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The Microbiome Solution by Robynne Chutkan M.D.
Americans today have only about two-thirds as many bacterial species as native tribesmen in the Amazon who haven’t been exposed to antibiotics. As we’ll learn in the second part of this book, restoring those lost microbes takes real commitment. While there is no perfect microbiome, some are clearly healthier than others, notwithstanding the incredible variation from one to the other. The Human Microbiome Project and other research efforts like it seek to establish what the “normal” human microbiome looks like today—an important endeavor, considering the rate at which our microbial landscape is changing. Companies like uBiome allow the citizen scientist to catalogue his or her own microscopic habitat, compare it to others, and reassess it as diet and habits change. The human microbiome may well be the next big frontier in medicine, providing answers to why we get sick and novel solutions for how to heal ourselves. In the next chapter we’ll learn more about what our gut bacteria actually do—besides make gas—and why they’re so essential to our health and well-being.
Since bacteria follow the food, instead of counting calories when we’re trying to slim down, a model that clearly falls short in accounting for weight gain or loss, we should be looking at how to shape our microbiome in a way that influences caloric extraction from food. Cutting down on processed grains and refined sugar can affect our microbiome in a positive way, but replacing those foods with too much animal protein and fat can be problematic, because they may crowd out the dietary fibers that are an important component of a microbiome associated with leanness. I see a plateau in weight loss in many of my patients who put themselves on restrictive low-carb diets or Paleo devotees who don’t eat enough vegetables, probably because they’re not cultivating the right microbes. I’ll go into more detail about the ideal mix of nutrients needed to optimize your microbiome and maintain a healthy weight in Chapter 9. Is Our Super-sanitized Lifestyle Making Us Fat?
I had been trained at world-class institutions and practiced gastroenterology at a leading teaching hospital, but, like most physicians, I had no idea that the antibiotics I thought were so helpful were actually creating illness by decimating her microbiome at a time when it was most vulnerable, making her more susceptible to infection and inflammation. I wish I had known then what I know now and what I continue to learn every day: that illness is often the result of a decreased, not increased, bacterial load, and that less is sometimes more when it comes to medical intervention. Rehab for Your Microbiome Every day in my gastroenterology practice I see patients with the telltale signs of a disordered microbiome: bloating, leaky gut, irritable bowel, gluten intolerance, Crohn’s disease, ulcerative colitis, eczema, thyroid disorders, weight problems, fatigue, and brain fog.
The Diet Myth: The Real Science Behind What We Eat by Tim Spector
biofilm, British Empire, Colonization of Mars, cuban missile crisis, David Strachan, double helix, Drosophila, epigenetics, hygiene hypothesis, life extension, Mahatma Gandhi, meta analysis, meta-analysis, microbiome, phenotype, randomized controlled trial, Steve Jobs
There was some variation, but within a year of entering the long-stay nursing home all the residents had very similar and unhealthy microbiomes. In elderly people there are many complex reasons why the body deteriorates. These include loss of muscle through lack of physical exercise, depression, social circumstances and loss of cognitive function. The loss of teeth, changes in saliva, and the increasing use of antibiotics and other drugs can also affect the microbiome. With age, we see increases in the number and dysfunction of the protective Treg cells, which as we know interact with our microbes and at this point in life can over-suppress the immune system. Even when all these other factors were accounted for, diet and nutrition remained the dominant factor in determining the microbiome and its relation to health in the elderly. The residents with the least diverse gut microbiomes were far more likely to be frail and suffer from illnesses – and whatever the cause, were more likely to die within a year.
While a great result for Mary, what this didn’t explain was why she hadn’t had problems earlier, or why her twin sister with the exact same genetic make-up was unaffected, despite following a similar diet. Once again, their microbiomes may have been to blame. Studies of other patients with lactose intolerance have shown the same variable response to milk, but when patients with consistent problems have been given a normally indigestible prebiotic substance called GOS (galacto-oligosaccharide) which can alter your microbiome, they saw dramatic benefits compared to subjects given the placebo treatment. After two months their microbiomes had changed quite dramatically.11 When questioned more deeply, Mary remembered she had suffered a bad stomach infection at the end of her trip to Delhi and had needed several long courses of broad spectrum antibiotics.
A microbe collaborator of mine, Paul O’Toole, who was working in Cork at the time, told me this story as typical of many in the area, in which a dramatic change in nutrition in an elderly person had preceded health problems. Paul’s research group is looking into the effects of the microbiome in the elderly, and particularly the effects of diet. In an important study they surveyed 178 Irish residents from local nursing homes aged 70 to 102, half of whom came temporarily for day care and the rest who lived there permanently.1 They found that within six months all the permanent residents on the same dull, institutional diet developed a similar microbiome. Unfortunately, it wasn’t a healthy mix and was lacking in diversity and many of the healthy microbes. It also indicated greater levels of inflammation. Those elderly part-time residents who sometimes cooked for themselves and ate non-institutional meals had healthier microbiomes than those with the communally prepared food. There was some variation, but within a year of entering the long-stay nursing home all the residents had very similar and unhealthy microbiomes.
Asperger Syndrome, Barry Marshall: ulcers, Berlin Wall, biofilm, clean water, correlation does not imply causation, David Strachan, discovery of penicillin, Drosophila, Fall of the Berlin Wall, friendly fire, germ theory of disease, hygiene hypothesis, Ignaz Semmelweis: hand washing, illegal immigration, John Snow's cholera map, Louis Pasteur, Maui Hawaii, meta analysis, meta-analysis, microbiome, phenotype, placebo effect, the scientific method
The DNA-sequencing technology invented during the Human Genome Project enabled another major genome-sequencing programme, but one that received far less media attention: the Human Microbiome Project. Rather than looking at the genome of our own species, the HMP was set up to use the genomes of the microbes that live on the human body – the microbiome – to identify which species are present. No longer would a reliance on Petri dishes and an over-abundance of oxygen hold back research into our cohabiters. With a budget of $170 million and a five-year programme of DNA sequencing, the HMP was to read thousands of times as much DNA as the HGP, from microbes living in eighteen different habitats on the human body. It was to be a far more comprehensive survey of the genes that make a person, both human and microbial. At the conclusion of the Human Microbiome Project’s first phase of research in 2012, not one world leader made a triumphant statement, and only a handful of newspapers featured the story.
In short, our environment: nurture. Now we have a third player, which sits uncomfortably between nature and nurture. Although the microbiome is strictly an environmental force at work on our eventual characteristics, it is genetic, and it is inherited. Not via eggs or sperm, not via human genes, but a good portion of the microbiome is passed from parents, especially mothers, to offspring. Many parents hope that they pass on the best of themselves to their children; films like Gattaca envisage a future where this wish is not left to chance. Most parents also hope to provide their children with the happiest and healthiest environment that they can manage. The microbiome, with its genetic influence but environmental control, gives parents the power to do both of these things. Despite all the hype, our human genome did not quite live up to our visions of becoming a blueprint for life, and a philosophy for living.
Nature Reviews Gastroenterology and Hepatology 9: 88–96. 16. Delzenne, N.M. et al. (2011). Targeting gut microbiota in obesity: effects of prebiotics and probiotics. Nature Reviews Endocrinology 7: 639–646. 17. Petrof, E.O. et al. (2013). Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut. Microbiome 1: 3. 18. Yatsunenko, T. et al. (2012). Human gut microbiome viewed across age and geography. Nature 486: 222–228. Coda 1. Markle, J.G.M. et al. (2013). Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science 339: 1084–1088. 2. Franceschi, C. et al. (2006). Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mechanisms of Ageing and Development 128: 92–105. 3. Haiser, H.J. et al. (2013).
The Driver in the Driverless Car: How Our Technology Choices Will Create the Future by Vivek Wadhwa, Alex Salkever
23andMe, 3D printing, Airbnb, artificial general intelligence, augmented reality, autonomous vehicles, barriers to entry, Bernie Sanders, bitcoin, blockchain, clean water, correlation does not imply causation, distributed ledger, Donald Trump, double helix, Elon Musk, en.wikipedia.org, epigenetics, Erik Brynjolfsson, Google bus, Hyperloop, income inequality, Internet of things, job automation, Kevin Kelly, Khan Academy, Law of Accelerating Returns, license plate recognition, life extension, Lyft, M-Pesa, Menlo Park, microbiome, mobile money, new economy, personalized medicine, phenotype, precision agriculture, RAND corporation, Ray Kurzweil, recommendation engine, Ronald Reagan, Second Machine Age, self-driving car, Silicon Valley, Skype, smart grid, stem cell, Stephen Hawking, Steve Wozniak, Stuxnet, supercomputer in your pocket, Tesla Model S, The Future of Employment, Turing test, Uber and Lyft, Uber for X, uranium enrichment, Watson beat the top human players on Jeopardy!, zero day
The next big medical frontier after genomics is also already on the horizon: the microbiome, the bacterial population that lives inside your gut. This is a field that I am most excited about because it takes us back to looking at the human organism as a whole. Scientists are coming to the conclusion that the microbiome may be the missing link between environment, genomics, and human health. They are discovering connections between what types of bacteria live inside your body, how your genes behave, and how healthy you feel. Microbiome: Bacterial Rainforest in Your Gut Many children are born with genetic predispositions to type-1 diabetes. Though some of those infants become diabetic in their earlier years, others do not. A key reason for this may lie in the microbiome. In February 2015, researchers from M.I.T. and from Harvard University released the results of the most comprehensive longitudinal study yet of how the diversity and types of gut flora affect onset of this type of diabetes.3 The scientists tracked what happened to the gut bacteria of a large number of subjects from birth to their third year in life, and found that children who became diabetic suffered a 25 percent reduction in their gut bacteria’s diversity.
But we may be able to work around that by creating ways to change the microbiome balance in our bellies using supplements or other delivery mechanisms. And here’s where a rapid pace in scientific advances pays off: a wide-ranging analysis of microbiomes to identify bacterial population patterns in the guts of millions of people could provide a blueprint for the gut contents of disease sufferers and healthy people. This census could inform treatment efforts and allow doctors to more effectively manipulate the microbiome. So a yogurt a day may keep the doctor away, and a tummy full of the right sorts of cheese may be better medicine for many metabolic syndromes than pharmaceuticals or other lifestyle changes. Genomic medicine, gene-targeted drug development, and microbiome manipulation all depend on the ability to read DNA.
In this light, the most promising and least controversial realm of breakthroughs discussed in this chapter is the ongoing analysis of the microbiome. Since this is more about restoring ancient healthy systems in our intestines that evolved naturally, rather than about permanently or radically altering life forms, the microbiome promises to be the least risky and perhaps the most important way to affect our health and quell the very lifestyle diseases that have proven so resistant to all manner of interventions. This will benefit everyone equally, will not lead to dependence on drugs and doctors, and will be affordable by all. It is where we must focus more energy—as we develop guidelines on how to safely use gene editing. Fortunately, the U.S. government agrees about the importance of doing so: the White House launched the National Microbiome Initiative in May 2016 to foster the integrated study of microbiomes across different ecosystems and committed more than $121 million for the research.16 PART FOUR Does the Technology Foster Autonomy or Dependency?
