What follows is a modified excerpt from Bunch of Amateurs: A Search for the American Character, out now.
On Fillmore Street in San Francisco, in that stretch that’s still mostly boho coffee joints with a head shop and an art gallery or two, I met Meredith Patterson. She didn’t exactly stand out among the denizens of the Lower Haight. In her 30s and pushing 5ʼ10ʼʼ in her combat boots, she had on a tough-looking leather jacket and cat’s-eye glasses that finished off her look with a nice hint of 1950s girl nerd. Patterson is classic self-invented obsessive. A computer programmer and language theorist by day, she’s somebody who’s loved anything do-it-yourself since she was a little girl, working beside her dad fixing the family car or rewiring the house. Not long ago, she found herself in the grip of a new enthusiasm: homebrew bioengineering.
America has always been a place of ambitious amateurs. And the latest in the long line of them are self-taught biologists like Patterson. These synthetic biologists, so called because they try to engineer new forms of life, are trying to do for the chromosome what Steve Jobs did for the computer. In the bigger cities, they have started to form “synbio” clubs, the same way radio enthusiasts did in the early 1900s or computer programmers did in the 1970s or robotics amateurs did in the ’00s. A few of those clubs have even opened brick-and-mortar labs where members can practice tweaking various genomes as a group.
Ask most people about the amateur spirit, and they’ll say, well, that was then. It’s almost common wisdom that the golden age of the self-invented upstart ended sometime about a generation ago. But the fact is, we’ve been hearing this line for at least a century, and it’s always wrong. The time of outsiders and amateurs and cranks is not a bygone era, but rather a cycle that comes around just when you think it’s over. This cycle is an essential part of America’s history—arguably the country’s genesis story.
Ever since Ben Franklin left Boston for Philadelphia, and continuing right up through when Mark Zuckerberg abandoned Harvard Square for Palo Alto, there has been this sense that a certain kind of creativity happens on the fly, often on the lam, after beginning in one of those proving grounds of American ingenuity: the dorm room, the weekend hobby club, the garage. For Patterson, that proving ground happens to be a tabletop lab situated in the breakfast nook just outside the kitchen of her apartment. She had invited me out to check out her rig—a collection of mostly repurposed and (fairly) common household devices that she uses to fiddle around with the building blocks of life—and to help her with the next step of her latest project. She wanted to insert a plasmid of jellyfish DNA into a bacterium so that later she might cultivate a modified form of yogurt, one that tasted great but also glowed in the dark.
Before we got to any serious bioengineering, Patterson said we’d have to visit one of her go-to synbio supply stores: Trader Joe’s, which sold plain yogurt containing the bacteria we’d need, Lactobacillus acidophilus. During our walk, I noticed a tattoo on her ankle. She pulled her pants up above her boot. “This one’s not done yet,” she said. It was a steampunk biomechanical x-ray of her lower tibia and fibula, a series of mechanical cogs, robotic pistons and bicycle chains. “It’s kind of a joke, because I have these weird mutant ankles,” she explained. “I have this thing called an accessory navicular bone.” Patterson has a number of tattoos, all of which relate in some way to her sense of herself as an off-the-grid scientist. On one arm she has a rose window and sword from her favorite anime serial, “Revolutionary Girl Utena.” Down the bicep is the iconic image of Atlas holding up the heavens, most familiar as the paperback cover art of Ayn Rand’s novel Atlas Shrugged. And keeping the burdened Titan company is the Page of Pentacles, the tarot-card figure who, she says, signifies the “eternal student.”
The crucial ingredient for Patterson’s “Glo-gurt” is a gene known as green fluorescent protein, or GFP. Originally found in jellyfish and a species of polyp called the sea pansy, GFP allows these creatures to bioluminesce when disturbed. In 2000, an artist named Eduardo Kac created “GFP Bunny,” a genetically altered albino hare that glowed bright green in the presence of ultraviolet light. Since then, the gene and its colorful relatives have been domesticated—very domesticated. Pet stores now sell GFP-altered zebra fish as GloFish ($7.99 a piece, $6.99 if you buy three—now available in Starfire Red, Electric Green, Sunburst Orange, Cosmic Blue and Galactic Purple). Three scientists who studied the gene won a Nobel Prize in 2008, and GFP is more seriously used as a marker to track all kinds of changes and effects at the genetic level. Patterson’s aim with Glo-gurt is not quite so high. She thought it would be cool, she told me, to go to a rave with glow sticks she could eat.
