Synthetic Biology Breakthrough: Your Questions Answered

21 May 2010 5:36 pm

Yesterday, researchers led by J. Craig Venter reported that they had built a genome from scratch and used it to control a cell. We asked if you had any questions about the discovery—which raises important scientific and ethical issues—and you responded in force. Below is a selection of some of our favorites (edited for length and clarity), compiled from our Web site, e-mail, and Facebook. Science reporter Elizabeth Pennisi, who wrote a news story about the discovery, and Mark Bedau, a philosopher and scientist at Reed College in Portland,Oregon, and editor of the scientific journal Artificial Life, offer their answers and opinions.

Q: Does the advance really represent the creation of new life?

M.B.: There are a couple of reasons why this achievement should not be called the creation of “new” life. First, the form of life that was created was not new. What was essentially done was the re-creation of an existing bacterial form of life, except that it was given a prosthetic genome (synthesized in the laboratory), and except that the genome was put into the cytoplasm of a slightly different species.

The methods used here could relatively easily be used to produce something that would be “new” in the sense of never having existed before. This would be done by introducing enough new genes (or removing enough existing genes). This is technically feasible today, and eventually taking advantage of this potential is the primary motivation for creating “synthetic cells” in the first place. However, it should be emphasized that it will probably be very difficult to make very new forms of life. This is because even the simplest form of life is very complex, so it is very difficult to predict what will happen when you substantially change their genomes.

Now, even if the synthetic genome was substantially different from any existing form of life, one might still object to calling this the creation of new life, because the synthetic cell was made by modifying an existing form of life. Almost all of the material in the synthetic cell comes from a previously existing form of life; only the genome is synthesized. In this respect, one might say that a synthetic cell qualifies as “new” life only if the whole cell is synthesized. A handful of research teams around the globe are working on trying to create fully synthetic cells (sometimes called “protocells") using materials obtained solely from a chemical supply company. Even a living protocell would still not qualify as creation from nothing, of course, since it would be created from pre-existing materials.

Q: Can this technology help us increase human life span? Can it help cure diseases like diabetes and cancer?

E.P.: Although this achievement was a milestone for synthetic genomics, it represents just a very small step toward harnessing synthetic biology to improve health and cure diseases. Next the team is going to try to make synthetic genomes that carry the instructions for bacteria to make a flu vaccine, but no one knows how difficult that step will be.

Q: Can the synthetic cell reproduce? If so, are its daughter cells viable?

E.P.: The cell with the transplanted genome reproduced, as did the resulting daughter cells. In fact, the colony went through a billion rounds of replication before the researchers froze the cells for archiving.

Q: What would happen if the bacterial cells are accidentally released into the environment? Are there precautionary measures?

M.B.: Researchers working in this field are well aware that there is a big ethical difference between creating synthetic cells that exist only in research laboratories and creating synthetic cells that are released in the environment. Environmental release has much more significant risks. For this reason, any environmental release would occur only under appropriately stringent conditions. Nevertheless, there is still the chance that an accident could happen and unintended environmental release might occur. In this case, there are a couple of points to appreciated.

First, it is not easy to keep synthetic cells alive even under ideal conditions in the laboratory. So, an accidental environmental release of synthetic cells might well lead to their quick extinction.

Second, there is active discussion and planning to build in multiple safeguards in synthetic cells. These include such things as: giving them a strictly limited lifespan, installing an on/off switch, making them depend on foods or conditions that are not present naturally in the environment, and/or taking steps to prevent them from evolving. In addition to safeguards, it is important to build in unique identifying marks, so that any damage could be traced back to the responsible parties. It is notable that Venter’s team already included such “watermarks.”

Q: Did this work only replace the DNA in the nucleus of the cell, or also the mitochondrial DNA? And how close are we from synthetically creating the cell, too?

E.P.: Bacterial cells lack nuclei and mitochondria. Researchers studying the origin of life have worked for years to build a self-replicating cell from the bottom up and have made some progress on this, but it’s not clear how one would build one that was sophisticated enough to read and carry out the instructions of a synthetic chromosome. It’s a chicken and egg problem that could take a long time to work out.

Q: Does the discovery challenge religious notions about the creation of life and the concept of a spirit?

M.B.: The creation of life from nonlife (fully synthetic cells) might well impact some religious and cultural world views, and the achievement of a partly synthetic cell already opens the door to these implications. The achievement of Venter’s team vividly demonstrates that the genome of simple life forms is nothing more than a complex molecule constructed out of nothing more than certain chemicals. (Most molecular biologists have already believed this for many generations, of course.) This result strongly implies that fully synthetic cells would likewise be merely very complex chemical devices, created out of nothing more than chemical ingredients that are organized in the appropriate way. There is no need for a concept of “spirit” or nonchemical “vital spark” to explain simple bacterial life. This, in turn, in my opinion, implies (but does not prove) that more complex forms of life, including humans, are essentially nothing more than exceedingly complex chemical devices, and so there is no need for a concept of “spirit” or “vital spark” to explain what make humans alive.

Q: What is the taxonomic classification of these synthetic cells? Which species do they belong to?

E.P.: Microbial taxonomists have not yet weighed in on how synthetic life should be fit into the tree of life. But because the synthetic chromosome was basically a copy of the bacterium, Mycoplasma mycoides, with a few changes, the resulting bacterium was just a new strain of M. mycoides. The team is taking a cue from software developers in naming these new strains: This one is called M. mycoides JCVI-syn1.0.

Q: At which point would/should the policymakers come in? Are there plans in progress to regulate such research and monitor the consequences?

M.B.: A number of teams of scientists, ethicists, religious leaders, policy analysts, et cetera from the U.S. and Europe have been scrutinizing the social, ethical, and policy implications of this and related research. This work has been going on for a number of years, and the results to date are typically freely available to the public. Policy makers at all levels, including the highest levels, are already in the loop, and plans for certain kinds of regulations are well under way (e.g., regulation of the synthesis of large pieces of DNA). Further kinds of regulation are actively being discussed.

Q: Is the DNA synthesis part now a "solved problem"? Could you reliably create a DNA strand that encoded, say, the complete works of Shakespeare, without regard for its genetic function?

M.B.: It would be relatively trivial now to encode the works of Shakespeare in DNA, but it would presumably have no biological function. The main significance of the achievement of Venter’s team is that the synthetic genome actually functions just like a normal genome.

Q: This breakthrough is "decades in the making," but how long would it take to reproduce the experiment today?

E.P.: It took years for these researchers to work out the bugs in making a synthetic genome that looked very much like a natural one and in booting it up in the cell of another species. That experiment now takes about a week, and it seems now that synthesizing the genome, while quite expensive, is not the rate-limiting step. But as the team starts to manipulate the genome and add different genes, it is delving into new territory where such manipulations might make the recipient cell reject the synthetic genome or the synthetic genome may lead to emergent properties incompatible with life. Then the team will have to go back to the drawing board to try to figure out why the experiment didn’t work.