For the ambitious budding cancer biologist

I’m teaching cancer biology in the fall, and if you want to get a head start over the summer, here are the texts we’re going to be using:

Biol 4103: Cancer Biology

Introduction to Cancer Biology, by Robin Heskith
Cambridge University Press, 1st ed.
ISBN 978-1107601482

The Emperor of All Maladies: A Biography of Cancer, by Siddhartha Mukherjee
Scribner, reprint ed.
ISBN 978-1439170915

Last time around, I used Weinberg’s The Biology of Cancer, which is an excellent, in-depth text, but was really heavy going for an undergraduate course — it’s more of a graduate/MD level reference book. The Heskith book is very good, giving more substantial introductions to the difficult concepts, and also as a bonus, is one third the price. Just having general chapters on cell signaling in normal cells, for instance, will be a big help in bringing students up to speed.

For you outside observers, sorry, but this class won’t be going the supplementary blogging route. I’ve got some other cunning schemes I’m going to try on the students instead.

The first day of the rest of my summer!


It’s going to be a good season, I can tell already. It’s finals week, so I’ll still have an abrupt pile of grading to do on Thursday, but otherwise, my teaching obligations are done for the semester. Now I’m trapped, trapped I tell you, in Morris for almost (I do have two quick trips to Europe planned) the entire summer with a collection of administrative responsibilities, but the good part of that is that I have ambitious plans for what I’ll be doing in the lab. I’m also going to be living the good life.

So this morning I slept in to 7:00. I know, it’s slothful of me, but I have the freedom to indulge myself a little bit now and then. After I got up, I took a nice brisk walk downtown, did some shopping, stocked up on some fresh vegetables, and once I got home, chopped them up and set them to soak in a tasty marinade. I’ll roast them up for dinner tonight.

Then I started reading up an accumulated mass of papers that’ll give me some implementation ideas for the work I have planned.

I’ll have a student working with me, and we’ve got a couple of projects in the works.

  1. There’s some boring scut work to be done: lab cleanup, clearing out old reagents from the refrigerator, making up new stock solutions. Don’t be disillusioned, but part of the research life is janitorial…so much dishwashing.

  2. My grand plan requires an expansion of my fish colony to include multiple genetic strains, so we’re going to be scrubbing tanks, sterilizing surfaces, setting up new tanks with boring feeder fish to get the nitrogen cycle going and condition the water, getting the brine shrimp hatchery (live fish food!) thriving, all that sort of stuff that qualifies you to be a clerk in a pet store.

  3. Once all the tanks are bubbling away happily, we’re getting some new strains from the zebrafish stock center. Then it’s a few months of nursing them along, collecting eggs, propagating new generations and raising them to adulthood to get the whole colony self-sustaining, and to prepare for crosses to produce hybrid strains. After all this, my student will be well-trained to be a hobbyist aquarist.

  4. Concurrently, we’ll be doing some real science on the embryos we get, analyzing their behavior quantitatively to identify consistent differences between strains, and also in response to different environmental stresses. This is going to require a bit of computer work and — oh, no! — basic math to develop image analysis protocols. That’s what I’ve been reading about; I’ve done some of this in the past on an obsolete software system, so I’m going to have to piece together some custom bits to make it all work. I’ve been reading about Fourier analysis and power spectra all morning, and I’m kinda jazzed. Math! Computers! Embryos! Science!

  5. The dream is that once we’ve found some subtle differences between different strains, we can start doing crosses to dissect out and isolate the genetic components, if any, of the behavior. That’s going to take a couple of generations of crosses, which means that if I’m lucky we’ll get those results next year, or at worst, the year after. Behavioral Genetics! Yay! Long generation times! Boo!

It’s step #4 that’ll give us some quick quantitative results, I hope, and maybe something presentable at a meeting or even publishable. It’s all going to be preliminary and descriptive, but that’s what you need to do to establish a foundation for experiments.

Unfortunately for you, I won’t be blogging about any of the details of the work this summer — I’ve been scooped before when I foolishly posted protocols on the web, and especially when you have a very small lab with limited humanpower to throw at a problem, that costs. But I might just occasionally say a few general things about the kinds of analyses we’re doing.

Or I could talk about the moldy stuff we throw out of the refrigerator. That’s probably safe.

What I taught today: FINAL EXAM TIME!

I’m in Arizona, on my way to Orange County, but that doesn’t stop me: I’ve given my students a take home final exam. I wouldn’t want them to be bored over finals week, you know.