When we arrived back at her apartment, Patterson showed me a sample of the glow-in-the-dark plasmid that she had obtained; she kept it sealed in a bag in her freezer next to some frozen chicken wings and a box of Eggos. She had ordered it from the Carolina Biological Supply Company in North Carolina the same way someone else might order a sweater. Her basic plan was to grow a batch of the yogurt bacteria, introduce the GFP gene into the cells, and then use that modified bacteria to make yogurt again. To do so, we would need to improvise an electroporation device that could help usher the glow-in-the-dark gene into the Lactobacillus.
Electroporation is a common genetic procedure that involves exposing cells to a 2,500-volt, pulsed electrical field. In bacteria, the charge changes the permeability of the cell membrane, making it possible to pass the GFP plasmid through it. “Essentially,” Patterson said, “we’re going to taser them.”
Patterson does all of her work, high-voltage and otherwise, in her apartment, a place shared by a changing cast of roommates. It’s all very familiar—a friendly wreck of used furniture, piles of books and boxes, coats, beanbag chairs, and a potted glade of houseplants clustered desperately at the windows. Scattered on the table that serves as her lab is her improvised genetic gear. Patterson long ago solved the problem of obtaining lab-quality pipettes (because they can run around $200) by purchasing, from an online pharmacy, cheap disposable insulin needles that can measure down to the microliter. She reengineered a nine-inch floppy-drive motor from a computer she bought used for $5 to serve as a centrifuge for spinning vials of liquid containing bacteria. Her autoclave is a pressure cooker, and her incubator is a tailgater’s fridge from Sharper Image that can cool or warm. “Someone was getting rid of one of these for $30,” she said. “Mine now.”
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“I started with dried ground-up peas,” she said, “and I put those in a saline buffer.” She quickly translates for me: “regular old saltwater.” Then, she continued, “you shake it up a little bit and add some shampoo, which contains a detergent, which breaks apart the fatty cell wall. To that you add meat tenderizer, which contains papain, which is a protease that breaks down the nucleus.” So the shampoo gets us inside the cell, and the meat tenderizer gets us inside the nucleus where the DNA resides and releases it from the proteins that accompany it. Then you let it sit for a while until it turns into what Patterson calls a “slurry” of “digested goo.” This gunk is put into a salad spinner to separate the solids from the liquids. After pouring off the liquid, you add rubbing alcohol. DNA likes alcohol about as much as oil likes water, so it tends to bunch together to separate itself from the rest of the liquid. Sticky strings begin to form. This is pure, extracted DNA, ready for bioengineering.
Part of the freedom and pleasure that amateurs feel while doing their research derives from the fact that their workspaces usually contain no black boxes. Among Patterson’s lab equipment, there’s nothing store-bought whose processes she doesn’t understand. She’s built and rebuilt everything. When I asked, for instance, about the broth in the tubes—that is, the food that would feed our bacteria as they grew overnight—she said, “Normally when you are growing lacto, you use MRS broth. MRS stands for a couple of guys [three scientists: J.D. DeMan, M. Rogosa and M.E. Sharpe]. But that stuff is expensive,” so she made her own. “What I did was manage to track down an article Paul Elliker wrote in the Journal of Dairy Science.” The article was written in 1956. Talk about going back to basics. “I could have solved the problem by throwing money at it,” she said, “but what I’ve generally found is that old articles tend to have the cheapest but still effective way of going about anything.”
