Although scientists were divided over phytic acid’s nutritive value, proponents like Sabin pointed to its role as an antioxidant. With this strength in mind, he sat down at his typewriter and began tapping out an argument for full-fledged animal studies to examine phytic acid’s potential for protecting against heart disease and cancer. He sent his proposal to the Linus Pauling Institute of Science and Medicine in Palo Alto, California, and hoped for good news.

A positive answer arrived quickly. “They said I could do the work if I could fund it,” Sabin recalls. He arrived at the institute in the summer of 1984 for a crash course in laboratory protocols and then got down to work. Each project required armies of Fischer rats, the pink-eyed albinos widely used in biomedical research. Sabin wrote checks totaling more than $100,000 to get his projects off the ground. In one study, the object was to determine whether phytic acid could retard cancer in rodents. The results, published in Nutrition Research in 1988, showed reduced tumor growth rates in animals receiving phytic acid, but not in a control group. In a similar heart study, rodents dosed with phytic acid registered a drop in serum cholesterol of 
32 percent and a decrease in triglycerides of 64 percent. That work, which proved the hypothesis that phytic acid could lower key markers for heart disease, was published in the Journal of Applied Nutrition in 1990.

Last January Sabin coauthored another study, his most gratifying to date, in the Journal of Alzheimer’s Disease. The paper grew out of research at the Oregon Health and Science University, yet another project involving phytic acid. Sabin donated $20,000 to the investigation, which also received substantially larger grants from the United States Department of Veterans Affairs and the National Institutes of Health. The study tested phytic acid in an Alzheimer’s mouse model and in a human cell line. The double-barreled study showed that phytic acid reduced the production of beta-amyloid protein, which is associated with the degenerative brain disease, and pointed to a possible new treatment. (A study currently under way in mice shows that phytic acid might be therapeutic for patients with Parkinson’s disease as well.) “I see myself as a medical pioneer,” Sabin says. “But I recommend that anyone who wants to do this think long and hard about it. You’ll mostly be working alone.”

Hugh Rienhoff’s attic office has provided a peaceful elevation from which to ponder in solitude the mutation that affects his daughter Beatrice—and what it might do to her as she grows older. Although he has achieved a measure of fame as a DIY gene-searching dad (he was one of the stars of a UCLA conference last year on “outlaw” biology), Rienhoff is by no stretch an amateur. Now graying and in his fifties, he studied genetics in the 1980s under the late Victor McKusick, one of the most accomplished medical geneticists of the last half-century. McKusick had once been part of a panel considering whether Abraham Lincoln might have been affected by Marfan syndrome, an uncommon genetic disorder involving the body’s connective tissues.

McKusick hadn’t been convinced, but after Beatrice was born, Rienhoff started wondering whether the rare syndrome could explain the constellation of symptoms affecting his little girl. In particular, his baby’s feet were especially long, a feature often associated with Marfan.

Concerned too that Beatrice never extended her fingers, Rienhoff and his wife took her to the first of many Bay Area specialists when she was 10 days old. It was a seemingly small deficit, yet Rienhoff and Hane worried that it was a sign of something deeper, possibly related to her apparent lack of muscle mass.

The doctor they consulted suggested Beals syndrome, a condition like Marfan but with less serious consequences. In the end, however, Rienhoff became convinced that neither diagnosis fit. Beatrice lacked the heart problems associated with Marfan as well as the constricted knees and elbows seen in Beals.

When Beatrice reached 18 months, her muscle mass still deficient, Rienhoff contacted colleagues at Johns Hopkins, then caught a flight to Baltimore, cradling his daughter in his arms. Certainly, he figured, doctors there would have a clue.

In the medical genetics department at Rienhoff’s alma mater, a colleague introduced him to Bart Loeys, an expert physician and geneticist who found Beatrice had a split uvula, the projection of the soft palate at the back of the throat. Rienhoff was not prepared for the diagnosis Loeys offered. “He said she had Loeys-Dietz syndrome,” Rienhoff says, referring to a genetic condition of the connective tissue named after Loeys and his Hopkins collaborator, pediatrician and geneticist Harry Dietz. A split uvula is a key feature of the condition, which, like Marfan, affects the heart, threatening to kill its carriers through a rupture of the aorta at an average age of 27 years. Marfan and Beals syndromes affect genes that code for fibrillin, a protein that helps form elastic fibers in connective tissue. In contrast, Loeys-Dietz is traced to a genetic defect in the TGF–beta (transforming growth factor–beta) signaling pathway. That pathway affects a vast number of cellular activities, including muscle development and myostatin, the growth factor responsible for muscle size.