1. In the last lecture, I tried to give you a little context, and explained that a dynamic picture of biology would include evolution, ecology, and development, all subdisciplines that deal with change over time. You’re all upper level students; explain to me how developmental biology fits into the perspective on biology that your experience here at UMM has given you so far. Are there pieces you wish our curriculum emphasized more? Why?

2. We’ve spent most of the semester talking about animals — as it currently stands, evo-devo has an unfortunately limited emphasis on metazoans, with an occasional nod to higher plants. Explore a little deeper. What would an evo-devo of fungi, or bacteria, or protists talk about? Is the toolkit we’ve been talking about truly universal? Give me a brief precis of the developmental principles for any other kingdom.

3. Imagine that after you graduate, you find yourself in an unexpected job: you’re working in university press office or as a science journalist. You have to explain scientific research to the public every day. What general principles would guide you? These should be ideas about ethics, effective communication, psychology, etc. in addition to purely scientific concerns. Tell me what standards you’d have to become a great reporter of science.

There. That should make them think.

What I taught today: toroids!

Hox 11/13 expression in an echinoderm blastula

It was the last day of classes for us. I brought donuts.

Dammit, I just realized I missed a golden opportunity. I should have talked to them about Thrive and Pivar and Fleury and Andrulis. Crackpot fringe developmental biologists all seem to have a thing for donuts.

Rats. Well, I’ll just send all my students an email and tell them they have to come back. They don’t even realize the importance of our little snack together.

What I taught in the development lab today

After our disastrous chick lab — it turns out that getting fertilized chicken eggs shipped to remote Morris, Minnesota during a blizzard is a formula for generating dead embryos — the final developmental biology lab for the semester is an easy one. I lectured the students on structuralism and how there are more to cells then genes (there’s also cytoplasm and membranes and environment) earlier today. This afternnon I’ve given them recipes for soap bubble solution and told them to play. They’re supposedly making little model multicellular organisms by chaining soap bubbles together, and observing how the membranes follow rules of organization just like the ones we see in living tissue.

In case you’re wondering what the recipe is so you can do it too, here’s my bubble soap formula:

  • 5ml Dawn dishwashing soap

  • 100ml DI water

  • 1ml glycerine

It gets better as it ages — there are perfumes and a small amount of alcohol solvent in the dishwashing liquid which evaporate off with time. The students are playing with concentrations, and if you’re making it up fresh and don’t want to wait until tomorrow, you can increase the concentrations of soap and glycerine.

The more glycerine you add, the more long-lasting the bubbles are…and unfortunately, the heavier they are. If you want bubbles that will waft gently on the breeze, you’ll want less glycerine. It’s a very forgiving recipe, just play.

I’ve also provided the students with a couple of books: the classic Soap Bubbles: Their Colors and Forces Which Mold Them by C.V. Boys, and The Science of Soap Films and Soap Bubbles by Cyril Isenberg. They’re more about math and physics, but they have some nice illustrations. These are projects you can do at home with cheap ingredients bought at the grocery store, so those of you with kids might try playing with it this summer. There are simple rules about the angles of intersection between bubbles — if you’re mathematically inclined, take pictures and use a protractor and see if you can work them out. There’s also some really cool stuff going on with colors, since the bubbles have a gradient of thickness from top to bottom and you get wonderful colors caused by refraction and reflection and phase shifts across the membrane.

OK, if you don’t have kids, you have my permission to play with soap bubbles, too. Tell everyone who looks at you funny that you’re doing Science!

What I taught today: a send-off with an assignment

Today was the last day I lecture at my developmental biology students. We have one more lab and one final class hour which will be all about assessment, but this was my last chance to pontificate at them…so I told them about all the things I didn’t teach them, and gave them a reading list for the summer. (I know, there’s no way they’re going to take these to the beach, but maybe when they move on in their careers they’ll remember that little reference in their notes and look it up.)

So here are the books I told them to go read.

We’ve been all up in the evo-devo house this semester, so I urged them to read the antidote, just to get some perspective. This is the great big book all the grown-up developmental biologists read and admire and regard as gloriously wrong in many ways, but still an important reminder that physical and chemical properties of whole cells and organisms matter — it’s not all genes. And of course that legendary book is On Growth and Form by D’Arcy Wentworth Thompson. I tell all my students that if ever they want to get serious about developmental biology, they must read Thompson.

