Sunday, May 25, 2014

Defining Oneself by the Group

Human beings are not like buttons, defined by only one or two attributes such as shape, color, material, or intended use. Humans in their genotype, phenotype, biometrics, social situation, and their hundreds of other attributes are multi-dimensional beings.

Consider a person who is female, raised Catholic, sexually active as a lesbian, African-American by some blending of genes for skin color and other physical features, who works as an accountant, is coping with diabetes and incipient arthritis, and is a devotee of the martial arts.1 If you had to pick one feature to define this woman, what would it be? When would you use it? How completely would it define her? Each feature—and so each potential categorization—comes into play in different aspects of her life, at different times in her life, and with the different people to whom she relates.

To put her in a single group—say, African-American based on a few genes, or martial artist based on a pastime—and then claim that’s the most important aspect of her life is to miss the complexity of the person as a whole. It would be to claim her for your purposes and not necessarily for her benefit.

I can imagine some people who are so lacking in skills, interests, and imagination, whose lives are otherwise so empty, that they cling to one particular aspect of existence as their own self-identification. I imagine such a person might be an Irish patriot first, with all else—family, religion, his day job, his pint of Guinness stout, and his favorite soccer team—coming in a distant and distracting second. Or someone who is a political revolutionary first and allows nothing else to matter. Such people may make their mark in the world. They may be ready to die for that one aspect of existence. And this might make them heroes, martyrs—or villains, depending on your viewpoint.

But such a uni-dimensional life is not very interesting, outside of the drama which that single aspect and its struggles may generate. Such people are not interesting to know, spend an afternoon with, be shipwrecked with, or have in the family. Moreover, such a life is not … robust. Let the cause for which he or she fights become lost or, just as bad, be resolved peacefully, and the person will be suddenly without purpose. Then the person might go through a spiritual crisis and adopt some other aspect of life as a raison d’être, or try to rekindle the lost cause at some more radical and violent level, or simply fade into depression and die. Only one of these responses is life-affirming, and the entire pattern is too fragile for the rough and tumble of human life.2

It’s going to be a long life, too. And, given the advances in molecular medicine that are occurring right now, it’s going to be even longer than you can imagine or than anyone else before you has experienced. Medicine is on the cusp of a huge breakthrough with the unlocking and analysis of the DNA-RNA-protein regime that controls all life.3 We are already isolating stem cells—those partially differentiated cells with which the body repairs damaged tissues—and using them to grow new, relatively simple, organs. When we can decode and reprogram the RNA signals that guide cellular development, we will be able to devise from these stem cells specific tissue types, create more complex organs, adjust bodily processes on the fly, and perhaps even reverse the aging process. Humans—with a little help from right diet, regular exercise, and a bit of physical caution—will be able to live through several lifetimes.4

Think of all the sociological, economic, environmental, and relational changes you would go through in a life that moves on well past the age of one hundred. Would your allegiance to any ethnic or national background, profession or trade, political party or religious doctrine survive the next hundred years of history?5

To take just one example, consider the divorce rate in this and other advanced countries. Yes, it was only the changes in informal religious doctrine and social attitudes that made divorce more possible for the average person fifty or sixty years ago. But the underlying need, the driver, was the suddenly perceived fact that people are beginning to live longer, more productive lives, with senescence postponed until later and later. A marriage bond that will last “until death do us part” is workable if you marry at age eighteen or twenty, can expect to live only into your late fifties or early sixties, and perhaps die a lot younger through disease or accident. It’s a different proposition if you expect to live to into your late eighties or nineties and remain vigorous and active right up to the end. Our society has gone from once-and-for-all-time marriage vows, with divorce or remarriage after death being the exception, to a state of “serial monogamy” for almost everyone. Yes, you are only married to one person at a time, but often for no more than ten or fifteen or twenty years. And in that time your and your spouse’s interests will have grown apart, your life situations will have changed, you will find yourself growing bored, and you’ll be ready for romantic adventure and a new life partner.

To take another example, the nature of work has changed tremendously in the past century or so. In the developed countries, we’ve gone from the largest fraction of our population living on the farm and producing food; to living in the cities and working in centralized industries and factories; to living wherever may be convenient and telecommuting to “knowledge” jobs that arrange for the supply, distribution, and marketing of goods made in automated factories. As a writer and editor in my mid-sixties, I’ve seen the work in a few particular areas of focus—publishing, process documentation, and communications—go through waves of technical changes. I’ve had to learn new skills like electronic page layout, website design, and video production. I’ve had to reinvent myself five or six times as my job or my industry changed. And such waves of change are not going to stop anytime soon.

