It’s spring of 2014, I’m teaching a course that I have not taught since my SCALE-UP epiphany, and thus, this blog will morph yet again. But what could be more appropriate for a morphing blog than a course in Developmental Biology? It’s been a while, but I have taught this class before, and as I’ve already told my students, it is my absolute favorite class to teach. What? More fun than Cell and Molecular Biology? Even better than Cancer Biology? Yes, it’s that good.

I’m not entirely certain why but throughout my graduate education and career as a cell, molecular and developmental biologist, the title of developmental biologist was always the most comfortable fit for me. Developmental biology is about change, upon which I thrive, but even more than that, it’s about progress, about moving forward toward ambitious yet achievable milestones – gastrulation, organogenesis, hatching (or birth).

In my own research, I studied the development of frogs. I found frogs to be a particularly compelling model organism because, just when this creature seems to have mastered something (e.g. swimming from predators), BAM!, it’s time to switch gears completely, active new developmental programs, and start all over again. Let’s lose that tail and grown some legs!

fertilized Xenopus eggs

My research program focused on a particular developmental milestone called   the midblastula transition, or MBT, in the South African clawed frog, Xenopus laevis. Prior to the MBT, Xenopus embryos undergo rapid cell divisions, such that within five hours of fertilization, one relatively large cell, the egg, has become 4096 microscopic cells. With mitosis occurring every 30 minutes in near synchrony across the embryo, there is little time for the embryo to do anything else. No time for growth, no time for gene expression (the embryo relies entirely upon maternally stored mRNA and proteins), and apparently no time to worry about mistakes. This last characteristic is where I made my contributions to the field of frog development. I was interested in cell cycle checkpoints, those mechanisms present in eukaryotic cells that put the breaks on the cell cycle when something is seriously wrong such as damaged or unreplicated DNA. But early Xenopus embryos didn’t seem to engage these checkpoints.  We blasted embryos with gamma rays and X-rays to damage the DNA and the embryonic cells kept dividing in synchrony with their untreated siblings, every 30 minutes. We treated the embryos with a drug called aphidicolin to completely block DNA replication and they kept on dividing. With no DNA….

blastula stage (pre-MBT) embryos

….until the MBT, when Xenopus embryos with damaged or unreplicated DNA engaged in what I came to refer to as the mother of all checkpoints. At the stage when embryos should have initiated transcription of their own genomes for the very first time, those with damaged or unreplicated DNA committed apoptosis, or programmed cell death (Sible et al, 1997). And it wasn’t subtle. Dying cells would come spewing out of the blastocoel, the hollow cavity of the embryo, like a tiny little volcanic eruption. I spent hours upon hours peering through the microscope, in morbid fascination of these embryonic suicides.

embryos undergoing apoptosis

Why in the world would this happen? I lost a lot of sleep over this question. My favorite speculation was that the “apoptotic checkpoint” as we called it, provided distinct advantages for the organism. Frog embryos do not have mouths to eat nor tails to swim away. Floating around in the pond, they are about as vulnerable as a human infant. It is in the best interest of the embryo to develop quickly into a tadpole. The first order of business is cell division, which as I mentioned, happens quickly. Up until the MBT, the embryo is little more than a ball of undifferentiated cells, and it is only after gene expression begins at the MBT that one cell is significantly distinctive from another. Perhaps, rather than wasting time engaging checkpoints at every cell cycle, Xenopus embryos have evolved to divide unchecked until the MBT, the first time when damaged or unreplicated DNA would have a consequence, and at that stage, use the apoptotic checkpoint to clean house, ridding the embryo of any genetically damaged cells. In our experiments, we used insanely high doses of ionizing radiation or chemicals, but in the real world, these damaging events would likely be few and far between, with just a few of those 4096 cells in need of removal. Recent experiments by undergraduates working in my lab have supported this  hypothesis. They were able to ablate a certain percentage of cells before the MBT and the embryo would develop into a more or less normal tadpole (Mulholland et al, unpublished).

This story might have had a scientifically satisfying ending if it weren’t for the spring peepers. I love listening to them through my bedroom window at night, which got me interested in local species of frogs such as those studied by my friend and colleague Dr. Lisa Belden. Virginia is home to not only spring peepers, but also wood frogs, bull frogs, American toads, green frogs, gray tree frogs, and more. Under Lisa’s tutelage, I began mucking through puddles and swamps.  My neighbors would catch me sneaking into their cultivated fish ponds at night, flashlight in hand, looking for frog eggs. I became obsessed with collecting embryos from as may amphibian species  as possible. My children do not have fond memories of this period. I dropped one of them, then a toddler, into an ice-crusted pond in February while reaching for wood frog eggs. She marks that as the day that she decided to become a lawyer, not a scientist.

My goal was simple – establish the apoptotic checkpoint in as many species as possible, then publish the findings in a good journal. Once I established some credibility with the ecology crowd, I could pursue the ‘why’ questions about the apoptotic checkpoint though field studies.

The experiments were straightforward. We collected pre-MBT embryos from native species, blasted them with X-rays, then waited for them to die at the MBT. We waited, and waited, and…..waited. Nothing happened. The embryos did not undergo apoptosis, but they did not move past the MBT into gastrulation either. They just sat there with arrested development. We waited for hours and hours. We waited days. We waited weeks. Nothing happened. Eventually the embryos died, but not in any developmentally meaningful way. The dishes in which we kept them would become contaminated and moldy. Or someone would forget to add more medium and they would dry up. So much for easy answers, or publications for that matter. I didn’t know what to make of these data, and honestly I still don’t. Xenopus laevis is one of a handful of established model organisms for studying vertebrate development. We extrapolate our findings to fish and mice and people. But these data suggested that the discovery of the apoptotic checkpoint, although it had later been demonstrated in zebrafish (Ikegami et al, 1999), did not apply to all frogs, certainly not to Virginia frogs. Even more puzzling, our data suggested that embryonic development could be arrested, for a long time, maybe even perpetually. This was not what I signed up for when I became a developmental biologist. I wanted embryos with ambition, with a future, that knew where they were going and got there fast. That’s how I rolled.