Once again, though, Beatrice suffered none of the major deficits that normally come with a Loeys-Dietz diagnosis. The Hopkins specialists had some important insights, but Rienhoff felt they hadn’t nailed it. Back in California, he 
concluded that if he wanted an answer, 
he would have to dig for it himself.

Rienhoff started in 2006 by taking a blood sample from Beatrice and driving south to a nearby university, where a friend with a lab allowed him to centrifuge it, separating the blood’s components. The next step was purchasing a used thermocycler, a machine for amplifying DNA, for a little less than $800. The machine enabled Rienhoff to perform polymerase chain reaction, or PCR, a process that copies a minuscule tidbit of DNA up to a billion times. Ensconced in his basement, he heated Beatrice’s white blood cells in his thermocycler until the double-stranded helix of her DNA unwound, leaving single strands in its place. Primed by enzymes that Rienhoff added, the single-stranded molecules served as templates for building others, which were used to synthesize more single strands, en masse.

By repeating this process for hours, Rienhoff collected more than four dozen microliter ampules of genetic material, enough to send to a lab that sequenced Beatrice’s myostatin receptor genes, where he suspected the problem might lie. When the printout of that section of Beatrice’s DNA came back, Rienhoff found nothing that could explain her condition. So he broadened his search, asking another friend to sample Beatrice’s blood and sequence her entire genome, but even that information seemed to lead nowhere.

Night after night Rienhoff tediously compared his daughter’s DNA sequence with reference sequences stored in several major genomic databases—Ensembl, Heidelberg, and the UCSC Genome Bioinformatics gene bank, among others. Because of the Loeys-Dietz diagnosis, he focused particularly on genes in the TGF–beta signaling pathway, but nothing significant seemed to turn up. Last summer Rienhoff thought he had caught the culprit in a gene called CPNE1, but he quickly discarded the possibility because the mutation turned out to be too common to explain such a rare disorder.

Rienhoff dug deeper and studied harder, obtaining higher-resolution genetic data on Beatrice and comparing it with the genes of his entire family. He worked up from the roots and out to the branches of his small family tree, hoping to find a change in his daughter alone. Then, on an otherwise ordinary day last October, something extraordinary happened. Rienhoff found it: a mutation, a rare genetic miscue, the likely DNA signature of Beatrice’s lack of muscle mass. It was deep in the TGF–beta signaling pathway in a gene involved with uvula development. Why it hinders muscle growth is unclear, but it could interfere with production of myostatin in the womb.

Rienhoff is now rushing to confirm his finding and continuing to collect data in preparation for a paper he hopes to publish in a major scientific journal. He is also trying to puzzle out the mechanism by which the mutation affects his daughter’s muscles and joints. “The mutation Bea has could be unique in her genome,” he says, “but we will be looking for other cases, and I think we’ll find them.”

If do-it-yourself biotech has a global hub, Cambridge, Massachusetts, could be it. Not only is it the birthplace of the movement’s major mouthpiece, DIYbio.org, but it is also the originating site of IGEM, an annual competition for well-trained students trying to build synthetic organisms and biological machines. Some retrofit microorganisms with BioBricks, Lego-like snippets of DNA that perform well-defined genetic functions, producing everything from antibiotics to biofuels. Others genetically alter microbes to communicate with computers or even function as crude computers themselves. Thousands of competitors from around the world have taken part in IGEM since its inception by four MIT scientists in 2004, converging on Cambridge each fall for the IGEM Jamboree.

The city is also home to some of the most elite do-it-yourselfers and their celebrated biohacker spaces—independent labs tucked away in closets and lofts. These citizen scientists explicitly identify with the computer hackers of a generation ago. Like those young electronics wizards working out of garages who ushered in the personal computing boom, today’s young DIYbio enthusiasts are driving an underground tech revolution, this time in the science of life.

One of them is Kay Aull, who built a sophisticated biology workstation in her bedroom closet after graduating from MIT. Smart, bespectacled, curious, Aull is a member of its first class to receive bachelor’s degrees in biological engineering, in 2008. She has been tinkering with genes since childhood, when, like an elfin Mendel, she spent long hours crossbreeding plants in her parents’ garden. Today she has one of the tiniest full-fledged synthetic biology laboratories in the world, making her one of DIYbio’s brightest stars.