In the midst of this maelstrom, who would nail just a single flag to his or her masthead? Who would be prepared to sail and fight, sink and die, under that one flag? We will all have to be flexible and adaptable if we’re going to survive the next couple of hundred years.

We human beings are individuals first, with our own unique needs, desires, dreams, fears, skills, attractions, and aversions. We are members of any group only as a distant second and for a limited period of time. And, even then, that group relationship will be a poor garment that barely covers the largeness of who and what we are.

This is the true diversity of the human spirit.

1. A fictitious person, to be sure, created as an example, but still intended as a completely possible human being.

2. To quote Robert A. Heinlein: “A human being should be able to change a diaper, plan an invasion, butcher a hog, conn a ship, design a building, write a sonnet, balance accounts, build a wall, set a bone, comfort the dying, take orders, give orders, cooperate, act alone, solve equations, analyze a new problem, pitch manure, program a computer, cook a tasty meal, fight efficiently, die gallantly. Specialization is for insects.”

3. See just part of this story in The Chemistry of Control from May 11, 2014.

4. I’m right now finishing up a novel on this subject, tentatively titled Coming of Age, that follows two main characters through five succeeding generations over the next hundred years. Look for the book early this fall.

5. This recalls a story I once heard, about a woman who turned one hundred years old and was asked by a reporter if she had any regrets. Oh yes, the woman said. She regretted that she did not start learning the violin at age sixty—because by now she would have been playing for forty years.

Sunday, May 18, 2014

Fantasy as Public Policy

The San Francisco Chronicle, our hometown newspaper, recently ran a front-page story1 about a $355,000 grant awarded by “pollution regulators” to research installing rigid, carbon-fiber sails on the ferries that ply San Francisco Bay to supplement their diesel engines. The idea was supposedly inspired by the success of the America’s Cup catamarans last year: if the AC72s can get up to 55 mph in the Bay winds, then whoo-hoo! Why not a ferryboat carrying hundreds of people?

I guess sailors and scientists can do any experiments they want, and regulators can spend taxpayer money any way they choose. But this is fantasy as public policy, on the shallow order of “Wouldn’t it be nice if …?” or “Ooo, there’s an idea!”

For the record—because for about two weeks I watched the America’s Cup finals almost every day—the AC72s are not great boats. They attain their marvelous speeds by being extremely light, fragile, and ungainly craft. They have hulls 72 feet long and 46 feet wide that weigh just 13,000 pounds, six and a half tons—which is ridiculously light for a boat that size. They have masts and sails 130 feet tall. Their cargo capacity is a crew of 11 brawny men, all of whom work damn hard to keep the boat in proper trim and upright. They sail in a narrow window of the wind—between 5 and 20-25 knots, depending on the month—which means they do really well in light winds but fold over and break in gusts of about 30 mph. Gusts are not all that uncommon on the Bay.

The AC72s are designed to do one thing very well: sail up and down the San Francisco waterfront on late-summer afternoons at dizzyingly fast speeds for the excitement of large crowds. That waterfront is beautifully placed along a wind-tunnel–like channel shaped by the northern end of the San Francisco Peninsula and the Marin Headlands, which produces steady west-to-east winds of the specified velocity over relatively flat water. And still, too many of the races in the final match had to be called off when the winds were too strong.2

Suggesting this kind of sailboat, or any aspect or part of it, as a model for public transportation is like trying to turn a light and elegant two-person sailplane—a “glider” to most people—into a jumbo jet for transcontinental service. Don’t hold your breath.

Ferries are already a form of public transport. Burning carbon fuels to move hundreds of people across the Bay—rather than have them drive across the bridges—is considered good, green policy. Trying to reduce their carbon footprint even further by adding sails is fancifully misdirected.