At least, that’s how I used to roll, until about a month ago when I was rolling at a good clip down a hill on my bike. Then, before one could say ” midblastula transition”, I was on the ground surrounded by a patch of black ice with a fractured inferior pubis ramus. “What can I do to accelerate the healing?”, I asked the orthopedic. “Rest”, he replied. “How about cycling on the trainer? Physical therapy? Hot yoga?”, I persisted. “Nothing”, he growled. “The only thing you can do to get better is do nothing!”

I was sentenced to at least 8-12 weeks of arrested development, something extremely difficult for a distance athlete to come to terms with. But I complied and did nothing. A whole lot of nothing. I held out as long as I could stand it, until I started to feel kind of moldy and dessicated. Then I thought, “Hmm, development always moves forward, and that’s not an option, but what if it could move backwards? What if, under the right circumstances, a frog could undergo reverse metamorphosis? What if global warming and melting of polar caps will eventually cause the de-evolution of land animals back into creatures with fins and gills?”

So I took to the water, and am learning to swim despite the nagging of my inner frog, “wrong direction, lady”.  It’s the one time I can move without asking anything of His Excellency Pubis Ramus. Perhaps becoming  a swimmer is my MBT, or my likely my MLC (mid-life crisis). At any rate, it feels good to be moving again.

tadpoles!

A public service announcement from your friendly Assistant Vice President:

For students and faculty alike, this may be the most stressful week of the year. Taking exams, grading exams. It’s hard work all around. I’m grading final projects, rather than exams, which is a whole lot more fun, but I still need to get up and move every so often, and I’ll bet you do too.

So shut your office/dormitory door, and take a little dance break. Or better still, if you dare, open that door wide and crank up the music. This is the stuff flash mobs are made of.

Here’s what I’m listening to. Feel free to add some music of your own, especially you sweet young things, since some of these songs date back to my undergrad years:

 June Bug – the B-52s

June Bug from the B-52’s Cosmic Thing. Very fond grad school memories of professors and students dancing all night to this album.

Lady – or pretty much anything by Lenny Kravitz

Lenny Kravitz, pre-Cinna

She Just Wants to Dance – Keb’ Mo’

Keb’ Mo’ -nothing beats the blues like his blues

Now back to work!

Tonight was the first of three sessions in which my Cancer Biology students present their final team projects. The assignment was simple: create a public work, using any medium of your choosing, to demonstrate understanding and add meaning to the Hallmarks of Cancer. The six hallmarks of cancer, as first articulated  by Douglas Hanahan and Robert Weinberg in a paradigm-shifting Cell paper in  2000, had been the focus of our class all semester.

My students had taken off in all sorts of different directions with this assignment, and I had seen outlines and bibliographies along the way, but it wasn’t until tonight that I would see the final products and the fruits of their labor.

I wanted this evening to be special. When teaching a subject like cancer, there is always the danger of irreverence, of getting so caught up in molecules and mutations that we disrespect those suffering from the disease. I definitely did not want to do that. I wanted tonight to be special. Event planning resides on the long list of tasks I undertake as a faculty member and they definitely did NOT teach me in graduate school, so I was a bit stressed out trying to get the programs from the printers at the last minute, test the A/V equipment and set out some food. And candles.

I decided the best way not to forget the people with cancer was to remember them – explicitly. So I made a little shrine, a place to light a candle and leave a note in remembrance of someone lost to cancer or in honor of a survivor. Because my daughters helped with the shopping, the candles were not novena-white, but rather a lovely palette of colors and smells.

Phew, 5:55. I had the room ready just in time. I quickly wrote my father’s name on a slip of paper and dropped it into the jar and lit a bright blue candle – the color of his eyes. Then the first students entered the room.

Remarkable. That’s the closest I can come to describing these student projects. Here’s a recount of just a few of them:

Team Totally Radical started the evening with a presentation on antioxidants and cancer. Their public work was a meal plan whereby fellow Virginia Tech students could follow a diet rich in antioxidants by choosing foods available in the dining halls. Their medium was simple but time-and-again proven to be the most effective mode for communicating with Virginia Tech undergraduate students – little cards that get placed on every table in the dining halls, particularly suited to this project.

The Fantastic Four Minus One (long story) were next. Early in the semester, this trio had latched on to the idea of writing a story book explaining the hallmarks of cancer for children who were dealing with cancer. Their metaphors were spot-on and the illustrations just delightful.

Next up was Team Pap Smears, who had created an educational brochure on cervical cancer, including critical information about prevention and human papilloma virus. The team passed out ribbons in cervical-cancer-teal (nice touch). They were dressed to the nines in coordinating black and white outfits. As they talked about safe sex and vaccinations, I couldn’t help but think of my own daughters with whom I would need to have these discussions soon. As a mother, I want the best for my daughters. I want them to be strong, intelligent and beautiful like these six women who were standing in front of me.

And now for something really amazing….  “What if we want to do something different than covering the hallmarks of cancer?”, Team for a Cure had asked me early in the semester. “As long as it’s truly awesome, better than what I assigned, them I’m OK with that,” I replied. That’s practically the last I heard from Team for a Cure. “How are you doing?” I would ask periodically. “Fine.”   Then last week, I got an e-mail from a colleague whose graduate student was mentoring this group. “Jill, I think we might be able to publish their project. How do you feel about that?” I was stunned. Tonight, I was just about speechless as the group provided an overview of a detailed set of analyses they have performed using a variety of publicly available genomics databases to explore  (and ultimately disprove) a popular hypothesis regarding aneuploidy (the loss and gain of chromosomes) and cancer. At the end, they described their plans for the next phase of the project. “Hello- this is your final presentation. Classes end tomorrow.” These students don’t care. They aren’t doing this for the grade. They aren’t doing this for ME. These are scientists, with a passion, on a mission. They are conducting original, authentic research, research that matters to them, and apparently to the world. “We put our presentation up on the web today, and we already have 100 hits.”

WOW! I’d love to take credit for this deschooling within school, but honestly, I didn’t do anything, except to create an assignment which they pretty much ignored to go off and do something better.

As you can see, it was quite the evening and I haven’t even described all of it, including the blog readings, which to be poetic, deserve a blog post all their own.

