On the Lysine Contingency

Some of the responses to my post about synthetically expanding the genetic code have highlighted some of the weaknesses in my argument about the safety of using a different genetic code. Namely, that "life finds a way", that we can't really ever know for sure what will happen when we release a synthetic organism in the wild, or how natural selection will act on them. The science fiction scenarios where engineered organisms escape, break out of the designed restrictions on their growth and take over in new and terrifying ways are compelling, frightening, and instructive for thinking about biosafety and synthetic biology, but it is also important to be, dare I say, realistic.


Muldoon: What about the lysine contingency? We could put that into effect!

Dr. Ellie Sattler: What's that?

John Hammond: It is absolutely out of the question.

Ray Arnold: The lysine contingency - it's intended to prevent the spread of the animals is case they ever got off the island. Dr. Wu inserted a gene that makes a single faulty enzyme in protein metabolism. The animals can't manufacture the amino acid lysine. Unless they're continually supplied with lysine by us, they'll slip into a coma and die.

Dr. Ellie Sattler: How could we cut off the lysine?

Ray Arnold: No real trick to it. Just stop running the program, leaving them unattended.

I argued that organisms engineered with alternate genetic codes, who need an external source of unnatural amino acids in order to survive, would not be able to survive in the wild where these unnatural amino acids do not exist, just like the "lysine contingency" in Jurassic Park. Of course, humans can't make their own lysine either, requiring it in our diet in order to survive (this is why it is an essential amino acid), and thank goodness lysine is everywhere in the environment, in the proteins of the plants and animals that we eat. In the case of unnatural amino acids it is possible to design chemicals that don't exist in nature, and molecules that cannot be made enzymatically. While it may be possible that in many many millions of years a biological pathway could evolve to create such an unnatural amino acid, it is vastly more likely that the escaped synthetic bacteria will have died first, its atoms scavenged by other micro-organisms that can't even read its DNA. Moreover, the mutations introduced are small, incremental changes to protein structures that better allow us to understand how proteins work rather than give the cells any vastly new behavior. In many respects, the products of synthetic biology are almost identical to natural cells. We shouldn't bush off concerns over safety with eye-rolling, but we also shouldn't let unrealistic fear take over either. What do you think?

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I think you'd need to be more worried about organisms living in an environment with a scarcity of the required amino acid rather than one with none of the amino acid. I'm thinking of Lenski's work with citrate and E. Coli.

By MiddleO'Nowhere (not verified) on 26 Feb 2010 #permalink

It would not be the first time that the fantasy and creativity lead to exaggerations of possibilities (and dangers) of new scientific developments. Mary Shelley's Frankenstein is basically the 19th century variant of Jurassic Park: electricity and vitalism played the role of synthetic biology, and the monster was the equivalent of ecological rampage.
Any new technology carries risks and potential benefits. Systems like these allow us to reduce risks and should therefore be taken seriously in any GM / synthetic life debate!

In terms of bacteria, scientists have been working with 'safe' versions of bacteria like E. coli for years now, and not once has a rampaging one got loose and got dangerous. Dangers do increase when working with more harmful strains though, but I don't think there's any reason at the moment for the public to have undue hysteria.

Synthetic biology is part of the iGEM project - hundreds of universities simply letting small groups of mostly unsupervised undergrads play around with synthetic genes and I think it's highly unlikely that any of them are going to create a monster.

You could design enzymes that required technetium to function. Make the new organisms totally dependent on the new technetium finger proteins (instead of zinc finger proteins) and they would be unable to survive without sufficient technetium.

Not just technetium - some relatively rare heavy metal that one could engineer into something that must be made in abundance. Like making hemoglobin dependent on some rare heavy metal rather than iron -- without eating food fortified with that metal, those dinosaurs will get anemia.

Or cripple some biosynthesis mechanisms for some substances that they make. Like taurine. We can make our own taurine and dogs can, but cats can't. However, that strategy will likely work well only on herbivorous and omnivorous dinosaurs, not on purely carnivorous ones.

By Loren Petrich (not verified) on 05 Mar 2010 #permalink

Yes, it is fortunate for us that lysine is abundant now. Otherwise some company(ADM for example) might try to corner the market on it or any other essential nutrient that we need to survivie. I guess it might be possible to corner the market on any essential nutrients by making sure that commonly available food products are depleted of it and then selling that nutrient as an essential food supplement. But I'm glad no one has thought about doing such a heinous thing. As long as we are willing to work hard and pay for it, those companies will be willing to keep us supplied with whatever nutrients they think we should have.

By Ninja Cat (not verified) on 05 Jul 2010 #permalink

JFYI: Tranexamic acid (LYSTEDAâ¢, cyklokapron, transamin) is a synthetic derivative of the amino acid lysine.