The Lucky Years: How to Thrive in the Brave New World of Health by David B. Agus
3D printing, active transport: walking or cycling, Affordable Care Act / Obamacare, Albert Einstein, butterfly effect, clean water, cognitive dissonance, crowdsourcing, Danny Hillis, Drosophila, Edward Lorenz: Chaos theory, en.wikipedia.org, epigenetics, Kickstarter, medical residency, meta analysis, meta-analysis, microbiome, microcredit, mouse model, Murray Gell-Mann, New Journalism, pattern recognition, personalized medicine, phenotype, placebo effect, publish or perish, randomized controlled trial, risk tolerance, statistical model, stem cell, Steve Jobs, Thomas Malthus, wikimedia commons
As I mentioned earlier, the microbiome is our term for the complex microbial world that thrives outside of our own cells, but still within us (micro for “small” or “microscopic,” and biome referring to a naturally occurring community of flora occupying a large habitat—in this case, the human body). Although the human genome is almost the same in every individual, give or take the genes that encode things like certain physical characteristics, risk factors for disease, and blood type, even identical twins can have hugely different gut profiles. The state of the microbiome is turning out to be so key to human health that it may actually be considered an organ in and of itself. And how we feel, both emotionally and physically, may hinge on the state of our microbiome. The NIH Human Microbiome Project started in 2008 as an extension of the Human Genome Project to catalog these microorganisms living in our body, and our appreciation for the influence of such organisms has grown rapidly with each passing year.9 Our growing knowledge about the microbiome comes from studying mice that have been altered so that they do not have any gut bacteria.
More than a century ago, he said that “oral administration of cultures of fermentative bacteria would implant the beneficial bacteria in the intestinal tract.” Yet only in the past decade has science validated and begun to understand Metchnikoff’s bold assertions. In 2015, more studies emerged showing the power of the microbiome, some of which showed how certain foods you eat can change the composition of the bacteria colonies in your gut to either lead your body down the path to metabolic syndrome and obesity, or keep you slender and humming to the right metabolic tune.11 We’ll be exploring more about these findings and the microbiome in chapter 4. In the future, leveraging your microbiome for the better will likely be part of your health equation. In 2008, the European Journal of Immunology paid tribute to Metchnikoff on the hundredth anniversary of his Nobel Prize in a beautifully written article chronicling his life and his contributions to society.12 He was the first scientist to understand natural immunity to infection, the significance of inflammation, the role of digestion in immunity, the importance of gut flora, the implications of “self” versus “nonself” within the context of immunity so the body knows the difference between its own cells and foreign invaders.
For this reason, it should come as no surprise that a significant disturbance in the human body can profoundly alter the makeup of otherwise stable microbial communities coexisting within it and that changes in the internal ecology known as the human microbiome can result in unexpected and drastic consequences for human health.15 Once again, we see the power of context. Bacteria were earth’s first inhabitants. In 2013, the oldest signs of life on earth—3.5 billion years old—were discovered in a remote region of northwest Australia, where evidence of a complex microbial ecosystem is locked in ancient rock formations. It was part of our evolution to forge a symbiotic relationship with bacteria. The science of understanding the microbiome is still in its infancy, but I expect it will explode in the coming decade. We’ll soon begin to understand how different microbiotic profiles, much like genetic profiles, are related to certain diseases or to optimal health. And we will begin to learn how we can leverage the microbiome to prevent and treat a variety of ailments, from neurodevelopmental challenges in early life to neurodegenerative problems and chronic illnesses in later life.
The End of Illness by David B. Agus M. D.
Danny Hillis, discovery of penicillin, double helix, epigenetics, germ theory of disease, Google Earth, impulse control, information retrieval, meta analysis, meta-analysis, microbiome, Murray Gell-Mann, pattern recognition, personalized medicine, randomized controlled trial, risk tolerance, Steve Jobs, the scientific method
Bacteria obviously have their own DNA operating within us, and newly emerging technologies are finally helping us tune into these bacteria and their effects on us, for better or worse. One overarching feature that studies on the microbiome are revealing is the diversity of bacteria in the human body, akin to a rain forest. Different regions of the body are home to different combinations of species. From one person to another, we’re finding tremendous variety. I could have an entirely different colony of bacteria thriving in my mouth than you, which affects whether my diet helps me to maintain a healthy digestive system. In the future, perhaps I’ll know more about my unique enterotype to keep my digestive system running as smoothly as possible. Within the next ten years researchers will uncover mysteries of the microbiome and begin to find ways in which we can manipulate it to support health. The microbiome—not levels of vitamin D, for example—may explain why people who live at higher latitudes have a higher risk of developing cancer.
Until babies can eat solid foods, they get plenty of what they need from breast milk, formula, and, yes, even mushy baby foods probably created in a pulverizer. Mining and Minding the Microbiome Before we move on, I need to mention one more fact for your consideration. We are all different in how we metabolize our food, absorb its nutrients, and need or use the nutrients. This area of nutrition has to be personalized and will be in the future when new technologies become available that will allow each of us to tune in to our personal nutritional needs. Certainly genetics will play a role here, too, but the larger role will be played by the microbiome—the bacteria that fill your intestinal tract and that participate in your digestion, metabolism, and overall health. We each have bacteria in our GI tract. Within the body of a healthy adult, microbial cells are estimated to outnumber human cells by a factor of ten to one.
We had assumed this was due to diet—after all, so much can be blamed on the Western diet, and certainly immigrants probably start devouring our processed, packaged foods like the rest of us when they land in the United States—but it turns out that the microbiome plays a major role here. It controls how you metabolize your food, how fast and how much you absorb, and what enters your bloodstream, thereby affecting your hormone levels among other things. In turn, this influences the risk of developing certain cancers, such as prostate or breast. It’s common to categorize people by blood type, or in some cases by ethnicity. In the future, we’ll also begin to type people by “bug”—by the prevailing bacteria that inhabit their digestive tracts. In one of the more provocative studies to emerge, published in April 2011 in the journal Nature, a team of researchers led by Peer Bork of the European Molecular Biology Laboratory in Heidelberg, Germany, reported on three distinguishable “types” of people based on their microbiome. Each of the three types is composed of a different balance of species.
Messy: The Power of Disorder to Transform Our Lives by Tim Harford
affirmative action, Air France Flight 447, Airbnb, airport security, Albert Einstein, Amazon Mechanical Turk, Amazon Web Services, assortative mating, Atul Gawande, autonomous vehicles, banking crisis, Barry Marshall: ulcers, Basel III, Berlin Wall, British Empire, Broken windows theory, call centre, Cass Sunstein, Chris Urmson, cloud computing, collateralized debt obligation, crowdsourcing, deindustrialization, Donald Trump, Erdős number, experimental subject, Ferguson, Missouri, Filter Bubble, Frank Gehry, game design, global supply chain, Googley, Guggenheim Bilbao, high net worth, Inbox Zero, income inequality, industrial cluster, Internet of things, Jane Jacobs, Jeff Bezos, Loebner Prize, Louis Pasteur, Marc Andreessen, Mark Zuckerberg, Menlo Park, Merlin Mann, microbiome, out of africa, Paul Erdős, Richard Thaler, Rosa Parks, self-driving car, side project, Silicon Valley, Silicon Valley startup, Skype, Steve Jobs, Steven Levy, Stewart Brand, telemarketer, the built environment, The Death and Life of Great American Cities, Turing test, urban decay, William Langewiesche
But Professor Knight is now running a controlled study of much the same technique with babies born by cesarean section in Puerto Rico.9 Finally there is the simple fact that our microbiome is partially heritable, passed from mothers to daughters. It follows that if one generation thins out the messy diversity of their microbiome through antibiotics and antiseptics, the following generation will start from a less diverse foundation.10 It is worth acknowledging that these ideas have already become a fad—a great deal of nonsense is now being talked by quacks and purveyors of probiotic yogurt aiming to promote a “healthy microbiome.” There is no such thing, or rather there is a vast range of healthy microbiomes. People can have very different microbiota, yet still be perfectly healthy; the biological makeup of the same person can also change rapidly, day by day.
TED Talks, 2011, http://www.ted.com/talks/jessica_green_are_we_filtering_the_wrong_microbes/transcript?language=en. 9. Alanna Collen, “‘Microbial Birthday Suit’ for C-Section Babies,” BBC Magazine, September 11, 2015, http://www.bbc.com/news/health-34064012. 10. Blaser, Missing Microbes. 11. Ed Yong, “There Is No ‘Healthy’ Microbiome,” The New York Times, November 1, 2014, http://www.nytimes.com/2014/11/02/opinion/sunday/there-is-no-healthy-microbiome.html, and Gabrielle Canon, “Sorry, Your Gut Bacteria Are Not the Answer to All Your Health Problems,” Mother Jones, October 27, 2014, http://www.motherjones.com/environment/2014/10/microbiome-health-gut-bacteria; Blaser, Missing Microbes, pp. 31–32. 12. Jane Jacobs, The Death and Life of Great American Cities (New York: Vintage, 1992), p. 50. 13. Ibid., p. 193. 14. Maryann P. Feldman and David B. Audretsch, “Innovation in Cities: Science-Based Diversity, Specialization and Localized Competition,” European Economic Review 43 (1999). 15.
Some, such as H. pylori, can be dangerous or beneficial depending on the situation.3 Martin Blaser has become one of the leading champions of the view that our bacterial guests are starting to become less diverse, and that this thinning of the microbiome is doing us harm. Researchers at the University of Toronto found that it was easier to stay slim in the 1980s: looking at data about diet and exercise for tens of thousands of people since the early 1970s, they found that people today seem to be heavier than their forebears, even when they ate the same and were equally as active. One of the favored explanations for this is that young people today have denuded gut bacteria; a separate large study of European microbial genes has shown that a less diverse microbiome is correlated with a tendency to be obese. Meanwhile a team at the University of California at San Francisco found that Lactobacillus sakei—another of the bacteria we have cluttering up our bodies—appears to prevent sinusitis, presumably by outcompeting the more harmful bacteria that might inflame our sinuses.