I have sailed on the Bay. It’s great fun. You get those light winds in many places, which the AC72s would love, but they leave a heavier boat rolling and flapping. In the lee of San Francisco itself, immediately south of the Bay Bridge, which is on the main route of the Alameda ferries, there’s a dead zone you just have to waddle and drift through. The same goes for the lee of Angel Island, where the Larkspur and Vallejo ferries travel. But then, as you come out of the city’s wind shadow and cross toward Angela Island, you experience what we used to call “the slot.” This is the raceway wind that the America’s cup boats exploited. In a helluva hurry, you can go from drifting along to canting over on your beam-ends with your mast at a 45-degree angle pointing off toward Berkeley.3

The Bay is a challenging place to sail, not all that dangerous, but not like a lake, either. It is not one kind of place with a steady wind and no excitement. And on more days than you’d think—especially in summer, when the Central Valley heats up and draws a steady, onshore breeze—you can get small-craft warnings at the Gate and in the North Bay. Then it may not even be safe to drive on the Bay Bridge or the Richmond-San Rafael because of crosswinds. And some days—especially in May and October, when the Bay Area gets its only hot, still days—the wind does not blow at all and the flags hang limp.

With computers, we can design more efficient sails, just as we can design more efficient windmills. But we’re still faced with the wind as a variable and sometimes missing resource. To quote Captain Jack Aubrey in the Master and Commander movie: “I can harness the wind but I ain’t its goddamn creator.”

Fossil-fueled engines are a technological advancement, because they can take you safely and reliably in any direction, regardless of where and whether the wind’s blowing. To supplement them with a sail would be to take us back to the 1850s, when scows traveled up and down the Bay hauling lumber and grain. To supplement them—for the sake of their carbon footprint—with a hundred-foot-tall, fixed and rigid, carbon-fiber sail that you can’t take down in a blow and that will act as an air brake in a calm … would be lunacy.

But it’s such a lovely idea!

1. The Chronicle story is behind a subscription pay wall, but the same article is available for free at the newspaper’s online doppelganger,

2. If the races had been held outside the Bay, out on the Pacific Ocean, where the real rollers start, the AC72s would have been floating high-tech, carbon-fiber scraps before they even reached the starting line.

3. Once I was at the helm of my brother’s 32-foot Pearson sloop and he had gone below to fix lunch. Then we entered the slot. It’s sobering to have an object as big as a mobile home and weighing five tons lie down like that. Yes, it has a big lead-weighted keel that keeps it from rolling right over, but the yowl and crash of crockery from the sandwich-makings below is still frightening.

Sunday, May 11, 2014

The Chemistry of Control

When I joined Applied Biosystems in the spring of 2000, the Human Genome Project Centers and our sister company Celera were just finishing up and publishing the first draft of the human genome, which had been made possible by our own high-volume sequencing machines. One of the surprises from this first draft was that only about ten percent of the human body’s DNA is involved in coding for proteins—and protein-coding had become the offhand definition of the word “gene.”1 The other ninety percent of the genome was a mystery. Many people at the time began calling this ninety percent “junk DNA.” By this they meant leftovers from our species’ long evolution, old genes we no longer used and which were slowly degrading by random mutation into genetic mush.

One day, however, I was walking across campus with one of our chemists who doubted the junk hypothesis. The human body, she said, invests way too much energy in copying the DNA of every cell every time it divides. Why would we waste that energy copying junk? This is obvious, of course, when you remember that the same phosphate bonds used in the backbone of the DNA molecule’s single strands are also used in the adenosine triphosphate molecule, which supplies energy throughout the cell. Phosphorus is a relatively rare element in the body. You don’t want to go sequestering it inside junk strands.

A year or two later, genetic scientists began focusing on short strands of transcribed DNA that were only about twenty to fifty base pairs long, which they dubbed “microRNAs.” These bits of material were first associated with “gene silencing.” Researchers had observed that adding them to the cells of a plant, say, could turn a variety with the genes to produce a red flower into one that produced a white flower—silencing the genes for red pigment.

It wasn’t long after this, about 2004, that Applied Biosystems hosted an in-house lecture by Eric Davidson, a researcher at the California Institute of Technology. He was working with sea urchin embryos and had discovered an intricate dance that occurs in the nucleus of the cells in a blastula—the hollow sphere that forms right after the egg is fertilized and right before the embryonic cells began differentiating into the sea urchin’s various body parts. By sacrificing tens of thousands of sea urchin eggs at spaced intervals following fertilization and studying their nuclear DNA, he was able to trace a pattern of microRNAs being transcribed from the DNA, annealing to other patches of the DNA inside the nucleus, and promoting the transcription of even more microRNAs. This cascading pattern differed among the cells, depending upon where in the blastula they resided and how much time had passed since fertilization. Davidson traced out this cascade of microRNAs, compared it to the cascades found in species that had not shared a common ancestor with sea urchins for many millions of years, and determined that this cascade of differentiation was highly conserved. That is, it’s probably common to all multi-celled life, including our own.2

