I just finished reading Evelyn Fox Keller's wonderful biography of Barbara McClintock, A Feeling for the Organism. Barbara McClintock was probably the best corn geneticist of all time and definitely one of the sassiest female scientists ever. In the 1940s and 1950s she discovered transposition, the process by which pieces of genes can literally jump out of one part of the chromosome and land back in another part. These jumping elements are controlled by master regulating elements in other parts of the genome and can turn different genes on and off at different times. This incredible discovery (for which she was awarded the Nobel prize in 1983) remarkably came at a time when no one even knew what genes were made out of. The structure of DNA had not been discovered, and it wasn't even definitively known that the genetic material was actually DNA in the first place. Before McClintock's discovery (and for decades afterward), almost no one believed that genes were regulated by environmental conditions, but that instead all genes were "on" at all times. Even after the beginning of the molecular biology revolution and the discovery of the DNA structure, Francis Crick's "central dogma" didn't allow for information to flow backwards, to affect the DNA and the expression of genes. McClintock's work was so far ahead of her time, so counter to prevailing models, and so tied to corn, a passÃ© model organism, that it was totally ignored for many years. Of course it also didn't help that her papers and talks were dense and hard to understand or that she was a woman in a field dominated by men. When scientists began to see that expression of genes in E. coli is controlled by the environment in the 1960s and 70s, several researchers began to realize the parallels between their work and McClintock's decades earlier, and she finally began to receive the recognition she deserved.
The book goes through everything that went into McClintock's discoveries and her amazing career as a scientist, from her fiercely independent childhood, to her education at a time when most women were persuaded that advanced degrees were only for men, to her lonely and transient scientific career. Even though she had proven herself as a brilliant geneticist as a graduate student and research assistant at Cornell, she was unable to find a permanent academic position for years because such jobs just did not exist for women, and then once she was settled at Cold Spring Harbor, she was unable to get people to understand the implications of her work. One line in the book affected me in particular though, as my friends and I get to the part of grad school where the emotional investment is the highest and most difficult:
Good science cannot proceed without a deep emotional investment on the part of the scientist. It is that emotional investment that provides the motivating force for the endless hours of intense, often grueling labor.
McClintock's obsession with all the intricacies of each corn plant she grew, her "feeling for the organism" was able to sustain her through decades of loneliness and marginalization, keep her going when she literally had nothing else. While it was at times overwhelming to imagine what she went through, in general, McClintock's story is inspiring, in her passion and genius, her determination and her outlook on life and nature. When everyone around her was focusing on smaller and smaller details, losing sight of the complexities of the natural world that inspired the work in the first place, she maintained her connection to the whole organism, to every kernel, every leaf.
For McClintock, reason--at least in the conventional sense of the word--is not by itself adequate to describe the vast complexity--even mystery--of living forms. Organisms have a life and order of their own that scientists can only partially fathom. No models we invent can begin to do full justice to the prodigious capacity of organisms to devise means for guaranteeing their own survival. On the contrary, "anything you can think of you will find." In comparison with the ingenuity of nature, our scientific intelligence seems pallid.
I think that this is something important to keep in mind if synthetic biology is to transition from simple designed systems with only a few components to larger and more interconnected designed networks at larger scales. What are we missing in our models of biological systems that we are trying to recapitulate? By focusing on one synthetic pathway at a time, trying to isolate it from everything else, are we missing the point of how biological systems are interconnected, inextricable from their natural context? Synthetic biology is powerful and fascinating because natural biology is powerful and fascinating and that's something that we shouldn't lose sight of. It's difficult to think about the whole organism when we're pushing so hard trying to make a single synthetic pathway work in a cell, but maybe that's what we're missing.
I read A Feeling for the Organism years back and found it quite depressing. It painted McClintock as essentially a failure. She made great discoveries but was unable to communicate them to other scientists.
It wasn't until decades later when entirely different groups of researchers rediscovered transposons that her discoveries were assimilated. Her discoveries had precedence--and so the Nobel--but had no effect on the progress of the field.
A lovely book review - I now want to go out and read it. Thanks in particular for the quote about the emotional investment. So many non-scientists I know think we stifle our feelings. It's the contrary - we indulge them.
Yes, I think your last paragraph is correct. I think there is a great deal of missing the point in the enormous amount of complexity living systems have by focusing on one pathway at a time (or 10).
I think you are missing the control system that ties it all together, that makes everything work "in sync". Regulation of ATP production and consumption is key. They are always in balance, and to maintain that balance there is exquisite (and individual) regulation of each and every pathway that produces ATP and that consumes ATP.
You need to abandon the wrong idea of homeostasis and appreciate that living organisms didn't evolve stasis in anything, they evolved to survive, and any and all parameters are "fair game" to evolve so as to accomplish that. I am pretty sure that ATP concentration is one of the control parameters that regulates the myriad pathways that consume ATP. I talk about it here.
The physiological state âat restâ is the most complicated physiological state. Everything that the organism needs to do is held âat the readyâ, ready to be called on when needed, ready for the organism to trigger that physiological state âin a heart beatâ if necessary. It is physiological states under extreme stress that are more simple. When systems get âout of rangeâ, they are turned off. When every system gets âout of rangeâ, the organism dies.
The combined action of the multiple non-linear control systems is what produces the chaotic behavior of physiological systems. When those non-linear parameters get âout of rangeâ, and drop out, the system becomes more regular because there are fewer degrees of freedom. When it gets very regular, the organism is at death's door, with only one or a few pathways still regulating the parameter. This is why heart beat interinterval variability is chaotic in healthy people and regular in non-healthy people.
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This book seems interesting.
Believe it or not the only reason why I read Ventors 'a life decoded thing' was a review article in Nature on books young aspiring scientists should read. It claimed Ventor got his curiosity picked from having to do a book report on Waton's double helix in college, and the thrill of the chase was for him contagious. I took some tidbits from each book (his, where if you see him a a graduate he has a scraggly nerd beard, and watsons and crick, where they look completely and utterly different back in the 50s). thanks for this review. All good scientists are rebel.