For the more modern gang who like computers and math and logic puzzles, I point them at At Home in the Universe: The Search for the Laws of Self-Organization and Complexity and The Origins of Order: Self-Organization and Selection in Evolution by Stuart A. Kauffman. He’d really benefit from more time in a wet lab, but still, there’s some very provocative stuff in those books about how complexity can spontaneously arise. I also gave them a bit of an introduction to NK network theory.

There is always a philosopher or two in the class, so for them I suggest that they read The Ontogeny of Information: Developmental Systems and Evolution by Susan Oyama. Developmental Systems Theory suffers for its lack of applicability — it really is a little too abstract for most scientists — but I love it for its more holistic approach to development.

For the hardcore biologists, the ones who are ready to read a book where every page makes them think very hard, I suggest Developmental Plasticity and Evolution by Mary Jane West-Eberhard. It’s quite possibly the most brilliant book I’ve ever read, but it’s dense and challenging. Intentionally challenging: she really does question a lot of the dogma of evolutionary and developmental biology, and forces you to realize there are a lot of wide-open, intensely interesting questions out there.

And finally, I brought up a book I seriously think about making the class text every year, Ecological Developmental Biology by Scott F. Gilbert and David Epel. The course as it is now is a fairly traditional modern molecular genetics and development class, with a solid overlay of evolutionary biology. The Gilbert and Epel book integrates all that with ecology — and I firmly believe that the well-rounded biologist of the type a liberal arts university tries to generate ought to have a balanced conceptual understanding of ecology, development, and evolution.

That’s the short list. It’s too bad I don’t have total control of my students’ lives, or I’d have them studying ten or twenty books over the summer. Or they probably think it’s a good thing I don’t.

It’s another exam day!

I’ve been terrible about updating everyone about my class the last few weeks — we’re coming up on the end of the semester, so I’ve been going a little bit mad. We’ve been focusing on vertebrate development lately, and right now we’ve got a few dozen fertilized chicken eggs sitting in an incubator and developing embryos. Maybe. It is always a real pain to get these things delivered to remote Morris, Minnesota — I delayed this part of the lab to the very end of the semester, hoping the sun would emerge and warm the hemisphere enough that when UPS took their sweet time getting them to me, they wouldn’t freeze in the back of the truck. As usual, though, next day delivery turned into two day delivery, and we haven’t seen Spring yet. So we’ll soon know whether they survived their harrowing journey through the frigid Northlands, and if they haven’t, I’ll have to throw up my hands and cry.

Or I could torture my students to ease my frustration. Yeah, that’s the ticket. So it’s exam day.

Developmental Biology Exam #3

This is a take-home exam. You are free and even encouraged to discuss these questions with your fellow students, but please write your answers independently — I want to hear your voice in your essays. Also note that you are UMM students, and so I have the highest expectations for the quality of your writing, and I will be grading you on grammar and spelling and clarity of expression as well as the content of your essays and your understanding of the concepts.

Answer two of the following three questions, 500-1000 words each. Do not retype the questions into your essay; if I can’t tell which one you’re answering from the story you’re telling, you’re doing it wrong. Include a word count in the top right corner of each of the two essays, and your name in the top left corner of each page. This assignment is due in class on Monday, and there will be a penalty for late submissions.

Question 1: One of Sarah Palin’s notorious gaffes was her dismissal of “fruit fly research” — she thought it was absurd that the government actually funded science on flies. How would you explain to a congressman that basic research is important? I’m going to put two constraints on your answer: 1) It has to be comprehensible to Michele Bachmann, and 2) don’t take the shortcut of promising that which you may not deliver. That is, no “maybe it will cure cancer!” claims, but focus instead on why we should appreciate deeper knowledge of biology.

Question 2: There is an interesting tension in evo devo: on the one hand, we like to talk about the universality of molecular mechanisms, but on the other hand, we’re also very interested in the differences, both in phenotype and genetics. This is an old debate in evolutionary theory, too, so it’s not unique to development, but how do you reconcile unity and diversity simultaneously?

Question 3: When I told you about axis specification in Drosophila, the story was relatively straightforward: maternal factors switch on a chain of zygotic genes that set up the pattern. When I told you about the same process in vertebrates, though, I didn’t give you the same level of detail—I gave you buckets of transcription factors and said they had various roles. Dig deeper. Pick ONE of these vertebrate dorsalizing factors out of the bucket and tell me more about it: noggin, chordin, frizbee, goosecoid, pintallavis.

