Monthly Archives: September 2011

This is embarrassing. My students in Cell and Molecular Biology are working harder than ever and my time spent in SCALE-UP are some of the happiest hours of my day. Each week, the students validate the pedagogy. Give students the keys and they will drive. They will take you on an educational journey you could never plan or even imagine. So what is the matter? Well, and this is not the first time I’ve done this, I decided to bring these progressive educational practices to my other students – my third grade Sunday School class.

The topic was virtue, which seemed both fuzzy and dry for a third grader. I wanted them to own virtue, to taste it. But how do to that with a group of little rowdies who have been known to draw Indiana Jones and Tony Hawk into the Nativity scene. Then I had my inspiration… superheroes.

I told the class that they were going to create their own superheroes today. Their superhero could have any superpower they wanted, but they also had to possess a virtue. The rule was that to retain the superpower, the  hero had to consistently exercise his or her virtue. Lose the virtue, lose the power. What a lesson plan! I was enabling my students to construct knowledge .. and virtue,  in the most tangible of ways. It would be active learning at its best.

The activity started well enough. We brainstormed an impressive list of virtues – honesty, integrity, generosity, faith, etc…. as well as a starter set of superpowers – the ability to fly, to become invisible, to shape shift. We had all the bases covered. Then I handed out the paper and markers and my class got busy.  They worked themselves up into quite a fervor of creativity and virtue.

After they finished, it was time to share. Sharing time started out well enough. The first superhero was a shapeshifter who was always kind. The next was “butterfly girl” who could fly but never told a lie. Then it was Billy’s  turn. (His name has been changed for his mom’s sake). His superhero was kind, honest, brave, faithful and generous. “That is excellent Billy”,  I said. “But what is his superpower?” “Sonic farting”, Billy replied. I was sure I hadn’t heard him correctly so I asked him to repeat himself. “SONIC FARTING”, he said in a superhero-sized voice. This was wrong, terribly wrong. I’d been to many seminars on active learning, even presented at some myself. No one ever discussed what to do when your student chose sonic farting as a superpower. I had to think fast. “Billy”, I said. “I’m sorry but there is no way that your superhero could be virtuous while using that superpower. You’ll have to think of something else.” “But, Miss Jill,” Billy said. “Instead of killing bad people, my superhero just stuns them with his gas and they are powerless.” What could I say? He had me.

So big kids,  please be patient with me this week. I may be a bit more hesitant than I usually am about handing over the reigns of learning. I don’t want to stifle anybody, but I’ve had a long week and it’s only Sunday. So please be gentle with me. Otherwise, I might have to unleash one of my superpowers on you.

 

I realize this is not a novel topic. Books have even been written on the subject. Much of the controversy tends to revolve around the fact that Rosalind Franklin provided the crystallographic evidence that grounded Watson and Crick’s model for the structure of DNA. Not to mention the questionable way these data may have come into W and C’s possession, not to mention, the treatment Franklin received as a woman in science. These issues remain important even today, but I do not think I have anything new to add to that discussion.

My current deliberation about whether or not W & C deserved the Nobel Prize focuses on a much simpler question: did they work hard enough to earn the Nobel Prize? Many accounts, including Watson’s own Double Helix, paint a charming picture of gentlemen who spent leisurely days in conversation with colleagues at King’s College, roaming the halls until happy hour, when they would hit the pub and talk some more. In every picture I have ever seen of Watson and Crick, they look so relaxed, almost languid. Which is why I am questioning their right to the prize. Did Watson and Crick work hard enough to deserve the prize? Did they suffer?

I realize that I am an experimentalist, a bench scientist who produces tangible stuff as evidence of a productive day’s work in the lab. Gels, mutant embryos, proteins that took blood, sweat and tears to generate in microgram quantities. As a scientist, I have suffered. Watson and Crick were theoreticians. I collaborate with theoreticians. They do not get their hands dirty or handle radioactivity. They tend to dress better than I do. However, they also tend to spend 48 consecutive hours without leaving their computer terminals, subsisting on coffee and stale donuts, and spinning out reams of parameter sets, bifurcations graphs, and code. In other words, they suffer.

In my high school year book, I wrote of three things to which I aspired. One was to win the Nobel Prize. I am pretty sure that is not going to happen. For years, I berated myself for not working harder. Another experiment, another paper, another grant. I matured enough to no longer covet the prize, but I still had my heart set on doing something BIG in science. No matter how much data I produced, I vowed to double my effort and produce even more the next week. I loved my work, but I also suffered.

Looking back, I now wonder if I should have learned something more from W & C than just the fundamentals of semi-conservative replication. Maybe I should not have worked harder, but possibly just a little less “hard”.

The creative process requires sufficient space and ATP. I am not sure the present scientific culture in the US and many other industrialized nations fosters the sort of thought and collaboration that Watson and Crick brought to bear on one of the most challenging problems of the 20th century. In a world of “publish or perish” there is little time for wandering the halls to chat with colleagues let alone for drinking beer.