23andMe, 3D printing, Affordable Care Act / Obamacare, Anne Wojcicki, Atul Gawande, augmented reality, bioinformatics, call centre, Clayton Christensen, clean water, cloud computing, commoditize, computer vision, conceptual framework, connected car, correlation does not imply causation, creative destruction, crowdsourcing, dark matter, data acquisition, disintermediation, don't be evil, Edward Snowden, Elon Musk, en.wikipedia.org, Erik Brynjolfsson, Firefox, global village, Google Glasses, Google X / Alphabet X, Ignaz Semmelweis: hand washing, information asymmetry, interchangeable parts, Internet of things, Isaac Newton, job automation, Joseph Schumpeter, Julian Assange, Kevin Kelly, license plate recognition, lifelogging, Lyft, Mark Zuckerberg, Marshall McLuhan, meta analysis, meta-analysis, microbiome, Nate Silver, natural language processing, Network effects, Nicholas Carr, obamacare, pattern recognition, personalized medicine, phenotype, placebo effect, RAND corporation, randomized controlled trial, Second Machine Age, self-driving car, Silicon Valley, Skype, smart cities, Smart Cities: Big Data, Civic Hackers, and the Quest for a New Utopia, Snapchat, social graph, speech recognition, stealth mode startup, Steve Jobs, the scientific method, The Signal and the Noise by Nate Silver, The Wealth of Nations by Adam Smith, Turing test, Uber for X, Watson beat the top human players on Jeopardy!, X Prize
Being able to tap into the whole range of an individual’s RNA transcripts, proteins, and metabolites at any given moment creates quite an extraordinary opportunity to understand one’s instantaneous biology, in an unbiased fashion. The Microbiome It’s hard for most of us to accept that we are nine parts microbe and only one part human, at least as far as a count of our cells goes. The era of sequencing has been especially instructive about the trillions of microbes (bacteria, viruses, fungi) that live within or on us. The diversity of DNA in us from microbes far outstrips our own DNA, with one hundred trillion instead of thirty-seven trillion cells, over eight million genes instead of only approximately nineteen thousand, and more than ten thousand species instead of one.18 The microbiome represents the interface between the individual and her environment. For example, one’s diet has a strong influence on one’s microbiome. And the medical importance of these microbes has escalated far beyond what most of us envisioned, with their influence in obesity, cancer, heart, allergic and autoimmune diseases, and many more conditions, in which the gut microbiome is particularly prominent.
The diagnosis also led Snyder to change his lifestyle and restore normal glucose homeostasis, and then go on to check this in some relatives who turned out to have unrecognized glucose intolerance, and for whom diet and exercise proved similarly helpful. More recently, Snyder’s Stanford forty-member research group has expanded the initial effort with sequencing Snyder’s epigenome, gut microbiome, and use of multiple biosensors. Getting this GIS-like information has generated a massive amount of data: 1 terabyte (TB, a trillion bits) for DNA sequence, 2 TB for the epigenomic data, 0.7 TB for the transcriptome, and 3 TB for the microbiome.5 For perspective, 1 TB would equate to one thousand copies of the Encyclopedia Britannica and 10 TB, which is approximately how much Snyder’s panoromic project amassed, would hold the entire Library of Congress. In the world each year about five zettabytes of data—or forty sextillion bits—are generated.20 If we divided this by the world’s seven billion people, this would put an average individual at nearly 1 TB of data generated per year.
Malnutrition is exceptionally important in the developing world both because it predisposes individuals to infection, and because the cause of many infections is highly influenced by the gut microbiome.35–39 More than twenty million children worldwide suffer from severe malnutrition, and fatality rates for hospitalized children with kwashiorkor—a protein-deficient form of malnutrition—is as high as 50 percent. A randomized trial in rural Malawi, representative of sub-Saharan Africa, tested two different antibiotics and matching placebo in 2,767 children, ages six months to five years (Figure 14.9). There was a significant reduction in fatalities with antibiotics, but it is clear the number of deaths is still exceedingly high on treatment.40,41 But in another study of 317 twin pairs from Malawi, with only one of the twins suffering from acute malnutrition, the gut microbiome showed that the imbalance in bacterial populations could be restored with fortified peanut butter.37 That represents a significant change from the typical Malawian diet, which is very high in starch.
Cooked: A Natural History of Transformation by Michael Pollan
biofilm, bioinformatics, Columbian Exchange, correlation does not imply causation, creative destruction, dematerialisation, Drosophila, energy security, Gary Taubes, Hernando de Soto, hygiene hypothesis, Louis Pasteur, Mason jar, microbiome, peak oil, Ralph Waldo Emerson, Steven Pinker, women in the workforce
A landmark article seeking to apply the lens of ecology to the microbial communities inhabiting the human body. Song, Yeong-Ok. “The Functional Properties of Kimchi for the Health Benefits.” Food Industry and Nutrition 9, 3 (2004): 27–28. Turnbaugh, P.J., et al. “An Obesity-Associated Gut Microbiome with Increased Capacity for Energy Harvest.” Nature 444 (2006): 1027–31. ———, et al. “The Human Microbiome Project.” Nature 449 (2007): 804–10. ———, et al. “A Core Gut Microbiome in Obese and Lean Twins.” Nature 457 (2009): 480–84. Walter, Jens. “Ecological Role of Lactobacilli in the Gastrointestinal Tract: Implications for Fundamental and Biomedical Research.” Applied and Environmental Microbiology (August 2008): 4985–96. Zivkovic, Angela M., J. Bruce German, et al.
* Margulis theorized that both photosynthesis and cellular metabolism in animals began when bacteria took up residence in the evolutionary ancestors of plant and animal cells, contributing their metabolic expertise; eventually these invaders became the chloroplasts in plant cells and the mitochondria in the cells of animals. * Turnbaugh, Peter J., et al., “An Obesity-Associated Gut Microbiome with Increased Capacity for Energy Harvest,” Nature 444 (2006): 1027–31; Turnbaugh, P. J., et al., “A Core Gut Microbiome in Obese and Lean Twins,” Nature 457 (2009): 480–84; Turnbaugh, Peter J., et al., “The Human Microbiome Project,” Nature 449 (2007): 804–10. † This particular probiotic is found in some kinds of yogurt. (Bravo, J. A., et al., “Ingestion of Lactobacillus Strain Regulates Emotional Behavior and Central GABA Receptor Expression in a Mouse via the Vagus Nerve,” Proceedings of the National Academy of Sciences 108 No. 38 : 16050–55)
.* No doubt scientists will soon find other examples of our microbiota mediating our relationship to the rest of nature, speeding our ability to adapt. In effect, the microbiome vastly extends our genome, giving us access to a tremendous bag of tricks we did not need to evolve ourselves. So it made very good sense, evolutionarily speaking, for us to join forces with the microbes, which are simply more skilled than we are at all the ways of biochemically contending. During the two billion years of natural selection that bacteria have undergone before more complex multicellular creatures arrived on the scene, they managed to invent virtually every important metabolic trick known to evolution, from fermentation to photosynthesis. (According to Lynn Margulis, who until her death in 2011 was the microbiome’s most eloquent human advocate, the only important biochemical innovations to come along in the billion years since then are snake venom, plant hallucinogens, and—this is a big one—cerebral cortices.)
The Cancer Chronicles: Unlocking Medicine's Deepest Mystery by George Johnson
Atul Gawande, Cepheid variable, Columbine, dark matter, discovery of DNA, double helix, Drosophila, epigenetics, Gary Taubes, Harvard Computers: women astronomers, Isaac Newton, Magellanic Cloud, meta analysis, meta-analysis, microbiome, mouse model, Murray Gell-Mann, phenotype, profit motive, stem cell
id=chronic-inflammation-cancer] More references are in my notes for chapter 10. 43. molecules called sirtuins: For a review see Finkel Toren, Chu-Xia Deng, and Raul Mostoslavsky, “Recent Progress in the Biology and Physiology of Sirtuins,” Nature 460, no. 7255 (July 30, 2009): 587–91. [http://www.ncbi.nlm.nih.gov/pubmed/19641587] 44. the genes residing in the microbes: Steven R. Gill et al., “Metagenomic Analysis of the Human Distal Gut Microbiome,” Science 312, no. 5778 (June 2, 2006): 1355–59. [http://www.sciencemag.org/content/312/5778/1355.short] 45. a Human Microbiome Project: Peter J. Turnbaugh et al., “The Human Microbiome Project,” Nature 449, no. 7164 (October 18, 2007): 804–10. [http://www.nature.com/nature/journal/v449/n7164/abs/nature06244.html] 46. “ ’omics”: Joshua Lederberg christened the microbiome, and in a short essay, “Ome Sweet ’Omics,” he commented on the naming phenomenon: The Scientist 15, no. 7 (April 2, 2001): 8. [http://lhncbc.nlm.nih.gov/lhc/docs/published/2001/pub2001047.pdf] 47. separate the ridiculome from the relevantome: I thought I had invented these words, but an Internet search turns them up in a PowerPoint presentation: Andrea Califano, Brian Athey, and Russ Altman, “Creating a DBP Community to Enhance the NCBC Biomedical Impact, A National Center for Biomedical Computing Work Group Report,” July 18, 2006, National Alliance for Medical Image Computing website.
The genes inside these single-celled creatures transmit signals from microbe to microbe, and they can also exchange signals with human cells. Although we think of the bacteria as passengers, they outnumber our own cells by about ten to one. Even more impressive, the total number of microbial genes each of us harbors—the microbiome—outnumbers our human genes by 100 to 1. There is even a Human Microbiome Project to sequence the genomes of these cellular free agents. Cancer is a disease of information, of mixed-up cellular signaling. Now there is another realm to explore. The genome, the epigenome, the microbiome—scientists also now speak of the proteome (the entire set of proteins that can be expressed in a cell) and the transcriptome (all of the RNA molecules of various sorts). There is the metabolome, lipidome, regulome, allelome … the degradome, enzymome, inflammasome, interactome, operome, pseudogenome.
…A curious law of nature … Contemplating the odds CHAPTER 2 Nancy’s Story Food pyramidology … Pascal’s wager … Folates, antioxidants, and Finnish smokers … Fruits, vegetables, and giant steaks … Carcinogenic estrogen … The real risks of cigarettes … Emanations from the earth … Cancer clusters … A worrisome lump … Nancy’s cancer CHAPTER 3 The Consolations of Anthropology In the boneyards of Kenya … Face-to-face with Kanam man…Palaeo-Oncology…Hippocrates and the crabs … The wild beast of cancer … Metastasis in a Scythian king … Skeletons and mummies … Visions of an ancient paradise … Counting up the dead CHAPTER 4 Invasion of the Body Snatchers “Large and beautifully pellucid cells”…Morbid juices … Seeds and soil … The mysteries of metastasis … A horrifying precision … The ebb and flow of lymph … The surgeon’s diagnosis … Weeds from outer space CHAPTER 5 Information Sickness Man-made mutations … Funny-looking chromosomes…“A new kind of cell”…Matter that comes alive … The Radium Girls … Coal tar and tumors … Viral invaders … Oncogenes and tumor suppressors … Cellular suicide … Intimations of immortality … A conspiracy of cells CHAPTER 6 “How Heart Cells Embrace Their Fate” Embryos and tumors … Snail, slug, and twist … Sonic hedgehog … the Pokémon gene … Cyclopean sheep … Holoprosencephaly … 1 + 1 = 3 … Prayers of an agnostic … An endless day at the hospital CHAPTER 7 Where Cancer Really Comes From The surprising aftermath of Love Canal … What “environment” really means…“The Causes of Cancer”…An environmental turncoat … The carcinogens in coffee … Mitogenesis and mutagenesis … Making sense of the cancer statistics … A maverick presidential report CHAPTER 8 “Adriamycin and Posole for Christmas Eve” Cancer cells and magnets … The penicillin of cancer … A rare kind of malignancy … Disheartening statistics…“The Median Isn’t the Message”…Flying farolitos … A visit to MD Anderson … Rothko’s brooding chapel CHAPTER 9 Deeper into the Cancer Cell A physics of cancer … Epigenetic software … The stem cell conundrum … An enormous meeting in Orlando … Espresso and angiogenesis … The news from Oz.…Communing with the microbiome … Beyond the double helix … Dancing at the Cancer Ball CHAPTER 10 The Metabolic Mess Chimney sweeps and nuns … A “mysterious sympathy”…The case of the missing carcinogens … The rise and fall of vegetables … A mammoth investigation … The insulin-obesity connection…“Wounds that do not heal”…A hundred pounds of sugar … Skewing the energy equation CHAPTER 11 Gambling with Radiation Flunking the radon test … A ubiquitous carcinogen … Down in the uranium mines … Tourism at Chernobyl … Hiroshima and Nagasaki … Exhuming Curie’s grave … A pocketful of radium … Robot oncologists … Relay for Life CHAPTER 12 The Immortal Demon A flight to Boston … Stand Up to Cancer … A tale of two cousins … The return of the hedgehog … Where weird drug names come from … Waiting for super trastuzumab … Orphaned cancers … Biological game theory … Contagious cancer CHAPTER 13 Beware the Echthroi On Microwave Mountain … Cell phones and brain waves … Is cancer here “on purpose”?
