Looking back to chart a course to the future

This coming lunchtime*, former New York Times columnist Denise Caruso will discuss the promise and pit-falls of synthetic biology with Center for American Progress senior fellow and former Washington Post science reporter Rick Weiss.  Given the track record of both participants, I’m anticipating a stimulating and spirited discussion, which will draw on Caruso’s just-published article on an overview and recommendations for anticipating and addressing emerging risks from synthetic biology.

But rather than focus on Denise’s piece [which as you would expect from a talented writer, speaks quite eloquently enough for itself], I thought I would provide a slice of back-story to synthetic biology.  And to do this, I want to use a rather good paper published last year by Brian Yeh and Wendell Lim (of the University of California San Francisco)…

The paper—which is an engaging and easy read for anyone with a rudimentary grasp of chemistry and biology—was published in Nature Chemical Biology back in September 2007.  Freely available here, it looks at the parallels between synthetic biology and synthetic chemistry, and considers how these might inform the development of synbio.

The story goes something like this:

The mid-1900’s saw a radical shakeup in chemistry:  Instead of simply analyzing existing chemicals, scientists learnt the tricks of making them.  And as their skills grew, they started to add new molecules to the list of those they could synthesize—including some molecules that did not occur naturally.  This shift from observing chemicals to making them led to a profound change in chemistry—one we are still seeing the ramifications of today.  It’s hard to find an area of life that isn’t affected in some way by the products of synthetic chemistry.

Synthetic chemistry came about as new ideas, experimental techniques and measurement abilities coalesced together.  It’s early champions didn’t understand everything about how and why atoms and molecules behave, but they were sharp enough to see the utility of what they were achieving, and how things could be improved by systematic experimentation.  And unconstrained by more recent distinctions between pure and applied science, their results-driven research ended up leading to a more fundamental understanding of chemical structure and reactivity.

Now, holding this image of the transition between analytical and synthetic chemistry in your mind, go back to biology.  Until recently, biology was largely an observational science.  But the development of new tools, techniques and ideas in recent years has opened the door to changing and manipulating what we could previously only observe—particularly at the molecular level.  Advances in biotechnology are now allowing scientists to not only map out functional sequences of DNA, but to design and build their own sequences.  In effect, there is a move towards being able to make—to synthesize—the basic components of living organisms.  And this in turn is opening up biology to systematic manipulation and control.

In effect, biology at the beginning of the twenty first century is where chemistry was one hundred and fifty years ago.  And by inference, the shift from analytical to synthetic biology is poised to have a profound impact on our understanding of biology, and how it can be used.

This analogy between synthetic chemistry and synthetic biology is both comforting and concerning.

Comforting, because it suggests that the development of synthetic biology can be guided by historic precedent—the future is not as foreign as we at first thought.  And the analogy also helps place synbio in a continuum of technological development.  Just as synthetic chemistry built on analytical chemistry, synthetic biology builds on our understanding of what makes life work.

In fact what sets synthetic biology apart from biotechnology up to this point is not so much a shift in basic understanding, as the application of new ideas about how that understanding can be used (augmented by rapidly developing techniques for analyzing and manipulating biological molecules).  This is remarkably close to what sparked the rise of synthetic chemistry.

[As an aside, I was intrigued to read that the parallels between synbio and “synchem” are so close that there were some that feared the advances of synthetic chemistry could lead to the creation of living beings—sound familiar?]

But the analogy is also concerning.  While synthetic chemistry has had a profound impact on society, it has not always been a positive impact.  The “suck it and see” approach to chemistry has led to some notable disasters, and chemicals regulations are still trying to play catch-up.  And while I would defy anyone to deny that the products of synthetic chemistry make their lives better, there is the rather philosophical question of whether we are reliant on these products because we needed them, or because their use fosters dependence?

In addressing these questions, synthetic chemistry provides a useful basis to ask what has worked in the past, what has gone wrong, and what needs to be done better.  But in doing so, we must be careful not to loose sight of two things:

First, the ideas and abilities currently being thrown into the synthetic biology melting pot are primed to lead to a radical—and largely unpredictable—shift in what is possible.  And while we might be able to gain some comfort in the thought that this step-change in technological ability isn’t anything new, I’m pretty sure the consequences will be.  No two ways about it—synthetic biology will bring with it with challenges as unique as the opportunities it presents.

And second, synthetic biology gets into the very heart of what makes the biological world go round.  While the synthetic chemistry revolution allowed us to tinker around with the “hardware,” we are now getting into the “software” of life itself.  This raises a number of ethical questions as well as purely practical questions—just because we can alter the code that determines biological identity, should we?  And if something goes wrong, can we “reboot?”

However synthetic biology pans out, we can be sure of an exciting few years ahead of us.  Given major challenges facing global communities like hunger, disease and energy shortages, it’s hard to justify not embracing this technology—it promises to open the way to solutions unachievable through other routes.

But the challenges to using it wisely will be immense.  Yeh and Lim suggest that synthetic biology will require sociological reorganization of how biologists work on problems—I suspect the reorganization will need to extend far beyond the bounds of biology if sustainable synbio solutions are to emerge.

The good news is that the successes and failures of synthetic chemistry at least give us a taster of what we are in for, and what we need to think about if synthetic biology is to reach its potential.

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*For those of you unfortunate enough to be reading this after 12:30 PM (Eastern Time) on Friday November 14, the conversation between Weiss and Caruso can re-lived here.

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