After the final presentation, I begged off the students’ offers to stick around and help me clean up and carry the leftovers to my car. “Thanks, but go on. I, um, need to check my e-mail before I go.” The truth of the matter was, I needed to be alone in that space for a little while. Since my fortunate return from the tragic Boston Marathon, I’ve pledged to live most fully in the present and to take nothing for granted. To take no one for granted.

I walked over to my little shrine.  My dad’s candle had extinguished but many others were shining brightly. I dimmed the lights then lit one more candle, a sunny yellow one, and said a little prayer of thanksgiving for my students and for the hope that they give me for our future.

“Race for the Cure” “Until We Find a Cure” The disease is so ubiquitous, no one one even bothers to name it anymore. When I was younger, I believed there might be a cure. At one point, I even believed I might discover the cure.

But that was before I came to appreciate that it was not one disease in need of a cure, but hundreds, or taken to the extreme point of view, that every incidence was as unique as a snowflake, at least from a genetic point of view. That was before this disease reached its current incidence of affecting 1-in-3 women and 1-in-2 men. I believed in a cure before cancer killed my father. After that, I believed that the problem of cancer was too big, too complex for anyone to cure.

Ten years later, I still hold to that belief. The more I learn about cancer biology, the more daunting the problem becomes. But recently, especially as I view cancer biology through the eyes of my students, I have hope. Cancer may be too big a problem for any ONE person to solve. Indeed cancer has proven too much for a host of scientists and clinicians spending millions upon millions of dollars in research. But what if we opened up the problem of cancer to EVERYBODY who wanted to contribute? For a number of unrelated and somewhat anecdotal reasons, I am hopeful this strategy might work:

1. Jack Andraka – Several of my students have been blogging about Jack Andraka. Caitlyn’s post is the most recent. Jack is a 15-year-old who has developed a rapid, sensitive and super-cheap (3 cents!) early detection test for pancreatic cancer. Jack was inspired when he lost a close family friend to this disease. He conducted his research on the Internet, initially with simple Google searches. And after contacting 200 ‘real’ scientists, he found one, a professor at Johns Hopkins, who let Jack into his lab to test his ideas. How many other Jack Andraka’s might be out there?

2. Foldit – The Foldit story is well known now. To whom does science turn  to solve the protein folding problems that elude the world’s leading structural biologists? To gamers, of course. Scientists had been unable to solve the structure of the HIV protease, a key target for AIDS prevention and treatment, for decades. Players of Foldit, a free Internet game, discovered the protease structure in just three months.

3. Naked mole rats – Naked mole rats never get cancer. Never ever. Their near relative, the garden variety rat, has a 70% lifetime incidence of cancer if something else doesn’t kill it first. The National Cancer Institute doles out the majority of its funding to support research on just a handful or so of ‘model organisms’ for cancer. Rats, mice, fruit flies, brewer’s yeast. While these organisms span quite a phylogenetic range, they do not begin to represent the diversity of species that might offer insight into this disease. Bolker and Raff made this point  eloquently years ago (Bolker and Raff, 1997, J. NIH Res. 9:35-39) as a backlash to a bold assertion that zebrafish need be the only model organism for vertebrate development. What are we missing by not investigating cancer, or the lack thereof, in as many organisms as possible?

I suspect that many scientists would argue that there just aren’t enough of us to go around. We can’t study everything.  I get it. As a developmental cell biologist, I spent well over a decade investigating the first five hours of life in a single species of frog. So what if we deputized a few thousand – maybe a few million – other people to help us out? So what if they don’t have PhDs? Jack Andraka doesn’t have a PhD. I’m not even sure he can drive a car yet.

What if cancer, which is already everybody’s problem, became everybody’s problem to solve? What if in addition to asking everyone to open their hearts and their wallets, we asked them to open their minds? What if?

Here’s a post that will double for my Cancer Biology class blog and for my personal blog. How’s that for efficient?

Teaching cancer biology is a love/hate situation for me. Love the students. Hate cancer. Love the cells, the molecules, the signaling pathways, the microscopy. Hate cancer. Love how engaged my students are becoming with the material and how hard they are working. Hate, hate, hate cancer!

One of the first pieces of information that I share with my students is the lifetime probability of getting cancer. In the US, it’s 1 in 3 for women and 1 in 2 for men. Those are staggering, haunting statistics. When I taught graduate cancer biology almost a decade ago, the focus of discussion was treatment, and while that is still a significant part of the current course, science, society and my students have noticeable shifted attention to the topic of prevention.

Given today’s lifestyles, it might be more efficient to talk about what doesn’t cause cancer. Avoiding carcinogens seems almost impossible. This morning while I was fighting obesity, which shows a strong correlation with cancer, by running hill repeats my neighbor was warming up his car for 30 minutes in his driveway located at the top of the hill!!! I might as well have rewarded myself with a Marlboro after every lap.

Sometimes it’s hard to sort out the facts from the urban legends with respect to carcinogens. I often rely as much on my ‘mom intuition’ as much I do on my PhD in cell, molecular and developmental biology. And I think most moms would agree that anything that does this to your kid’s tongue – and face – and hands….

…just can’t be good for you.

Artificial food colorings make me nervous in general, but I am particularly frightened of reds. In 1976, red dye No. 2 was banned by the FDA because of studies showing that high doses could cause cancer in rats. Goodbye red M&Ms. And hello to a longstanding war between moms and artificial dyes. I’d consumed a good eight years worth of red dye No. 2 so my mom was able to blame it on pretty much everything that was wrong with me. In recent years, red dyes have been correlated with everything from ADHD to depression to potentially, cancer.

Apparently, this red-o-phobia never quite made it to the Southeastern US. When I first moved to Virginia, I was introduced to that southern delicacy known as red velvet cake.

mmm, red velvet cake

Ooh, that was good stuff. Being a pretty serious baker myself, it wasn’t long before I attempted my first red velvet cake and was horrified when I read the ingredients list. Two tablespoons of red food coloring. TABLESPOONS! That had to be a typo, right? Maybe two drops or teaspoons at worst. I found another recipe. FOUR TABLESPOONS! That seemed like enough red dye to kill off a whole colony of rats. I double-checked the food coloring box to make sure red dye No. 2 wasn’t still marketed down South.

