Debunking myths on genetics and DNA

Monday, October 31, 2011

The "jumping genes" of the brain

Have you ever wondered how a single cob of Indian corn can display so many beautiful colors? The answer came in 1948 thanks to scientist Barbara McClintock: she discovered that 50% of the maize genome is made of transposons, DNA sequences that can "jump" around in the DNA of a single cell. As they move around, these "jumping genes" can "stretch" the DNA by adding repeated copies, but they can also cause new mutations to appear. In the case of corn, the new mutations are responsible for the different colors displayed by the kernels.

Since McClintock's discovery (for which she was awarded the Nobel Prize in 1983), transposons have been found in many other organisms: fruit flies, bacteria, and, of course, humans. Transposons play an important role in evolution, as roughly 50% of our genome is derived from these movable bits of DNA [1]. They are responsible for many evolutionary processes, like new gene formation, the progressive increase in size of genomes, alternative splicing, and the introduction of new epigenetic regulations. Recombination between these DNA elements can cause deletions and mutations in the DNA, and some have been associated with diseases like Alzheimer's and breast and lung cancers.

There are two ways transposons can achieve mobility.

Retrotransposons are "cut and pasted" from the genome in two phases: first they are copied from DNA to RNA, and then the RNA is copied back to RNA through reverse transcription, and reinserted into the genome at a different position. This ability to switch back and forth from DNA to RNA reminds us of retroviruses, doesn't it? In fact, a portion of the endogenous retroviral sequences present in our DNA are retrotransposons. On the other hand, DNA transposons are able to "move" without the intermediate RNA step. Instead, they use an enzyme called "transposes" that binds to the transposon and also to the target site where it will deliver the bit of DNA.

Several studies have shown that in the human genome retrotransposition happens during embryonic development [2]. In particular, using mouse models with human genes, Kano et al. showed that "de novo retrotransposition events can occur even after the time of establishment of germ cells, or even in adult tissues, which cannot be transmitted to the next generation. These nonheritable retrotransposition events in somatic tissues may play a significant role in creating genomic diversity within an individual."

Indeed, this is what Baillie et al. [3] found when they looked at the brain tissue from three healthy donors and mapped retrotransposons from two regions in particular, the hippocampus and the caudate nucleus. They investigated three families of transposons found in the human genome: L1, Alu, and SVA, and found thousands of somatic insertions. Using deep sequencing, the researchers were able to link somatic retrotransposition to neurobiological genes. They found in particular high activity in the hippocampus, and hypothesized that this may be related to neural plasticity. In other words, even though highly mutagenic, this kind of somatic changes may also be linked to the normal functioning of the brain and confer its innate ability to constantly re-adapt to the environment.

These findings are extremely fascinating because they indicate, once again, that there's a lot more to a genome than genes. The high frequency of somatic retrotransposition activity found by Baillie et al. may explain why for example homozygote twins may have discordant behaviors and/or disease outcomes, and, to link to a previous post of mine, could also explain the "missing heritability" puzzle for some types of diseases.

[1] Cordaux R, & Batzer MA (2009). The impact of retrotransposons on human genome evolution. Nature reviews. Genetics, 10 (10), 691-703 PMID: 19763152

[2] Kano H, Godoy I, Courtney C, Vetter MR, Gerton GL, Ostertag EM, & Kazazian HH Jr (2009). L1 retrotransposition occurs mainly in embryogenesis and creates somatic mosaicism. Genes & development, 23 (11), 1303-12 PMID: 19487571

[3] Baillie, J., Barnett, M., Upton, K., Gerhardt, D., Richmond, T., De Sapio, F., Brennan, P., Rizzu, P., Smith, S., Fell, M., Talbot, R., Gustincich, S., Freeman, T., Mattick, J., Hume, D., Heutink, P., Carninci, P., Jeddeloh, J., & Faulkner, G. (2011). Somatic retrotransposition alters the genetic landscape of the human brain Nature DOI: 10.1038/nature10531

Photo: detail of sculpture by Warren Cullar, Santa Fe, NM. Canon 40D, shutter speed 1/50, focal length 85mm, f-stop 9, ISO speed 100.

"Editors: are you real?" A conversation with Muse editor Elizabeth Preston

I'm very excited about my guest today because she's not just a science writer: she writes for kids! A Williams College graduate, Elizabeth Preston is the editor of Muse, an award-winning children's magazine that covers science and ideas for kids ages 10 and up. Elizabeth is also the author of the science blog Inkfish, and, besides Muse, her writing has appeared on National Geographic as well. 

EEG: Elizabeth, it's a great pleasure to have you here today! Tell us when and how you started writing about science.

EP: The summer before my senior year in college, I started work on a biology thesis on the evolutionary genetics of malaria resistance. My advisor, Jason Wilder, knew I was interested in science writing--in that I was a biology and English double-major without a plan for after graduation--so he invited me to help him write a review paper on malaria resistance. Everyone's heard of sickle-cell anemia, but there are actually several other genetic mutations that confer some resistance to the malaria parasite but also have a health tradeoff.