This kind of improvisational approach to research and experimentation lends a certain levity of purpose to any amateur endeavor. When things went perfectly, Patterson’s work gave way to moments of intense and obscure beauty. To add distilled water to our vials of bacteria, she cleaned her hands and carefully removed a single sterilized corked tube. With one elegant motion, she drew up some water with a syringe; with the other she one-handedly popped the cork. She looked sideways at the open tube so that her slight breathing wouldn’t contaminate her work. Then she pipetted just enough in, recorking the tube once the process was finished. Twenty times, perfectly, like a tiny private ballet.
In less-than-perfect moments, when something went wrong, Patterson just stepped back, thought about things for a while, and dove back in. She doesn’t get frustrated easily, a trait she ascribes to her parents’ constant encouragement when she was a kid. But it’s also the case that amateurs simply have a different relationship to frustration, and even failure. At an office, failure and success are binary modes, down and up (and often linked directly to pay). Public failure, too, can be discouraging and embarrassing. In the worst cases, it can get you marginalized or fired.
But if the entire rig on your kitchen table is your creation, hatched from street cast-offs and dairy farmers’ lessons dating from the Eisenhower administration, then failure is just a glitch in the system you’ve built. Putting one’s hands in there, e-mailing other kindred scientists for advice, checking out colleagues on a common wiki, fixing what’s wrong, and moving one’s investigations forward are simply short-term variations of success.
On one of the many long nights that Patterson and I would spend together piecing together her system, we had a brief discussion of flow, the notion developed by Mihaly Csikszentmihalyi (pronounced “me-high chick-sent-me-high”—perhaps the most fun name to say, ever). This Hungarian-American psychologist holds that there is a very satisfying state of mind that occurs when one is totally absorbed by an action. It may sound as if this is some rare state of being, like a kind of secular nirvana, but it’s not. We all experience flow. It doesn’t require special meditative skills, only the love of doing something so much so that one gets lost in the labor. One might experience flow while painting a complex landscape or painting the front porch. Or chaperoning growing bacteria.
Its commonness is why we have so many phrases for this pleasant state of existence: being in the zone, losing ourselves in our work, being on the ball, in the groove. “Oh,” Patterson said, suddenly recognizing what I was talking about. “You mean codespace,” as programmers call it, “where the world just sort of disappears.” She knew it well. “That’s a good head space to try new things, especially if there’s something I think should work. So I try it and see if it does: ‘That didn’t quite work the way it was supposed to. Let’s check a few settings and see if this works.’ Sweet.”
The word “amateur” comes from the Latin word for “love,” which, when encouraged with money, becomes a profession. An amateur’s love is typically free of direct pay, such that while money might ultimately be involved, it’s not the day-to-day incentive. It’s a kind of love that hasn’t very well spoken its name. It’s neither eros nor agape, nothing involving filial bonding or generous charity. It may, in fact, be the least described love—a peculiar version of self-love, charged with the hope of finding that new thing just over the horizon.
In the months before my visit, Patterson had already been working to coax the glow-in-the-dark gene into her yogurt bacterium. She had tried to use the heat-shock method to drive it into the cells. “When bacteria get to a certain temperature, they start producing these heat-shock proteins, which also open up some holes,” she explained. And in that brief moment, the new genes sloshing around nearby can slip in. “In my head, it’s like: Holy shit, it’s hot in here, let’s open some windows.”
But heat shock hadn’t worked, so she had moved on to electroporation. When she first described it to me, I pictured the bacterium ballooning like a cartoon character with its finger in a socket—its flagella sticking out like hair and its microscopic pores bulging open like wide eye sockets—such that the GFP plasmid could rush in. For us, the question was how to administer these shocks to our bacteria. Patterson had configured the timing mechanism on an Arduino, an easily customized computer board. It would handle the literally split-second timing. All we needed now was 2,500 volts (the precise amount, I recently learned, once used to carry out the missions of famous 20th-century electric chairs, the insanely powerful ones with nicknames like Gruesome Gertie, Yellow Mama, Old Smokey and Sizzlin’ Sally).