Phew. This was red dye No. 40. Forty!!! What happened to red dyes No. 3 – 39? How many poor rats would have to keel over before people realized that cakes were not meant to be red?

Which brings us to Valentine’s Day and a mother’s dilemma. Cool moms make cupcakes. Really cool moms make chocolate cupcakes with pink frosting. I want to be a really cool mom. But I also don’t want to be feeding my kids carcinogens, real or imagined.

Thank goodness for for Joy the Baker! This lady is a baker, and a blogger, after my own heart. Kroger, the local grocery store, is featuring her recipes, which is how I discovered her defense against artificial red dyes: chocolate beet cake with beet cream cheese frosting. I know what you are thinking:  “EEEEWWW!” That was my first reaction too. I’m not a beet fan, but I was desperate enough to try anything to substitute for red dye No. 40. My daughter Chloe and I used the recipe to make cupcakes, and I must say they were delicious – rich, moist, very pink, and not beety at all.

a baker’s dozen. For me, that’s 12 minus the one I ate.

Not only do beets not cause cancer, but they might actually guard against cancer, colon cancer in particular. So the next time you are in the mood for something sweet and red, consider trying Joy’s recipe at the link above. It can’t be beet (sorry, I couldn’t help myself).

2013 may prove to be the year of challenges for me. A new administrative job with some awesome opportunities and the responsibilities to go with them. The Boston Marathon, at last. And far from least, offering a cancer biology class in an active learning format.

When I was first asked to teach the course, I thought, “no problem.” I’ve been teaching a sophomore cell and molecular biology course for 50+ students in a SCALE-UP setting for three years now, and each iteration worked better than the last. Cancer Biology was a senior level class. The students would be even more mature and many would be repeaters from Cell and Molecular Biology. The material was inherently interesting. And I’d taught a graduate level course in cell cycle and cancer many times. I felt a little guilty, as I often do when it comes to teaching. I really shouldn’t get paid to have this much fun. Then I asked about the enrollment. I didn’t want to take up precious time in the SCALE-UP classroom if we could all fit around a conference table. Or maybe we could just have class at Panera until the weather turned warmer and then we’d sit under a tree.

“A hundred twenty.”

“A hundred twenty, WHAT?,” I asked.

“Students.”

Gosh. We’d have to find a really large tree.

And therein I found the challenge. And hopefully the opportunity to earn my faculty paycheck. An “active learning” setting is the way to go, I am convinced. And really, as many others have said before me, does authentic learning ever occur if the learner is not active?

But to replicate the SCALE-UP setting for 120 students seemed near impossible. How would I find the time to connect with each student? And cancer biology is a dense and rich discipline. The best material comes from the scientific literature, and I want the best for my students. But that literature is difficult to locate and even harder to read. So how could I connect with and guide 120 students through this horrifying, fascinating and murky landscape called cancer biology? In the end, I reached way down into the recesses of my bag of teacher tricks and pulled out:

1) scare them away. Honestly, I didn’t mean to use this one. For the first day of class, I put on my cutest dress and smile and my cowgirl boots determined to sell everybody a ticket on  the Cancer Biology Express. I was a bit flustered when the pseudo-SCALE-UP classroom didn’t deliver everything promised and my laptop did not want to play nice with the projector, but all-in-all, I thought the first day went pretty well. However, by the end of the week 120 was down to 100 and today down to 93. Wow! I’ve never lost that many before. What happened? I’ve been told by some senior biological science students before that they reach my class without ever having had to write  or speak or work in a group for a science lecture class. If that’s the case, I can see how a class that incorporates blogging and team projects and daily discussion could seem like too much work or just plain scary. I’m sad to see them go, but 93 does feel a whole lot more manageable I have to admit.

2)- and this is what I really intended to blog about – lecturing. I’ve become a strong critic of professors whose exclusive teaching tool is the stand-and-deliver lecture. The sage on the stage who delivers a monologue while the students obediently try to capture his every word. Or go on Facebook. Or text their moms. Lecturing may be active teaching, but for the student, the experience seems the antithesis of active learning. But for 120 (OK, 93) students trying to learn content and context as advanced as cancer biology, I couldn’t think of any better way to help them through some of it.

So I decided to lecture once a week on Fridays. The first lecture was OK, but I was rusty. I wasn’t used to talking to students for more than 20 or 30 minutes, and I actually got a little winded. The second week, I had planned to talk about the discovery of oncogenes. It’s a wonderful story, one of the best in science. In the early 20th century, people thought cancer was contagious. And then one scientist discovered that sometimes it is, at least in chickens. Then he isolated the infectious agent and it turned out to be a virus. Interesting. Then decades later, early molecular biologists pinpointed the viral gene responsible for causing cancer and discovered that the gene’s origin is the chicken itself. And the chicken gene was perfectly normal and found in every cell. And the same could happen in humans, for example with human papillomavirus, which causes cervical cancer. As I was lecturing, I grew more and more animated. I wasn’t satisfied with my students learning the information, I wanted to captivate them with this tale. Yes, I wanted them to care as much about the src gene as I did. Gosh, I wanted to convert them.

Lecturing can be a bit of a rush, and by the end, I was feeling downright evangelical. In fact, after dedicating the class to one of my favorite college professors, Dr. Andy Laudano, who first told me the story of the src gene, I preached to  my students to make the effort to give a word of thanks to their favorite professors because that appreciation means a lot. Perhaps I went a bit too far. I hope not.

I’m more convinced than ever that lecturing can be dangerous, and I’ll be careful. On Sundays, I go to church and listen with both ears to the good word for an hour or so. Then I spend the rest of the week trying to put into practice what I heard. Sometimes it’s not easy, but that is when I learn the most. And while my lectures may be trivial in comparison, I hope that they offer a small measure of inspiration for my students to do the same.

