The last session at Synthetic Biology 2.0 was full of hand-wringing about the very name of the thing. "Synthetic" seems to conjure up too many bogeymen for the likes of of many attendees. The arguments against the name were all centered around the fact that "synthetic" is un-PC these days. Never mind that we live in a world consisting entirely of synthetic food, clothes, houses, computers, solar panels, windmills, and liquid fuels. Synthetic is just bad, evidently.
This debate is essentially about politics. It seems the new field is scaring people just by it's name. So perhaps we should choose a new name in order to finesse the acceptance of the science and technology? After all, why fight more battles than you need to?
Okay, fine. Go ahead and try to rename it. I'll just watch this time, thanks. Besides, I think the present name is both appropriate and inevitable, but more on that in a moment. We started with a different name, once upon a time, and that one didn't go over so very well either. In 2000, while trying to describe the way biology was about to change (here is the PDF), or at least the way Drew Endy and I were conceiving of a new biological engineering, I floated the phrase "Intentional Biology." The text on that web page was last modified in late 2000, but the story is basically the same today. Through predictive design, biological systems should be both easier to understand and more useful. These engineered systems would behave as intended, rather than displaying random and mystifying behaviors often encountered when genetically modified organisms are introduced into new environments or set loose in the wild; i.e., unintended behaviors. Roger Brent, Drew, and I, even organized a meeting to figure out how to make this happen. "After the Genome 6, Achieving an Intentional Biology", was held in Tucson, AZ, in December of 2000. Alas, that name had unintended consequences, namely that the biologists attending the meeting thought we were asserting that all prior molecular biology had been unintentional. If rotten vegetables had been available, I'd have been pelted during my talk.
Not the best start. Can't win them all. A good lesson, too.
Fast forward to mid 2001 or so, when Drew and I are at a cocktail party in San Fransisco thrown in celebration of the opening of the new local office for Nature. We wind up in a conversation with Carlos Bustamante, who regales us with the origin of the field of Synthetic Chemistry, and how this gives us the name for Synthetic Biology. Drew and I are convinced. But, of course, it wasn't up to Drew and I to name a new field. We were simply looking for a name to distinguish what we wanted to do from how things had been done previously. The phrase "Synthetic Biology" certainly isn't new, and was emerging from other sources at the same time (Steven Benner, in particular, if memory serves).
Drew has flirted with other names in the last 5 years, among them "constructive biology" and "natural engineering". Craig Venter insists on calling it Synthetic Genomics. Frankly, these aren't any more compelling to me than Synthetic Biology, and they also seem to require even more explanation. At this point, I don't really care what it is called. The work is going to happen regardless, and there is no way to turn back. The name is only a lightening rod for criticism because, as Oliver Morton and others have pointed out, the community keeps drawing attention to itself and all the bad things it might facilitate. But where is the good news? I have tried in this space to point out the connections between Synthetic Biology and vaccines, to the possibility that Synthetic Biology might be our best hope to beat a pandemic, but it appears most people want to focus on the negative aspects of rapid and distributed DNA synthesis. The recent SB 2.0 meeting started with a focus on biological production of energy, another excellent beneficial application, but any subsequent optimism was lost by the third day.
Now onto why the name is inevitable. What we are doing has been called Synthetic Biology for almost a century. Here is some text from my book:
Ch 4: The Second Coming of Synthetic Biology
"I must tell you that I can prepare urea without requiring a kidney of an animal, either man or dog.” With these words, in 1828 Friedrich Wohler announced he had
irreversibly changed the world. In a letter to his former teacher
Joens Jacob Berzelius, Wohler wrote that he had witnessed, “The great
tragedy of science, the slaying of a beautiful hypothesis by an ugly
fact.” The beautiful idea to which he referred was vitalism, the
notion that organic matter, exemplified in this case by urea, was
animated and created by a vital force and that it could not be
synthesized from inorganic components. The ugly fact was a dish of
urea crystals on his laboratory bench, produced by heating inorganic
salts. Thus was born the field of synthetic organic chemistry.
Around
the dawn of the 19th century, chemistry was in revolution right along
with the rest of the western world. The study of chemical
transformation, then still known as alchemy, was undergoing systematic
quantification. Rather than rely on vague and mysterious incantations,
scientists such as Antoine Lavoisier wanted to create what historian of
science and technology Bruce Hevly calls an “objective vocabulary” for
chemistry. Through careful measurement, a set of clear rules governing
the synthesis of inorganic, non-living materials gradually emerged.
In contrast, in the early 1800s the study of organic
molecules was primarily concerned with understanding how molecules
already in existence were put together. It was a study of chemical
compositions and reactions. Unlike the broader field of chemistry
taking shape from alchemy, making new organic things was of lesser
concern because it was thought by many that organic molecules were
beyond synthesis. Then, in 1828, Wohler synthesized urea. Suddenly,
with one experiment, the way scientists did organic chemistry changed.
The ability to assemble organic molecules from inorganic components
altered the way people viewed a large fraction of the natural world
because they could conceive of building much of it from simpler
pieces. Building something from scratch, or modifying an existing
system, requires understanding more details about the system than
simply looking at it, poking it, and describing how it behaves. This
new approach to chemistry helped open the door to the world we live in
today. Products of synthetic organic chemistry dominate our
environment, and the design of those products is possible only because
understanding the process of novel assembly revealed new principles.