My ulterior motive

In case you’re wondering why I’m experimenting with video, there actually is an ulterior motive, and it’s the same one that got me into blogging in the first place: teaching. I’m teaching science at an undergraduate institution, and contrary to many people’s expectations, a bachelor’s degree does not confer a deep understanding of science, and it can’t. Students come out of high school with an ability to read and do basic math (at least the ones we admit to college!), and have wildly varying abilities in writing, analysis, and thinking. I think the undergraduate university’s role is more to deepen the student’s abilities in those general skills, and also to provide a broad knowledge base in a discipline of their choosing. We’re preparing students to go off and do science, if that’s what they want to do. I’ve done my job if my students go to graduate school competent and confident, ready to get to work and explore the natural world. Or if they choose not to follow a science career, they’re open to read and think about the world in a scientific way.

So there are a couple of things I do in my upper level lab courses. I take a hands-off approach: I teach students how to use the tools in my lab, give them a general idea of what would be cool to do or see, and turn them loose. If I see a combination of frustration (“I can’t get it to work! How do I get it to work?”) and play (“What if we do this?”), it’s a success. I have them blogging because it’s a sneaky way to get them to think about the subject of the class outside of class, and also to get them to blend their interests — which usually aren’t identical to mine! — with what I’m teaching.

And then there are presentations. Communicating your work is an important part of doing science, too. I try to get them to do that with the blogging, but also our university promotes a capstone experience, our senior seminars. Before a student can graduate, they have to do a one hour talk on some subject in their discipline, and it’s a big deal/ordeal to the students, and also a big deal/ordeal for us faculty in one of the largest majors on campus. Their quality varies all over the place, even though many of my colleagues and I do incorporate requirements for giving in-class presentations in our upper level courses, and we have a preparatory course on writing that includes giving presentations. There’s a limitation on doing that in class, though: you’ve got 20 students, you can’t chew up multiple class hours getting them all to do rehearsals and rehearsals under your supervision. We usually get an abstract and a promise and a conversation with them to help explain the data, and then boom, they do their talk to the class. It’s one shot and they’re done. That’s not the way to learn.

So I’ve had this idea…this is a generation that’s comfortable with their camera phones, that whiles away hours on facebook and youtube. What if I tried to combine that with doing presentations? What if, in one of my lab courses, I made the final project to be producing a short youtube video explaining some piece of data that they’d gotten in the lab? Put a micrograph or a chart or a time-lapse video on the screen and explain it with a voice-over, or stand in front of a camera while discussing some fine point of theory, or make a how-to video on how to use the microscope. It’s something they could tweak until it looks good, I’d be able to review work in progress fairly easily, and then what they put up for final evaluation might be a little more polished. This would be a useful skill for the future. I’m also rather impressed with how Casey Dunn has his students make creature features.

One catch: to have the students do it, I have to be able to do it. So in my spare time (hah!), I’ve been tinkering with ideas. I got some clamp lamps to play with lighting, I’ve got some cheap and simple backdrops to play with, I read Steve Stockman’s How to Shoot Video That Doesn’t Suck (which has a lot of damn good basic practical advice), and I’ve been doing some experimenting, most of which will never see the light of day. I’m learning stuff, which is always fun.

And it’s useful stuff, too. For instance, I’m a words and typing sort of guy, so my approach so far has been to write a script and then wrap video and images around it. That doesn’t work so well. I’m slowly learning that in this medium you start with video and images and wrap words around them. And that’s exactly what we do routinely in a science talk! You’ve got these chunks of data in the form of images and numbers, and what you do in a presentation is show them and add your verbal explanation on top. Man, I ought to know this stuff already. I just have to adapt.

So this summer you might be seeing more of my unphotogenic face in videos as I clumsily try to get some basic skills in this medium. The payoff, though, is that in a year or so I’ll be able to teach my students how to do it better, and then we’ll get a fine new crop of video stars who are comfortable explaining science in front of a camera.

But don’t worry, you don’t have to suffer through my struggles, just don’t watch me.

What I taught today: O Cruel Taskmaster!

