Sunday, May 12, 2013

On self-limiting enzymes, playfullness in science, and mothers... (Books - The Statue Within by Francois Jacob)

Over the last ten days, I attended the annual conference of the International Society for Autism Research, in San Sebastian Spain, where I presented some of my research and heard about the work of many, many others.  It was impressive to see the huge amount and diversity of efforts focused on autism spectrum disorders.  On my travels there and to nearby Barcelona, I also managed to get a little reading done.

I had started The Statue Within, the memoir of French biologist Francois Jacob a while ago, but never really got going.  The conference put me in the mood to pick it up off the pile again and just as I began, I learned that Dr. Jacob had died at 92 years of age.  Dr. Jacob's contribution to our understanding of how living organisms work was to be the first to observe and describe how the level of an enzyme produced in a bacterium can be responsive to its environment, eventually earning him, Jacques Monod and and Andre Lwoff the Nobel Prize in Physiology or Medicine in 1965.  He saw that e. coli, for example, could digest the sugar lactose for energy instead of glucose, but it produced the necessary digestive enzyme (lactase) only when lactose was present.  How was this possible?  It was learned around the same time that the production of any protein (such as an enzyme) was the product of certain sequences in our DNA (we call those sequences genes).  These sequences became a template for RNA which, in turn, became a template for the production of a protein. The e. coli's genes were always equipped to produce lactase but, typically, a repressor (also a protein) was bound to the portion of our DNA responsible for producing lactase.  In the presence of lactose, the repressor binds lactose instead of those genes.  This accomplishes two things: 1) the lifting of the repression which means that the genes facilitate the production of lactase which digests the lactose and 2) it creates a self-limiting loop such that, when the lactose is gone, the repressor then binds the DNA once again and the production of lactase is turned-off.  This was important to biology not just in understanding how e. coli are responsive to their environment, but because this model extends to any gene in any organism. Dr. Jacob and Jacques Monod realized for us that genes interact with their environment.  Genes being present in an organism are not sufficient to accomplishing their action, they must be turned on" by some signal or, to use the term biologists use, they must be "expressed."  Although, as is always true with biology, it is now understood that this is a general principle and this simple mechanism is, in fact, be varied upon and complicated infinitely.

Jacob's memoir The Statue Within is similarly, and unsurprisingly, interested in origins of behavior in an organism, although in this case, the organism is himself, and the behavior are the actions taken in his life.  These are remarkable both for their responsiveness to what seem the accidents of the moment (what literature might call "fate") and their subjective experience of continuity (what literature might call "character").  This duality is true too of the biology Jacob researched and was the subject of his contemplation: the responsiveness of the e. coli demonstrates how genetic mechanisms facilitate behavior even while the genome of the organism remains consistent.

Although Jacob went to medical school intending to become a surgeon, World War II got in the way.  Jacob served under de Gaulle as a surgeon and in active combat in North Africa, returning to France with serious wounds.  These precluded his ever practicing as a surgeon and after a series of false starts, Jacob found himself drawn to biological research, first with  antibiotics and, later, simply because the opportunity presented itself, to study bacteriophages.  These are viruses which insert their own genes into bacteria.  It was his struggle to understand how they accomplish their work which led Jacob to eventually unconver some of the mechanisms of genetic replication and signalling.

The memoir has a somewhat dated feel to it.  Writing that gilds the lily with a penchant for lyrical repetition. A story that seems fashioned precisely to endow a life with meaning, but occasionally making the product feel a touch too well-made.  Jacob displays the occasional gesture smacking of sexism or homophobia that could be excused as the product of their time and kindly be called old-fashioned, although there were people alive at the time who displayed neither limitation. But all in all, this is a thoughtful life account, full of modesty and insight.  It leads one to appreciate how a largely ordinary human being ended up making important discoveries as a scientist.
This endless race with time, this preference for desire over enjoyment is not without its drawbacks.  Too often, it prevents us from understanding, and nurtures the illusion of life rather than life itself.  It took me a long time to realize that this drive toward tomorrow has an advantage in at least one domain: in research.  Late, very late, I discovered the true nature of science, of how it proceeds, of the men who do it.  I came to understand that, contrary to what I had believed, the march of science does not consist in a series of inevitable conquests. or advance along the royal road of human reason, or result necessarily and inevitably from conclusive observations dictated by experiment and argumentation.  I found in science a mode of playfulness and imagination, of obsessions and fixed ideas.  To my surprise, those who achieved the unexpected and invented the possible were not simply men of learning and method.  More than anything else, they possessed extraordinary minds, enjoyed the difficult, and often were creatures of amazing vision.  Those in the front ranks displayed exotic blends of passion and indifference, of rigor and whimsy, of naivete and the will to power in a triumph of individuality.
Starting to work in Andre Lwoff's laboratory at the Pasteur Institute, I found myself in an unfamiliar universe of limitless imagination and endless criticism.  The game was that of continually inventing a possible world, or a piece of a possible world, and then of comparing it with the real world.  Doing experiments was to give free rein to every idea that crossed my mind...Every morning I ran to the laboratory to set up my experiments....In the morning, I prepared the bacteria and the viruses I was working on, and ran the experiment in the afternoon.  The next morning I got the results just in time to put together a further experiment to run later the same day. and so on.  A fiendish pace.  A race  without end.  The mad pursuit of the day after this one.   What mattered more than the answers were the questions and how they were formulated; for in the best of cases, the answer led to new questions.  I was a system for concocting expectation; a machine for making the future.  For me, this world of questions and the provisional, this chase after an answer that was always put off to the next day, all the was euphoric.  I lived in the future.  I always waited for the result of tomorrow.  I had turned my anxiety into my profession.

Jacob takes what would already be an interesting series of events during engaging moments in history and connects them to a professional career that helped start the field of genetic biology, a goal he seemed to undertake as much to give his life coherence for himself as he did for his reader. In this book as in his science, he was driven to understand how individual events add up to make one life and I was warmed and engaged by his open and probing account.  He seemed a scientist very aware of the creative process, the playfullness (as he puts it) behind his experiment making - an awareness he then brought into the act of creating a memoir.  This was a parallel that as an artist-turned-scientist that I found familiar and enjoyable to read about.

Finally, it seems just that I write on this book about where we all came from on this of all days.  In the U.S. today we honor where we all came from - Happy Mother's Day!

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