I read a lot of papers about malaria, genetics, and mosquitos. I tried to synthesize the literature and find the big ideas lurking behind it, and I had some exciting conversations with my advisor about the possibilities and unanswered questions in the research. I realized that it was like writing an English paper: I was coming into a narrative that was new to me, the story of the struggle between humans and the Plasmodium parasite, and insights into that story were accessible to me even though I wasn't a scientist.

Later that year, I completed my senior thesis project and learned that while things like malaria and genetics are exciting, PCR and DNA resequencing are really, really boring. So when I graduated, I didn't apply to a PhD program, but I did apply to work for a children's science magazine. Even though the review paper we wrote didn't get published, I was grateful for the experience because it showed me exactly what I enjoyed about science.

EEG: Believe me, I know what you're talking about. Sequencing and then aligning DNA is tedious. No software will do the job for you, and there always comes a time when you have to tweak things manually. And when you're done doing that... the lab sends you another dozen sequences and you have to start over again. The joys of working with DNA!

You have the wonderful and, I would imagine, arduous task of writing science for kids. How challenging is that?

EP: One of the biggest challenges is that I don't really have any kids in my life, so I can't just bounce sentences off a 10-year-old and see if I get a blank stare back. But I do read the mail they send, and the essays they submit to the magazine, and I hear what articles they respond to the most. So I have a sense of their voice and of what stories have been successful.

It can be hard. When I'm working on a story about something like nuclear fusion or geoengineering or genetics, I have to assume the kids have zero background knowledge. And I know there are 9-year-olds reading and there are 17-year-olds reading, so the story has to work on multiple levels. Even if a reader can't follow all of the specifics, I want the big idea to still come across. But for older kids, it can't sound babyish or they won't read it. I try to respect the readers' intelligence but also recognize their lack of knowledge.

When I started writing my blog, I found that I was really using all the same tools. I was writing, initially, for my friends, most of whom aren't science people. I just wanted to share some of the cool scientific stories that I came across in my work but that didn't make it into the magazine. I hoped to make the ideas accessible to anyone, regardless of how much background knowledge they had. But I also wanted my posts to be interesting to people who did have the background knowledge and knew the scientific context of the story.

EEG: Do you get a lot of feedback from your young readers?

EP: Oh my gosh, they write a lot of letters. Volumes and volumes. The youngest kids really love the Muses, the cartoon characters that Larry Gonick draws for the magazine; they just write directly to the characters. One 9-year-old wrote us a letter that said, "Editors: Are you real? I know the Muses are." I also saved a note from a kid who was probably 8 and signed his letter "Junior Palentolegest," which made my day.

The older kids say that they're our number-one biggest fan, Muse is the best magazine in the world, they spend every day waiting by the mailbox--they're prone to hyperbole. Sometimes they say that they brought in an article for their teacher, and the teacher shared it with the whole class. I love to hear that because it says the kid and the teacher are both excited about it. Additionally, those kids are desperate to have their letters published in the magazine. There's a tradition that they include really elaborate threats, like, If you don't publish my letter I'll send an army of orcs to attack you, and my pet hamster will chew your computer cords, and I will paralyze you using the curses from the Harry Potter books, which I have memorized.

The oldest readers sometimes write to us about how the magazine has influenced them as they've grown up. We got a letter recently from a 24-year-old who's still subscribing. She said that she loved science when she was young but drifted away from it in college: "After graduating, I realized my mistake, but wasn’t sure what else I wanted to do with my life. But MUSE was still showing up in my mailbox--this part of my childhood kept coming back to remind me of what I love. This, combined with some time with a career counselor, is what made me decide to return back to my dream of becoming a doctor." That's the most rewarding thing. You do all this work and it sometimes feels like you're sending it out into the void, but once in a while you get to hear from someone on the other end who's found it meaningful.

Now that I'm writing my blog, it's also been rewarding to see my readership grow and know that real non-tween people are reading my posts and sharing them with their friends. People have a ton of information and opinions coming at them constantly, so if they take the time to actually read and think about what I've written, that's really flattering. Plus they almost never threaten me with armies of mythical creatures.

EEG: Wow, it must be really rewarding to get that kind of feedback, and across all ages. And yeah, watch out, those Harry Potter curses can be pretty nasty!! Those stories are fantastic, thanks so much for sharing them with us! 

Folks, check out Elizabeth's blog Inkfish -- it's a lot of fun and it covers curious and amazing things of all sciences, from nature to psychology. And if you have kids, Carus Publishing offers a whole range of children's magazines, from Baby Bug to Cricket and, of course, Muse. 

Saturday, October 29, 2011

I love night shots

Disclaimer: the ISO speed is a bit high (I didn't have a tripod with me). I took these two photos from the Space Needle in Seattle last August, and then a Panoramio friend pasted them together. I thought the result was pretty cool! Click to appreciate the details (modulo the grainy texture from the non-optimal ISO...)