As soon as Aull decided to build her lab, she knew she would have to follow government safety protocols for a Biosafety Level 1 facility secure enough to handle well-known agents not implicated in human disease. For Aull that meant “being able to close the door of my closet and have screens on the windows. When fruit flies are used in labs,” she says “screens are very important.” But Aull had no plans to work with flies. Her first project involved genetically engineering E. coli into a new life-form.

Lacking space in her bedroom for a lab bench, she bought a vertical shelving unit and built her workstation straight up. Like Rienhoff, she needed a DNA thermocycler to do PCR. She managed to find one on eBay for $59. Her thermocycler is an antique model from the 1990s, but the machine’s age was not an issue. “You can do useful things with cast-off equipment,” Aull says. Encouraged, she went online for more, finding a $20 thermometer and $50 worth of terrarium parts she could assemble into an incubator to heat samples. Each of those units could have cost her thousands of dollars, had she purchased them new and at cost. Inventive in engineering, Aull built a centrifuge that was totally “home brew.” She rigged it from a plastic food container and a power drill. She went online to buy E. coli, DNA, plasmids (self-
replicating particles used to transport genes into foreign organisms), biochemical compounds, and restriction enzymes (proteins that serve as infinitesimal scissors to clip DNA in specific regions). Her total bill, including hardware store purchases, came to $500.

Her closet now humming with technological activity, Aull was ready to hack into the genome of ordinary intestinal bacteria. Her goal was to genetically modify them into a rudimentary logic system resembling the basic logic underlying computer processes. She titled her project “A Binary Counting System” and tweaked E. coli to respond to and then pass on molecular signals that toggle on and off, something like the computer’s alternating binary system of zeros and ones. Computers do this electronically as they process data. But cells also have electrical properties, and by genetically modifying the behavior of E. coli it is possible, Aull says, to reprogram the bacteria to function as units in a counting system; the difference is that the microbes turn on and off via an organic toggle switch composed of plasmids.

Her system included pulse-generating proteins that could send and receive signals. Aull swapped in a gene that colored the E. coli blue, allowing her to see her counting system in action. When she activated the toggle mechanism, she saw tiny pulses of blue, their pattern mimicking a computer’s logic when it carries a digital “one.”

For Aull, this achievement was just the start. Microbes that can be altered to perform simple processes of logic, she says, should also be capable of advanced operations now common to computers. This is a regular theme among DIYbio enthusiasts. Garage and closet techies point out that DNA functions like pieces of digital code, which makes it ideal for custom-designed organic machines. Last year a team of students in Hong Kong encrypted a mind-
boggling amount of data in a single gram of E. coli—as much data, the students reported, 
as can be stored in 450 state-of-the-art, two-terabyte computer hard drives.

Aull entered her binary counting bacteria into a freewheeling synthetic biology contest hosted by the sci-fi site io9.com, but she did not win first prize. That honor went to Vijaykumar Meli, a graduate student in India. He managed to hack bacteria so they would perform a vital service for young rice plants, helping them utilize nitrogen and grow more efficiently with less fertilizer. Aull did not go without accolades, though. She took second place, and her project was praised by her biohacking colleagues in Cambridge.

For her second DIYbio project, Aull tackled something only slightly less complex: developing a genetic test for the hereditary disorder hemochromatosis. Her father had been recently diagnosed and her paternal grandfather probably also had the condition, which results in the absorption of too much iron, leading to a damaging buildup of the metal in the liver. Hemochromatosis can also affect the joints, heart, pancreas, thyroid, and adrenal glands. It is one of the most common genetic conditions in the United States, and if left untreated, it can cause arthritis, liver cirrhosis, congestive heart failure, and some forms of cancer.

Commercial DNA tests for hemochromatosis have long been available, but Aull’s diagnostic had two specific aims. First, it was personal. She wanted to find out for herself whether she, too, carried the DNA flaw. Symptoms usually do not appear in women until the age of 50, and Aull was just 22. Second, her test would demonstrate that a noteworthy diagnostic could be developed in a makeshift biolab. “It’s not where you’re working, but what you’re working on that’s important,” Aull says, while admitting that she would have preferred a larger station—but “my room is only so big.”