The Human Age: The World Shaped by Us by Diane Ackerman
23andMe, 3D printing, additive manufacturing, airport security, Albert Einstein, augmented reality, back-to-the-land, carbon footprint, clean water, dark matter, dematerialisation, double helix, Drosophila, epigenetics, Google Earth, Google Glasses, haute cuisine, Internet of things, Loebner Prize, Louis Pasteur, Masdar, mass immigration, megacity, microbiome, nuclear winter, personalized medicine, phenotype, Ray Kurzweil, refrigerator car, Search for Extraterrestrial Intelligence, SETI@home, skunkworks, Skype, stem cell, Stewart Brand, the High Line, theory of mind, urban planning, urban renewal, Whole Earth Catalog
Joshua Lederberg, the Nobel-laureate biologist who, in 2000, coined the term “microbiome,” defines it as “the menagerie of the body’s attendant microbes.” Amid the hoopla surrounding the Human Genome Project, he urged, “We must study the microbes that we carry within us and on our surfaces as part of a shared embodiment.” If the Human Genome Project was a landmark feat of discovery, the Human Microbiome Project is gene cartography’s finest hour. NIH director Francis Collins compares it to “fifteenth-century explorers describing the outline of a new continent,” a triumph that would “accelerate infectious disease research in a way previously impossible.” For five years, a consortium of eighty universities and scientific labs sampled, analyzed, and audited over ten thousand species that share our human ecosystem, thus mapping our “microbiome,” the normal microbial makeup of healthy adults.
Researchers are thinking of cobbling them into infant formula to help ward off asthma, allergies, and such autoimmune triggermen as diabetes, eczema, and multiple sclerosis. Babies pick up other useful bacteria in Mom’s dirt-and-crumb-garlanded home and landscape. At least, they should. Doctors are embracing the idea of personalized medicine based on a patient’s uniquely acquired flora and fauna, as revealed in his or her genome, epigenome, and microbiome. No more antibiotics prescribed by the jeroboam on the off chance they might prove useful. Instead, try unleashing enough beneficial bacteria to crowd out the pathogen. No more protecting children from the hefty stash of derring-do white-knight bacteria they need but we’ve learned to regard as icky. Patients whose gut flora have been wiped out by certain antibiotics are prey to Clostridium difficile, an opportunistic weasel of a bug that causes severe, debilitating diarrhea.
., 299 geothermal warmth, 95 Germany, 72, 78, 83, 101, 124, 132, 298 solar panels in, 106–7 Gershenfeld, Neil, 202–3 gestures, 26–27 giraffes, 276 global consciousness, 18 global warming, 11, 38–42, 154, 307–8 agriculture and, 56 in Bangladesh, 51–53 and development of seas, 64–65 evidence of, 108 extreme weather and, 36–43, 314 fishermen and, 56–57 gardens affected by, 38–39 habitats rearranged by, 133–40 human rights and, 48 glowworms, 144 glucocorticoids, 283 golden eagles, 132 Golden Lion Tamarin Conservation Program, 123 golden toads, 162 Golding, William, 162 Google, 192, 210 Google Glass, 260–61 gophers, 115 gorgonian, 38 grains, 71 Grand Canyon, 126 granite, 58–59 GraphExeter, 184–85, 317 grasshoppers, 173–74 Grassy Key, 131 great apes, 202 great auks, 151 Great Depression, 108 Greece, 124 Green Apple concept car, 103 Green Belt Corridor, 124 greenhouses, 90 Greenland, 42 green mussels, 131 Green over Grey, 83 growing season, 42 Guam, 139, 157 Guam rail, 139 Guatemala, 88 Gulag Archipelago (Solzhenitsyn), 218 Gurdon, John, 150, 160 Gut Erlasee Solar Park, 106–7 Guthrie, Barton, 261 habitat loss, 154 Haiyan, Typhoon, 46 Hamilton, Clive, 314 Hansen, James, 314 Hansmeyer, Michael, 236 Harvard University, 235 Hastings, Battle of, 190 heart, 150, 239, 248, 249, 250–51, 281 heat, 41 heaters, 87 heat recycling, 95–108 Helm, Barbara, 114 Henri, Pascal, 84 herbs, 89 Hernandez, Isaias, 264–65 herons, 193–94 Heuchera plants, 80–81 High Line, 77 Hitler, Adolf, 273 hockey, 40 Holocene, 9 Homer, 262 Honda, 236 Hong Sun Hye, 102 horse chestnut trees, 153 Horse Island, 58 horses, 137–38, 140, 145–46 hostas, 125 Hudson River, 54–55 hulls, 91 human genome, 13 Human Genome Project, 270, 274, 282, 285, 289, 300 Human Microbiome Project, 289 human rights, global warming and, 48 humans: as eusocial, 288 geographic expansion of, 10 geography changed by, 11 history of, 71 orangutan genes shared by, 3 population growth of, 10 technological changes to bodies of, 13 tools used by, 7, 9 humans, environmental effects of: climate change, see global warming and possibility of nuclear winter, 8–9 hummingbirds, 126 hunter-gatherers, 71 Huntington’s disease, 271 Hurricane Irene, 57 Hurricane Katrina, 46 hurricanes, 31, 41, 43, 55 Hurricane Sandy, see Sandy, Hurricane hybrid cars, 100 Hyde Park, 142 hydroelectronic power, 100, 107 hydroponic gardening, 83, 89, 90 Icarus, 224 icebergs, 195–96, 197 Iceland, 77 ice packs, 41–42 iCub, 218–19 iGlasses, 261 igloos, 86 iguanas, 131 Ike Dike, 50 Iliad (Homer), 262 India, 88, 107, 132, 175 Indian mongoose, 132 Indonesia, 132, 313 induced pluripotent stem cells (IPS), 150–51, 160–63 industrial farming, 60 Industrial Revolution, 34, 106, 185–86, 232, 235, 267 Inheritors, The (Golding), 162 insects, 166 insulin pumps, 253 intelligence of plants, 205–7 International Union for Conservation of Nature, 313 Internet, 199–200, 235 Inuit, 86 invasive species, 132, 154 Iran, 147 Iraq War, 258 Ireland, 132 Irene, Hurricane, 57 irises, 125 iron fertilization, 53 Island of Dr.
Childhood Disrupted: How Your Biography Becomes Your Biology, and How You Can Heal by Donna Jackson Nakazawa
I felt all that weight of having to care for my mother and be the only grown-up in my adolescent world.” Over the course of many sessions, the pain of the past has begun to lessen. Mary feels a sense of “letting go.” 11. Managing the Mind Through the Gut Cell for cell, we’re largely made up of bacteria. In fact, single-celled organisms, mostly bacteria, outnumber our own cells ten to one. Many of these live in our gut. This gut “microbiome” determines the state of our digestive health, and influences the state of our brain. When you are under stress, the bacterial communities in your intestine become less diverse, allowing greater numbers of harmful bacteria to take over. Disorders of the gut such as irritable bowel and inflammatory bowel diseases are exacerbated by stress. Recent science shows that a sophisticated neural network transmits messages from those trillions of digestive bacteria to the brain, exerting a powerful influence on our state of mind—creating a feedback loop between the brain and the gut that goes both ways.
And second, good gut microbiota such as those found in probiotics have a direct effect on neurotransmitter receptors in the brain, such as GABA. Mice given probiotics had lower levels of stress-induced hormones, less anxiety, and less depression-related behavior. And guess how the messages between the bacteria exposed to the gut and the brain were transmitted? Via the vagus nerve—which is a primary mediator of the inflammatory stress response. That’s why scientists have begun to refer to our gut as “the second brain.” The gut microbiome heavily influences neural development, brain chemistry, emotional behavior, pain perception, learning, and memory. Some organisms in the gut might prove useful in treatments of stress-related disorders such as anxiety and depression. According to gastroenterologist Emeran Mayer, MD, PhD, director of the Center for Neurobiology of Stress at the University of California, Los Angeles, given the gut’s multifaceted ability to communicate with the brain, “it’s almost unthinkable that the gut is not playing a critical role in mind states.”
According to gastroenterologist Emeran Mayer, MD, PhD, director of the Center for Neurobiology of Stress at the University of California, Los Angeles, given the gut’s multifaceted ability to communicate with the brain, “it’s almost unthinkable that the gut is not playing a critical role in mind states.” Improving our diet and reducing our intake of processed foods and sugar, and adding in greens, fruits, and fermented foods rich in probiotics can play a critical role in healing the gut. This, in turn, can help patients who’ve suffered from early trauma to heal both body and brain. Because microorganisms in our gut control our brain, we need to do whatever we can to make our microbiome healthy, and give the pathways in our brain all the serotonin and nutrients they need to send the correct messages along our brain’s synapses. Why would you eat in a way that makes stress receptors more reactive when you are busy doing everything else you can to heal? A number of the individuals we’ve followed in these pages have used nutrition to promote healing. Ellie has used diet to reduce her autoimmune psoriasis, depression, and anxiety.
