Monthly Archives: October 2011

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.

Dad and Simonne

http://www.nytimes.com/2011/10/26/sports/julia-chase-brand-a-leading-pioneer-in-womens-running.html?_r=1&pagewanted=all%3Fsrc%3Dtp&smid=fb-share

Unrelated to cell and molecular biology, but too inspiring not to share.

"I feel more like myself when I'm out running."

reposted from my New Media Blog: This afternoon, in our New Media Seminar, we had the bizarre experience of following the Twitter stream of Marshall McLuhan, whose writings we were discussing. McLuhan passed away some time ago so apparently he was tweeting from the grave. I struggled a bit to comprehend McLuhan’s message that the “medium was the message.” How could the format, the vehicle, be more important than the content?

Regarding contemporary science, content is everything. More specifically, data are everything. Someone might articulate the most elegant and compelling theories regarding the most significant unknowns in the natural world, but until evidence in the form of reproducible data are generated to support those theories, little attention is given to these thinkers. Rare is the scientist-philosopher, and that is a shame.

How do scientists communicate their content, their data? Through the 20th century, “serious” scientific content was communicated in print, specifically, in peer-reviewed journals. The format of a scientific journal article in my field is fairly rigid: Abstract (150-300 words, depending on the journal), Introduction (literature review), Materials and Methods, Results, Discussion, References. Strict page or word limitations exist for most journals. The “meat” of the scientific article is the Results section, conveyed through a series of figures and tables (usually 5-10 per article). Each figure possesses a descriptive legend of a few sentences. The Results section also contains a narrative “walk” through the data in prose, with references to the figures and table.

The Discussion section that follows should provide deeper interpretation of the data and make connections to other published works in the field. For the most part, speculations that extend beyond the scope of the data are not permitted. Philosophizing is prohibited entirely.

There is little room for literary creativity in scientific articles. I once worked in the same department as a brilliant developmental biologist who submitted a research article with the Abstract written as a limerick. All of the requisite information was present, the abstract fell within the 200-word limit, and it began with “there once was an embryo from…” The journal refused to publish his article.

Scientific articles are written, submitted to the journal of choice and then reviewed by two or three scientists selected by the editors of the journal. The reviewers are kept anonymous. Depending on the opinions of the reviewers (the jury) and the final decision of the editor (the judge) the article will be accepted as is (rare), accepted with modifications, or rejected entirely.
How has scientific communication changed in the era of electronic media? Most journals are published both in electronic and print format. Some are published entirely on-line. Nowadays, the submission and review process is conducted electronically, which has accelerated the time from submission to decision from a matter of months to a matter of weeks. Beyond these efficiencies, the medium has not changed the message very significantly.

The switch to electronic journal format has not really altered the kinds of data submitted, with the exception of videos, which can provide compelling records of temporal experiments. Undoubtedly, each article typically contains more data, since page charges are no longer a restriction. However, much of these data are relegated to “Supplementary Materials” accessed only as a link from the main page. Perhaps the greatest change is in the references, which are now hot links to the article cited, accessible provided the linked article is published in an open access journal or the reader works for an institution with a paid subscription to that journal. This practice of linking journal-to-journal is a bit reminiscent of Bush’s Memex with the added dimensions of the World Wide Web.

With these exceptions, the electronic journals have adopted the conventions of the print medium: Abstract-Introduction-Methods-Results-Discussion-Reference. Reviewers remain anonymous, even more so, because in the old days, it was sometimes possible to determine the reviewer from the handwriting, and a few bold souls would proudly sign their reviews.

And most significantly, once an article is published, it becomes a fait accompli. The work becomes a defined and static entity, a unit known as a “pub”. This is where the greatest opportunities are missed, I believe. Once a scientific article is published, even in electronic format, there is no simple mechanism for amendment to that body of work. If the scientists who wrote the article discover that they made a mistake, they must submit a formal Erratum, which remains a real mark of shame in the scientific community. “You lazy bum – why weren’t you more careful in the first place.” It would be so simple and seems so logical in the current medium for scientists to be able to amend their own work, to post additional data, whether confirming or contradictory to the original conclusions, in order to continue a line of inquiry.

And the process of linking one data set to another remains hindered by the packaging of bodies of work into the conventions of an article. When one published article is linked to the referenced article therein, the link is to the other article in its entirely, not to the specific relevant figure or statement from that work.

In writing many of my own articles, I have wanted to compare my own results to a particular data set from another article. There is no convenient way to link to that information, even though it is readily available. Part of the problem is copyright, but equally challenging is the mindset that the body of work as originally published must be kept intact. Even with proper referencing and permission, it is simply not considered acceptable form to deconstruct a scientific publication in order to make new meaning.

Some journals have added moderated comment threads to the on-line version of the articles. I haven’t seen much dialog generated from these, but I suspect there are lively discussions on some of the most active and disputed areas of inquiry. Hopefully, this will be a step in the direction of a more free-flowing discussion and exchange of scientific ideas.

However, I doubt that many scientists will post unpublished data in such a forum for fear of being scooped. As long as (academic) scientists are judged by the number or publications and the impact factors of the journals in which they publish, scientific dialog will largely be restricted to the current norms.
However, if the medium is the message, then change seems inevitable. Much of that change is probably underway, but I lack the vantage point to see the forest for the trees that surround me. I look forward to the time in my life where I can appreciate these changes in scientific communication. The nature of the current medium seems to almost guarantee that the practice of science will be more collaborative and more inclusive than the environment in which I was trained. My students will be working in that new realm, and I pledge to do all that I can to help them prepare for what could well be another revolution in science.

Endosymbiosis fascinates me and seems to have this effect on many people. This week in class, we introduced the evolution of the eukaryotic lineage with a focus on two key events – the evolution of mitochondria, which are key organelles in nearly all eukaryotic cells, and the evolution of chloroplasts, and thus, plants.