Thursday, October 27, 2011

P53, the anti-cancer sentinel

In my post The Missing Heritability, I hinted at what I called "protective mutations." We know that people with "risk alleles" have a higher probability of developing certain cancers, but what about people who do have those alleles and never end up developing the cancer? Do they carry "protective alleles" that counter-effect the negative risk carried by the deleterious alleles?

An astute reader (thanks!) pointed me to the tumor-suppressant protein p53. I dug up the literature on this, and it is indeed a fantastic protein. It regulates the cell cycle and, by controlling the expression of many important genes, it activates proteins that have the ability to repair DNA when it's damaged by stress factors -- damage that may otherwise lead to cancer cells. When the damage isn't "fixable," p53 initiates cell death (apoptosis) and destroys the cell. P53 is also beneficial when it comes to viral infections, as it's been shown to inhibit viral replication in human papillomavirus infections [1].

What's the link between cancer and p53?

As Vogelstein and Kinzler state in this paper, cancer is a genetic disease that originates through the accumulation of "alterations in three types of genes responsible for tumorigenesis: oncogenes, tumor-suppressor genes and stability genes." In light of its role in regulating the cell life cycle (repairing damaged DNA and initiating apoptosis), p53 is indeed a tumor-suppressant protein. And in fact, mutations in the TP53 gene, the gene that codes p53, have been found in about 50% of all cancers [2], again indicating that a healthy p53 has the ability to keep our cells "in check," whereas, on the other hand, mutations in the TP53 gene can have disastrous effects.

Because of its multiple functions, p53 orchestrates many different proteins. So, it shouldn't come as a surprise that other genes have been linked to p53 in certain cancers and, interestingly, they have the ability to partially restore the p53 tumor-suppressing function. Rather than "protective alleles" (as I had originally hypothesized), these are genes that act in tandem with p53 and are found to be either mutated or under-expressed in cancer cell lines. By restoring them, researchers were able to restore the healthy functioning of p53 as well and observe a reduction in cancer cell proliferation. These findings point to possible cancer treatment strategies aimed at restoring the normal expression of cancer-suppressant genes.

This is what I found in the literature:

Hu et al. [3] found that the protein ZNF668 has the ability to suppress breast cancer cells by regulating the stability and activity of p53. They tested this both in vitro and in mouse models. They also showed that the ability to inhibit cell proliferation was impaired in two cancer-derived ZNF668 mutant genes. The authors conclude, "our studies identify ZNF668 as a novel breast tumor suppressor gene that functions in regulating p53 stability."

Similar results have been found when researchers investigated the interaction between the protein ANKRD11 and p53, again in breast cancer [4, 5]. The presence of p53 mutations and loss of expression of ANKRD11 is associated with poor breast cancer prognosis, and the mutant p53 is less effective in regulating cellular growth and apoptosis. The researchers found that ANKRD11 expression was downregulated in breast cancer cell lines [4]: they analyzed six breast cancer cell lines and found an 89% average reduction in gene expression (P<0.01) with respect to non-malignant breast cells. On the other hand, restoration of ANKRD11 expression suppressed the growth characteristics of breast cancer cell lines, for an average reduction in proliferation of 36% after 72 hours.

What about the effects of ANKRD11 on the mutated p53 protein in these cancer cells?

The authors found that ANKRD11 was able suppress the oncogenic properties of the mutant p53, and, furthermore, it had the ability to restore p53 functions by reverting it to its wild-type (non-mutant) conformation [5]. In order to see this, they used an antibody that binds to the "healthy" p53 and showed enhanced binding in the presence of the protein ANKRD11, thus proving the reversion from the mutant p53 to the wild-type one.

In conclusion, p53 is indeed a great sentinel that keeps us cancer-free, but when things go wrong, other genes can be targeted to try and revert the effect of deleterious mutations. Something to keep an eye on for future cancer treatments!

[1] Brown, C., Kowalczyk, A., Taylor, E., Morgan, I., & Gaston, K. (2008). p53 represses human papillomavirus type 16 DNA replication via the viral E2 protein Virology Journal, 5 (1) DOI: 10.1186/1743-422X-5-5

[2] Hollstein M, Sidransky D, Vogelstein B, & Harris CC (1991). p53 mutations in human cancers. Science (New York, N.Y.), 253 (5015), 49-53 PMID: 1905840

[3] Hu R, Peng G, Dai H, Breuer EK, Stemke-Hale K, Li K, Gonzalez-Angulo AM, Mills GB, & Lin SY (2011). ZNF668 Functions as a Tumor Suppressor by Regulating p53 Stability and Function in Breast Cancer. Cancer research, 71 (20), 6524-34 PMID: 21852383

[4] Neilsen PM, Cheney KM, Li CW, Chen JD, Cawrse JE, Schulz RB, Powell JA, Kumar R, & Callen DF (2008). Identification of ANKRD11 as a p53 coactivator. Journal of cell science, 121 (Pt 21), 3541-52 PMID: 18840648

[5] Noll JE, Jeffery J, Al-Ejeh F, Kumar R, Khanna KK, Callen DF, & Neilsen PM (2011). Mutant p53 drives multinucleation and invasion through a process that is suppressed by ANKRD11. Oncogene PMID: 21986947

Photo: clay jar hand-made by my wonderful friend Rosi. Focal length 85mm, shutter speed 1/10, f-stop 5.6.

