Controlling Our Creations Through Nutritional Requirements: Lessons from Science Fiction

Last week a group of over 100 environmental and watchdog organizations released a report proposing increased government regulation of synthetic biology, which they consider "extreme genetic engineering". The report calls for a moratorium on the release and commercial use of synthetic organisms until such regulations are in place. Their position is a that drastic measures are necessary to protect both the public and the environment.

Not surprisingly, not everyone agrees with that assessment. Representatives of the biotechnology industry have pointed out that synthetic biology is part of the ongoing development of genetic engineering technology that is already covered by rules and regulations. And in 2010 a presidential bioethics commission concluded that no new regulations covering the use of synthetic biology were necessary.

One concern expressed by all parties is that "synthetic" organisms could escape into the environment.Where the disagreement lies is whether current technologies are sufficient for containment.

The presidential commission's report suggests that such organisms could be designed to have limited lifespans or to be dependent on nutrients only available in the laboratory. Such biological barriers to the spread of genetically engineered organisms have been part of the earliest recommendations for safe use of recombinant DNA technology.

The groups calling for a moratorium on the development of synthetic organisms claim that such measures are likely not sufficient and further study is required to ensure that such biological barriers work outside the laboratory.

So what is the lesson that can be learned from science fiction? If creatures are unable to synthesize all the compounds necessary for their growth and sustenance - auxotrophs - can indeed be contained if their nutritional requirements are alien enough.

"Look, we're not fools. We understand these are prehistoric animals. [...]They might have no predators in the contemporary world, no checks on their growth. We don't want them to survive in the wild. So I've made them lysine dependent. I inserted a gene that makes a single faulty enzyme in protein metabolism. As a result, the animals cannot manufacture the amino acid lysine. They must ingest it from the outside. Unless they get a rich dietary source of exogenous lysine - supplied by us, in tablet form - they'll go into a coma within twelve hours and expire. These animals are genetically engineered to be unable to survive in the real world. They can only live here in Jurassic Park...."

Take, for example, the dinosaurs in Jurassic Park. As noted in the quoted text, they were designed to only be able to live on a diet with high levels of the amino acid lysine. Since the local plants and animals in the Park wouldn't be able to supply the necessary nutrients, they could only survive on a diet provided by their handlers. That worked, at least for a while, but the setup had a fatal flaw.

Lysine is an amino acid, one of the twenty standard building blocks of protein. If an organism cannot synthesize one or more of those building blocks in its own cells, then it must eat foods that contain those amino acids to survive.

Humans normally require nine such essential amino acids in their diet, including lysine. That means that a balanced human diet must include foods rich in lysine, such as meat or beans. And that also meant that when a few dinosaurs were able to escape their island in Jurassic Park, they were able to survive on lysine-rich crops and meats on the farms managed by the local human population.

A dietary restriction that can be easily filled by eating the local produce is not a great way to contain your engineered critter. A better approach would use a nutritional requirement that cannot be so easily filled by Earthly plants or animals.

You can find that scenario in science fiction as well. In Michael Flynn's novel Eifelheim alien travelers - Krenk - were stranded in 14th century Germany where they eventually begin to starve. One of the alien scientists explains the problem to the local priest:

"There are certain . . . materials – acids is your alchemic word–which are essential for life. Perhaps four score of these acids befall in nature–and we Krenken need one-and-twenty of them to live. Our bodies produce naturally nine, so we must from our food and drink obtain the others. That food which you have shared with us holds eleven of those twelve. One is lacking, and our alchemist found it nowhere in all the foodstuffs he proofed. Without that particular acid, there is one . . . I must call it a 'firstling', as it is the first building block of the body, though I suppose it shoudl wear one of your Greekish terms."
"Proteios,"Dietrich craoked. "Proteioi."
"So. It puzzles me why you use different 'tongues' to speak of different matters. This Greekish for natural philosophy; the Latinish for matters touching your lord-from-the-sky."
Dietrich seized the Krenk by his forearm. The rough spines that ran its length pricked his hand, drawing blood. "That makes nothing!" he cried. "What of thisprotein?"
"Without this acid, the protein cannot be formed, and lacking it, our bodies slowly corrupt."

Earth foods, it seems, don't contain the full range of amino acids essential to the Krenk diet. They try to sustain themselves by extracting the essential nutrients from their dead companions. And even so they died, because their lives depended on a diet with truly alien components.

So the science fictional lesson is to engineer organisms that require amino acids or other nutritional building blocks that found nowhere in nature if you want to make sure that they are truly unable to live outside the confines of a laboratory. And that may eventually become a reality.

Scientists have successfully been able to engineer microorganisms, animal cells, and even nematode worms  that are able to incorporate several different unnatural amino acids into their proteins. And, more recently, bacteria were engineered to incorporate a normally toxic modified nucleic acid base in their DNA. So the research looks promising.

But scientists are not yet able to create animals or plants that we can be reasonably certain would be unable to live in the wild. And life is so adaptable, there may always be the possibility that biological containment will ultimately fail.

So the question remains whether escaping organisms represent a high enough danger to the environment that current research should be more tightly regulated or put on hold. Or do the potential benefits of synthetic biology - novel sources of energy, more effective drugs, improved crops - outweigh the risks? I'm hoping for the latter.

Background reading:

• "The Principals for the Oversight of Synthetic Biology" (2012) (pdf)
• "New Directions: The Ethics of Synthetic Biology and Emerging Technologies", Presidential Commission for the Study of Bioethical Issues (2010)
• Berg P. et al "Summary Statement of the Asilomar Conference on Recombinant DNA Molecules" PNAS 72;1981-1984 (1975) doi:10.1073/pnas.72.6.1981 (pdf)
• Wang, Q; Parrish, AR; Wang, L. "Expanding the Genetic Code for Biological Studies". Chemistry & Biology 16 (3): 323–36. (2009) doi:10.1016/j.chembiol.2009.03.001.
• Young TS and Schultz PG "Beyond the Canonical 20 Amino Acids: Expanding the Genetic Lexicon" J. Biol. Chem. 285: 11039-11044 doi:10.1074/jbc.R109.091306
• Freie Universitaet Berlin. "Bacterium engineered with DNA in which thymine is replaced by synthetic building block." ScienceDaily, 28 Jun. 2011.

Top image: The bacteria Shewanella putrefaciens use chemical signals to coordinate biofilm formation and other community-level behaviors. [Credit: DOE Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory.]