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?

Deamer: Exactly.

Reuters‘s coverage concentrated exclusively on fuel and tied the story to an earlier announcement by General Motors that it had partnered with bioenergy company Coskata, a developer of industrial biotechnologies that employ cellular metabolisms. The Wall Street Journal likewise briefly mentioned producing clean fuels and sequestering carbon.

The BBC focused on the same potential uses of synthetic organisms while incorporating perspectives of scientists and ethicists. Hamilton Smith, a researcher who was part of the Science study, said the research team prefers the word “synthetic” rather than “artificial.” He explained: “With synthetic life, we’re re-designing the cell chromosomes; we’re not creating a whole new artificial life system.” Drew Endy of the Department of Biological Engineering at Massachusetts Institute of Technology, who was not directly involved in the research, said he is optimistic about being able to “routinely design and construct the genomes of any bacteria or single celled eukaryote” within five years. Simon Woods, a bioethicist at the Policy, Ethics and Life Sciences Research Centre at the University of Newcastle, UK, worried that scientists were acting in the complete absence of formal government regulations.

National Human Genome Research Institute director Francis Collins, as reported in Wired Science, called the new study a “methodological tour-de-force,” but cautioned that industrial applications will have to wait years while biologists learn more about what functions specific genes actually perform.

Other news reports raised questions about possible risks of synthetic biological research and even challenged Venter’s intentions.

Rick Weiss in the Washington Post framed the story as a debate between people like Venter who emphasize the benefits of the research, like biofuel production, and critics who emphasize the risks, like biological weapons and unintended environmental damage. In the same article, Harvard Medical School geneticist George Church criticized Venter for conspicuously ignoring or downplaying economic issues, such as the actual financial cost of performing the procedure, which Venter did not disclose.

The New York Times mentioned the same risks as the Post article: human pathogens and ecosystem destruction. In the Times, Jeremy Minshull, chief executive of DNA 2.0, a company that supplied some the nucleic acids used by the research team, was quoted surmising about Venter’s intention: “To some extent, it’s something that was driven by ‘I want to be the first person to do it.’” Also, Jim Thomas, a program manager at the ETC Group, a technology-focused NGO based in Canada, echoed Simon Woods by expressing concern for both the lack of regulation for synthetic biology research and Venter’s broad patent applications covering the Institute’s genetic work. The ETC Group is calling for a moratorium on synthetic biology research so stakeholders can debate its ethical, legal, and social ramifications.

Leo Hickman in Guardian Unlimited invoked Frankenstein, popular science fiction, and the fear of “playing God” to endorse the proposed ban on synthetic biology. The Creation Museum went a step further and claimed that the creation of synthetic life is simply not possible.

Experts on biological weapons, along with those who worry about novel threats to public health from any source, are watching these developments closely. To address concerns that the bacterium could be a pathogen, the lab disabled a gene that enables the bacteria to attach to human cells.

Reports indicate that Venter and colleagues believe the next step—using the DNA strand to govern a functional cell—could be accomplished within the year. When that happens, synthetic biology will have decisively left the arena of science fiction and could be the beginning of industries based on cellular factories.

Biopact.com summarized some of the leading criticisms of the report and JCVI’s approach to the possible hazards of synthetic biology. The ETC group criticized the report’s U.S.-centered approach and argued that it focused too much on the dangers of synthetic organisms being used for bio-terror at the expense of addressing bio-error, i.e.: the unintended mistakes of benign research.

ETC also criticized JCVI’s recommendation that biotech firms vest Institutional Biosafety Committees with the responsibility of evaluating synthetic genomic projects. ETC quotes Edward Hammond, Director of the Sunshine Project, a biotech and bioweapons watchdog, who argues that IBCs, “are a documented disaster… [and] aren’t up to their existing task of overseeing genetic engineering research, much less ready to absorb new synthetic biology and security mandates. ”

On a conceptual level, ETC felt that JCVI did not ask sufficient background questions such as whether synthetic biology is desirable or acceptable, who should control it, what the potential impacts might be, and who has the authority to make those decisions.

ETC released a report in January entitled “Extreme Genetic Engineering” where they call for a broad debate on the social and ethical implications of synthetic biology across all of civil society. They note that bio-terror and bio-safety are not the only issues; synthetic biology policy must also address matters of intellectual property and biodiversity.

In light of these fears, ZDNet offers a perspective-shifting quote from Venter, who spoke at the Web 2.0 summit a few weeks ago: “People get paranoid about bacteria. They are living on the wrong planet. We are in a complete bacterial spectrum.”

This new bacteria could lead to the creation of lifeforms that might play roles in novel medical treatments, such as biofuels generation or the digestion of atmospheric CO2. Or they could lead to lifeforms that could also be used to create deadly biological weapons.

But the AFP quotes Venter’s spokesperson Heather Kowalski as saying, “The Guardian is ahead of themselves on this.” She has also promised that Venter’s Institute will not announce the creation of artificial life until they publish a scientific paper on it. “We have not achieved what some have speculated we have in synthetic life,” she explained. “When we do so there will be a scientific publication and we are likely months away from that.”

Still, in October 2006 Venter did file for a patent on the essential Mycoplasmum laboratorium genome and synthetic “free-living organism.” Whatever the case, science bloggers and academics are already busy examining how Venter’s apparent quest could play out.

Ron Bailey at Reason’s Hit & Run blog has a summation of how artificial life will change the discipline of biology. Nature blogger Philip Ball has a blog post from June about the intellectual property implications of patenting the basic building blocks of synthetic biology, even if they are isolated by researchers. And Arti Rai has an article on possible solutions to this problem in PLoS Biology.

For an international perspective, India’s merinews has a skeptical article from a citizen, which claims that Venter’s proposed creation would not be an artificial life form since it is made from a naturally existing organism with 80 percent of its genes knocked out.

For more on Venter himself, The Guardian has an excerpt from his 400-page autobiography, set to be released on October 18.