To accomplish this, Patterson got hold of a transformer from an old neon sign. It takes in 12 volts and ramps it up to 3,000 volts, so it would seem to make sense that if we fed the transformer 10 volts, it would kick out 2,500. But Patterson’s voltmeter kept telling us something was slightly off here. We tried different connections and different transistors, and then we needed another part, and then there was a road trip to Fry’s, a kind of Home Depot for everything electronic, and then, was that the sun setting already?
We must have tested the input and outputs of the Arduino board 50 times. These tests amounted to us sitting on the wooden floor and carefully holding the (insulated) lines in place as we blasted away with potentially lethal streams of electricity. One day we spent 10 hours trying to configure one wiring setup after another. Hours of this fiddling passed, but it was as if no time had passed at all.
Meanwhile, the tiny amount of yogurt Lactobacillus we had placed in the incubator was growing away. But there was a flaw in that system, too. The incubator’s two-bit thermostat had busted. There was no longer a way to automatically regulate the heat inside, so Patterson would carefully monitor the temperature herself. She would turn the incubator off after a while and wait for it to cool down a few degrees before turning it back on. This way, she kept it from overcooking our bugs. We were now several days into constant experimentation, and we spent a lot of time together, staring at transistors, tending the incubator as if it were an old wood stove, sterilizing equipment, waiting for very slow things to happen. Patterson is a smoker, and in moments precisely like these, I allow myself a temporary relapse into a habit I enjoyed ages ago. So we’d take cigarette breaks, standing by her window.
Well into one evening, as we sat in our own groove, occupied by long stretches of work, suddenly there appeared a solution to the thermostat problem, like a bubble slowly popping at the surface of our flow. “What about one of those light timers you can get to fool burglars?” I asked. Patterson instantly got it. Yes. A light timer. We could program it to turn the incubator off and on. Then we could leave the apartment building for more than an hour. We raced downstairs and drove south to a late-night Home Depot in San Jose. The new models were perfect for what we were doing, and only a few bucks. Controls allowed you to customize the on/off cycle however you wanted—on for five minutes, off for 30, for instance.
Problem solved. By the time we got the timer set up, dawn was on the way. We would eventually have to return to our transistor flow, but for now, there was this intense pleasure. We both stepped back, looking at a light timer plugged into a surge protector with, absurdly, an exhilarating amount of self-satisfaction. Time to light up.
Endy predicts a time (soon) when someone will rewrite the DNA of an acorn to include George Jetson–like instructions that direct the future oak to assemble into a bookshelf. He also says that the leading synthetic biologists need to aid and abet amateurs like Patterson if this emerging science is going to rapidly advance. In 2003, he helped found iGem, the International Genetic Engineered Machine competition. Held at the Massachusetts Institute of Technology every year, iGem invites teams of college and high-school students and amateurs from all over the world to strut their bioengineering stuff and compete for a Lego-shaped BioBrick Trophy that comes complete with its own suitcase.
Endy is also working to standardize the parts that synbio researchers use, which could help to jump-start the amateur cycle. He loves to tell the story of William Sellers, an engineer who wrote an important paper around the time the Civil War was winding up. Sellers suggested that American engineers adopt a standard for all nuts and bolts. He proposed a formula that would create a standard pitch of screw thread conformed to the bolt’s diameter. In case you’re interested:
P = 0.24 √D + 0.625 – 0.175
Today Americans still screw, more or less, thanks to the Sellers system. The key feature of standardization, Endy says, was that every Sellers nut, when screwed into a Sellers bolt, behaved the same way. “When you pull on the nut,” Endy says, “it stays put. It doesn’t come flying off the bolt.” In other words, it does what it is supposed to do, a feature that Endy and other engineers call “reliable, functional composition.”