Tuesday, October 25, 2011

Master of the House of Darts

Remember my friend and wonderful writer Aliette de Bodard? She created a truly unique world that combines Aztec mythology, magic, and a compelling murder mystery, all topped off with her lyrical writing. Who's not to like that? Her new book, Master of the House of Darts, the third in her Obsidian and Blood series, is coming out in November in the UK, and today here in North America!

I've already downloaded my Kindle copy, have you? (On a side note, I'm loving the Kindle App for my Mac.)

Edited to add this link: Magical Mysteries in the Time of the Aztec Empire: Interview with Aliette de Bodard, in which Aliette discusses her final book in the trilogy. Enjoy!

Monday, October 24, 2011

The missing heritability

It's been dubbed the "dark matter of the genome" because… we know it's there and yet we can't find it.

Ever since the completion of the Human Genome Project, the hunt to disease variants has taken up much, if not most, of genetic research. The idea is simple: we take a sample of healthy people (the controls), a matched sample of diseased people (the cases), we type their DNA, stratify by other possible factors (this one depends on the study, but think of things like smoking, age, family history, socio-economic status, etc.), and then look at what variants in the DNA are statistically more prevalent in the cases. If the experimental design is solid, and the statistical analyses are well done, the result should be one or more loci in the genome that increase the risk of developing the disease.

This has been done for numerous cancers (a vastly known example are the two SNPs BRCA1 and BRCA2, which have been found to increase the risk of breast cancer), and also for heart disease, type 2 diabetes, schizophrenia, and other genetic pathologies.

Is this it? All you need to do to find out whether or not you'll develop something nasty in your lifetime is look at your DNA and breathe easily if nothing of the "red flags" are raised?


When you go back and combine the genetic variability of the trait and the environmental factors, you see that all together they explain only a small fraction of the disease's heritability. In other words, for any of these investigated maladies, the vast majority of the inherited cases remain unexplained. Think for example, of twin pairs where only one sibling develops the genetic disease.

First of all, a philosophical note: the above thinking falls within the so-called "gene-centered" view, which assumes a causal relationship between gene copies and phenotype. This may not be the case at all, as what I've learned so far is that genomes have a tendency to be far more complex than we can predict.

Having said that, here are some hypothesis on where the "dark matter" of the genome could hide.

(1) RARE VARIANTS: The causal relationship we're after could be hidden in what we call "rare variants," in other words, gene copies that can only be found in very few individuals. These alleles are so sparse in the population that even if you find a few, you have very little statistical power to detect their effects on the disease risk. This problem is currently being tackled with improved sequencing technology and new statistical methods to allow for these rare variants to be taken into account.

(2) EPIGENETICS: Recent studies have shown that epigenetic changes induced by environmental factors (such as diet, maternal physiology during pregnancy, parental behaviors, etc.) can be inherited across generations [1]. These "transgenerational genetic effects" are not encoded in the DNA itself, but in the way genes are expressed. They have been found in numerous mouse models, and they indicate that when we don't find anything and the disease is there, we may have missed the causal factor simply because we failed to look at the genetics and exposures of the parents and/or grandparents. Interestingly, as Nadeau points in [1], "in the cases that have been studied, the phenotypic consequences of transgenerational effects persist beyond the first generation but with progressively weaker effects." And, "all genetically predisposed progeny are affected regardless of inheritance of the parental gene." Let me stress the significance of this last statement: a transgenerational genetic effect takes place when an individual presents a specific phenotipic trait, even though the genetic change is not present in the individual, but only in the parent. A study recently published in Nature [2], for example, showed that epigenetic changes induced on a first generation of worms in order to elongate their life span were transmitted to the offsprings, too. Another one published in Science showed a similar result in plants [3].

(3) POST-TRANSCRIPTIONAL REGULATION: A recent paper published in Cell [4] looked at an aggressive form of brain tumor called glioblastoma, and found an association between the disease and the way genes in the cancer cells were expressed. In other words, rather than looking at the actual gene copies, they looked at which genes were translated into their subsequent products, and through what processes. Quoting from the abstract, they found:
"~7,000 genes whose transcripts act as miR ‘‘sponges’’ and 148 genes that act through alternative, non-sponge interactions. Biochemical analyses in cell lines confirmed that this network regulates established drivers of tumor initiation and subtype implementation." 
Let's try and understand this. Genes are transcribed into portions of RNA, which are then used to make proteins. However, in any given cell, some genes are expressed and some are not. In other words, genes can be "turned on" or "turned off," and this happens through very complicated processes. One way is to use tiny molecules of RNA (called miRNA or "micro" RNA) that are complementary to the gene RNA. After the gene has been transcribed, the miRNA binds to the complementary strand of RNA, making it double-stranded. Once the RNA is double-stranded it can no longer "produce" a protein, and therefore, the gene it came from is effectively "silenced," or turned off. So, the "miRNA sponges" found in the Cell paper effectively silence a network of genes and have an important role in cancer pathogenesis. This process is not encoded in the genes themselves (and hence it wouldn't be found by simply looking at the different alleles in the population). Rather, it affects the way genes are transcribed.

