Synthetic biology on the cusp

Oliver Medvedik on the grassroots future of biohacking and the problems with government overreach.

BioCoder image plants in dish with tweezersWhither thou goest, synthetic biology? First, let’s put aside the dystopian scenarios of nasty modified viruses escaping from the fermentor Junior has jury-rigged in his bedroom lab. Designing virulent microbes is well beyond the expertise and budgets of homegrown biocoders.

“Moreover, it’s extremely difficult to ‘improve’ on the lethality of nature,” says Oliver Medvedik, a visiting assistant professor at The Cooper Union for the Advancement of Science and Art and the assistant director of the Maurice Kanbar Center for Biomedical Engineering. “The pathogens that already exist are more legitimate cause for worry.”

On the other hand, it’s probably too much to expect kitchen counter fermenting vessels stocked with customized microorganisms exuding insulin, biodiesel, and can’t-believe-it-tastes-like-butter spreadable lipids.

“But I can see that kind of technology scaled up to the municipal level,” says Medvedik. “Large fermenter arrays could provide fuels, medicines, fiber — anything carbon-based. Not every city can afford or would want a petroleum refinery to supply its fuel and chemical needs. They’re expensive and dirty. But fermenting vessels are quiet, clean, versatile, and ultimately, cheaper.”

Medvedik is more associated with DIYbio than such industrial-scale applications. But his work at Cooper Union and Genspace, a nonprofit organization he founded to teach molecular biology at the community level, transcends his immediate educational mission. It’s going to take a lot of midwives to deliver the promises of synthetic biology; Medvedik is helping marshal the necessary cadre at the grassroots level.

That involves putting the technology directly in the hands of aspiring biohackers, of course. A current example:

“We’re working on a modular two plasmid system that is bridged by a phage trans-activating factor coupled to a phage promoter on the complementary plasmid,” Medvedik says.

Oliver Medvedik

Oliver Medvedik

He then adds: “It’s really a lot simpler than it sounds. Basically, one genetic component functions as an ‘on switch’ that is flipped on in response to different environmental stimuli — UV light, a toxin, or a food source, to give some examples. The other plasmid functions as the output, which is switched on via the first component. This can be an enzyme, a fluorescent protein, whatever.”

This system allows a student to “mix and match” different inputs and outputs, says Medvedik.

“For example, in response to UV light the cells glow green, or, if you prefer, you can swap out the output and have the cells turn yellow and smell like a banana when exposed to UV light. Or maybe respond to caffeine and glow red. Basically, it functions like a genetic switchboard.”

These are cool microbe tricks in and of themselves, but they could also have manifold practical applications, says Medvedik; biosensors come immediately to mind.

“You might activate a switch that causes cells to glow in the dark in the presence of arsenic,” he says, “and the degree of luminosity could be calibrated to arsenic levels. It could be a quick, cheap, and easy way to assay arsenic in drinking water.”
Such bio-components can be described and archived (as is currently the case at the Registry of Standard Biological Parts) and replicated via the cheap PCR machines that are now widely available. This, in turn, allows biohackers working in home and community labs to forego the tedious work of creating components each time from scratch; they will be able to use “plug-in” units from ever-expanding biocoded community libraries.

“That gives you plasmids that are largely characterized, so you have basic building blocks to conduct further analyses,” says Medvedik. “It just saves a lot of tedium, and allows people to get on with the fun stuff. Otherwise, it would be like taking a computer programming class — except that you’d have to build your own laptop before you could start programming.”

It has been said that DIYbio is at the point where computer science was in 1975, just before the PC revolution. Medvedik supports that view, observing that services and applications are still somewhat limited for synthetic biological systems, but that’s temporary.

“When PCs came out, there were no useful apps,” he says. “Then spreadsheet and word processing programs appeared, and in a very short period of time we had online commerce. I’m not saying you can draw direct correlations with silicon and carbon — you can’t. Microbes are different than computers. But they’re also nanomachines, capable of cranking out a vast array of products. All you have to do is feed them sugar. 3-D printers have nothing on them.”

Of course it’s the very versatility of microbial nanomachines that alarms some regulators.

“Again, microbes can be manipulated to turn out almost anything that contains carbon,” says Medvedik. “That includes pharmaceuticals, biofuels and polymers, but it could also include illicit drugs or explosives. It makes some law enforcement people nervous.”

It’s extremely difficult to “improve” on the lethality of nature.Too, some developments could make citizens nervous about law enforcement and marketers. Characterizing the genomes of tens of millions or maybe hundreds of millions of people could allow detailed correlations to individual genomes. Your physical appearance could be discerned by a printout of nucleotide sequences, along with your predisposition to obesity, violence, or substance abuse. “It could also include epigenetic data [changes to genetic material that accumulate during life],” says Medvedik, “such as if you or an ancestor went through a famine or other traumatic experience.”

You don’t have to be too paranoid to conjure up a “Minority Report” scenario, wherein the cops detain you based on genetic markers for bar-fighting, littering, or loitering. But things don’t have to get that dramatic before they’re intrusive.

“I could imagine a situation where a company obtains genetic samples from a given geographic area to determine regional likes and dislikes,” says Medvedik. “That would be a very powerful marketing tool.”

All of this could make anyone even remotely interested in synthetic biology want to cling fiercely to the DIY ethos. If biology is destiny, the goal is to learn more about — and control — that destiny. Or at least, not give it up blithely to McDonald’s or Homeland Security.

Medvedik, for one, isn’t worried about the thought police knocking on his door at midnight. But he is concerned about agency overreach — or at least, agency cluelessness. He cites the FDA’s decision to restrict 23andMe as an example of the kind of ham-handed policy making that needlessly hobbles accessible biotech.

Specifically, the FDA barred 23andMe from conducting reasonably-priced genomic SNP analyses for disposition to certain diseases and allergies. The tests were cheap, accurate, and popular, but the agency stated that some people who received unpleasant or unexpected results might injure themselves, or that physicians who misinterpreted the tests could perform unneeded or dangerous procedures. The ruling didn’t stop people from obtaining personal genomic information, of course, but it essentially required them to go through a sanctioned lab or hospital, with a concomitant spike in fees. 23andMe charged around a hundred bucks for the procedure; FDA-approved facilities may charge considerably more.

“I found that ruling ludicrous,” says Medvedik. “It wasn’t based on any sound rationale, and it needlessly restricts options for individual citizens.”

We can no doubt expect other puzzling decisions from the FDA as DIYbio gains momentum. But regulatory nit-picking won’t scotch the sector or discourage its growing ranks of practitioners, Medvedik says.

“Economics is the ultimate determining force for this, as it is for all technologies,” he says. “You can reasonably compare biocoding today to software research 25 or 30 years ago. ‘Wetware’ is different in its techniques and applications, of course — but I’m expecting similar impacts.”

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