“I didn’t hear about this experiment until I was a freshman at Brown”

At the Herbert Tabor Research Award Lecture at the American Society for Biochemistry and Molecular Biology meeting, in his talk “Chaperonin-mediated protein folding”, Prof. Arthur Horwich of Yale University and the Howard Hughes Medical Institute opened by regaling us with the story of the famous experiment by Christian Anfinsen.  The hypothesis was that all of the information required for a protein to fold into its three-dimensional shape was encoded in the amino acid sequence.  He tested the hypothesis by treating the protein with urea and beta-mercaptoethanol (BME), chemicals that cause the protein to unfold, then he slowly removed the urea and BME, and amazingly he recovered the protein’s activity, meaning that it had folded correctly.  This is amazing because the number of possible arrangements the protein could assume is huge, and yet it was able to find the right one.  The experiment is elegant, and it won a Nobel Prize in 1972.

It’s a common story to use when beginning a talk on protein folding, but I was more interested by what he said next: “I didn’t hear about this experiment until I was a freshman at Brown”, as if he had expected to have heard about it earlier.

I think this story illustrates the gulf between what scientists expect the public to know and what the public actually knows.  I went to an excellent high school, but my ninth-grade biology class didn’t really discuss biochemistry at a molecular level, and for pretty fair reasons: we didn’t have chemistry until tenth grade, so I’m not sure what would have been gained by talking about the fact that proteins are made of amino acids and the protein folding problem.  In Advanced Placement Chemistry in eleventh grade, we spent a good deal of time on intermolecular interactions, so we probably could have applied those principles to proteins, but it was a chemistry class, not a biochemistry class, so we didn’t.  So even as a definitely more-educated-in-chemistry-than-average student, I, as Prof. Horwich, entered college having never heard of the Anfinsen experiment, or indeed of protein folding.  We scientists would do well to remember that when trying to communicate with the public.

"Alternative" career panel

Mid-day Saturday, I attended the American Society for Investigative Pathology's 13th Annual Workshop on Graduate Education in Pathology, "We can't all be PIs: preparing graduate students for alternative career paths".

I think panels like these are just wonderful (supporting evidence: this event was extremely well-attended), but I thought the title of the event could have been better.  It's true that we call can't be PIs (principle investigators, or the traditional science professor): in order for it to be sustainable, each PI would, over the course of his or her career, train exactly one replacement.  In fact, many more students and even postdocs are trained than faculty positions are available.  But then this is precisely why "alternative" is not a great word to use here.  People who end up as tenure-track faculty are, in fact, a tiny minority of science PhDs, so it's the academic track that really should be called "alternative".

But also: not everyone wants to be a PI, even if they could be one.  This can be hard for many scientists to imagine (even people who are not, themselves, PIs: I was once at a career fair where an industrial scientist justified his job as "well, being a professor is clearly the best job, but we can't all do that"), but, in fact, not everyone loves doing bench science.  Not everyone loves writing grants.  It's not just that we can't all be PIs: even if we could, not all science PhDs would be happy doing that.  In fact, I think the fact that these sorts of panels are, in my experience, always extremely well-attended, is itself evidence that these sorts of people pursuing PhDs in science, the sort who don't want to be professors, are not that uncommon.  There are many, many important ways science PhDs can contribute to society, but calling these careers "alternative" and saying "we can't all be PIs" doesn't do much to remove the stigma.

It was an admittedly small sample size, so I'm not sure what if anything we can conclude, but I did make the following observation.  The panel had four members, three female and one male.  All three female panel members mentioned that one major reason they chose their careers (over, say, the coveted "PI" role, or even an industrial bench science role) was "work-life balance".  Also, it turns out that all three of the female panelists were married to scientists, of the more "traditional" type (two faculty, one industrial).  Meanwhile, the one male panelist mentioned that after working for a year and a half at a law firm, he started law school at night, while still working full-time at the law firm, with three children.  I don't know what the male panelist's life partner does, but I suspect she's a housewife.

It made me wonder about the degree environment contributes to our "choices" when it comes to work-life balance.  The high school teacher panelist was clearly very happy with the career she had chosen.  But if she had a stay-at-home husband, she may have chosen differently, either because she would have more time to dedicate to a job that required more hours because she could rely on her husband to provide child care, or because she would need a job with a higher salary in order to support her family.  I've heard that the choice of a spouse is the single most important career decision you will make.  I do think one major challenge facing women in STEM [science, technology, engineering, and mathematics] (and, therefore, everyone) is the fact that women in STEM are more likely to have spouses in STEM than men in STEM are.  "Traditional" careers in STEM (like most careers) are still built on the model of employing a breadwinner who has a homemaker at home to take care of things.  This model is not sustainable.

The microbes within us

Shorter thoughts are going to Twitter, but this will be the first in a series of longer posts of thoughts from #EB2013:

Bright and early on Saturday morning I attended the symposium "Managing the microbiome in human GI disease" put on by the American Society for Nutrition.  (The Experimental Biology meeting is made up of six societies: the American Society for Biochemistry and Molecular Biology (the reason for which I was ostensibly attending), the American Society for Nutrition, the American Society for Investigative Pathology, the American Society for Pharmacology and Experimental Therapeutics, the American Association of Anatomists, and the American Physiological Society.  These societies are themselves integrative and interdisciplinary, so any given symposium title could be difficult to assign to which society was sponsoring it.)

The emphasis of the symposium was on inflammatory bowel disease, but as an aside the speakers mentioned recent work on the relationship between obesity and the microbes inhabiting our guts.  For example, you can transfer the bacteria from a fat mouse to a lean mouse, and the lean mouse will gain weight (without changing how much it eats or its physical activity).

I was reminded of this later in the week when I met a graduate student who was researching obesity, but felt that she should move to some other disease for her postdoc, where she could contribute more to potential therapeutics and actually helping patients, since obesity is "preventable".

It got me to thinking about the way that we teach metabolism to the medical students.  We teach them that "calories in - calories out = weight gain", which is true: if you eat less and exercise more, you will lose weight.

But it's also true that for every human cell in your body, there are ten bacterial cells.  Most of these bacteria live in your gut, eating the same food you eat.  The calories they consume and expend are crucially important for how many calories are left available to you .  (The agricultural industry certainly appreciates this fact: they treat their livestock with low doses of antibiotics not to prevent bacterial infection, but to make them gain weight.)  As a society we tend to blame obese patients for making bad choices, but it's not like I chose what kinds of bacteria are living in my gut.

We're just beginning to learn about how specifically our gut bacteria contribute to our metabolism, so maybe that's why we don't want to include that when we teach metabolism.  We're not at the stage where we can tell people to eat certain brands of yogurt to solve certain medical problems (although I do know a scientist who believes he has cured his lactose intolerance by eating yogurt and colonizing his GI tract with the appropriate strains).  But we do know that our microbial communities are extremely important, and I think we're doing our students a disservice when we don't tell them that.