(4) PROTECTIVE ALLELES: So far the great focus has been on finding risk alleles. But what about protective alleles, or in other words, variants that counter-act the effect of the deleterious ones? I don't mean just alleles that carry a negative risk, but alleles that are proven to interact with the ones that induce a positive risk, and level them out. The existence of such alleles has been hypothesized and studies are under way to test this possibility too. I didn't find anything in the literature yet, but if you are aware of published studies on this, please let me know and I will include them here.

[1] Nadeau JH (2009). Transgenerational genetic effects on phenotypic variation and disease risk. Human molecular genetics, 18 (R2) PMID: 19808797

[2] Greer, E., Maures, T., Ucar, D., Hauswirth, A., Mancini, E., Lim, J., Benayoun, B., Shi, Y., & Brunet, A. (2011). Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans Nature DOI: 10.1038/nature10572

[3] Schmitz, R., Schultz, M., Lewsey, M., O'Malley, R., Urich, M., Libiger, O., Schork, N., & Ecker, J. (2011). Transgenerational Epigenetic Instability Is a Source of Novel Methylation Variants Science, 334 (6054), 369-373 DOI: 10.1126/science.1212959

[4] Sumazin P, Yang X, Chiu HS, Chung WJ, Iyer A, Llobet-Navas D, Rajbhandari P, Bansal M, Guarnieri P, Silva J, & Califano A (2011). An Extensive MicroRNA-Mediated Network of RNA-RNA Interactions Regulates Established Oncogenic Pathways in Glioblastoma. Cell, 147 (2), 370-81 PMID: 22000015

Photo: what happens when you put the camera on a tripod, leave the shutter open for thirty seconds, and three cars finally drive by. The original had a lamppost, but I edited out the post and left the lamp. You can find the original here.

Sunday, October 23, 2011

Another dawn, another amazing sky

Some mornings I open my eyes and the first thing I do is run for my camera. And sometimes I just can't decide which photo I like best. Some came out a little too dark, but they seem to have picked details in the sky that the lighter ones didn't capture. So, here they are, all of the ones I took this morning. If you want, you can tell me which is your favorite in the comments. Enjoy!

Photo #1: shutter speed 1/8, focal length 59mm, f-stop 5.0, ISO speed 100.

Photo #2: shutter speed 1/100, focal length 47mm, f-stop 5.6, ISO speed 100.

Photo #3: shutter speed 1/10, focal length 50mm, f-stop 5.6, ISO speed 100.

Photo #4: shutter speed 1/20, focal length 59mm, f-stop 5.6, ISO speed 100.

Photo #5: shutter speed 1/50, focal length 50mm, f-stop 5.6, ISO speed 100.

Photo #6: shutter speed 1/100, focal length 47mm, f-stop 5.0, ISO speed 100.

Photo #7: shutter speed 1/20, focal length 59mm, f-stop 5.6, ISO speed 100.

Photo #8: shutter speed 1/50, focal length 50mm, f-stop 5.6, ISO speed 100.

Thursday, October 20, 2011

Tess Gerritsen, the "Medical Suspense Queen"

I. Am. So. Unbelievably. Excited.
My guest today is a Stanford graduate, a medical doctor, an internationally acclaimed bestselling author, and winner of the very prestigious Nero Wolfe Award and the Rita Award. Publisher Weekly dubbed her the "medical suspense queen," and her Rizzoli thrillers have inspired the popular TNT series "Rizzoli and Isle," starring Angie Harmon and Sasha Alexander. Not to mention, she's delightful to talk to and she loves Italian food. What else could you ask for?

Yes, I can hardly believe it myself. Tess Gerritsen was so gracious to stop by today and answer my questions. What an incredible honor! I'll try not to faint and be up to the task.

EEG: Tess, thanks so much for being here! Besides avidly reading all of your books, I am also a fan of your blog because you reveal bits of your life I can easily identify with, like skipping breakfast because you have to finish a writing project and then facing your husband's grudges; or not being a "tiger mom." The part I want to ask you about is back when you were still working as a physician and scribbling bits of your stories as they came to you, for example while in a meeting. How hard was it back then? What do you think of those days now, when you look back?

TG: The hard part in the beginning was proving to myself -- and others -- that I really was a writer.  That occupation "writer" doesn't require a degree.  There's no diploma you can point to that qualifies you to claim that as your profession.  We are all, in some ways, writers, but the only writing that others seem to respect is published writing.  So at the beginning, I felt I had to earn that title, and the only way to earn it was to write something publishable.  It meant being persistent, determined, and willing to take a lot of knocks.  So when I look back at those days now, I remember that feeling of struggle, and being hungry to prove myself.

EEG: I still get the shivers when I think of the first chapter in The Surgeon. What was the idea (or image) that sparked the novel?