Beginning next week, our class will engage with the cell biology of cancer. Hanahan and Weinberg’s paradigm shifting “Hallmarks of Cancer”, published in 2000 and their recent sequel, “Hallmarks of Cancer: The Next Generation”, will guide our discussion. For over a decade, I have chosen this pathology as the basis for learning about cell signaling, cell cycle and cell death. Not only does cancer make sense as a conceptual framework for learning these topics, but cancer also evokes an emotional engagement with the topic. The American Cancer Society reports that 1 in 3 women and 1 in 2 men will develop cancer during their lifetimes. Given those statistics, I feel safe in concluding that cancer matters to everybody in my class.

While emotional engagement with educational subject matter can be a strong motivational tool, when we are talking about cancer, it can potentially be a roadblock. A discussion of cancer, no matter how factual or academic or cellular can take people to exactly the places they would rather avoid, especially when trying to focus on school. With an awareness of this challenge, I have always invited my students to share their cancer stories as a way of preparing themselves for the weeks ahead. Some choose to tell, some do not, and that is fine.  This year, I have extended the same invitation, but rather than hosting a discussion in class, I have suggested blogging as the forum for those who would like to tell their cancer stories. Here is mine:

I got the first phone call in the summer of 2000. I was an Assistant Professor at Virginia Tech with a promising research program investigating cell cycle checkpoints in frog embryos. Frog embryos share many properties with cancer cells, and I had recently been funded with my first big grant from the National Institutes of Health to support my work. Mom said that Dad had been to see his doctor, insisting on an X-ray because of a pain in his chest that was not going away. “Jill, the X-ray showed a black spot as big as my fist. What does that mean?”  What was I supposed to say? My family never really accepted the distinction between a Ph.D. and an M.D.  and assumed that if I had “Dr.”  in front of my name, I could answer all of their medical concerns. Also, that I would know what to do in situations like these.

The diagnosis came a few days later. Multiple myeloma. This is essentially a cancer of the bone marrow, of the precursor cells to B cells, which produce antibodies.  I began my research right way. “No cure.” “Estimated life span: 1 – 5 years.” “Etiology, unknown, some correlations to industrial exposure to chemicals.”

I rapidly became an expert on multiple myeloma. I understood the disease, the treatment options, the test results. What I didn’t have in hand, all that I really wanted, was the cure. The most promising treatment was autologous stem cell therapy. This option made perfect sense to me: remove stem cells from the bone marrow and separate the healthy from the cancer cells. Apply chemotherapy to essentially destroy the patient’s remaining bone marrow stem cells and then repopulate the hematopoetic system with healthy cells. There were risks to be sure, but the design was brilliant and had been successful for many people in clinical trials.

My Dad was scared but appreciated the logic of this approach and wanted to pursue this avenue. We read more. We attended workshops. We found the specialists. We were ready to move.

We were denied this treatment. The doctor explained that my Dad’s other health problems: high blood pressure, heart disease, rheumatoid arthritis, placed him in a category that was “statistically too risky for the procedure.” “My father is not a statistic”, I wanted to scream, but both the physicians and insurance company would not approve this approach. They offered the more alternative conservative treatments of surgery, then radiation then chemotherapy. Based on my reading, I surmised this would likely buy him a year or two, not the long lifetime he deserved, but we decided that by then, additional options would be available.

Dad was stoic throughout the course of treatment. He and Mom lived in Florida, so I was not a direct witness to the effects of the treatments. Dad told me he felt fine, and Mom told me the truth. After a rough 6 months, Dad was pronounced in remission.  He was put on thalidomide as a maintenance. He enjoyed several visits with his baby granddaughter, my daughter Simonne. He took her to the beach. He ate Cheerios with her.

About two years from the diagnosis, Dad declared he was cured. He and Mom talked about moving to Virginia to be closer to Simonne and the new grandbaby I was carrying. Then Dad started feeling tired. A routine visit to the oncologist showed his M protein count was up.

I have a hard time remembering much of the next few months. Everything happened quickly. Relapse. Aggressive chemotherapy. M counts up one week, down the next, and way up the third.

What I do remember distinctly is my visit with my parents in September 2002. It was my mom’s birthday. Dad had a break between chemo treatments. He slept most of the day and was very irritable. A life-long devout atheist, he initiated a prayer before dinner one evening, thanking God for bringing me and Simonne to see him. The next day, he asked my mom  take him shopping. He could barely walk but insisted on going to the florist and refused my mom’s offer to make the purchase for him. He came back to their house and presented me with a gorgeous bouquet that he picked out himself.

The next day Simonne and I were to leave for the airport and my Dad was scheduled for chemotherapy. I offered to come with him, but he insisted I get “on the road” and avoid the traffic. Simonne and I returned to Virginia. After I left, Dad told Mom he was not going to chemotherapy. Mom offered to reschedule. Dad said no. He was not going back anymore.

About a week later, September 17, 2002, I had the chance to take the Hokie Bird private jet to travel with some colleagues to Purdue University to visit their cancer research center. I enjoyed the flight immensely and fortunately, kept the morning sickness at bay. When I returned home late that evening, my husband was giving Simonne a bath. He looked up at me and said gently, “Your father passed away this morning.” He told me all that my mother had related to him and than added his own commentary. “He died with dignity and grace.”

It’s been nine years since Dad died. He never met Chloe but she loves to hear stories about Pap. On occasion, I still pick up the phone to call my dad. He was a brilliant engineer and used to talk me through fixing pieces of laboratory equipment that he had never actually seen. Dad had a stressful job but he never missed an evening with the family, refused to work weekends, and always, always had time for me. He may not be a physical presence in my life, but he is never very far.

I love you Dad.

Last week, I skipped my own my cell and molecular biology class to attend the Undergraduate Science Education Program Directors and Professors Biannual Meeting of the Howard Hughes Medical Institute. The meeting was held at the HHMI headquarters in Chevy Chase, Maryland, which is amazingly posh. I wanted to snag a few photos, but I am a newbie in this group and didn’t want to embarrass myself by acting like a tourist.

