on road trips.

You'll have to look elsewhere for advice and information on how to sleep longer and better. For an enjoyable survey of how humans have been sleeping, or not, Snooze is the book for you.