TG: A reader inspired that story.  I was on book tour for GRAVITY (about the space program) and a woman at a booksigning stood up and said "I'm not interested in the space program.  I want you to write a book about something I AM interested in: serial killers and twisted sex."  Well, that got me thinking.  How could I work medicine, serial killers, and twisted sex into a story?  So I started thinking about things that scare me or bother me about medicine.  And I hit upon the fact that so many faceless people have access to our medical data.  What if there was a blood technologist in a hospital lab somewhere who was also a serial killer?  What if he chose his victims because of something about their blood tests?  He'd know the patient's name, address, and marital status.  He'd know how to find them.  And since the blood tests come from doctors' offices all over town, the police wouldn't be able to pinpoint what links all the victims.  It was my vision of some quiet, brilliant, creepy guy in a laboratory that really got the story going.

EEG: Your characters Rizzoli and Isle are now a popular TV show. What did you feel the first time you watched the show? Aside from the excitement of seeing your own characters on screen, there must have been some moment when you thought, "But... that's not how I had imagined this!" What was your reaction to that?

TG: I was thrilled to have it come to TV at all.  And even though the actors don't look like the characters I imagined, their personalities come through.  I was also a huge fan of Angie Harmon's from Law and Order, so when I heard she'd been cast, I knew the show was going to be great.  Any jolts I might have felt about the differences in the book and TV characters were swept away by the sheer excitement of seeing these people come to life.  I've continued to write the books based on the original universe that I created, and the TV show follows its own parallel universe, but these are still characters who wouldn't exist if I hadn't created them.

EEG: Every novel of yours has some fun science tidbit folded in. How important is science in your writing?

TG: It's very important.  My background is science, and it irritates me to read a book where details are horribly wrong (for instance, when the author confuses bacteria with viruses!) so I try my very best to be accurate.  In a book like GRAVITY, about the shuttle program and medicine in microgravity, that meant a ton of research and visits to NASA.  It meant months of background reading about astronaut training and launch sequences and shuttle operations.  Do I get details wrong?  Undoubtedly.  There are so many different topics covered in every book, that it's bound to happen.  Most mistakes occur because you don't know what you don't know -- so you haven't even thought of checking the facts.  For instance, I didn't know that no American car companies manufactured any automobiles in 1945.  A reader pointed that out to me after I'd made the goof.  It was just an irrelevant detail in the story, and it never occurred to me that I might be wrong, so I didn't even think to confirm it.  But those are precisely the details you get wrong.

Now that I'm writing crime fiction, my science might be drawn from a wide array of specialties.  For instance, in THE SILENT GIRL, I had to go to an expert to find out what monkey hairs look like under a microscope.  I had to look up which techniques will identify specific species.  I had to find out if you can carbon-date an ancient sword.  And how those swords were made.  In books past, the scientific topics have ranged from ground penetrating radar to the identification of surgical sutures to the autopsy findings of organophosphate poisoning.  You just never know what new adventures a book will take you on!

EEG: Being a scientist I completely understand the need to thoroughly research everything. And that's exactly what I love about your books!

Tess, thanks so much for being here! Tess's last book, THE SILENT GIRL, came out in July from Ballantine Books, and it's another page-turner, read-in-one-sitting masterpiece. To find out more about all of Tess Gerritsen's thrilling novels, check out her website:

Wednesday, October 19, 2011

MHC molecules, mating, sniffing, and birthcontrol: believe me, there's a link!

Today we talk about… mating! Whoa -- did you just see that spike in the stats page? Haha, okay, but first you have to sit through the usual genetic lesson. Here it goes: we start talking about the major histocompatibility complex, or MHC.

I've mentioned many times in my previous posts that in order to trigger an immune response you have to make sure that the immune system recognizes the antigen, or "foreign" object. Antigens are made of proteins that, once inside the cell, are chopped into bits and pieces. The bits and pieces are then transported to the cell surface and "presented" to T-lymphocytes, which in turn recognize the bits as a "red flag" (as in, "ALARM! The cell has been infected with foreign and dangerous object!"), and destroy the cell. MHC molecules have the function of grabbing the bits of proteins inside the cell and presenting them to the cell surface. This is a very important step in the immune response, because without this "presentation" the immune system is unable to recognize the antigen.

Now, the genes that code the MHC molecules are highly polymorphic: what this means is that it's a DNA region that varies greatly across individuals. Why? Because the broader range of MHC molecules we have, the better chances to recognize even the rarest antigen that invades our body. Natural selection favors variety in the MHC genes. Having different alleles for these genes is beneficial for disease resistance. Basically, it makes our immune system stronger.

How do we get different alleles? Remember, we inherit one copy of each gene from our mother, and one from our father, and we get discordant alleles when the mother's copy is different from the father's. Studies have shown that mating occurs preferentially between MHC discordant alleles [1]. And how do we detect people with different MHC alleles than ours? By sniffing. Seriously.

