Interview: David Deamer Explains Synthetic Life
Unpacking the Latest Advance in Biology
Researchers at the J. Craig Venter Institute announced on Jan. 24 the creation of the first synthetic genome: a complete DNA blueprint for the bacteria Mycoplasma genitalium. Assembled from 101 “cassettes,” shorter strings of genetic material made at outside labs, the completed genome represents a major step forward for biological research aimed at creating “synthetic life.” To understand the implication of this advance in more detail, Science Progress spoke with David Deamer, professor of chemistry at the University of California at Santa Cruz, whose research focuses on the processes by which cells put themselves together. Deamer explained the fundamentals of synthetic biology in a previous article: “Synthetic Life: Should We Do It?” This interview has been edited and condensed.
Andrew Plemmons Pratt, Science Progress: Some critics have suggested that the government should slow or heavily regulate research in synthetic biology because of the dual-use dangers: someone with malicious intentions might use it to make pathogens for bioterrorism. Do these organisms actually pose a public safety risk, and do we need to regulate this kind of research?
I don’t see that it poses a significantly greater risk than what we can already do with simpler recombinant methods, or even what occurs naturally.
David Deamer: Ever since recombinant DNA came along, we have had the ability to move potentially dangerous genes from one species of bacteria to another. Previously, the genes were inserted with a plasmid, a small DNA construct, rather than with the whole-genome approach that Venter and his group use. That was possible thirty years ago, so the potential danger has been around that long. For example, someone could insert the botulin toxin gene into E. coli and spray it on a food crop. That would be pretty terrible to have people suddenly coming down with botulism from E. Coli designed to express the gene. By the way, E. coli is a common organism that’s found everywhere, and occasionally a new strain pops up with a toxin that makes people very ill from eating an undercooked hamburger or fresh spinach. The bottom line is that these dangers are already present. We live with risks and we can only go so far in minimizing those risks. As I look toward what might be possible with synthetic biology, I don’t see that it poses a significantly greater risk than what we can already do with simpler recombinant methods, or even what occurs naturally.
SP: Are there constructive uses for synthetic microbes that have not gotten a whole lot of press coverage? Many stories focus on the ability to make bugs that will eat pollutants or produce biofuels. Are there other medical applications that we might not be hearing about?
Deamer: Genentech was the first company to manufacture inexpensive insulin using bacteria, so that’s a good example of an engineered organism making a billion dollar industry possible. And they followed up with other proteins produced by engineered bacteria, including several versions of synthetic growth hormone, Herceptin for breast cancer, TNKase to break up the blood clots that cause heart attacks, and most recently Lucentis to treat macular degeneration that can lead to blindness. So companies are already making money in the medical and pharmaceutical industry by using engineered bacteria.
But the bacteria are engineered by inserting specific genes on a plasmid. The bacteria that actually take up the plasmid and begin to express it are selected for culturing, and suddenly you have a very valuable little organism. Now the problem with using live organisms is that a lot of stuff comes along with not much of the protein that you’re after. Even though they are engineered to over-express the desired proteins, you still end up extracting a relatively small amount of protein from this mass of other proteins that the bacteria need to stay alive and grow, and this can be expensive.
There is another approach to synthetic life. Venter is using a top-down approach in which bits and pieces of existing bacteria are synthesized, then stitched back together and, hopefully, inserted into a second bacterium to make a new species that does what you tell it to do. The other approach is to take those same pieces but put them into an artificial cell. The advantage here is that you can assemble a synthetic version of life from the bottom up and avoid the mass of other stuff that comes along with live organisms. Researchers at a start-up company called ProtoLife, in Venice, Italy, are trying to make this approach work. For instance, it might be possible to incorporate a protein synthesis system in an artificial compartment made of phospholipids with just those genes that code for the protein you want to manufacture. The protein will then be a major product that will require fewer purification steps.
SP: Are there other groups working on this same type of synthetic genome construction they’re doing at the Venter Institute?
I think it is likely that he will get his reconstituted genome to work in living cells this year.
Deamer: No, Venter’s group is the pioneer in top down reassembly of life, but other groups are trying the bottom up approach. Vincent Noireaux and Albert Libchaber at the Rockefeller University broke up E. coli cells, then encapsulated their ribosomes and other enzymes required for protein synthesis in phospholipid vesicles to produce artificial cells. They also included the messenger RNA for green fluorescent protein (GFP), a marker for protein synthesis. After a few hours of incubation in a medium containing amino acids, their cells began to glow green, demonstrating that a lot of GFP was being synthesized inside the vesicles. And Tetsuya Yomo and his colleagues at Osaka University and the University of Tokyo have prepared an encapsulated cascading genetic network that also makes GFP, but the gene is translated all the way from a gene in DNA. I think this approach might finally win the race because it does exactly what you want it to. The system efficiently produces the exact protein you’re after, rather than needing to extract it from a mass of live bacteria.
SP: Venter said that his institute would be disappointed if they did not create an entirely synthetic functional organism in 2008. How fast is this work really moving? When should we expect to see totally synthetic life built on the lab bench?
Deamer: Well, “totally synthetic life”—I think that goes too far. I would call Venter’s approach reconstituted life, rather than synthetic life. But quibbling aside, the results from Venter and his colleagues are truly remarkable, and represent a major advance in biotechnology. I think it is likely that he will get his reconstituted genome to work in living cells this year. The alternative bottom up approach is still years away from a similar success, but there is clear progress being made.
SP: So the next big announcement in synthetic biology would follow construction of an organism that did something functional, like produce large concentrations of specific proteins for a specific use?
Deamer: Yes. At some point we will find a way to assemble a molecular system with the fundamental properties of life: growth, reproduction, evolution, and the use of energy and nutrients from the external environment. We will construct its genome so that it is extremely efficient in producing a desired product. It is even possible that we can get it to evolve toward a desired goal, rather than designing it from scratch.
Life began on the earth perhaps 3.8 billion years ago, and was truly synthetic life in the sense that it self-assembled entirely from non-living components that happened to be available. That is what I would define as synthetic life. When we can discover how life began, how that scaffold of macromolecules came together on the early Earth, it will be an immense step forward in our understanding of life on Earth, a step that goes well beyond engineered and reconstituted life.
SP: So this work will actually teach us something historical about the original emergence of life?
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