Team:LA Biohackers/Practice and Policy

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Practice and Policy

Citizen Science: A Guide to Starting a Do it Yourself (DIY) Synthetic Biology Laboratory

5 Essential Ingredients

Since the late 1970s, engineers and computer programmers have pioneered citizen science. From rudimentary garage and basement based operations, innovators: Jobs, Noise, and Horowitz “hacked” computer networking technology into more applicable, socially relevant forms. These original DIY scientists took technology developed by more established organizations like the US government and CERN and made it more productive and useful than anyone could have imagined. Today a similar DIY movement is taking shape in the biological sciences. The emerging field of Synthetic Biology has inspired a growing contingent of professional and amateur scientists to create neighborhood laboratories in hopes of making meaningful contributions in this exciting area. Synthetic Biology is designing new, or redesigning existing, life forms using a combination of synthetic and natural molecules.1 Due to the rapidly declining cost of genetic sequencing and genome synthesis, the field has exploded over the past decade. Just like garage hacking of computer technology decades earlier, synthetic biology has the same potential for immeasurable social and economic progress. Engineering a ubiquitous life form, like bacteria to cure cancer or manufacture ethanol has its own self-evident miraculous quality that anyone would find compelling. In addition to a life changing idea, there are four other essential ingredients for a successful DIY Synthetic Biology laboratory: people, workspace and equipment, funding, and regulatory compliance.
The Idea

Within the broad field of synthetic biology there are innumerable ideas worthy of further investigation. Initially, most DIY synthetic biology labs have focused on developing genetically engineered biological machines to perform socially beneficial functions. Some organisms, including certain species of bacteria, are ready made for this type of modification because of their ability to readily uptake plasmids (small bits of genetic information) from the environment & recombine it into their natural DNA structure through cell division. This unique property allows synthetic biologists to code plasmids for the production of certain desirable proteins and easily incorporate them into the organism's existing structure. Once incorporated, these plasmids convert the host organism into a functioning bio-machine with the ability to produce the target protein. These target proteins can then be mass produced, combined or otherwise modified using similarly engineered bio-machines. Once the technology is developed at the DIY level, it can be expanded and optimized in more established, strictly regulated commercial and university laboratories to produce remarkable results. Synthetic biology allows for the expansion of conventional uses of bio-machines, like breaking down organic matter at your local water treatment plant, to encompass a multitude of other specific functions. Biochemical processes like molecular sensing to detect toxins/disease, selectively delivering drugs/nutrients, metabolizing oil, or producing ethanol from excess plant matter are just a few of the potential applications.

The People

DIY organizations can utilize people across the entire spectrum of skill and experience. High school students, weekend hobbyists, and retired persons all have a place in DIY science. As a result, these laboratories function as arenas of interpersonal education and community development in addition to their primary scientific initiatives. DIY laboratories are also a useful educational vehicle for giving volunteers access to basic safety training, professional laboratory equipment and reagents, and hands on experience performing lab techniques commonly used in biotechnology. In short, in exchange for their time and attention, volunteers given a new skill set and the opportunity to work on a project with tremendously beneficial social implications. Despite these incentives, finding ample volunteer time is often a challenge. As a result, DIY research projects are most likely to succeed in large metropolitan areas or specialized academic settings (Ann Arbor, MI or Charlottesville, VA for example) where a critical mass of scientifically minded people is often present.

Even if an sufficient number of motivated volunteers can be found, some projects still struggle to become functional. Seattle DIYbio group, for example, had the required critical mass of volunteers and the initial spark to begin research, but eventually folded2 due to a leadership vacuum. Finding a structuring and organizing force is often challenging in the start up sphere where freedom and creativity typically reign supreme. Someone, however, needs to ultimately be responsible for the organization in order for it to sustain its existence. Whether it be a charismatic champion (Robert Carlson, author of Biology is Technology & founder of Biodesic3; Corey Tobin, founder of LA Biohackers4) or a board of directors, some entity needs to be in place to make decisions. This kind of effective leadership ensures lab resources are efficiently allocated towards a common direction. Principled guidance is also instrumental in maintaining a productive working atmosphere. In order to cultivate such an environment, effective managers promote a culture of accountability and encourage supportive, colloquial interactions between staff members.