Eric Davidson’s work suggests that, while ten percent of the genome codes for the messenger RNAs that go out into the cell body and become translated by the ribosomes into proteins—in other words, this is our body’s parts list—the other ninety percent codes for all these tiny microRNAs that stay inside the nucleus and control the timing of a cell’s development and differentiation into various tissues, organs, and body parts. That is, this ninety percent of DNA constitutes our body’s assembly manual.

It was three or four years later, while I was still at Applied Biosystems, that scientists began discussing a new field called “epigenomics.”3 In its most common form, methyl groups (CH3) become attached to one or more C-G sequences in the promoter regions that lie just ahead of protein-coding gene sequences. Where this occurs, the transcription factors that normally bind to the region and force the gene’s transcription into RNA are blocked, and the gene is silenced or suppressed—that is, it cannot be selected for expression and is no longer used by that cell to make proteins.4

Davidson showed how cells became differentiated by selectively promoting the expression of various genes. Liver cells, bone cells, brain cells, tooth-budding cells—all become what they are in the final adult organism by differentially expressing the genes that are available in the complete copy of the genome that’s inside every cell. But how does the body stop that expression? Some proteins are only needed by the cell when the embryo is developing, such as when limbs are budded and grow outward from the embryo’s developing trunk, or when fingers and toes are multiplied across the ends of the sprouting arms and legs. Some proteins are only needed at certain juvenile stages, such as when we grow our first set of baby teeth, or again when we grow our adult teeth at around age seven. Then cells in the jaw begin secreting the bonelike dentine and the hardened mineral called enamel to create a tooth. But after the tooth is formed, they must stop secreting these materials.

If some method of shutting off the genes did not exist, chaos would surely follow. Every cell in the body would try to reproduce every protein the body ever needed, all the time, clogging and rupturing the cell. Or cells might randomly express proteins not associated with their function: brain cells producing liver proteins, liver cells producing brain proteins, skin cells producing patches of enamel, until the body fell apart.

Methylation and the other ways of shutting off a gene appear to be the solution to this problem. Once a cell has achieved its primary function, the chemical addition of methylation shuts down its development and enables only the proteins needed in its adult life. And we know this must be so because a distinct enzyme, methyltransferase, exists to copy the methylation pattern of the adult cell’s DNA whenever the cell divides, so that the daughter cells each inherit the original’s suppression configuration.5

The epigenome is usually spoken of as some kind of environmental accident. A gene’s promoter region is said to become methylated—presumably because of too many methyl groups floating around in the environment—and it unpredictably shuts down the gene. This action of the epigenome is usually cited for the differences found in identical twins as they mature. Although pairs of young twins may be virtually indistinguishable as babies, toddlers, and children, older twins—especially those raised apart, in different environments—may appear quite different, even though both have the same gene set.

I would maintain that this kind of accidental variability is a side effect of the epigenome’s operation. The main show is stopping the promotion of genes after their developmental usefulness has passed and so settling the cell as a single tissue type. The existence and function of methyltransferase tends to suggest this.

The epigenome and the selective methylation of genetic promoter regions is one of the most important parts of cell growth, development, and function. And up until the last ten years, scientists had no notion of its existence. Like microRNAs—those tiny bits of transcribed DNA that never go on to code for proteins—the epigenome was an undiscovered country, a function and the solution to a problem that geneticists had never even considered, until we began probing the genome and the mystery of how the four-base code becomes a microbe, a plant, an animal, or a human being.

Research into the origins and chemical nature of life accelerated a hundredfold after the deciphering of, first, the human genome and, then, the genomes of many other organisms which are used for study or as stand-ins for human biology. Now epigenetic studies, as well as the study of microRNAs and other aspects of the genetic code, are proceeding apace at universities, institutes, and industrial laboratories all over the world. The results of these research efforts are shared almost hourly by electronic and print journals. Molecular biologists are closing in on a complete understanding of the human body, of the cell, and all its systems—not just in genomics or epigenomics but in other areas like proteomics (the study of proteins), metabolomics (the study of metabolic inputs and outputs), biomics (the study of the body’s microbial ecology), and all the other “–omics” yet to come.