We are week 4 into the semester and I can see the fervor for science rising in a subset of my students. This stuff is amazing and they want to be a part of it. I feel an obligation to keep them grounded and I do so with the reality check components of my assignments. “Calculate the cost of the experiment you just proposed.” “What are the ethical implications of the discoveries we just discussed?” “How long would this take you to do?”
But some cowardice remains when it comes to sharing some of the harshest realities of life as a biomedical scientist. Do I tell them about the old boys network and how hard it is for a young scientist to get started? Do I tell them about the esteemed scientists who troll scientific meeting looking for ideas to steal? Do I tell them about spending three sleepless months writing and rewriting ones best ideas ever only to find out six months later that the grant proposal was judged so poor as to be “unscorable”? No, I don’t think I want to tell them about that. Instead, I think I’ll tell them about Joe.
I met Joe in 2002. I was a young assistant professor selected to give a talk at a conference at the Cold Spring Harbor Labs. The Nobel Prize had just been awarded in our field and two of the three laureates were scheduled to attend the meeting. My work was edgy, risky, novel to be sure, or so I thought. This was the work that would make me famous…. or at least get me tenure. Then  I read the abstract of the presentation scheduled back-to-back with mine. To be presented by some post doc named Joe. It was nearly the same set of experiments as mine! Who was this Joe guy and what right did he have inhabiting the same scientific world as me?
To make a long story short, I went to that meeting with my fists up, ready for a fight. I sought out this Joe guy (or he sought out me) and it took all of about 10 minutes to remember that a scientific competitor was not necessarily an enemy, but someone who was passionate about the same scientific questions as one’s self. Over the course of the conference and a few late night discussions over beers, Joe and I bonded. When one of the laureates snubbed both of our talks, we became scientific soul mates.
I have known Joe for nearly a decade now. We have reviewed each other’s papers, and I value his criticism above that of all others. He is a superb scientist. After the first encounter, whenever we were both invited to present at a conference, we would consult each other to coordinate our presentations. No, not matching outfits, but we tried to make the most of the collective time we were allotted to tell a compelling story of the science and the approach to science in which we both so deeply believed. Over the years, Joe and I have discovered that we share a love of teaching and care as much about our students as we do our publications. And we care about people, and the planet. I can’t remember the last time I thought of Joe as a competitor. Joe is my friend and friendships like these make up for all the other things that I didn’t want to tell my students.

This week we move on to proteins and enzymes, which means time spent with some of my favorite enzymes, protein kinases. Proteins kinases are enzymes that attach phosphate groups to other proteins. Considering the size of a typical protein, this addition of a few atoms (one phosphorous and three oxygens) does not seem like a big deal. Sort of like the little sprig of mint dressing an amazing entree at a nice restaurant. But that is not the case.. the addition of a little phosphate can have drastic consequences on the structure, and consequently, the function, of a protein molecule. An enzyme modified by a phosphorylation event may change one hundredfold or more in its activity, upward or downward, depending on what the phosphate does to the shape of the protein. The power of the phosphate resides in that one little negative charge that it carries. A few extra electrons strategically placed can change everything.

Many, many proteins are regulated by phosphorylation. Not only can the activity be affected, but also the stability, localization, substrate specificity and more. And it is not uncommon for one protein kinase to have its activity regulated by another protein kinase, which in turn is regulated by yet another protein kinase, and so on and so on and so on.

The phosphate groups are removed by opposing enzymes called protein phosphatases. We do not know nearly as much about these enzymes. I heard a fascinating seminar about an attempt to design protein phosphatase inhibitors, including inhibitors for my all time favorite phosphatase (Cdc25A – long story). There is some promise that these inhibitors might help treat a host of problems, from cardiovascular disease to cancer.

When one spends too much time thinking about kinases, phosphatases and phosphate groups, one sometimes develops the mindset that phosphorylation rules the world, or at least, rules the cell, from which all living systems are made.

Phosphorylation is a very digital event. A given amino acid in a protein is either phosphorylated or it is not. The phosphate confers a single negative charge. The subtleties and gradations arise as they might in any digital system. In a given protein, there may be multiple phosphorylation sites, some of which are occupied and some which are not in any given condition. This allows for an enzymes to be active to varying degree rather than just “on” or “off”. Or in a population of many enzyme molecules, not all may be phosphorylated at a specific site if the kinase activity is low. There are stochastic elements to be sure.

I realize this is an incredibly reductionist view and one about which I am not particularly proud, but if I can convince myself that digital devices are not scarier than the cells I know and love, then maybe I won’t be so afraid of that other cell in my life – the one called iPhone that my 8 year old daughter has to teach me how to operate.

This week my class will be creating models of the building blocks of cells using foods that contain those building blocks. A phospholipid bilayer made out of french fries and donuts. Glycogen made out of angel hair pasta. You get the picture. Almost every cell and molecular biologist I know likes to cook, and I am no exception. I have often wondered why. So much of our best work is microscopic or even submicroscopic. Maybe we get a thrill at coming home from the lab and making something we can actually see. And so much of our work (especially the molecular processes) has to be so precise. 1 microliter of this, 2 microliters of that. Deviate from the protocol (recipe) just a little and you’ve wasted $1500 in reagents (ingredients) and may have set your dissertation back several months. After a day like that, it can be incredibly cathartic to leave those measuring spoons in the drawer, ignore the Joy of Cooking, and start throwing things in the pan. I may be a scientist but there is an artist inside dying to crack some eggs.

Don’t stifle my creativity. Except, of course, when it comes to meringues. Then I’m smuggling my analytical balance and thermometer that reads to .001 degrees home from the lab in the hopes of getting it just right this time.