I realize that many of my students have not yet attended a scientific meeting, and while this meeting was a bit atypical – the focus was on science education rather than an area of scientific research – it might be valuable to share some of my perspective from this meeting. Also, it might assuage some of my guilt for skipping my own class. (How’d it go guys? Were you OK without me?) So here’s a recap of day 1:

On the opening night, typical of many scientific meetings, we had a social hour (read: beer and wine), a big dinner (read: more wine and ice cream), then our first presentation from 7 – 9 PM. These evening sessions are always a challenge for me. At meetings, I try to counteract the eating and drinking with some serious exercise, and that morning, I set out for an 8-turned-12-mile-run where I got very lost. Consequently, I was dragging as I entered the auditorium and said a little prayer that I wouldn’t embarrass myself by falling asleep, or if I did, that at least I wouldn’t snore.

I hadn’t looked at the meeting program very carefully, so when I walked into the auditorium,  I was surprised to see that the title of the evening session was “Science Education through Film”. Film? Not the usual meeting fare, even for an education meeting. I like movies. This session might not be half bad.

And it wasn’t. The session was quite good indeed, and just like some of my favorite movies (e.g. The Usual Suspects), the real plot twist came at the very end, and jolted me right of out of that comfortably numb state of being passively entertained for a half hour or more. The movie, The Day the Mesozoic Died, was a compelling documentary about the key discoveries that led to contemporary understanding that dinosaurs really did go extinct rather abruptly due to a cataclysmic collision of an asteroid with Earth. The movie was produced and narrated by Dr. Sean Carroll, a notable evolutionary biologist and science writer and Vice President for Undergraduate Education at HHMI. Carroll was clearly proud of his work. The target audience is K-12 classes, with an obvious intention to combat creationist momentum, but also to hopefully inspire future generations to become scientists with a compelling story of scientific discovery. I felt Carroll had done a good job, but then the film ended, and as the lights were raised, the plot took an unexpected twist.

Even before Carroll asked if there were any questions, a hand near me shot up. The man who spoke had been noticeably agitated through much of the film. Was he too an evolutionary biologist or maybe a paleontologist? Was he itching to posture that the world was 67 not 66 million years old?

“Why did you exhaust 30 minutes of footage featuring the work of 27 white male scientists without acknowledging the work of a single female or minority?”

I was dumbstruck. Me -who has published on strategies for teaching science for gender equity. Me – winner of the 2007 Diversity Award. Of the 2011 Inclusion and Access Award. I was enjoying this movie so much, that I hadn’t even noticed. Bias in science. In many science education discussions, we call it the elephant in the room. On this evening, I was too captivated by the dinosaurs to notice the elephant.

To say a lively discussion ensued would be euphimistic. Sean Carroll was barraged with criticism from all sides of the auditorium. Why, why, in 2012 did he make a film featuring only white males to be shown in public schools? “I’m a journalist. I had to be honest. Those were the people who did the work.”  Then why not include current work in the field, by a more diverse group of scientists? “Because this is film; I felt the story needed to be conclusive.” (I suspect that Carroll was nervous about presenting any ambiguities or uncertainties in the field of evolution, but of course they exist, as in any field of science. That’s why we need to inspire more people to study evolution.) Why not tell a different story then? “Because this is the story I wanted to tell!”

“This is the story I wanted to tell.” Therein, I believe, lies the real answer to why Sean Carroll made this film, and therein lies the real problem. Sean Carroll wanted to tell this story, and who could blame him? It’s an excellent story, and he did a fantastic job with the film. Perhaps the mysterious disappearance of the dinosaurs haunted Carroll when he was a child. Perhaps this story inspired him to become the successful scientist he is today. But will it inspire everyone?  Probably not.

By coincidence, this is the week in my class  in which I ask my students to tell a story. We are gearing up to learn some hard core molecular biology techniques and I feel it is helpful to spend some time in advance of that appreciating the decades of research and discovery that form the foundations of what we take for granted today (polymerase chain reaction, molecular subcloning, gene transfer). Back in the days when I taught in a traditional lecture format, I would recount a few hundred years of key discoveries in defining and ultimately manipulating the gene. To convey the passage of time, I would pause after each breakthrough and play a song from that era. I had compiled a lovely soundtrack and my students always cited that class as their favorite of the semester. In retrospect, I see that the only problem was that I was the only one telling the stories, the stories I wanted to tell.

Fast-forward to 2010 and beyond. In SCALE-UP, I ask each student team to identify and research  a breakthrough in molecular biology. They can choose anything they want, as long as each team picks a different event. In addition to describing the experiment, they will discuss the scientists who did the work, the place where the work was done, and what was happening in the world at that time. They will pick a song from that era. My job is to buy the songs, and compile the playlist.  The students will tell the stories about the science and the scientists who inspire them. I’m just a resource and a DJ.

This year, I do intend to indulge just a bit and tell one of my own stories. Sir John Gurdon, a developmental biologist who, like me, worked with frog embryos, just won the Nobel Prize in Physiology or Medicine. For decades, I’ve been inspired by Gurdon’s classic experiments, his big picture thinking, and I admit, by his charming British mannerisms. Gurdon conducted his Nobel winning experiments in 1962, a fantastic era for music. I’m not sure I can pick a single song. But, this is all stuff for next week’s blog post… It’s getting late and I still need to check under my bed for elephants.

“There’s no ‘I’ in ‘team’, Dr. J.”  At least one student offers me this comment every semester I teach in SCALE-UP. Most of the students, especially the athletes, are sincere, but often, there is a hint of sarcasm dished up with the mantra.

Boston Red Sox team photo at 1912 World Series

Teamwork. It’s one of the fundamental learning outcomes for this course. We draw upon loads of psychological and educational research to create the best possible opportunity for functional team experiences. Teams of three works best, or so I’m told. The tables must be exactly seven feet in diameter. Any smaller, the students will get crowded and crabby. Any larger, the distance across the table will feel too far for intimate discussion. Just give them one networked laptop. Then they will have to work together. The approach to teaching teamwork is all very scientific. I like that. I’m a scientist after all.

A scientist. “Scientists are team players”, I tell my students. “We have to be, especially in the 21st century where solving the ‘big’ problems in the world –  related to hunger, water, disease, energy – will require multidisciplinary approaches.” Sounds great. But does the culture of science truly embrace teamwork? Do I?

What has me wondering and worrying about teamwork is this post by Maria Popova in her Brain Pickings blog. Popova reminds us what talents from Steve Wozniak to Stephen King have reminded us: that the creative process requires significant amounts of solitude.