3D printing, agricultural Revolution, AI winter, Alan Turing: On Computable Numbers, with an Application to the Entscheidungsproblem, algorithmic trading, artificial general intelligence, augmented reality, autonomous vehicles, basic income, bitcoin, blockchain, clean water, cognitive dissonance, Colonization of Mars, complexity theory, computer age, computer vision, constrained optimization, corporate personhood, cosmological principle, cryptocurrency, cuban missile crisis, Danny Hillis, dark matter, discrete time, Douglas Engelbart, Elon Musk, Emanuel Derman, endowment effect, epigenetics, Ernest Rutherford, experimental economics, Flash crash, friendly AI, functional fixedness, Google Glasses, hive mind, income inequality, information trail, Internet of things, invention of writing, iterative process, Jaron Lanier, job automation, John Markoff, John von Neumann, Kevin Kelly, knowledge worker, loose coupling, microbiome, Moneyball by Michael Lewis explains big data, natural language processing, Network effects, Norbert Wiener, pattern recognition, Peter Singer: altruism, phenotype, planetary scale, Ray Kurzweil, recommendation engine, Republic of Letters, RFID, Richard Thaler, Rory Sutherland, Satyajit Das, Search for Extraterrestrial Intelligence, self-driving car, sharing economy, Silicon Valley, Skype, smart contracts, speech recognition, statistical model, stem cell, Stephen Hawking, Steve Jobs, Steven Pinker, Stewart Brand, strong AI, Stuxnet, superintelligent machines, supervolcano, the scientific method, The Wisdom of Crowds, theory of mind, Thorstein Veblen, too big to fail, Turing machine, Turing test, Von Neumann architecture, Watson beat the top human players on Jeopardy!, Y2K
What if, instead, an AI were more like a multicellular organism, a eukaryote evolution beyond our prokaryote selves? What’s more, what if we weren’t even the cells of such an organism, but its microbiome? And what if the intelligence of that eukaryote today was like the intelligence of Grypania spiralis, the oldest known multicellular eukaryote—not yet self-aware as a human is aware but still irrevocably on the evolutionary path leading to today’s humans. This notion is at best a metaphor, but I believe it’s a useful one. Perhaps humans are the microbiome living in the guts of an AI that’s only now being born! We know that without our microbiome we would cease to live. Perhaps the global AI has the same characteristics: not an independent entity but a symbiosis with the human consciousnesses living within it. Following this logic, we might conclude that there’s a primitive global brain, consisting not just of all connected devices but also of the connected humans using those devices.
SEJNOWSKI AI Will Make You Smarter SETH LLOYD Shallow Learning CARLO ROVELLI Natural Creatures of a Natural World FRANK WILCZEK Three Observations on Artificial Intelligence JOHN NAUGHTON When I Say “Bruno Latour,” I Don’t Mean “Banana Till” NICK BOSTROM It’s Still Early Days DONALD D. HOFFMAN Evolving AI ROGER SCHANK Machines That Think Are in the Movies JUAN ENRIQUEZ Head Transplants? ESTHER DYSON AI/AL TOM GRIFFITHS Brains and Other Thinking Machines MARK PAGEL They’ll Do More Good Than Harm ROBERT PROVINE Keeping Them on a Leash SUSAN BLACKMORE The Next Replicator TIM O’REILLY What If We’re the Microbiome of the Silicon AI? ANDY CLARK You Are What You Eat MOSHE HOFFMAN AI’s System of Rights and Government BRIAN KNUTSON The Robot with a Hidden Agenda WILLIAM POUNDSTONE Can Submarines Swim? GREGORY BENFORD Fear Not the AI LAWRENCE M. KRAUSS What, Me Worry? PETER NORVIG Design Machines to Deal with the World’s Complexity JONATHAN GOTTSCHALL The Rise of Storytelling Machines MICHAEL SHERMER Think Protopia, Not Utopia or Dystopia CHRIS DIBONA The Limits of Biological Intelligence JOSCHA BACH Every Society Gets the AI It Deserves QUENTIN HARDY The Beasts of AI Island CLIFFORD PICKOVER We Will Become One ERNST PÖPPEL An Extraterrestrial Observation on Human Hubris ROSS ANDERSON He Who Pays the AI Calls the Tune W.
Are we going to control these machines? Can we insist that they be motivated to look after us? No. Even if we can see what’s happening, we want what they give us far too much not to swap it for our independence. So what do I think about machines that think? I think that from being a tiny independent thinking machine, I am becoming a tiny part inside a far vaster thinking machine. WHAT IF WE’RE THE MICROBIOME OF THE SILICON AI? TIM O’REILLY Founder and CEO of O’Reilly Media, Inc. G. K. Chesterton once said, “The weakness of all Utopias is this, that they take the greatest difficulty of man and assume it to be overcome, and then give an elaborate account of the overcoming of the smaller ones.”5 I suspect we face a similar conundrum in our attempts to think about machines that think. We speculate elaborately about some issues while ignoring others that are fundamental.
The Case Against Sugar by Gary Taubes
Albert Einstein, British Empire, cuban missile crisis, epigenetics, Everything should be made as simple as possible, Gary Taubes, Isaac Newton, meta analysis, meta-analysis, microbiome, phenotype, pre–internet, Ralph Nader, RAND corporation, randomized controlled trial, selection bias, the new new thing, the scientific method, Works Progress Administration
All of this is triggered by something in our diet and lifestyle, which is what we ultimately have to explain. Another issue that has recently added still another layer of complication to the science is the role played in obesity and diabetes by the bacteria in our guts, known as the gut microbiota or microbiome. New technologies will lead inevitably to new areas of research, new observations, and new discoveries. The ability to sequence the genomes of these bacterial species has opened up a new frontier of research, just as the ability to measure blood pressure, cholesterol, or insulin sensitivity did for earlier generations of researchers. The microbiome research, because it’s brand-new, is at a very preliminary stage. Still, as the new new thing (to borrow a phrase from the journalist Michael Lewis) in obesity and diabetes research, gut bacteria get an inordinate amount of attention, particularly from the media, though we may not know for decades what to make of the observations that ensue—what is signal and what is noise.
Still, as the new new thing (to borrow a phrase from the journalist Michael Lewis) in obesity and diabetes research, gut bacteria get an inordinate amount of attention, particularly from the media, though we may not know for decades what to make of the observations that ensue—what is signal and what is noise. Most of the work so far has been done in laboratory mice and rats, and the relevance to human life (or even to other laboratory animals) is unclear. The observations that come from human studies and the very few human experiments are still impossible to interpret reliably. Certain alterations in this gut microbiome associate with obesity, metabolic syndrome, and diabetes, but, as the researchers will acknowledge, “it remains to be determined whether these are the results of altered glucose metabolism and insulin resistance or contribute to their development.” Since the 1950s, if not earlier, researchers have known that the foods we eat and the form in which they come—indigestible fiber, refined grains and sugar, and all the rest—will influence which species of gut bacteria thrive and which don’t.
Hoogwerf, and F. C. Goetz. 1983. “Postprandial Glucose and Insulin Responses to Meals Containing Different Carbohydrates in Normal and Diabetic Subjects.” New England Journal of Medicine 309, no. 1 (July 7): 7–12. Barker, T. C., D. J. Oddy, and J. Yudkin. 1970. The Dietary Surveys of Dr Edward Smith 1862–3: A New Assessment. London: Staples Press. Barlow, G. M., A. Yu, and R. Mathur. 2015. “Role of the Gut Microbiome in Obesity and Diabetes Mellitus.” Nutrition in Clinical Practice 30, no. 6 (Dec.): 787–97. Barnard, E. F. 1928. “Too Much Sugar for the World to Eat.” New York Times, April 8: 112–14. Bart, P. 1962. “Advertising: Calorie Craze and Its Impact.” New York Times, Feb. 25: F12. Bashford, E. F. 1908a. Third Scientific Report on the Investigations of the Imperial Cancer Research Fund. London: Taylor and Francis. ———. 1908b.
Whole Earth Discipline: An Ecopragmatist Manifesto by Stewart Brand
agricultural Revolution, Asilomar, Asilomar Conference on Recombinant DNA, back-to-the-land, biofilm, borderless world, Buckminster Fuller, business process, Cass Sunstein, clean water, Community Supported Agriculture, conceptual framework, Danny Hillis, dark matter, decarbonisation, demographic dividend, demographic transition, Elon Musk, Exxon Valdez, failed state, Geoffrey West, Santa Fe Institute, glass ceiling, Google Earth, Hans Rosling, Hernando de Soto, informal economy, interchangeable parts, Intergovernmental Panel on Climate Change (IPCC), invention of agriculture, invention of the steam engine, Jane Jacobs, jimmy wales, Kevin Kelly, Kibera, land tenure, M-Pesa, Marshall McLuhan, megacity, microbiome, New Urbanism, out of africa, Paul Graham, peak oil, Richard Florida, Ronald Reagan, Silicon Valley, smart grid, stem cell, Stewart Brand, The Fortune at the Bottom of the Pyramid, Thomas Malthus, University of East Anglia, uranium enrichment, urban renewal, wealth creators, Whole Earth Catalog, Whole Earth Review, William Langewiesche, working-age population, Y2K
Bacteria have been found living in profusion a mile below the bottom of the seafloor, possibly as old as the sediment around them—111 million years. Look closer to home. Ninety percent of you isn’t you—only a tenth of the cells in your body are human; the rest are microbes. We are a portable swamp. One program of the emerging worldwide Global Metagenomics Initiative is called the International Human Microbiome Consortium, which is busy shotgun-sequencing all of the microbial communities that share our bodily life. We humans have 18,000 distinct genes; our microbes have 3 million. We are one species; they are diverse—a thousand species in our digestive tract (a twenty-one-foot-long bioreactor running on 100 trillion microbes), another thousand in our mouth, five hundred on our skin, another five hundred in those of us with a vagina.
My wife, Ryan Phelan, had just sold a company, so we put some money into gathering the world’s leading taxonomists and systematists in San Francisco for a meeting to decide whether a push to identify all life was useful and feasible. Ed Wilson hosted a follow-on meeting at Harvard a few weeks later. The universal message from the scientists was to go for it. As the project took shape, I got to participate in species inventories in Costa Rica, in the Great Smoky Mountains National Park, and inside a wood rat. (Why inside a wood rat? As with the human microbiome project, we are learning the degree to which life lives on life. Carl Zimmer wrote in Parasite Rex : “There’s a parrot in Mexico with thirty different species of mites on its feathers alone. And the parasites themselves have parasites, and some of those parasites have parasites of their own. . . . According to one estimate, parasites may outnumber free-living species four to one. In other words, the study of life is, for the most part, parasitology.”)