Workspace and Equipment

Due to the US manufacturing decline over the past several decades obtaining a physical laboratory workspace is not terribly difficult or expensive. Most synthetic biology DIY labs rent raw, warehouse, or industrial space. This is commonplace because most reagent providers will not ship to home addresses due to federal regulations imposed on their operations. Obtaining workspace divorced from residential areas is also a good idea because DIY synthetic biology takes up a significant amount of space. Bacteria must have counter space to grow in a petri dish, plants time to germinate and grow in a greenhouse, and lab bench space is needed to mix reagents and perform extracting and inserting procedures. In addition to the requisite space, synthetic biology also requires substantial analytical equipment. The immense expense associated with instruments like a PCR thermocycler (DNA amplifier), autoclave sterilizer, electrophoretic separator, optical devices, and microscopes were some of the greatest initial barriers to DIY synthetic biology projects. Over the last decade, prices of these machines have fallen dramatically while existing machines have become more rapidly outdated.These effects mean outfitting a lab is much cheaper and less time consuming than in previous years.

Today, obtaining basis biology lab equipment costs a few thousand dollars on eBay and can be assembled in a short time.1 Additionally, online shopping gives DIY synthetic biologists access to a global marketplace of enzyme and chemical reagent suppliers. Alternatively, Corey Tobin's group, LA Biohackers, equipped itself through more conventional methods. The group collected donations to purchase old equipment at auction from local universities. These acquisitions were bolstered by successful dumpster diving ventures which produced two thermal cyclers from behind the University of California, Los Angeles, and DNA sequencer cast aside by the University of California, Santa Cruz. Furthermore, people readily build their own equipment using specification and fabrication instructions posted online. BioCurious a DIY Biology Lab based in Sunnyvale, CA, for example, engineering a bio-printer from scratch.2 The group transformed an old inkjet printer and motors scavenged from CD drives into a printer capable of extruding bacteria into any desirable configuration.

Funding

In addition to being an information Mecca the internet is its own virtual gold mine. Crowd sourced funding organizations like Kickstarter5 and Indiegogo6 have already enabled numerous DIY technology developments. Along these lines, more conventional solicitation methods could improved by coupling local advertising with a web presence. A good website which displays the lab's initiatives and results gives potential donors a better idea of the cause they are supporting. Additionally, the virtual nature of online transactions enables DIY laboratories to communicate with and accept donations from interested parties anywhere in the world.

Monetizing the educational component of a synthetic Biology DIY laboratory is another proven successful funding model. BOSSLAB5, Boston's open source science center, exemplifies this approach by charging a $200 class fee for the safety & techniques training class it administers to potential volunteers.2 The group also offers weekend workshops for unaffiliated members of the community for a fee. Alternatively, the membership model similar to a gym service or professional organization has also proven effective. BUGSS (Baltimore Underground Science Space)7 charges a membership fee of $85 a month to keep its operations running.2

Regulatory Compliance

The lack of DIY specific legislation is sensible in light of the fact amateur scientists lack the resources to be capable of harming to the public or the environment. A 2010 report from the Presidential Commission for the Study of Bioethical Issues summarized the limitations of amateur science by recognizing costs are too high to develop a new organism in a home–based lab1. Even if DIY labs were capable of researching projects with potentially serious complications, the desire to harm society at large is an exceedingly rare characteristic of members of a generally good natured community.

Additionally, independent innovation and inventing are part of the fabric of America. A multitude of Constitutional (Free Speech, Freedom of Expression & Freedom of Association) issues and practical barriers discourage regulating a dispersed industry akin to home woodworking and gardening1. In lieu of aggressive, prohibitive regulation, governments have taken an outreach and education approach. Lawmakers realize harsh policing would push even legitimate, well-intentioned DIY scientists underground. Alternatively, maintaining a dialogue with scientists promotes disclosure and puts the government in the best position to respond just in case a benign research project takes a serious turn. The National Science Advisory Board for Biosecurity (NSABB), a subsidiary of the National Institutes of Health’s Office of Biotechnology Activities is federally administering the issue. In their 2011 report, the board promoted this culture of responsibility over regulation. Either way there are numerous protections already on the books which could potentially ensure the nation’s safety and security. Everyone, however is not convinced communication offers enough protection.

Critics of DIY Synthetic Biology worry about three primary forms of risk: lab safety, environmental safety, and bioterrorism.8 Lab safety is governed internally through the scientific community and insures against accidental harmful exposures of research staff. Uniform codes of laboratory safety and best practices are promulgated by research organizations like the American Chemical Society, ACS. To prevent carelessness and ensure lab efficiency and efficacy, this basic code of laboratory conduct is universally embraced and followed within the scientific community. Additionally, scientific specializations, even relatively new ones like synthetic biology, are built upon a strong ethical foundation that practitioners take very seriously. This ethical code is both an essential component of lab safety and an integral part of accurate data collection and reporting.