To start, she used a cotton swab to get a sample of cells from her cheek, boiled them in a test tube in her kitchen to free the DNA, then added primers, nucleic acids that mark the part of the sequence. Next Aull put her DNA in the thermocycler for amplification. Finally she ran her genetic material through a gel-electrophoresis machine, a Lucite box containing a semi-porous gel. DNA fragments are placed in the gel and exposed to an electrical field. The DNA migrates in response to the field, with smaller fragments moving most quickly. Her end product looked like a bar code. The distribution of those lines of DNA suggested to Aull that she had the mutation linked to hemochromatosis. Follow-up screening by a professional laboratory confirmed that she is a carrier who can pass on the mutation but is not likely to develop the disease.

Beginners considering home-based biology projects probably would not want to start with complex experiments in synthetic DNA, Aull cautions. “If you start talking about the deep-future benefits, you also bring about the deep-future fears and the Michael Crichton scenarios. I wanted to set a benchmark: I am a professional. I wanted to show what you can do in your closet for $500. It took a month and a half of weekends and whatever supplies I could get my hands on as a private citizen.” After completing her two major closet-based experiments, Aull started working out of a couple of hacker spaces, one in Cambridge and another in nearby Somerville, where she would have more room to spread out.

In 2010 President Obama asked his Commission for the Study of Bioethical Issues to assess the nascent field of synthetic biology. The biotech industry had already taken precautions against the DIY-ers, prohibiting companies from selling deadly pathogens to anyone without serious credentials and a certified lab. But in May 2010, when entrepreneur J. Craig Venter announced the creation of Synthia, a bioengineered life-form capable of replicating itself, the science underlying synthetic biology suddenly seemed worth scrutinizing in depth. Synthia had been created with off-the-shelf parts, mostly purchased online. The commission’s panelists completed their report in December 2010, recommending that hobbyists be watched but neither regulated nor barred. The conclusion unleashed a torrent of protest, including a letter warning of possible inadvertent releases and environmental and public health threats, which was signed by 58 organizations from 22 countries around the world. Even Harvard molecular geneticist George Church got into the act, opining that DIYbio hobbyists should be licensed, much like amateur pilots, fishing enthusiasts, or shortwave radio operators.

DIYbio.org founder Mackenzie Cowell 
agrees that some regulation may be appropriate as experiments become more sophisticated but dismisses the notion of scary life-forms emerging from a hacker space, where most of the hobbyists are just not that skilled. “It’s not easy to take a genetic sequence and turn it into something that is alive,” he says.

Aull echoes that sentiment. “DIYbio is one of the least efficient ways to kill people that I have ever come across,” she says. “If you have the know-how to do something even remotely dangerous in your basement, you are smart enough to get a job at a major lab and pocket something on your way out the door.” DIYbio is taking the mystery out of science, she adds, “but these kinds of rules will scare people off.”

Eckard Wimmer, a Stonybrook University microbiologist who made headlines when he constructed a polio virus from scratch in 2002, argues that it would be virtually impossible to create a pathogen of polio’s magnitude in a makeshift lab. “I have never heard of anyone who set up a lab in an attic or garage and put together a virus. You would need more than a garage; you would need a great garage and a lot of money. And it’s not trivial. You need the oligonucleotides to stitch genes together, and as far as I know, most companies will check the order if the sequence represents that of a dangerous virus.” He estimates that re-creating the polio virus cost about $300,000 and required his expertise as well as a team of graduate students.

At FBI headquarters in Washington, D.C., meanwhile, supervisory special agent Ed You is pursuing a collaborative relationship with the DIYbio community. He and his colleagues in the Weapons of Mass Destruction Directorate's Biological Countermeasures Unit have been developing a rapport with leaders in the DIYbio community for the past few years, encouraging a kind of neighborhood watch. If any suspicious activity ever arose, community members would probably be the first to catch wind of it.

“We are looking for a partnership,” says You, who holds a master’s degree in molecular biology and biochemistry and worked in both cancer and gene therapy research before joining the FBI. “That’s the rationale behind our outreach efforts.” The directorate wants to connect with biohackers, and You says his office does not want to see the community overburdened with regulation. In his view, the freedom of homegrown bio is good for science and science literacy. “There is a lot of innovation and resourcefulness coming out of the DIYbio community,” he says. At the same time, the FBI’s outreach suggests the agency worries about hackers working under the radar. You acknowledges that the tools of biotechnology are getting easier to come by and that “with the emergence of synthetic biology and the availability of equipment, the barrier to do mischief is getting lower and lower.”