Guanacaste Conservation Area, Costa Rica Guardian Guidetti, Geri Gwadz, Robert Haeckel, Ernst “Half Century of United States Federal Government Energy Incentives, A” (Bezdek and Wendling) Hallwachs, Winnie Hamming, Richard Hansen, James Hansson, Anders Harris, Michael Harrison, Jim Haseltine, William Hawaii Hawken, Paul Hawks, John heat waves Hebert, Paul Henderson, Donald herbicides Herman, Arthur Higgs, Eric High Country News Hillis, Danny Hiroshima, Japan HIV/AIDS Holdren, John Holistic Management (Savory) Homer-Dixon, Thomas Hopis horizontal gene transfer horses Howard, Albert Humanitarian Golden Rice Network hurricanes hybrid seeds hydroelectric power hydrogen ice-to-water albedo flip Idea of Decline in Western History, The (Herman) IEEE Spectrum iGEM Jamboree Iglesias-Rodríguez, Débora Illicit (Naím) “Implications of Rising Carbon Dioxide Content of the Atmosphere” (Conservation Foundation) Inconvenient Truth, An Independent India genetic engineering and Green Revolution and nuclear power and slums and Industry Association of Synthetic Biology informal economy infrastructure insect resistance insulin integral fast reactors integrated pest management intelligent design Intergovernmental Panel on Climate Change (IPCC) International Atomic Energy Agency (IAEA) International Consortium for Polynucleotide Synthesis International Council of Science (ICSU) International Human Microbiome Consortium International Maize and Wheat Improvement Center International Rice Research Institute International Soil Reference and Information Centre International Union for Conservation of Nature and Natural Resources (IUCN) Internet Internet Engineering Task Force Intertribal Bison Cooperative Intervention (Caruso) iron irrigation Islam, Muslims Italy jaguars Janzen, Daniel Japan atomic bombing of genetic engineering and nuclear power and Jefferson, Richard Jennings, Lois Judson, Horace Juniper, Tony Kahn, Herman Kahn, Lloyd Kaplan, Robert Kareiva, Peter Kaufman, Wallace Keeling, Charles Keith, David Kelly, Brian Kelly, Kevin Kenya Keynes, John Maynard Khosla, Vinod King, Franklin Hiram Kirk, Andrew Klaassen, Johann Kleiber’s law Knight, Tom Kohm, Kathy Korea, North Korea, South Kunstler, James Howard Kyoto Protocol (2001) L-1 Point (Inner Lagrange Point) Lackner, Klaus Lake Nyos, Cameroon, disaster in Lamarck, Jean-Baptiste Lament for an Ocean (Harris) landraces Langewiesche, William Lansing, Stephen Laquian, Aprodicio Last Forest, The (London and Kelly) Last Whole Earth Catalog Latham, John Latin America genetic engineering and see also specific countries Laws of Fear (Sunstein) LeBlanc, Steven LEED rating system Lehmann, Johannes Lerner, Jaime Lewis, John Liberation Biology (Bailey) Liferaft Earth Limits to Growth, The (Meadows et al.)
Aurora by Kim Stanley Robinson
Some pathogens had to be tolerated, others had to be killed, if possible; but any attempt to kill bacteria meant that resistant surviving strains of that species would become more dominant and more resistant, in the usual way of things at the micro levels of life, or at all levels of life perhaps. Dangerous to try to kill things, Freya reminded them. She knew full well, with a sinking sense that she was remembering her earliest memories, that Devi had believed that trying to kill any invasive species usually created more problems than it solved. A destabilized microbiome often caused more harm than anything a balanced microbiome could inflict. Better, therefore, to try to balance things with the least amount of intrusion. Subtle touches, all designed to finesse things for balance. Balance was the crucial thing. Teeter-totters, gently teeter-tottering up and down. Devi had even been an advocate of everyone getting an inoculation of helmiths, meaning ringworms, to give them better resistance to such parasites later.
The outstanding questions often had to do with what they called the Universal Minimum Metabolic Rate, the slowest viable speed of a metabolism, which was nearly constant across all Terran creatures, from bacteria to blue whales. A downshift in any species’s metabolism almost certainly could not go below this universal minimum rate; on the other hand, that rate was very slow. So the theoretical possibility seemed to exist to put humans and their internal microbiomes into a very slow state, which would last for a long time without ill effects. It would involve a slowed heartbeat (bradycardia); peripheral vasoconstriction; greatly slowed respiration; very low core temperature, buffered by antifreeze drugs; biochemical retardations; biochemical infusion drips; antibacterials; occasional removal of accumulated wastes; and physical shifts and manipulations, small enough not to rouse the organism too much, but nevertheless very important.
23andMe, airport security, Albert Einstein, Black Swan, Buckminster Fuller, carbon footprint, cognitive dissonance, Columbine, correlation does not imply causation, Dean Kamen, game design, Gary Taubes, index card, Kevin Kelly, knowledge economy, life extension, lifelogging, Mahatma Gandhi, microbiome, p-value, Parkinson's law, Paul Buchheit, placebo effect, Productivity paradox, publish or perish, Ralph Waldo Emerson, Ray Kurzweil, Richard Feynman, Richard Feynman, selective serotonin reuptake inhibitor (SSRI), Silicon Valley, Silicon Valley startup, Skype, stem cell, Steve Jobs, survivorship bias, Thorstein Veblen, Vilfredo Pareto, wage slave, William of Occam
So far, two primary strains of bacteria have been found to influence fat absorption, almost regardless of diet: Bacteroidetes and Firmicutes. Lean people have more Bacteroidetes and fewer Firmicutes; obese people have more Firmicutes and fewer Bacteroidetes. As obese people lose weight, the ratio of bacteria in their gut swings confidently over to more Bacteroidetes. This finding has significant enough implications for national health that the National Institutes of Health (NIH) launched the multi-year Human Microbiome Project in late 2007. It is like a Human Genome Project for bacteria and intended to explore how some of the 40,000+ species of micro-friends (and fiends) are affecting our health and how we might modify them to help us more. This could take some time, but you don’t need to wait to act. There are a few things you can do now to cultivate healthy and fat-reducing gut flora: Get off the Splenda.
In a randomized, double-blind, placebo-controlled study of 39 patients with chronic fatigue syndrome, Lactobacillus casei strain Shirota was found to significantly decrease anxiety symptoms. Probiotics (bifidobacteria is one example) have also been shown as an effective alternative treatment for depression because of their power to inhibit inflammatory molecules called cytokines, decrease oxidative stress, and correct the overgrowth of unwanted bacteria that prevents optimal nutrient absorption in the intestines. Give your good bacteria an upgrade and get your microbiome in shape. Faster fat-loss and better mental health are just two of the benefits. TOOLS AND TRICKS Twelve Hours of Bingeing in Photos (www.fourhourbody.com/binge) See the binge from this chapter as I captured it in real time and posted the photos on Flickr. It will give you an appreciation for the quantity. Super Cissus Rx (www.fourhourbody.com/cq) This is the brand of CQ I used during the experimentation.
.], and sex, 19.1, 19.2, 20.1 GL (glycemic load), 8.1, 12.1 glucose monitor, 12.1, 12.2, 12.3, 12.4 GLUT-4 (glucose transporter type 4), 9.1, 9.2, 10.1, 10.2, 18.1 glutathione gluten glycemic index (GI), 8.1, 12.1 glycemic load (GL), 8.1, 12.1 GnRH (gonadotropin-releasing hormone) Goethe, Johann Wolfgang Goldacre, Ben, 43.1, 44.1 goLITE, 23.1, 23.2 GOMAD (gallon of milk a day) goose liver pâté Go Raw Carob Cashew Smoothie (recipe) gout Green Machine Pudding (recipe) green tea flavanols, 10.1, 10.2 g-spot, 19.1, 20.1 Guadango, Mike (Asshole) Guillette, Louis Gumbel, Bryant H Habit Forge Hackett, George Hahnemann, Samuel half military crawl Hall, Mike hamstring pull Harajuku Moment, 4.1, 4.2 Hartford Marathon Hartley, Nina, 19.1, 19.2 Hartmann, Gerard Hawthorne Effect HCB (Hungarian Core Blaster) hCG (human chorionic gonadotropin) headaches: and blood sugar dehydration heartburn heart rate monitor heat, and fat loss Heinlein, Robert helplessness, learned Hemwall, Gustav A. Herbert, Frank Hiei monk/athletes Hill, James hip extension Hippocrates HIT (high-intensity intermittent) exercise Hite, Shere Hoehn, Charlie holding your breath homeopathy Horton, Zar hot sauce Houdini, Harry HRM (heart rate monitor) human chorionic gonadotropin (hCG) Human Microbiome Project humidifier, 23.1, 23.2 hummus recipe Hungarian Core Blaster (HCB) Hutchins, Ken Hyde, Andrew hypertrophy hyperzine-A hypothalamus, 21.1, 33.1 I IAS (Insulin Autoimmune Syndrome) ice baths ice packs IF (intermittent fasting) IGF-1 (insulin-like growth factor 1) II (insulinemic index) imbalance, 27.1, 27.2 inaction, excuses for infertility injuries, reversing active-release technique AMIT biopuncture cocktail Egoscue method menu prolotherapy, 25.1, 25.2 shoe heel removal injury-proofing chop and lift cross-body one-arm single-leg deadlift fixing Functional Movement Screen (FMS), 27.1, 27.2 schedule sets and reps single-leg flexibility assessment testing Turkish get-up two-arm single-leg deadlift insomnia onset, 23.1, 23.2 insulinemic response insulin-like growth factor 1 (IGF-1) insulin release insulin sensitivity inulin in vitro fertilization iron excess Iron Penis Kung-Fu Irwin, Nic isoleucine IVF (in vitro fertilization) J James, William Japan, life expectancy in Japanese natto, 9.1, 46.1 Jarmey, Chris, The Concise Book of Muscles JayC (eating more) Jeff (variety) Jell-O, sugar-free Jeter, Derek Johnson, Ben, 29.1, 32.1 Johnson, Michael Jones, Arthur, 2.1, 2.2, 16.1, 16.2, 16.3, 16.4, 16.5 Jones, Brett Jones, Marion Jones, Reese Julee (bodyfat) jumping, 28.1, 33.1n Jurek, Scott, 30.1, 31.1, 31.2, 47.1, 47.2, 48.1 K Kaku, Michio Kamen, Dean Karlan, Dean Karnazes, Dean, 16.1, 31.1 Karwoski, Kirk, 33.1, 33.2, 33.3 Kauai Marathon Kay, Alan kefir Keith, Lierre Kelley, Johnny Kenya, marathoners of Kersschot, Jan ketogenic dieting kettlebells, 14.1, 14.2 for biceps certification, 30.1, 32.1 Fleur’s regimen Russian kettlebell swing Turkish get-up Zar Horton’s method Kimball, Charlie kimchi King, Martin Luther, Jr.
23andMe, Albert Einstein, Alfred Russel Wallace, banking crisis, Barry Marshall: ulcers, Benoit Mandelbrot, Berlin Wall, biofilm, Black Swan, butterfly effect, Cass Sunstein, cloud computing, congestion charging, correlation does not imply causation, Daniel Kahneman / Amos Tversky, dark matter, data acquisition, David Brooks, delayed gratification, Emanuel Derman, epigenetics, Exxon Valdez, Flash crash, Flynn Effect, hive mind, impulse control, information retrieval, Intergovernmental Panel on Climate Change (IPCC), Isaac Newton, Jaron Lanier, John von Neumann, Kevin Kelly, lifelogging, mandelbrot fractal, market design, Mars Rover, Marshall McLuhan, microbiome, Murray Gell-Mann, Nicholas Carr, open economy, Pierre-Simon Laplace, place-making, placebo effect, pre–internet, QWERTY keyboard, random walk, randomized controlled trial, rent control, Richard Feynman, Richard Feynman, Richard Feynman: Challenger O-ring, Richard Thaler, Satyajit Das, Schrödinger's Cat, security theater, selection bias, Silicon Valley, stem cell, Steve Jobs, Steven Pinker, Stewart Brand, the scientific method, Thorstein Veblen, Turing complete, Turing machine, Vilfredo Pareto, Walter Mischel, Whole Earth Catalog, zero-sum game
In one-fifth of a teaspoon of seawater, there are a million bacteria (and 10 million viruses), Craig Venter says, adding, “If you don’t like bacteria, you’re on the wrong planet. This is the planet of the bacteria.” That means that most of the planet’s living metabolism is microbial. When James Lovelock was trying to figure out where the gases come from that make the Earth’s atmosphere such an artifact of life (the Gaia hypothesis), it was microbiologist Lynn Margulis who had the answer for him. Microbes run our atmosphere. They also run much of our body. The human microbiome in our gut, mouth, skin, and elsewhere, harbors three thousand kinds of bacteria with 3 million distinct genes. (Our own cells struggle by on only eighteen thousand genes or so.) New research is showing that our microbes-on-board drive our immune systems and important parts of our digestion. Microbial evolution, which has been going on for more than 3.6 billion years, is profoundly different from what we think of as standard Darwinian evolution, where genes have to pass down generations to work slowly through the selection filter.