This is actually an old study (1995), and many of you may already know about it, but back then the genetics wasn't known, and that's the part I'd like to add here. Anyways, Wedekind et al. [2] enrolled a sample of male and female students. They had the male participants wear the same T-shirt for two consecutive nights, and then they asked the ladies to rate the "odor pleasantness" of six T-shirts, chosen so that three came from MHC-similar males, and three from MHC-dissimilar males. A curious trivia is that the women in the study used nasal sprays to enhance their sense of smell, and they had all read Suskind's novel "The Perfume." Interestingly, the researchers found a correlation between odor preferences and discordant MHC.  

Let's look at the genetics behind the scenes. The genes that regulate olfactory receptors are all over our genome. However, Ehlers et al. [3] found a very large cluster (36 genes) very close to the HLA complex on chromosome 6. This entire region is in strong linkage disequilibrium, which is a very complicated way geneticists use to say that basically we tend to inherit these genes together. You know how chromosomes split before they turn into oocytes or spermatocytes? Well, the splitting is not completely random, and it turns out that these olfactory receptor genes are highly correlated to the HLA genes (they tend to "stick" together), which would explain how odor preferences would correlate to discordant MHC types.

Wow, I've managed to weave a link through the first three items in my schizophrenic title. Now to the fourth one: birth control pills. Well, the Wedekind study found that the correlation varied depending on the women's hormonal status and, furthermore, the trend reversed for women on the pill. In other words, women on the pill seemed to prefer the T-shirts from MHC-similar men.

Okay, all of the above made a fantastic punchline, but… how about the caveats?

For starters, Roberts et al. [4] in 2008 repeated the exact same experiment Wedekind et al. did and, alas, couldn't reproduce the results. What they did find was that single women seemed to prefer the odor from MHC-similar men, while women in a relationship preferred odors form MHC-dissimilar men.

By the time I came to the end of the paper, they had done so many tests that any p-value they found would have to be taken with a grain of salt. And in all fairness, what they propose to measure in these studies are variables extremely hard to quantify. The likeability of a certain odor varies not only from person to person, but from day to day. Have you ever shopped for a fragrance? After spraying a few testers, don't they all smell the same?

As for the biology caveats (and for this part I have to thank my dad!):

1) In mammals sexual stimuli are regulated through pheromones. While generic smells are perceived through the olfactory receptors in the epithelium inside the nasal cavity, pheromones are sensed through the vomeronasal organ. The two are regulated by different genes.

2) In humans the vomeronasal organ has lost its function, mostly because it got replaced by the fact that we can see colors. This has caused a shift: most sexual stimuli in humans are perceived through sight, and the genes regulating the vomeronasal organ have become pseudogenes (non-coding).

3) Lastly, how we react to odors is not simply a genetic behavior, but it is highly correlated to the environment. In fact, it changes throughout our lifetime as we "learn" to like certain smells more than others, and this is due to the way our brain changes and reacts to the environment.

Nonetheless, these are certainly interesting experiments as they point to "trends" in human behavior. They give some insights on how much we are driven by hormonal changes, and on the complex ways physiology and environment weave together into making who we are.

[1] Milinski, M. (2006). The Major Histocompatibility Complex, Sexual Selection, and Mate Choice Annual Review of Ecology, Evolution, and Systematics, 37 (1), 159-186 DOI: 10.1146/annurev.ecolsys.37.091305.110242

[2] Wedekind C, Seebeck T, Bettens F, & Paepke AJ (1995). MHC-dependent mate preferences in humans. Proceedings. Biological sciences / The Royal Society, 260 (1359), 245-9 PMID: 7630893

[3] Ehlers A, Beck S, Forbes SA, Trowsdale J, Volz A, Younger R, & Ziegler A (2000). MHC-linked olfactory receptor loci exhibit polymorphism and contribute to extended HLA/OR-haplotypes. Genome research, 10 (12), 1968-78 PMID: 11116091

[4] Roberts SC, Gosling LM, Carter V, & Petrie M (2008). MHC-correlated odour preferences in humans and the use of oral contraceptives. Proceedings. Biological sciences / The Royal Society, 275 (1652), 2715-22 PMID: 18700206

Monday, October 17, 2011

A planet of viruses: an interview with award-winning biology writer Carl Zimmer

My guest today is such an eminent figure in the field of science writing that, besides being highly honored by his presence here, I don't know where to begin to introduce him. Carl Zimmer is the contributing editor and columnist of Discover Magazine, and the author of numerous popular science books like A Planet of Viruses, Parasite Rex, Evolution: the Triumph of an Idea, and many more. He travels all over the country giving lectures and promoting science, and his articles have appeared in the New York Times, National Geographic, Scientific American, and many, many others.

EEG: Carl, thank you so much for being here, especially knowing how busy you are with all your public engagements. When and how did you decide to become a science writer?

CZ: I always was writing in school. After college, I got a job at Discover, just in the hopes of getting into journalism somehow. After a while, I realized that it was an excellent fit for the kinds of things that interested me. So I can't say I actually decided!

EEG: What fascinates you the most about science and biology in particular?

CZ: There is always a surprise. I've been writing about science now for 20 years--I've written articles and books--and yet every week there's something that makes me widen my eyes.