It
was this step of moving to Synthetic Chemistry, and then to an
engineering of chemistry, which radically changed the way people
understood chemistry. Chemists had to learn rules that weren’t
apparent before. In the same way that Chemical Engineering changed our
understanding of nature, as we begin engineering biological systems we
will learn considerably more about the way biological pieces work
together. Challenges will arise that aren’t obvious just from watching
things happen. With time, we will understand and address those
challenges, and our use of biology will change dramatically in the
process. The analogy at this point should be clear; we are well on our
way to developing Synthetic Biology. [Auth. note: Clear if you've read the first three chapters of the book, anyway.]
Before going further,
it is worth noting that this is not the original incantation of the
phrase “synthetic biology”. Whatever the reception this time around,
the first time it was a flop. In her history of the modern science of
biology, Making Sense of Life, Evelyn Fox Keller recounts
efforts at the turn of the 20th Century to discover the secret of life
through construction of artificial, and synthetic, living systems; “To
many authors writing in the early part of the [20th] century, the
[path] seemed obvious: the question of what life is was to be answered
not by induction but by production, not be analysis but by
synthesis.”(Keller, p.18) This offshoot of experimental biology
reached its pinnacle, or nadir, depending on your point of view, in
attempts by Stephané Leduc to assemble purely physical and chemical
systems that demonstrated behaviors reminiscent of biology. As part of
his program to demonstrate “the essential character of the living
being”(ibid, p.28) at both the sub-cellular and cellular
level, Leduc constructed chemical systems that he claimed displayed
mitotic division, growth, development, and even cellular motility. He
described these patterns and forms in terms of the well-understood
physical phenomena of diffusion and osmotic pressure. It is important
to note that these efforts to synthesize life-like forms relied as much
on experiment as upon theory developed to describe the relevant physics
and chemistry. That is, this was a specific program to use physical
principles to explain biological phenomena. These efforts were
described in a review paper at the time as “La Biologie synthetique”(ibid, p.31-32).
While
the initial reception to this work was somewhat favorable, Leduc’s
grandiose claims about the implications of his work, and a growing
general appreciation for complicated biological mechanisms determined
through experiments with living systems, led to something of a backlash
against the approach of understanding biology through construction. By
1913, one reviewer wrote, “The interpretations of M. Leduc are so
fantastic…that it is impossible to take them seriously”(ibid,
p.31). Keller chronicles this episode within the broader historical
debate over the role of construction and theory in biology. History
regards the folks in the synthetic camp, and related efforts to build
mathematical descriptions of biology, particularly in the area of
growth and development, as poorly regarded by their peers. Perhaps
inspired by the contemporaneous advances in physics, it seems that the
mathematical biologists and the synthetic biologists of the day pushed
the interpretation of their work further than was warrented by
available data.
In response to what he viewed as theory
run rampant, Charles Davenport suggested in 1934 that, “What we require
at the present time is more measurement and less theory…There is an
unfortunate confusion at the present time bewteen quantitative biology
and bio-mathematics…Until quantitative measurement has provided us with
more facts of biology, I prefer the former science to the latter”(ibid,
p.86). I think these remarks are still valid today. Leduc, and the
approach he espoused, failed because real biological parts are more
complex, and obey different rules, than his simple chemical systems,
however beautiful they were. And it is quite clear that vast forests
have been felled to publish theoretical papers that have little to do with
the biology we see out the window. But theory, drawn from physics,
chemistry, and engineering, does have a role to play in describing
biological systems. Resistance to the tools of theory has been, in
part, cultural. There has always been a certain tension in biology
over the utility of mathematical and physical approaches to the subject;
To
put it simply, one could say that biologists do not accept the Kantian
view of mathematics (or, rather, mathematization) as the measure of a
true science; indeed, they have often actively and vociferously
repudiated any such criterion. Nor have practicing biologists shown
much enthusiasm for the use of mathematics as a heuristic guide in
their studies of biological problems.(Keller, p. 81)
Fortunately, this appears to be changing.
Mathematical approaches are flourishing in biology, particularly in the
interpretation of large data sets produced by genomic and proteomic
studies. Physicists and engineers are making fundamental contributions
to the quantitative understanding of how individual proteins work in
their biological context. But I think it is important to acknowledge
that not all biologists think a synthetic, bottom up, approach will
yield truths applicable to complex systems that have evolved over
billions of years. Such concerns are not without merit, because as the
quotation from Charles Davenport suggests, biology has traditionally
had more success when driven by good data rather than theory. The
challenge today is to build quantitatively predictive design tools
based on the measured device physics of real biological parts, and to
implement designs within organisms in ways that work in the real world.
Thus the present project is truly different than the biology that has come before. Synthetic Biology is based on an explicit reliance upon mathematical models. My own particular bent here is in developing technology that enables better measurement of biological systems so as to test and constrain models and also to provide required capabilities for biological engineering. Without that, we are stuck with Charles Davenport's criticism of seventy years ago.
"Synthetic Biology" fits, both linguistically and historically. Why are we stuck on this same damn topic two years after the first meeting? We have better, and more important, things to worry about. And lot's of work to do. Synthetic Biology 3.0 will take place in Zurich, Switzerland, 24-27 June, 2007.