This reliability is one of those structural changes to early American manufacturing that drove its rapid progress in the 19th century. Endy thinks a similar reliability is possible for DNA research. For instance, MIT maintains a Registry of Standard Biological Parts, a one-stop shop for DNA standards. Geneticists anywhere can order various plasmids or other strings of DNA known to cause a catalog’s worth of biological features. And it works the other way, too. You can register a new DNA strand with a novel functionality—for example, a “biosynthetic device” that changes the nasty manure-like odor of growing lab bacteria into the pleasant aroma of a banana. This bio-widget, or “banana odor biosynthetic system,” has been standardized and registered, available in the catalog as part BBa_J45900. The idea is that the registry will become a kind of RadioShack for DNA parts, so that DIY folks and academics alike will start playing and creating, advancing the science quickly. The number of standard biological parts doubles every year, and, Endy has said, “the same thing is happening with the number of teenagers who would like to do genetic engineering; it’s doubling every year.” Five teams competed at iGem in 2004; 165 competed last year.
If you listen to Endy—with his talk of iGem and the parts-registry and his “gene bashing” lingo—you’d begin to think he could single-handedly guide synbio into the mainstream. But he is just one of a kind of secular trinity of academic leaders birthing this new field. The others are Jay Keasling of the University of California at Berkeley and George Church of Harvard University.
A biochemical engineer, Keasling does not talk about making synbio cool or bashing genes. Instead he focuses on making synthetic biology do very specific things. For instance, he’d like to cure malaria. The treatment for that disease involves a substance called artemisinin, which derives from the slow-growing sweet wormwood plant. Keasling developed a bacteria that quickly pumps out artemisinin, and in 2010, he announced that he was beginning production of the drug. If all goes well, he’ll commercialize it this year.
Perhaps the most practical of the synbio leaders is George Church. He is a towering 6ʼ5ʼʼ, with a lumberjack’s beard, a commanding presence, and a seductively hyperactive and chatty mind, not to mention a brilliant scientific eccentricity: He suffers from narcolepsy. So the great man can be speaking to you and, boom, he blinks out for five seconds and then boots right back up. It’s the equivalent of Einstein’s hair, notice given that you are in the presence of wild and ranging genius.
Church talks up synbio’s economic potential, specifically fuels. He wants to engineer something that makes a lot of money and gets positive attention. The obstacle to turning piles of organic material such as switchgrass into easy biofuels is that the sugars in the plant are bound up by cellulose. To get it out, the cellulose has to be extracted. What if you could design a bacterium that transforms cellulose into usable sugars? That would have a worldwide market almost immediately. “Biofuels are the low-hanging fruit of synthetic biology,” Church told me in his office one afternoon. Pharmaceutical cures might earn good press, but the demand for them is small relative to the demand for fuels, “where the markets are huge.”
Everyone involved in synthetic biology recognizes that if robotics, say, is a weekend amateur pursuit whose clubs are in their mature phase, then synbio is in utero. So they worry constantly about public relations and imagery. They know that some story will break the field into the pop culture—a brilliant discovery, a cool movie, but also, possibly, a tabloid freak-out that calls down Homeland Security.
“NASA had the moon shot,” Church said, as he pondered how the public comes to understand the complexities of any new scientific discipline. “There was the homebrew computer club. Even robotics had a cinematic push.” He recognizes that Hollywood prefers to deal in a “dystopic version of biology.” He considered the ill effects of Jurassic Park, Gattaca or I Am Legend. “There is one isolated nondystopic movie,” Church said: Lorenzo’s Oil, the story of parents who will stop at nothing to find a cure for their child’s rare affliction. The movie was not exactly a hit. “You can see how hard it is for Hollywood to make a blockbuster out of lipid chemistry,” he said.
“Something lights up—well, hello.”
“That’s a 15k resistor. Again, didn’t work.”
“I’m wondering if I’ve misunderstood which pin is which. If I did, that would be stupid.”
“Things that do not make sense include . . .”
“Where the hell are you coming from?”
“Plug us in.”
“Again, we’re not getting squat.”
We both stare at the tiny board one more time.
“We want red to go here and black to go here, and somebody needs to touch this wire to the base. So if you want to just hold these, I can plug it in. First, make sure you are not touching the lead. Good.”
A vicious snapping sound shatters the concentrated silence of the room. Some lights go out, throughout the building. Patterson pulls the plug. “Time for a cigarette break,” she says.