Although he is formally charged with policing the DIY-ers, You cannot help but marvel at their skills. He describes the winners of an IGEM competition a few years ago, a team from Slovenia that developed a vaccine against H. pylori, a bacterium that causes stomach ulcers. The pathogen infects more than half the world’s population and also can contribute to stomach cancer. The Slovenian students genetically modified E. coli to produce the vaccine, suggesting a less costly means of manufacture and immunization down the road.

The agent momentarily loses sight of his law enforcement role to voice his astonishment. “These were kids—kids—who didn’t even have bachelor’s degrees.”

Brooklyn 
to Big Bioscience: 
Fuhgeddaboudit
As the president of Genspace, a community laboratory in downtown Brooklyn, New York, Ellen Jorgensen is helping to democratize biology—making it less the purview of academics and Big Pharma and more an enterprise accessible to anyone who wants a hands-on scientific experience. Here on the top floor of an old bank building, lab benches are fashioned from former restaurant countertops, and the doors are open to the public. Want in? Just apply for membership or attend a workshop.

The lab has physically existed only since last December, but Jorgensen and her Genspace cofounders first encountered one another two years ago. All had been searching for like-minded citizen scientists in New York City but had come up empty—at least until they logged on to the DIYbio Google group for amateur biologists. “I wrote, basically saying ‘Let’s meet,’ ” says Jorgensen, an adjunct professor of pathology at New York Medical College. “I set a time and place, and three people showed up. The four of us formed the core group of Genspace.”

In addition to Jorgensen, who holds a doctorate in molecular biology, founding members include science writer Daniel Grushkin; Sung Won Lim, a physics undergraduate; and Russell Durrett, who studies biotechnology and entrepreneurship at the Polytechnic Institute of New York University. They were quickly joined by Oliver Medvedik, an instructor at Harvard, and artist Nurit Bar-Shai. Throughout 2009 and most of last year, the group gathered periodically to pursue rudimentary experiments under Jorgensen’s guidance, first in Grushkin’s living room and then in a hacker collective in the Brooklyn neighborhood of Boerum Hill. All along, though, they longed for their own full-fledged lab.

Their search for dedicated quarters led them to the top floor of the aged Metropolitan Exchange Building on Brooklyn’s bustling Flatbush Avenue. The 500-square-foot space rents for $750 per month, a cost divided among Genspace’s members. The landlord, whom Jorgensen affectionately calls a “pack rat,” used recycled sliding glass doors to cordon off the portion of the floor where the actual laboratory work is done; a biotech firm donated equipment. Now Genspace has a “wet lab,” a work space for experiments involving biological materials and water.

One of Jorgensen’s first acts after starting Genspace was to inform local law enforcement and the FBI that she and her colleagues had created a lab. “We reached out to our local weapons of mass destruction coordinator,” she says of the FBI division tasked with preventing bioterrorism. “We are very friendly with our local FBI representative. He has come to our workshops and he came to our opening. The FBI wishes us well because they know the more educated the public is about what could constitute a biological threat, the easier its job is going to be.”

Genspace qualifies as a Biosafety Level 1 lab, suitable for handling life-forms that present no risk to humans. Federal designations go up to BSL-4, for facilities that handle highly contagious airborne pathogens like smallpox, ebola, or avian flu.

Since its founding, Genspace has grown to 12 members. A few hail from the sciences. The chief technology officer for Bodega Algae in Boston tries out new ideas here as she attempts to create an algae-based biofuel. But most of the Genspace DIY-ers come from the arts, banking, architecture, and other areas far removed from the world of genes and cells. The learning curve can be steep. Jorgensen estimates that it takes an hour to teach new hobbyists how to use a standard laboratory pipette.

Funding for Genspace has been tight, in part because so many of its outreach efforts are done for free. In one project, local school-children were taught to extract DNA from strawberries. Classes typically cost just $300, lab materials included. “I teach a biotech crash course, and Dr. Medvedik teaches synthetic biology,” Jorgensen says.

One common teaching tool at Genspace is BioBricks, preassembled DNA sequences that allow do-it-yourselfers to program organisms the way a software engineer assembles lines of code. Many projects here quickly reach beyond the lab and out into the world. “We are sending a weather balloon into the stratosphere to do microbial sampling,” Jorgensen says. “Hopefully this will result in microbial mapping of the stratosphere and become a blueprint for other groups interested in putting together a community laboratory of their own.”