Biology needs a Grothendieck (or at least a Hilbert)

By: Tony Kulesa

Recently passed away last month is the storied mathematician Alexander Grothendieck, who, in between his early quest to personally assassinate Hitler and his later (asc)descension into anarchist hermitdom, amassed a Christ-like following of mathematicians to rebuild entire fields of mathematics into a single theory of sublime generality, starting with the definition of a point.

Steven Landsburg gives a fitting layman’s description of Grothendieck’s profoundly powerful approach to mathematics:

“Imagine a clockmaker, who somehow has been oblivious all his life to many of the simple rules of physics. One day he accidentally drops a clock, which, to his surprise, falls to the ground. Curious, he tries it again—this time on purpose. He drops another clock. It falls to the ground. And another.

Well, this is a wondrous thing indeed. What is it about clocks, he wonders, that makes them fall to the ground? He had thought he’d understood quite a bit about the workings of clocks, but apparently he doesn’t understand them quite as well as he thought he did, because he’s quite unable to explain this whole falling thing. So he plunges himself into a deeper study of the minutiae of gears, springs and winding mechanisms, looking for the key feature that causes clocks to fall.

It should go without saying that our clockmaker is on the wrong track. A better strategy, for this problem anyway, would be to forget all about the inner workings of clocks and ask “What else falls when you drop it?”. A little observation will then reveal that the answer is “pretty much everything”, or better yet “everything that’s heavier than air”. Armed with this knowledge, our clockmaker is poised to discover something about the laws of gravity.

In other words, [Grothendieck’s] philosophy was this: If a phenomenon seems hard to explain, it’s because you haven’t fully understood how general it is. Once you figure out how general it is, the explanation will stare you in the face.”

To me, this analogy begs the question, what would have happened had the Isaac Newton of the apple-falling legend been one of today’s molecular biologists? Rather than writing down a new theory of gravity, would he have been looking for the genetic mutations that lead to the apple’s fall from its tree branch (armed with a tree farm, apple collecting robots, and a MiSeq, all on the NIH’s tab)?

What, as Landsburg puts it, is staring us in the face if we could just figure out how to ask the right question? In simple concepts like the definition of a point, Grothendieck saw the potential to build entirely new ways of thinking about geometry that turned long outstanding problems into obvious truths. What would a person like Grothendieck make of the basic axioms from which we build biology? Perhaps there are alternative ways of thinking about the basic building blocks, a gene, an enzyme, an organism, a species, that freshly reinterpret their functions in a way that would reinvent our field.

There are likely many reasons why Grothendieck was able to do what he did for mathematics, but many that knew him suggest the most significant to be his courage. Not only is it tremendously risky to spend years trying to reinvent existing fields, but its also lonely, and surely he would not have achieved anywhere near as much without the support of his peers. There are some biologists that come to mind, indeed even in our own department, who have voiced or even dedicated bodies of work to theoretically “out-there” ideas, and are widely dismissed by their colleagues. In light of Grothendieck’s triumph in mathematics, maybe we shouldn’t so quickly dismiss wild theories, but embrace and encourage them.

 

Steven Landsburg’s piece on Grothendieck:

http://www.thebigquestions.com/2014/11/17/the-generalist/

 

For the love of pipettes and alchemy

By Diana Chien

One of my friends once asked her dental hygienist how she had chosen her career. With cheerful satisfaction, the hygienist replied, “I like it when things are really clean.”

When I heard this story, I was charmed by a) the hygienist’s honesty and b) the non-grandiosity of her answer. While I’m sure she’s also invested in healthcare, quality of life, and patients’ teeth not falling out, the basic motivation for her day-to-day work remained a very personal, low-level satisfaction in removing schmutz from people’s dentition.

Hearing this story sparked an appreciation in me for the littler motivations in life – for the way that our career choices are often informed by personality tics and hankerings that can seem silly and inconsequential, yet can generate a surprising amount of satisfaction, even delight, when fulfilled by daily work.

When I first had the chance to do work in a molecular biology lab, back in high school, I loved the intricate genetic systems we worked with, the sleek experiments and sharp people. All par for the course for a future grad student.