Recent advances in the life and physical sciences have made possible new and even unexpected expansions of this concept. The map of the human genome and of the diploid genomes of individuals; the map of our geographic spread; the map of the Neanderthal genome—these are new tools to address the age-old issues of human unity and diversity. Reading the life code of DNA does not stop there; it places humans in the vast and colorful mosaic of earthly life. “Otherness” is seen in a new light. Our microbiomes—the trillions of microbes on and in each of us, and essential to our physiology, become part of our selves. Astronomy and space science are intensifying the search for life on other planets—from Mars and the outer reaches of the solar system to Earth-like planets and super-Earths orbiting other stars. The chances of success may hinge on our understanding of the possible diversity of the chemical basis of life itself: “otherness” not among DNA-encoded species but among life-forms using different molecules to encode traits.
Blockchain: Blueprint for a New Economy by Melanie Swan
23andMe, Airbnb, altcoin, Amazon Web Services, asset allocation, banking crisis, basic income, bioinformatics, bitcoin, blockchain, capital controls, cellular automata, central bank independence, clean water, cloud computing, collaborative editing, Conway's Game of Life, crowdsourcing, cryptocurrency, disintermediation, Edward Snowden, en.wikipedia.org, ethereum blockchain, fault tolerance, fiat currency, financial innovation, Firefox, friendly AI, Hernando de Soto, intangible asset, Internet Archive, Internet of things, Khan Academy, Kickstarter, lifelogging, litecoin, Lyft, M-Pesa, microbiome, Network effects, new economy, peer-to-peer, peer-to-peer lending, peer-to-peer model, personalized medicine, post scarcity, prediction markets, QR code, ride hailing / ride sharing, Satoshi Nakamoto, Search for Extraterrestrial Intelligence, SETI@home, sharing economy, Skype, smart cities, smart contracts, smart grid, software as a service, technological singularity, Turing complete, unbanked and underbanked, underbanked, web application, WikiLeaks
Blockchain technology, in the form of a universal model for record keeping and data storage and access (a secure, decentralized, pseudonymous file structure for data stored and accessed in the cloud) could be the technology that is needed to move into the next phase of industrialized genomic sequencing. This applies to genomic sequencing generally as an endeavor, irrespective of the personal data rights access issue. Sequencing all humans is just one dimension of sequencing demand; there is also the sequencing of all plants, animals, crops, viruses, bacteria, disease-strain pathogens, microbiomes, cancer genomes, proteomes, and so on, to name a few use cases. There is a scale production and efficiency argument for blockchain-based transnational genomic services. To move to large-scale sequencing as a “universal human society,” the scope and scale of sequencing and corresponding information processing workloads suggests not just transnationality, but more important, heavy integration with the cloud (genomic data is too big for current forms of local storage and manipulation), and the blockchain delivers both transnationality and the cloud.
Think Like a Freak by Steven D. Levitt, Stephen J. Dubner
Albert Einstein, Anton Chekhov, autonomous vehicles, Barry Marshall: ulcers, call centre, Cass Sunstein, colonial rule, Edward Glaeser, Everything should be made as simple as possible, food miles, Gary Taubes, income inequality, Internet Archive, Isaac Newton, medical residency, Metcalfe’s law, microbiome, prediction markets, randomized controlled trial, Richard Thaler, Scramble for Africa, self-driving car, Silicon Valley, Tony Hsieh, transatlantic slave trade, éminence grise
Brandt, “Fecal Microbiota Transplantation: Past, Present and Future,” Current Opinion in Gastroenterology 29, no. 1 (January 2013); “Jonathan Eisen: Meet Your Microbes,” TEDMED Talk, Washington, D.C., April 2012; Borody and Khoruts, “Fecal Microbiota Transplantation and Emerging Applications,” Nature Reviews Gastroenterology & Hepatology 9, no. 2 (2011); Khoruts et al., “Changes in the Composition of the Human Fecal Microbiome After Bacteriotherapy for Recurrent Clostridium Difficile–Associated Diarrhea,” Journal of Clinical Gastroenterology 44, no. 5 (May/June 2010); Borody et al., “Bacteriotherapy Using Fecal Flora: Toying with Human Motions,” Journal of Clinical Gastroenterology 38, no. 6 (July 2004). / 85 Looks like chocolate milk: That is according to Josbert Keller, a gastroenterologist at the HagaZiekenhuis hospital in the Hague, an author of “Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile,” New England Journal of Medicine 368 (2013):407–415; see also Denise Grady, “When Pills Fail, This, er, Option Provides a Cure,” New York Times, January 16, 2013. / 85 Colitis “previously an incurable disease”: See Borody and Jordana Campbell, “Fecal Microbiota Transplantation: Techniques, Applications, and Issues,” Gastroenterology Clinics of North America 41 (2012); and Borody, Eloise F.
Bold: How to Go Big, Create Wealth and Impact the World by Peter H. Diamandis, Steven Kotler
3D printing, additive manufacturing, Airbnb, Amazon Mechanical Turk, Amazon Web Services, augmented reality, autonomous vehicles, cloud computing, creative destruction, crowdsourcing, Daniel Kahneman / Amos Tversky, dematerialisation, deskilling, Elon Musk, en.wikipedia.org, Exxon Valdez, fear of failure, Firefox, Galaxy Zoo, Google Glasses, Google Hangouts, Google X / Alphabet X, gravity well, ImageNet competition, industrial robot, Internet of things, Jeff Bezos, John Harrison: Longitude, John Markoff, Jono Bacon, Just-in-time delivery, Kickstarter, Kodak vs Instagram, Law of Accelerating Returns, Lean Startup, life extension, loss aversion, Louis Pasteur, Mahatma Gandhi, Marc Andreessen, Mark Zuckerberg, Mars Rover, meta analysis, meta-analysis, microbiome, minimum viable product, move fast and break things, Narrative Science, Netflix Prize, Network effects, Oculus Rift, optical character recognition, packet switching, PageRank, pattern recognition, performance metric, Peter H. Diamandis: Planetary Resources, Peter Thiel, pre–internet, Ray Kurzweil, recommendation engine, Richard Feynman, Richard Feynman, ride hailing / ride sharing, risk tolerance, rolodex, self-driving car, sentiment analysis, shareholder value, Silicon Valley, Silicon Valley startup, skunkworks, Skype, smart grid, stem cell, Stephen Hawking, Steve Jobs, Steven Levy, Stewart Brand, technoutopianism, telepresence, telepresence robot, Turing test, urban renewal, web application, X Prize, Y Combinator, zero-sum game
Right now your toothpaste is mostly chalk and flavoring, but with synthetic biology, it can be specifically designed to fight your breed of bad breath microbes. “That’s not all,” continues Hessel. “It can have tooth-polishing nanoparticles designed to continue cleaning long after you’ve stopped brushing. It can be designed to detect infection or cancer or diabetes, turning different colors in the presence of each, or to release custom-designed probiotics that balance your microbiome. It can do all of these things. And that’s just the first thing you do in the morning.” To many, synthetic biology still sounds like science fiction, but what is transforming it into science fact is the same force driving all the other exponential technologies—Moore’s law. Because DNA is nothing more than a four-letter code, when genetics went digital, it was transformed into an information science and thus hopped on the exponential expressway.
Grain Brain: The Surprising Truth About Wheat, Carbs, and Sugar--Your Brain's Silent Killers by David Perlmutter, Kristin Loberg
., “Ingestion of Lactobacillus Strain Regulates Emotional Behavior and Central GABA Receptor Expression in a Mouse Via the Vagus Nerve,” Proceedings of the National Academy of Sciences 108, no. 138 (September 20, 2011): 16050–55. 10. A. C. Bested, et al., “Intestinal Microbiota, Probiotics and Mental Health: From Metchnikoff to Modern Advances: Part I—Autointoxication Revisited,” Gut Pathogens 5, no. 1 (March 18, 2013): 5. See also Parts II and III of the same report. 11. J. F. Cryan and S. M. O’Mahony, “The Microbiome-Gut-Brain Axis: From Bowel to Behavior,” Neurogastroenterology and Motility 23, no. 3 (March 2011): 187–92. 12. Michael Gershon, MD, The Second Brain: The Scientific Basis of Gut Instinct and a Groundbreaking New Understanding of Nervous Disorders of the Stomach and Intestines (New York: Harper, 1998). 13. For more about the brain-gut connection, check out the work of Dr. Emeran Mayer, MD, director of the University of California Los Angeles’s Center for Neurobiology of Stress.
How to Read a Paper: The Basics of Evidence-Based Medicine by Trisha Greenhalgh
call centre, complexity theory, conceptual framework, correlation coefficient, correlation does not imply causation, deskilling, knowledge worker, meta analysis, meta-analysis, microbiome, New Journalism, p-value, personalized medicine, placebo effect, publication bias, randomized controlled trial, selection bias, the scientific method
But the withdrawal rate from the trial was high, partly because when participants found a medication that worked, they just wanted to keep taking it rather than swap to the alternative! But despite its conceptual elegance and a distant promise of linking to the ‘personalised medicine’ paradigm in which every patient will have their tests and treatment options individualised to their particular genome, physiome, microbiome, and so on, the n of 1 trial has not caught on widely in either research or clinical practice. A review article by Lillie and colleagues  suggests why. Such trials are labour intensive to carry out, requiring a high degree of individual personalisation and large amounts of data for every participant. ‘Washout’ periods raise practical and ethical problems (does one have to endure one's arthritis with no pain relief for several weeks to serve the scientific endeavour?).
Seveneves by Neal Stephenson
clean water, Colonization of Mars, Danny Hillis, digital map, double helix, epigenetics, fault tolerance, Fellow of the Royal Society, Filipino sailors, gravity well, Isaac Newton, Jeff Bezos, kremlinology, Kuiper Belt, microbiome, phenotype, Potemkin village, pre–internet, random walk, remote working, selection bias, side project, Silicon Valley, Skype, statistical model, Stewart Brand, supervolcano, the scientific method, Tunguska event, zero day, éminence grise
“Do we even need to bother watching how this goes?” Bard asked. And then he looked to Ty to give the answer. It had not been a rhetorical question. He was awaiting orders. Beled Tomov looked at him too. “How is she?” Ty asked. “Pulse, respiration okay?” “I think it is the usual,” Beled said with a nod. Meaning that abrupt hormone shifts in Kath’s system were giving her something akin to morning sickness. Her microbiome—the ecosystem of bacteria that lived in her gut and on her skin—had been thrown into disarray, and she was being colonized by any old germs, including ones from the Diggers that had never been exposed to a Moiran body. “Can you put her on your back or something?” Beled nodded and dropped to one knee. He had been carrying a pack on his back. He emptied its contents on the ground and began slashing leg holes in its bottom corners so that Kath could just be inserted into it, like an infant into a carrier.