It is my belief that in twenty years or so, plus or minus a decade, we will have a pretty good picture of the entire chemical nature of life itself. … And then the fun will begin.

1. That’s according to the old “central dogma” of molecular biology, which stated that the flow of information was always from the nuclear DNA, which was transcribed into messenger RNA, which then migrated out into the cell body, where it was translated into proteins. As this article shows, we’ve learned a lot since then.

2. See also the stories told in The Flowering of Life from August 25, 2013 and “Gene Deserts” and the Future of Medicine from December 5, 2010.

3. “Epigenome” refers to chemical changes to the genome, the DNA inside the cell’s nucleus, and to the arrangement of its strands around protein blocks called histones around which the chromosomes coil. Nothing in the epigenome changes the base-pair sequences of the genome itself, merely the body’s access to them in making proteins. The word derives from the Latin and Greek root epi, meaning “upon,” “on,” or “to.”

4. This is the most common pattern: methylation in the promoter area to suppress a gene. But in some cases methylation within the coding sequence itself has been shown to stop expression. And now researchers are also learning that enhancer regions—patches of DNA not adjacent to a gene itself, like the promoter, and sometimes quite far away from it—can become methylated. When this happens, the gene may be variably suppressed. That is, it’s not just turned on or off, but sometimes on and sometimes off, depending on conditions that are yet to be understood. Suppression of enhancer regions seems to be more often associated with genes involved in cancer. See DNA Methylation in Cancer Goes the Distance via Enhancers.
       Another method of gene regulation is histone modification, which changes the protein blocks around which the DNA strands of a chromosome are wound. In one case, an enzyme adds an acetyl group (CH3CO–) to the histone, changing its positive electrical charge and so reducing its attraction for negatively charged DNA. This loosens the coiled DNA strand, so that it can be more easily transcribed and the genes in that area activated. In other cases case, the arrangement of the chromatin fiber itself—the sequential pieces of DNA as they wrap around nearby histone proteins—is remodeled by one of several chemical changes, such as methylation, acetylation, phosphorylation (addition of a phosphate group, PO43–), ubiquitination (addition of a small regulatory protein found in almost all tissues—that is, “ubiquitously”—of multi-celled organisms), and other chemicals.

5. Methylation and the other chemical methods of epigenomics also seem to be the key to inducing pluripotency—that is, capability of becoming more than one cell type—in creating stem cells from the normal, tissue-typed cells in the body. If you can strip away some or all of the methyls and other groups that lock a cell into functioning as one kind of tissue or another, you can make it more adaptable and available for reprogramming.

Sunday, May 4, 2014

The Zen of the Machine

A recent Facebook posting by a former colleague of mine at Life Technologies reminded me about the approach to industrial controls called Six Sigma and the various programs associated with it. Many of them were developed by the Japanese and bear names in that language. I never trained in Six Sigma techniques, but I worked alongside a black belt in that practice who was trying to improve our manufacturing processes for reagents and other biotech consumables. I also wrote articles about the practice and its components for our employee website, so that everyone would know about our efforts to improve products and efficiency.1

Six Sigma tries to prevent variations in manufacturing or other processes through a five-step mental process: 1. Defining the basic manufacturing steps, 2. Measuring the output of each step, 3. Analyzing data from these measurements, 4. Designing the best approach to each new step or redesigning existing steps to improve or optimize their action in the overall process, and 5. Verifying or controlling the implementation of the steps to achieve the desired results. These steps may adjusted or added as either corrective or preventive actions. An associated process from the Japanese is called “kaizen” and means continuous improvement: dedicating oneself and one’s team to the philosophy that any process can be analyzed and tightened many times over, continuously increasing its accuracy and efficiency. A further related philosophy is “lean manufacturing,” which considers any expenditure of effort that does not directly contribute to the satisfaction of the end customer as wasted effort.

In thinking about these approaches and philosophies again, I suddenly realized that Six Sigma and its components are all about making people think and work precisely and efficiently. It is rather like making them see the world as an engineer would, but without first having to teach them the complete course in engineering. Such a rigorous education starts with basic high-school physics, chemistry, and calculus and proceeds from there through college and graduate-level courses in the various mechanical, civil, electrical, and other disciplines.