The part that I haven’t admitted to many people is that I also simply liked doing the labwork. I like playing with gadgets and glassware. I like organizing complex assortments of physical stuff. I like fine motor tasks. (My hobbies include knitting and drawing.) When I was exhausted and overwhelmed by classes in undergrad, doing lab chores could even become an imaginative retreat: making media and cleaning glassware allowed me to pretend that I was a medieval alchemist.

While all of the above remains subordinate to the desire to do good science and make a contribution to my field, my years of life in lab have been made far more agreeable by my recognition that I locate substantial enjoyment simply in working with interesting tools and materials, and in finding opportunities for imaginative play. fact, I’m sure I would have had fewer tense, unhappy days in lab had I reminded myself more often that I’m allowed to enjoy labwork, and to actively seek out opportunities to do so. (This is in the past tense because I’m presently in a long spell of computational work, and hence considering my relationship with labwork at a fond distance.)

A concluding anecdote, because different strokes are for different folks: one of my grad-school friends is a lifelong math-y person, turned computational biologist. Last year, he completed his first-ever internship in a wet lab. Of his experience, he offered the following summation: “I learned how to pipette this summer. I hated it.”

Image credit: Arturas Slapsys

The true champions of biomedical research

By Sean Kearney

Historically, Thanksgiving has been one of my least favorite holidays. I love to eat, but I’m vegan and it can be really unpleasant to be around carnivorous family members constantly remarking on my dietary restrictions, saying, “Life would be so much easier if you just ate butter.” I often feel like a maverick, the Lorax, if you will, proclaiming, “I am the Sean and I speak for the animals!”

In reality, I don’t speak for the animals, and I don’t think there are many people who do. Despite our technological advancement, we’re still so barbaric and, in a sense, backwards that we forcibly impregnate animals, steal their babies, and use them for whatever purposes we see fit. It’s especially poignant in scientific settings, where we not only forcibly impregnate animals, but also then use them to test the effects of drugs or to see how we can reverse cancer or fend off infections that we gave them in the first place. We may have come a long way in being more conscientious in our care and use of animals, but in many ways the scale and scope of animal experiments only makes it more likely that we’ll inadvertently or, in some cases, intentionally harm or misuse animals just to please an intractable reviewer.

We’re often at a distance from the animals in our lives – it’s easy to view the hamburger you’re eating as never having been an animal who lived, breathed, experienced pain, joy, frustration, and ultimately death. With lab animals, we remove this distance. We interact with them and sometimes get to know them. But with large experiments, the interactions become more transient, and I think it’s easy to become complacent, to view the animals as objects of a research goal rather than the enablers and, really, champions of science they are.

I’ve wondered if we could honor experimental animals by recognizing them more explicitly in papers; in addition to mentioning (n=5) the animals used in successful experiments, also recognize the others that died only to produce inconclusive results. If nothing else, it may encourage authors to reconsider whether they need 100 mice for an experiment that only calls for 10. When we acknowledge the contributions of animals in our work, we stop perpetuating the notion of animal as object and encourage stewardship and respect for the lives of others.

I’ve worked with experimental animals – as much as I hate to admit it, certain scientific questions are today (and maybe for a long time) impossible to answer without the use of animals. I love animals, and I’ve never felt more uncomfortable or conflicted than when working with lab animals. I still haven’t found a way to justify using them in this way, and I don’t think I ever will. But I’d rather the people doing these experiments today are the ones who really care about animals and care that the work they’re doing will make it so that we don’t do these things to animals in the future.

As biomedical scientists, we’ve committed ourselves to bettering the lives of others. We should keep this commitment in mind and treat animals as the living, feeling beings they are.

References:

Lappe, Frances Moore. Diet for a Small Planet. 1971. Ballantine Books.

Safran Foer, Jonathan. Eating Animals. 2009. Little, Brown, and Company.

Sinclair, Upton. The Jungle. 1906. Doubleday, Jabber, and Company.

Singer, Peter. Animal Liberation. 2009. HarperCollins.

Image credit: 23 and me