With electroporation out, Patterson explains, we’ll have to resort to the next best way to get a plasmid into a bacterium: an ultrasound bath. This involves the same technology that allows us to peer inside a womb and look at a fetus. “Ultrasound is used in labs normally for lysing cells, for ripping them open and getting out the DNA,” she explains. “And it is also used for sterilization. A really high amplitude of ultrasound can be used to kill off bacteria. When the frequency is in the 40-kilohertz range, you can actually use it for transsection, one of the terms for introducing plasmids into things.” (Having failed at frying the bacteria and then shocking them, we now hoped to yell at them.) The question is, how do you get an ultrasound machine? “This thing ran 40 bucks,” she says—this thing being a “jewelry cleaner operating at 40 kilohertz.” The machine is small and compact, easy to handle. Dozens of them are offered for sale on eBay on any given day.
Even as she presses forward in search of Glo-gurt, though, Patterson tells me her interests have recently shifted to something more functional. She’s started a conversation with an Internet pal on the DIYbio listserve about synthesizing a bacterium that would react in the presence of melamine. Recall that in 2008, this substance began showing up in Chinese imports of milk products, eggs, baby food and pet food and led to numerous deaths of people and animals. Melamine-contaminated milk alone sickened some 50,000 people. The reports caused a food scare and focused attention on the fact that American agencies were not testing for the presence of these lethal chemicals. Patterson and her online research partner call their creation the Melaminometer.
One approach they are considering is to create bacteria that, in the presence of melamine, would break down the substance into ammonia and water. Not all that tasty, but it beats getting sick. Maybe they can make the chemical taste like bananas when they get around to Melaminometer 2.0. Like so many amateurs, Patterson sees in the possibilities of all these plasmids what William Sellers saw in a dependable, well-threaded screw—a better future.
As Patterson and her peers start trying out their ideas and experiments, a public debate will eventually arise: Just what are we permitting here? And the usual anxieties will erupt. Are we unleashing a generation of Dr. Frankensteins? How soon before we hear about the possibility of weaponized flu in some kid’s suburban den? All the more reason, the DIY supporters say, to encourage the local synbio clubs. Members are struggling right now to define the appropriate standards, general ethics and good lab protocol. Of course, if history is any teacher, then an ambitious prosecutor might well swoop into these clubs. On the other hand, if Endy, Keasling and Church can stage-manage synbio’s image well enough, the clubs could flourish and foster novel approaches to genomics. There are always natural concerns when any new set of tools is handed to the next generation. But the way this anxiety gets addressed—as the next 4H club or as the next national security threat—will reveal a lot about how we currently view American innovation.
The elder statesman of theoretical physics and a big synbio fan, Freeman Dyson, wrote an influential essay in the New York Review of Books in 2007 in which he called for precisely the kind of synthetic biology research we are now beginning to see. “Every orchid or rose or lizard or snake is the work of a dedicated and skilled breeder,” Dyson wrote. “There are thousands of people, amateurs and professionals, who devote their lives to this business. Now imagine what will happen when the tools of genetic engineering become accessible to these people.
“There will be do-it-yourself kits for gardeners,” Dyson continued, “who will use genetic engineering to breed new varieties of roses and orchids. Also kits for lovers of pigeons and parrots and lizards and snakes to breed new varieties of pets. Breeders of dogs and cats will have their kits too. Domesticated biotechnology, once it gets into the hands of housewives and children, will give us an explosion of diversity of new living creatures, rather than the monoculture crops that the big corporations prefer. New lineages will proliferate to replace those that monoculture farming and deforestation have destroyed. Designing genomes will be a personal thing, a new art form as creative as painting or sculpture.”
It’s not a brave new world that Dyson envisions, but rather the same old mundane one, just gussied up with the middlebrow creations of housewives and teens. And the exquisite dreams of a Meredith Patterson. Maybe that is where we’re headed, but make no mistake about how we will get there. Dyson and his co-enthusiasts want to put the toolbox for life itself into the hands of an amateur designer. Presumably, an intelligent one.
Adapted from Bunch of Amateurs, published by Crown Publishers, a division of Random House, Inc.
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