I cannot argue with that view.  My Myers-Briggs profile:  INFJ, emphasis on the I. Like Nelson Mandela, Mahatma Ghandi and Hitler. Notable people to be sure, but not exactly team players.

sunrise runs… just me and the cattle

I cherish alone time – to think, to dream and to write. I run and cycle for hours at a time, bringing myself as remote as I dare, almost hoping to get lost, out of cell phone range and thus truly unreachable for a spell that never feels quite long enough. I’ll wake up at 5, 4:30 even 4 in the morning to catch the stillest of hours, when even my dog cannot be bothered to bother me. I love staying in hotel rooms in unfamiliar towns, where nobody knows my name, and still, I might hide in the bathroom to work.

I love my family, my colleagues, and people and dogs in general. And undoubtedly, my best ideas about cell biology, education and a host of other subjects were not developed in a vacuum. SCALE-UP, blogging, and Course Networking were not my inventions, although I hope that I can bring something original to their application. Like many scientists, I am fascinated by complex problems and understand that the solutions are beyond my grasp or that of any individual. I love learning from people whose domain knowledge exceeds mine on just about any topic from physics to art to poetry. And I love sharing my own expertise with anyone who truly cares. More than just about anything, I love synchronicity, which happens with far greater frequency when I spend time with diverse and interesting people.

But I also need time alone. Time for my neurons to arrange all the disparate puzzle pieces gathered from social, multi-disciplinary endeavors into a construction that has meaning  and matters to me. Time to create something of value to share with my colleagues, my teammates. Ironically, blogging, a medium that could hardly be any more public, has become that opportunity for solitude and deep introspection.

So to my students: while I don’t apologize for making you work in teams, I do understand how difficult it can be. I’m happy to talk with you about this anytime. Just come to my office, up on the top floor of Derring,  way down the hall, nestled all the way in the back, where it’s nice and quiet and you’ll likely find me all by myself.

In just about every relevant context, I’ve always maintained that it’s the people who matter, not the place. A vibrant religious community depends upon the faith and character of its members, not upon the grandness of its temple. And I’ve always felt that learning communities should be able to thrive in any place where two or more curious individuals with sufficient freedom or courage find one another. There are so many examples where this is true.

I don’t what these Sudanese girls are studying, but sign me up!

Regardless of the subject and whether we are fully aware of this or not, we as learners shape not only the context in which we learn but also the very content. If I were ever to re-take a class in Western literature, I’d like to take it with Azar Nafisi.

I’ve probably read The Great Gatsby a dozen times, but I’m certain that I would find new meaning in just about every page if I were to gather with Nafisi’s students in her living room, shades drawn, and read Fitzgerald through their eyes.

Certainly people shape the leaning experience and culture shapes people, but what about the physical environs? If I try to solve quadratic equations sitting in my office or Starbucks or a crowded terminal at Dulles International Airport, will I be equally successful? For me, I’ve always felt the answer was yes. When I’ve got work to do, I focus, hyper-focus actually, and become oblivious to my surroundings. Remember the 5.8 earthquake we had in Virginia last August? I don’t.

Even after building the SCALE-UP classroom and witnessing for two-going-on-three years the almost miraculous transformation in attitude and aptitude for learning that takes place in this setting, I remain a skeptic that it is the place that makes the difference.  To be honest, I’ve come to take this amazing learning space for granted – until now- when I may actually have to go back.

Back to a conventional classroom – a lecture hall – where every student faces forward – all eyes on the teacher – on me – expecting me to do something brilliant – or at the very least entertaining.

Next semester, after I’ve transitioned from associate dean who can teach whatever I want, wherever I want, to a rank-and-file professor who teaches what I am asked, I may not have SCALE-UP at my disposal. I’ve been asked to teach Cancer Biology, and I’m thrilled with the subject and the potential of teaching students in a 4000-level course with whom I’ve worked before in my 2000-level class. I’ve been told to expect 100 to 120 students. That’s great, except that we don’t have a SCALE-UP class that large. And I won’t be associate dean anymore. I may not be able to make a few phone calls and score one of the few flexible large classrooms on campus.  Maybe they’ll put me in McBryde 100.

Oh no! McBryde 100.

Maybe space does matter, at least in part. But people matter more. Of that I am certain. Perhaps my students, the ones with whom I am sharing time and space in SCALE-UP this fall, can help me figure out the what, how, and where for creating an equally vibrant learning experience for Cancer Biology class next spring.

A few weeks ago in anticipation of beginning a new semester of Cell and Molecular Biology, I wrote about the natural phenomenon of hysteresis. While I have investigated hysteresis as a mechanism that regulates the irreversible transitions of the cell cycle, blogging about hysteresis left me far more contemplative about its potential in life’s transitions. I wrote:

“In the past few months, and more pointedly in the past few days, I have the unsettling sensation that I am in the midst of a professional hysteretic transition, moving from one stable steady state to the next…. and I’m not quite sure where I’m headed. I’ve even tried to turn back, but find that I cannot. I’m propelled, which is thrilling and terrifying at the same time. I’ll report back when I land.”

Well, I’ve landed, and guess where? Right back where I started, which is about the last place I expected to be.

Just a few days before the semester began, I made the painful but absolutely correct decision to step down from my position as the Associate Dean for Curriculum, Instruction, and Advising in the College of Science. It wasn’t exactly a life of sex, drugs, and rock-and-roll, but I was paid very well.  And I had resources and autonomy to impact higher education for the betterment of our students. Until I didn’t. And that’s why I quit.

Enough said about that. It’s where I find myself now that really matters. After a hysteretic transition, a system generally comes to rest at a stable steady state. That has a nice ring to it. Rest. I could use some of that after an insane year. Stability. Aaaah. For the foreseeable future, I’ve returned to the life of a biology professor. Less money. Smaller office. More time to wonder about the mysteries of the cell. More time to spend with students.  I couldn’t be happier.

But there is an eeriness to this transition that cannot go unmentioned. Much like the cell cycle, my life has really come full circle. Last fall, the first Cell and Molecular Biology class met just hours after I had to put down my sweet Comet. His death haunted my semester.