I’m out of town! Class is canceled today! But still, my cold grip extends across the Cascades, over the Palouse, the Rockies, the Dakota badlands, the old homeland of the American bison, the the great farms of the midwestern heartland, to a small town in western Minnesota, where I crack the whip over a tiny group of hardworking students. They’ve been mastering the basics of timelapse video microscopy in the lab this week, I hope, and will be showing me the fruits of their labors on Monday. I’m also inflicting yet another exam on them over the weekend. Here are the questions they are expected to address.

Developmental Biology Exam #2

This is a take-home exam. You are free and even encouraged to discuss these questions with your fellow students, but please write your answers independently — I want to hear your voice in your essays. Also note that you are UMM students, and so I have the highest expectations for the quality of your writing, and I will be grading you on grammar and spelling and clarity of expression as well as the content of your essays and your understanding of the concepts.

Answer two of the following three questions, 500-1000 words each. Do not retype the questions into your essay; if I can’t tell which one you’re answering from the story you’re telling, you’re doing it wrong. Include a word count in the top right corner of each of the two essays, and your name in the top left corner of each page. This assignment is due in class on Monday, and there will be a penalty for late submissions.

Question 1: One of the claims of evo devo is that mutations in the regulatory regions of genes are more important in the evolution of form in multicellular organisms than mutations in the coding regions of genes. We’ve discussed examples of both kinds of mutations, but that’s a quantitative claim that won’t be settled by dueling anecdotes. Pretend you’ve been given a huge budget by NSF to test the idea, and design an evodevo research program that would resolve the issue for some specific set of species.

Question 2: Every generation seems to describe the role of genes with a metaphor comparing it to some other technology: it’s a factory for making proteins, or it’s a blueprint, or it’s a recipe. Carroll’s book, Endless Forms Most Beautiful, describes the toolbox genes in terms of “genetic circuitry”, “boolean logic”, “switches and logic gates” — he’s clearly using modern computer technology as his metaphor of choice. Summarize how the genome works using this metaphor, as he does. However, also be aware that it is a metaphor, and no metaphor is perfect: tell me how it might mislead us, too.

Question 3: We went over the experiment to test the role of enhancers of the Prx1 locus which showed their role in regulating limb length in bats and mice. Explain it again, going over the details of the experiment, the results, and the interpretation…but without using any scientific jargon. If you do use any jargon (like “locus”, “regulation”, “enhancer”), you must also define it in simple English. Make the story comprehensible to a non-biologist!

Yeah, you don’t have to tell me. I’m evil.

What I taught today: those oddball critters, the vertebrates

We’ve been talking about flies nonstop for the last month — it’s been nothing but developmental genetics and epistasis and gene regulation in weird ol’ Drosophila — so I’m changing things up a bit, starting today. We talked about vertebrates in a general way, giving an overview of major landmarks in embryology, and a little historical perspective.

We take a very bottom-up approach to studying fly development: typically, fly freaks start with genes, modifying and mutating them and then looking at phenotype. Historically, vertebrate embryology goes the other way, starting with variations in the phenotype and inferring mechanisms (this has been changing for the last decade or two; we often start with a gene, sometimes from a fly, and use that as a probe to hook into the genetic mechanisms driving developmental processes). What that means is the 19th and early 20th century literature on embryology is often comparative morphology, looking at different species or different stages and trying to extract the commonalities or differences, or it’s experimental morphology, making modifications (usually not genetic) to the embryo and asking what happens next. Genes were not hot topics of discussion until the last half of the 20th century, and even then it took a few decades for the tools to percolate into the developmental biologists’ armory.

And much of 19th century embryology went lurching down a dead end. We talked about Haeckel, the grand sidetracker of the age. There was a deep desire to integrate development and evolution, but they lacked the necessary bridge of genetics, so Haeckel borrowed one, his theory of ontogenetic recapitulation. A theory that quickly went down in flames in the scientific community (jebus, Karl Ernst von Baer had eviscerated it 50 years before Haeckel resurrected it). We actually spent a fair amount of class time going over arguments for and against, and modern interpretations of phylotypy — it isn’t recapitulation, it’s convergence on a conserved network of global spatial genes that define the rough outlines of the vertebrate body plan.

Finally, I gave them a whirlwind tour of basic developmental stages of a few common vertebrate models: frog, fish, chick, and mouse. We’re going to talk quite a bit about early axis specification events in vertebrates (next week), and gastrulation (probably the week after), so I had to introduce them to the essential terminology and events. I think they can see the fundamental morphological events now — next, β-catenin and nodal and Nieuwkoop centers and all that fun stuff!

(Today’s slides (pdf))