This system of ethics and professional standards has been largely successful in policing internal lab activities. As a result, local, state, and federal regulations focus on guarding against bioterrorism and protecting the environment. Local zoning codes stand as the first line of defense against environmental exposure. These local ordinances partition potentially harmful research from residential and high traffic commercial areas by designating zones for special land uses like scientific research. In Los Angeles for example, Title 22 of the Los Angeles County Code9 specifies zone SR-D for scientific research and development. In order to comply with this zoning code, laboratory space is required to maintain permitted use, structure size, required parking, building set back, and maximum lot coverage. Los Angeles County Department of Regional Planning enforces these provisions by monitoring land usage and ensuring land owners comply with the requirements of the code.

In addition to zoning laws, state and federal agencies regulate hazardous waste disposal to prevent DIY laboratories from contaminating their surrounding environment. Federally, hazardous disposal is regulated under the Resource Conservation & Recovery Act10 (RCRA). In California, the California Environmental Protection Agency11 administers this federal statute in addition to provisions of the California health and safety code through is child agency the California Department of Toxic Substances Control (DTSC). DTSC has more than one thousand employees, and is headquartered in Sacramento. The agency also maintains regional offices across the state including two environmental chemistry laboratories, and field offices in Sacramento, Berkeley, Los Angeles, Chatsworth, Cypress, Clovis (Fresno), San Diego and Calexico.

Under the RCRA, disposal without a permit is permitted in most states9. The law, however, augments this freedom by specifying three acceptable avenues of disposal: elementary neutralization, treatment in accumulation containers, and treatment as part of a disposal process or treatability study.9 Elementary neutralization is appropriate for handling chemicals that are hazardous only because they are corrosive (pH < 2; pH > 12.5). Upon neutralization, these substances are safe to put down the drain to any publicly owned water utility as long as the waste complies with their localized standards. Alternatively, small quantity generators (< 100kg a month) may store waste in accumulation containers. These entities have no time limit on how long they may collect waste but are required to dispose of their waste at an approved disposal site once more than 1000kg of waste is accumulated. DIY and other laboratories are also permitted to experiment w/ novel ways to reduce waste without facing legal liability by conducting in house disposal studies. Since products are not considered waste until producer declares them as such, green thinking laboratories are encouraged to develop effective methods for reducing the overall environmental impact of their operations.

Bioterrorism is the most controversial, serious, and difficult to regulate of three aforementioned concerns. Doomsdayers are alarmed about the possibility of a catastrophic biological attack through release of some deadly disease or virus. Recent publications in Nature and Science detailing ways to create new variants of H5N1 influenza that are transmissible between mammals through the air12 exacerbate these fears. Similarly, reports of DIY scientists conducting dangerous experiments, like atom splitting in a microwave or vaccine synthesis in facilities akin to “your mother’s spare bedroom”13 do not inspire much confidence.

In an effort to quell concerns about bioterrorism, the DIY synthetic biology community has outwardly divorced itself from the term “hacker” due to its malevolent public perception. As a brief aside, a “hacker” is actually “someone who enjoys solving problems, taking things apart, building things from scratch and prioritizes technical competence and aptitude over appearances or hubris.” 1214 Most hackers are benevolent creatures worlds part from the stealthy computer thief mainstream media most frequently associates with the term. As a result, the DIY community continues to embrace hacker as part of its identity.

Returning to topic, the Federal Government has also responded to concerns about bioterrorism. In 2011, the NSABB identified dual use material getting into the wrong hands as the most probable source of a bio-terrorist attack. Dual use materials can be used for both constructive and nefarious purposes1 and are ubiquitous in biological research. Everything from influenza strains to drug delivery devices has dual use potential. The board recommended engaging the DIY community on this issue by educating it about the hazards that dual use materials might pose to the nation’s biosecurity. Consensus between the government and the scientific community has established education and communication as the best way to avoid accidental exposure. Other agencies like the FBI, NSA, CIA, and DOD bolster this collaborative atmosphere by aggressively policing and monitoring biochemical weapons. This dual front solution seems like the most reasonable balance between maintaining national security and promoting innovation.

In some ways, concerns about bioterrorism are analogous to copyright owners’ objections to computer copying and distribution technologies. Both DIY critics and copyright owners publicize dooms day scenarios in which new technology used in the wrong way by the wrong people causes vast social and economic damage. So far copyright owners have found other ways to successfully monetize their copyrights as tightening regulation of online copyright infringement is chilled by political unpopularity. New technology is always disruptive, but rarely are such disruptions catastrophic. As more and more labs responsibly enter and thrive in the DIY synthetic biology space, those more fearful and less supportive of this technology may soon have to find a different tune as well.