Last Wednesday, on the one-year anniversary of Comet’s death, my friend Ed rescued Bruce.  Bruce is best described in brief as a lover and a runner. Bruce needed a home and our family needed Bruce.

I’m convinced that in life, at least in my life, there will be a dog waiting and wagging at every stable steady state.

In the hysteresis post, I also wrote about closing my research lab this year: “I spent the last of my grant dollars from the National Institutes of Health, hung up my lab coat, and shut the door to Derring 5029 where I had spent the most – and some of the best- waking hours of my career. ”

As I looked for some place on campus to call home when I left the dean’s office, my department head in Biological Sciences asked me, “What would you think about moving back into your old office and lab?”

What would I think? I’d think I was pretty darn lucky. Like a student who moves back home for a while after college and finds her bedroom has not been turned into Mom’s home gym or Dad’s new man-cave. Since I announced I was stepping down as associate dean, countless people have recited the cliche, “when one door closes, another one opens.” Who knew it would be the door to good ol’ Derring 5029?

One final word on hysteresis: as discussed in my earlier post, even at the same steady state, the behavior of a hysteretic system is dependent upon its history. In other words, I may be returning to the faculty ranks and back in my old office, but I am not the same professor who left to become an administrator four years ago. An obvious example is my focus on science education rather than experimental science. I still bring in significant grant dollars from places like the NIH and NSF, but the projects focus on the learning of science rather than experimental cell biology. But that’s the obvious. I expect my behaviors will be changed in many other ways. I can already perceive an enriched appreciation for many aspects of my new-old life, especially for the hours of learning, laughter and who-knows-what-else in Cell and Molecular Biology.

Just three weeks out from the start of the semester and nagging thoughts of cell biology are already creeping into my day dreams. Shortly after our cell and molecular biology course completed last year, I shut down my experimental cell biology research program to focus full time on being a science educator rather than a scientist. I spent the last of my grant dollars from the National Institutes of Health, hung up my lab coat, and shut the door to Derring 5029 where I had spent the most – and some of the best- waking hours of my career. Based on what I know about the ‘rules’ of an academic research career, I’m fairly certain there is no turning back on this decision – or is there? Which brings me to hysteresis.

Hysteresis is an irreversible, switch-like behavior that can occur between two steady-states in a system. The state in which a system resides depends not only on the current conditions, but also on the history of the system.  Here are a few classic examples:

rubber bands: With no force applied, a rubber band exists stably in its unstretched state. However, once stretched beyond a certain point, the rubber band is permanently stretched, even when the force is removed. Same conditions, different state, depending whether the rubber band had experienced a threshold stretching. Importantly, hysteretic transitions are considered to be essentially irreversible.

some solid-liquid transitions: Think about Jello. After you dissolve the gelatin in boiling water, Jello won’t solidify unless you refrigerate it. However, once it is solid, Jello can sit out at room temperature and it will remain solid (except maybe in August).

Hysteretic transitions are not truly irreversible. However, the energy required to push a system into a particular steady state is much greater than what is required to keep it in a steady state. It’s nature’s way of preventing slippage. Thermostats are designed with this principle in mind. Otherwise, a climate control system would be switching back and forth between heating and cooling mechanisms to maintain a room at exactly 25°C.

As a cell biologist, my most rewarding work was testing the prediction of my colleagues John Tyson and Bela Novak, that cell division was regulated by hysteresis. When cells commit to the cell cycle, the process by which they duplicate their DNA precisely and other cell contents less precisely, then divide into two daughter cells, the commitment is irreversible. Cells  may pause or even arrest the cell cycle if something is wrong, but the cell cycle never moves in reverse. Both my students and my colleague and friend Joe Pomerening found compelling evidence for John and Bela’s theoretical predictions of hysteresis. Cells synthesize a protein called cyclin, and a threshold concentration is required to drive the cell into mitosis, the final stage of the cell cycle where cell division occurs. In order to exit mitosis, the level of cyclin must drop to a distinct inactivation threshold concentration that is measurably below the activation threshold.

The cell cycle example illustrates that the state transitions are not truly irreversible, but in essence, may require a bigger ‘push’ to get out of one state, than was required to get into that state in the first place. When there are certain types of feedback, a system can oscillate between one state and the other in what is called a hysteresis loop. This is what happens with the cell cycle.

Does hysteresis only exist in the natural world? Wikipedia has a pretty good description of the phenomenon, including examples from economics (e.g. unemployment levels) that are described as hysteretic.

Which makes me wonder, which of life’s transitions are hysteretic and which are not?

Closing a research program? Probably hysteretic. Not impossible to go back but the deck would be stacked heavily against an investigator with a significant gap in her funding record, more so than a young scientist applying for her first grant.

Becoming a parent? Definitely hysteretic. There’s really no turning back from that one, but who would want to?

Marriage? In contemporary society, marriage hardly seems hysteretic, and to be honest, I prefer to view marriage as an unstable, rather than stable, steady state. That view keeps me intentional about what it means to be a loving and committed spouse rather than taking the relationship  for granted.

In the past few months, and more pointedly in the past few days, I have the unsettling sensation that I am in the midst of a professional hysteretic transition, moving from one stable steady state to the next. Graphically, hysteretic transitions appear as jumps, sharp transitions, never as gently sloping curves.

from Sha et al., 2003

The ride has not been entirely pleasant, the transition not anticipated in time to fasten my seat belt, and I’m not quite sure where I’m headed. I’ve even tried to turn back, but find that I cannot. I’m propelled, which is thrilling and terrifying at the same time. I’ll report back when I land.

….. one more thought on hysteresis. As one approaches a hysteretic transition, a phenomenon known as “critical slowing down” occurs. John was convinced that we would find evidence of critical slowing down in the cell cycle. While the theoretical predictions were compelling, it was hard, damn hard, to generate experimental evidence. Here it is:

evidence for “critical slowing down” in the cell cycle

If you are not impressed at the precision it took to achieve this evidence, believe me that Wei Sha, whose data are shown here, and Joe Pomerening  are among the few individuals in the world who could have done this experiment.

Critical slowing down? That may explain a few things in my life as well. I’ve been trying to fight that aspect of the transition too, but perhaps resistance is futile.