I can see from a few Google searches that endosymbiosis is considered a theory. That does not mean it didn’t happen! It simple means that we do not know precisely how it happened. And that is what really fascinates me.

According to the theory, an aerobic bacterium (one that can respire using oxygen as a final electron acceptor, and thus, derive much more ATP from a single molecule of sugar than one that must simply rely on anaerobic glycolysis), came to live within a larger anaerobic bacterium. How did that happen? Was it swallowed? Or did it sneak inside, more like a covert operation? And did it happen just once, and that single, random event gave rise to the entire eukaryotic lineage? Or did it happen many times simultaneously? In either scenario, the advantage must have been tremendous for this event to have survived and propagated. The alternative, of course, would have been that the swallowed or invaded organisms might have evolved mechanisms to avoid the other. Most of life as we know it would have been over before it even got started.

And then it happened again, with the precursors of chloroplasts. Imagine the course of evolution if photosynthesis and the ability to fix carbon from carbon dioxide never made it beyond a few single celled prokaryotes. We certainly wouldn’t be here to theorize about all this.

When we look at contemporary cells, we realize that there is no turning back. Since mitochondria and chloroplasts were derived from independently living bacteria, it is no surprise that they possess their own genomes, can replicate and transcribe these genes, and have the machinery to translate their own proteins. What nearly blows my mind is not that they can make their own proteins. That makes sense. However, mitochondria and chloroplasts synthesize only about 10% of their own proteins. The rest are imported into these organelles from nuclear encoded genes. How did these genes get into the nuclear genome??? The fact that these genes are there, means of course, that a mitochondrion or chloroplast can no longer survive on its own, outside of the cell. No more than a liver or a heart or a lung can survive for long outside of the body. Hence, we  call these subcellular structures, organelles. What about the converse, could a eukaryotic cell survive without mitochondria? Probably, at least under pampered conditions, but once the energy requirements exceeded a certain threshold, that cell would waste away for lack of sufficient ATP.

To try to make sense of all this, I try to think of useful metaphors for endosymbiosis. Is endosymbiosis like a long-term romantic relationship? Not a very functional relationship, in my opinion, with one partner sequestering the other from the rest of the world. “I’m only trying to protect you, darling.” The other partner gets even in a sort of passive-aggressive way by controlling the ATP production. “Tired, honey? Here, let me make you feel better.” No, that metaphor is not working at all. Perhaps endosymbiosis is better compared to a corporate merger, a highly functional one. I have friends in the business world who have worked for little companies that were taken over by larger companies. They tell me that their working groups still largely function as a company-within-a-company. They perform a specialized role within the larger operation. However, over time, the boundaries soften a bit. A few employees move in and out between this group and the larger organization. The big company provides the health insurance, the pension and the overall vision. However, if the little subcompany were to pick up and leave, the operation as a whole would come to a standstill, or nearly so.

I can understand how this all happens in the business world. People talk, deals are made, many lawyers are involved. But how this happened eons ago to give rise to eukaryotic cells in all their glory, still baffles and amazes me.

This week, students reported on their favorite breakthrough in molecular biology. As part of the assignment, to help provide a sense of the passage of time, they included information about what else was happening in the world when the breakthrough was made. I also asked them to name the title and artist for a song that was popular at that time. I’ll be putting together a playlist for class on Thursday to set the mood for their reports. The time period spans the 1920’s through 2011, and the playlist includes Bobby Darin, Gloria Gaynor, Poison, Bruno Mars, Blondie and Nat King Cole.

By chance, my husband sent me this link to Bjork’s lastest project, called Biophilia:

http://www.npr.org/2011/10/10/141183659/bjorks-biophilia-interactive-music-pushing-boundaries

Bjork's Biophilia

This week, I am defaulting to a bad habit I have developed on Facebook. When I don’t have anything particularly interesting to post (which happens quite often) I do what many of my friends do – I post about my kids. For this blog, I’ll reference my ‘big kids’ (meant as a term of endearment rather than a diminutive), my students in Cell and Molecular Biology. I just finished grading Assignment 5, which contains one of my favorite pieces of the year. The subject is DNA replication, which can be conceptually challenging. How do the leading and lagging strands, which are oriented in opposite directions and must replicate in a specific direction (5′ to 3′) replicate simultaneously while the replication fork moves unidirectionally? And where do all those players fit in? DNA polymerase I, DNA polymerase III, topoisomerase, single stranded binding proteins, helicase?

I’ve always found that no matter which textbook I’ve adopted, only a subset of my students “get” DNA replication by looking at the figure in the textbook. I would provide figures from three or four different textbooks, and that helped a little. In recent years, YouTube offered some nice animations. But there were always students, quite a few, who still could not conceptualize DNA replication. Most science teachers employ metaphors. The human genome is the “book of life”, for example. After considerable frustration in trying to come up with the best  metaphor for DNA replication for my students, it finally dawned on me. DUH! Let the students make their own metaphors.

Here is where I step aside and let the work of my big kids speak for itself:

Laura, Caitlyn, Cari Lynn and Anna reminding us the ice cream is the answer to most of life's difficult questions.

Julie put her talents to work to crochet a fork complete with Okazaki fragments, RNA primer, SSBs (pins), helicase (scissors) and ligase (ribbon).

From last year, the team who called themselves Dumbledore's Army identified spells that could carry out the action of each enzyme on the fork.

Once again, Esther, John and Brandon managed to make us all hungry.

Lauren created "every Hokies favorite replication fork"

And just so my ‘little kids’ don’t feel left out, here’s a recent Facebook post about them. Just when I thought they had outgrown the kiddie pool, they invented a new game they call “Fast Turtle”.Fast Turtle