“She saw Doc and Memmie die, and suffered a blunt- force trauma to her arm, and was forced to draw her kat, and to use it. As soon as it happened she went into what I’m guessing is a classic POTESH.” This was military jargon for post-traumatic epigenetic shift. “That is confirmed,” said Hope, who seemed to have finished an initial scan of Kath’s vital signs. “Higher metabolism and hyperacute senses are observable. Her microbiome is a mess; I’m tuning it up with probiotic supplements that’ll be a better fit with her new phenotype. Suggested by the nausea are big hormone shifts. Possibly predictive of some future . . .” “Testosterone poisoning?” Ty suggested, finishing Hope’s thought. Hope responded with a diffident nod of the head. Ty turned his attention back to Arjun. “So three billion people just learned that the Diggers exist.
carbon footprint, clean water, collective bargaining, dark matter, Deng Xiaoping, Exxon Valdez, Filipino sailors, Google Earth, illegal immigration, indoor plumbing, intermodal, Isaac Newton, means of production, microbiome, Panamax, Pearl River Delta, post-Panamax, profit motive, Skype, statistical model, Thorstein Veblen, traveling salesman
When he boarded the Louis in Resolute, he’d brought with him, in addition to Erin Freeland-Ballantyne, a number of supernumeraries whom he referred to as VIPs—luminaries of oceanography, all dressed, like him, in matching fleece cardigan vests onto which was embroidered the logo of this expedition—the C30 project, Carmack had called it, for Canada’s Three Oceans. His idea for the second leg of our voyage was to turn the Louis into a kind of icebreaking, traveling oceanographic lyceum. During the lectures the VIPs delivered, I learned many interesting facts—for instance, that in the “microbiome” of the human body, only a portion of our cells, genetically speaking, are human in origin. The rest are bacterial. (While learning this, I found myself looking down, examining my midriff, into which, in the main mess, I’d recently deposited some potatoes, carrots, and buttery cod. The cloth between the buttons of my quick-dry adventure shirt was puckering over the waistband of my quick-dry adventure pants in an unflattering way, and I tried to smooth the puckers flat.)
Antifragile: Things That Gain From Disorder by Nassim Nicholas Taleb
Air France Flight 447, Andrei Shleifer, banking crisis, Benoit Mandelbrot, Berlin Wall, Black Swan, Chuck Templeton: OpenTable, commoditize, creative destruction, credit crunch, Daniel Kahneman / Amos Tversky, David Ricardo: comparative advantage, discrete time, double entry bookkeeping, Emanuel Derman, epigenetics, financial independence, Flash crash, Gary Taubes, George Santayana, Gini coefficient, Henri Poincaré, high net worth, hygiene hypothesis, Ignaz Semmelweis: hand washing, informal economy, invention of the wheel, invisible hand, Isaac Newton, James Hargreaves, Jane Jacobs, joint-stock company, joint-stock limited liability company, Joseph Schumpeter, Kenneth Arrow, knowledge economy, Lao Tzu, Long Term Capital Management, loss aversion, Louis Pasteur, mandelbrot fractal, Marc Andreessen, meta analysis, meta-analysis, microbiome, money market fund, moral hazard, mouse model, Myron Scholes, Norbert Wiener, pattern recognition, Paul Samuelson, placebo effect, Ponzi scheme, principal–agent problem, purchasing power parity, quantitative trading / quantitative ﬁnance, Ralph Nader, random walk, Ray Kurzweil, rent control, Republic of Letters, Ronald Reagan, Rory Sutherland, selection bias, Silicon Valley, six sigma, spinning jenny, statistical model, Steve Jobs, Steven Pinker, Stewart Brand, stochastic process, stochastic volatility, The Great Moderation, the new new thing, The Wealth of Nations by Adam Smith, Thomas Bayes, Thomas Malthus, too big to fail, transaction costs, urban planning, Vilfredo Pareto, Yogi Berra, Zipf's Law
Psychology Press. Gray, John, 2002, Straw Dogs: Thoughts on Humans and Other Animals. London: Granta Books. Gray, John, 2011, The Immortalization Commission: Science and the Strange Quest to Cheat Death. Allen Lane. Greenwood, R., and R. Suddaby, 2006, “The Case of Disappearing Firms: Death or Deliverance?” Journal of Organizational Behavior 27(1): 101–108. Grice, E. A., and J. A. Segre, 2011, “The Skin Microbiome.” Nature Reviews Microbiology 9(4): 244–253. Griffith, S. C., I.P.F. Owens, and K. A. Thuman, 2002, “Extrapair Paternity in Birds: A Review of Interspecific Variation and Adaptive Function.” Molecular Ecology 11: 2195–212. Grob, Gerald N., 2002, The Deadly Truth: A History of Disease in America. Cambridge, Mass.: Harvard University Press. Guadalupe-Grau, A., T. Fuentes, B. Guerra, and J. Calbet, 2009, “Exercise and Bone Mass in Adults.”
Data Scientists at Work by Sebastian Gutierrez
Albert Einstein, algorithmic trading, Bayesian statistics, bioinformatics, bitcoin, business intelligence, chief data officer, clean water, cloud computing, commoditize, computer vision, continuous integration, correlation does not imply causation, creative destruction, crowdsourcing, data is the new oil, DevOps, domain-specific language, Donald Knuth, follow your passion, full text search, informal economy, information retrieval, Infrastructure as a Service, Intergovernmental Panel on Climate Change (IPCC), inventory management, iterative process, lifelogging, linked data, Mark Zuckerberg, microbiome, Moneyball by Michael Lewis explains big data, move fast and break things, move fast and break things, natural language processing, Network effects, nuclear winter, optical character recognition, pattern recognition, Paul Graham, personalized medicine, Peter Thiel, pre–internet, quantitative hedge fund, quantitative trading / quantitative ﬁnance, recommendation engine, Renaissance Technologies, Richard Feynman, Richard Feynman, self-driving car, side project, Silicon Valley, Skype, software as a service, speech recognition, statistical model, Steve Jobs, stochastic process, technology bubble, text mining, the scientific method, web application
With Quid, we have a lot of users who are asking questions that we think are valuable ones to have answered well, so the question is then, are we really helping them answer those questions well? In this case, it’s really good to keep the users continually in mind. Its good to understand them well enough that you can then regularly use the product the way they would, and see where it falls short, and make sure you’re working towards fixing that. For us that has also meant, does the product satisfy our own curiosity? Can I quickly learn about Bitcoin or the microbiome or Apple using it? It’s definitely the case that it’s really easy to get into weeds with the stuff, as there are always thousands of options of different algorithms you could try and different tweaks you could do. You have to work hard to stay focused on the big picture. Some of it is also having hunches about what’s going to have the most value. I think you have to go there and make those decisions.
The Body Keeps the Score: Brain, Mind, and Body in the Healing of Trauma by Bessel van Der Kolk M. D.
anesthesia awareness, British Empire, conceptual framework, deskilling, en.wikipedia.org, epigenetics, false memory syndrome, feminist movement, impulse control, Louis Pasteur, meta analysis, meta-analysis, microbiome, phenotype, placebo effect, profit motive, randomized controlled trial, selective serotonin reuptake inhibitor (SSRI), theory of mind, Yogi Berra
In 2010 Thomas Insel, director of the National Institute of Mental Health, published an article in Scientific American entitled “Faulty Circuits,” in which he called for a return to understanding mind and brain in terms of the rhythms and patterns of electrical communication: “Brain regions that function together to carry out normal (and abnormal) mental operations can be thought of as analogous to electrical circuits—the latest research shows that the malfunctioning of entire circuits may underlie many mental disorders.”34 Three years later Insel announced that NIMH was “re-orienting its research away from DSM categories”35 and focusing instead on “disorders of the human connectome.”36 As explained by Francis Collins, director of the National Institutes of Health (of which NIMH is a part), “The connectome refers to the exquisitely interconnected network of neurons (nerve cells) in your brain. Like the genome, the microbiome, and other exciting ‘ome’ fields, the effort to map the connectome and decipher the electrical signals that zap through it to generate your thoughts, feelings, and behaviors has become possible through development of powerful new tools and technologies.”37 The connectome is now being mapped in detail under the auspices of NIMH. As we await the results of this research, I’d like to give the last word to Lisa, the survivor who introduced me to the enormous potential of neurofeedback.
The Information: A History, a Theory, a Flood by James Gleick
Ada Lovelace, Alan Turing: On Computable Numbers, with an Application to the Entscheidungsproblem, Albert Einstein, AltaVista, bank run, bioinformatics, Brownian motion, butterfly effect, citation needed, Claude Shannon: information theory, clockwork universe, computer age, conceptual framework, crowdsourcing, death of newspapers, discovery of DNA, Donald Knuth, double helix, Douglas Hofstadter, en.wikipedia.org, Eratosthenes, Fellow of the Royal Society, Gödel, Escher, Bach, Henri Poincaré, Honoré de Balzac, index card, informal economy, information retrieval, invention of the printing press, invention of writing, Isaac Newton, Jacquard loom, Jacquard loom, Jaron Lanier, jimmy wales, John von Neumann, Joseph-Marie Jacquard, lifelogging, Louis Daguerre, Marshall McLuhan, Menlo Park, microbiome, Milgram experiment, Network effects, New Journalism, Norbert Wiener, On the Economy of Machinery and Manufactures, PageRank, pattern recognition, phenotype, Pierre-Simon Laplace, pre–internet, Ralph Waldo Emerson, RAND corporation, reversible computing, Richard Feynman, Richard Feynman, Rubik’s Cube, Simon Singh, Socratic dialogue, Stephen Hawking, Steven Pinker, stochastic process, talking drums, the High Line, The Wisdom of Crowds, transcontinental railway, Turing machine, Turing test, women in the workforce
Of course, it acts and moves and procreates as a unit, and furthermore, in the case of at least one species, it feels itself, with impressive certainty, to be a unit. The gene-centered perspective has helped biologists appreciate that the genes composing the human genome are only a fraction of the genes carried around in any one person, because humans (like other species) host an entire ecosystem of microbes—bacteria, especially, from our skin to our digestive systems. Our “microbiomes” help us digest food and fight disease, all the while evolving fast and flexibly in service of their own interests. All these genes engage in a grand process of mutual co-evolution—competing with one another, and with their alternative alleles, in nature’s vast gene pool, but no longer competing on their own. Their success or failure comes through interaction. “Selection favors those genes which succeed in the presence of other genes,” says Dawkins, “which in turn succeed in the presence of them.”♦ The effect of any one gene depends on these interactions with the ensemble and depends, too, on effects of the environment and on raw chance.