My dad was a mechanical engineer,2 and although I never trained in any of his disciplines, I absorbed a lot of the engineering viewpoint from him as I grew up. Engineers see almost everything as a system: push here, pull there, action and reaction, forces in balance or out of balance, processes full of frictions and flows. When you have that vision, you naturally want more smoothness, more precision, less waste, less friction. Elegance is simplicity, least effort, greatest harmony. You are in tune with the Zen of the Machine.

While Zen masters might meditate on the harmonies of nature or the disruptive paradoxes of a koan, an engineer contemplates the balance of forces, or their imbalance, in a process or piece of machinery. He—and sometimes, although less rarely these days, she—can become mesmerized by the thrust of pistons, the reciprocating rise and fall of connecting rods, and the turning of a crankshaft to produce horsepower. In an open-work machine, like a marine triple-condensing steam engine, the engineer not only sees the flying masses of metal but listens to the hiss of the valves and the song of the bearings. He is in tune with its intention, senses its function, and feels any misstep or hesitation as a cry of discord.3 I myself have fallen into a trance while watching a Harris printing press at work: the precision with which the ink rollers, the inked plate, and the printing surface interact to spread ink on paper, coordinated with the lift and flow of each separate sheet from the feed stack to the output. It’s a marvel of speed, simplicity, and precision.

In his novel Stranger in a Strange Land, Robert A. Heinlein introduced the Martian word grok, meaning “to drink,” as a term for a person becoming absorbed with, or fully understanding and participating in, a concept or a process. To grok is to identify oneself with the thing so closely that you become the thing, see the world from the thing’s viewpoint, and can predict the reactions and consequences of the thing as if they would be your own. Engineers grok a machine.

To say that the human body is a vast and intricate chemical machine is just a metaphor. But in the way that an engineer can grok a steam engine, a doctor can grok the body and its functions. Through a trained imagination and intuition based on experience, the doctor puts him- or herself inside the body and its processes, feels them out, analyzes the results of tests from biomarkers like temperature, pulse, and blood pressure; chemical composition of blood, urine, and other fluids; reactions of the skin to pressure and the iris of the eye to light; and other direct observations in order to understand and diagnose possible diseases and bodily conditions. It might one day be possible to create an expert system, an artificial intelligence, that will collect these various readings and test results, refer them to a matrix of symptoms and diseases, and arrive at a statistically likely diagnosis. But I doubt that any machine-mind will be able to sympathetically enter the flow of the body’s functions through a trained imagination and conceive a feeling, an intuition, for what might be going wrong. A machine that could do this would, for all practical purposes, be operating at a human level.

In the same way, it would be only a metaphor to describe as a machine any biological process, such as the energy flows among predators and prey, symbionts and commensals in a rain forest environment, or the interplay of genetic mutations and protein variations in an evolutionary descent, or any physical process, like the equilibrium of pressure and temperature at a stellar core, or the interplay of gravity and inertia at the event horizon of a black hole. But a biologist or physicist can grok these interactions and forces, delving mentally into their complexity, following the flow in the same way an explorer follows a river through the geological deformations of hills and valleys, or a hunter follows a game trail through the forest, participating in the experience as if assuming the identity of the land mass or the game animal.

The human expert—engineer, doctor, biologist, physicist, explorer, hunter—participates in the process at an intuitive level. Knowing techniques like Six Sigma and equations like F=ma or E=mc2 are a shortcut to understanding. But the true knowledge, won from the inside, requires years of study, practice, and experience. One drinks, immerses oneself, and becomes part of the flow.

Whenever a person enters that meditation, he or she becomes attuned with the Zen of the Machine.

1. “Six sigmas” is a reference in statistics to a degree of accuracy or consistency, in which a product run is defect-free or a process produces accurate results 99.999% of the time. Technically, the term represents six standard deviations between the process mean and the nearest specification limit—and if I could explain that to you in English, I’d be an engineer. The initial practice of Six Sigma techniques originated at Motorola in the 1960s, was picked up by Jack Welch at General Electric, and has since become a standard in many industries to reduce process variation, increase process efficiency, and improve overall product quality. People take formal training in these techniques by proposing and completing improvement projects and are awarded with metaphorical green and black belts, much like a martial art.

2. See Son of a Mechanical Engineer from March 31, 2013.

3. In the novel The Sand Pebbles by Richard McKenna, the ship’s engineer is able to diagnose a badly installed crankshaft bearing by its raw sound among all the harmonious clatters, squeals, and whistles of the engine room.