EEG: You wrote a book on evolution and you give public lectures on evolution. What do you make of the fact that Darwin's ideas are still debated today? I don't mean just from a religious point of view, but even among scientist themselves (see, for example, the debate that Lynn Margulis started about symbiosis...)

CZ: Every science has its debates. The debates within evolution are so interesting to the public. It's an indication of our fascination with our origins, and with the natural world

EEG: I couldn't agree more. 152 years after the publication of the Origin of Species, and here we are still debating and arguing over it. It's the truly revolutionary ideas that generate this kind of debates. And, since we're at it, I'd like to mention not only Darwin, but also Lamarck, whose work has been overlooked for years until recently, when new insights into epigenetics proved that his views, too, captured a fundamental aspect of evolution.

Thanks so much, Carl, for stopping by to answer my questions.

Check out Carl's award winning blog, The Loom, on Discover Magazine, to find out more about his books and his fantastic stories around the world of science.

Sunday, October 16, 2011

A chimeric virus to cure leukemia? Yes, we can!

Last week I talked about gene therapy and vaccines targeting tumor cells. Following those posts, a friend of mine (thanks, Alex!) pointed me to a recent case report published in the New England Journal of Medicine, which describes a successful use of gene therapy to treat leukemia [1]. Since you know I like to talk about chimeric viruses and all the wonderful things you can do with them, I was instantly drawn to the paper.

Leukemia is a type of cancer that causes an abnormal increase in white blood cells. The patient discussed in the NEJM case report was affected by a type of leukemia called B-cell neoplasm, which, as the name indicates, causes the abnormal proliferation of B-cells.

So, how do you address the problem using gene therapy?

This is what we need: (a) a target on the tumor cells that will tell the immune system to destroy them; (b) a weapon for the immune system to recognize and kill the tumor cells; (c) a way to "give" the weapon to the immune system.

The answer to (a) comes from a receptor called CD19, which is expressed by malignant B-cells. The "weapon" (b) is a genetically engineered anti-CD19 antigen receptor, which enables T-cells (our immune system "soldiers") to recognize the malignant B-cells and destroy it. The big question is (c): how do we make T-cells with the anti-CD19 antigen receptor?

This is where gene therapy and chimeric viruses come into play. How do we use gene therapy to transfer the genes that express the anti CD19 antigen receptor into the T-cells? We need "something" that does this for a living -- transfer genes into cells. Remember what that is?

Absolutely, a virus.

Now, remember what virus in particular targets T-cells?

HIV, of course!

And that's exactly what the authors of this study did: they created an HIV chimeric virus and endowed it with the genes of the anti-CD19 antigen receptor. T-cells were collected from the patient, transduced (which means that the genetic material was transferred inside the T-cells using the modified HIV virus), then infused back into the patient.

Like in all best stories, at first things seemed to go terribly wrong: two weeks after the transfusion, the patient started having high fevers; three weeks after treatment the patient had to be hospitalized and treated for metabolic complications consistent with leukemia treatment.

And then the miracle. One month after the infusion there were no more tumor cells in the patient's blood. At the time the paper was written -- ten months after the therapy -- the patient was still in remission, and the antigen recognizing T-cells were still proliferating.

Interestingly, this case report reminds of an almost symmetric case reported in 2008: an HIV-positive patient who developed leukemia was treated with a bone marrow transplant from a donor who had the Delta32 CCR5 mutation I discussed in this post. The mutation modifies T-cells in a way that they can no longer be infected by the HIV virus and, indeed, after the bone marrow transplant, the patient's viral load dropped and never recovered. As far as I know, the patient is the only one ever to be cured of AIDS.

[1] Porter, D., Levine, B., Kalos, M., Bagg, A., & June, C. (2011). Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid Leukemia New England Journal of Medicine, 365 (8), 725-733 DOI: 10.1056/NEJMoa1103849

This post was chosen as an Editor's Selection for

Saturday, October 15, 2011

Yellows, reds, and golds

Not many fall pics this year. My favorite trail is sill closed due to Las Conchas fire. Sigh.

Photos: focal length 85mm, f-stop 14, ISO 100. Shutter speed: top, 1/100, bottom 1/80.

Friday, October 14, 2011

Murder is her day job!

No, it's not "Murder, she wrote," it's... "Murder, she analyzed"!

Lisa Black is a forensic scientist and the New York Times best selling author of the Theresa MacLean suspense novels Defensive Wounds, Trail of Blood, Evidence of Murder, and Takeover. After spending five years at the Cuyahoga County Coroner’s Office, analyzing gunshot residue on hands and clothing, hairs, fibers, paint, glass, DNA, blood and many other forms of trace evidence (the "happiest years of her life," she writes in her bio), Lisa is now a latent print examiner for the city of Cape Coral, Florida, police department, working mostly with fingerprints and crime scenes.

And when she gets home from her day job... she writes gripping, grab-by-the-throat suspense novels! It is my great pleasure to have Lisa Black as my guest today!

EEG: Lisa, I'm insanely curious about your day as a forensic scientist: what is it like?

LB: There is no such thing as the average day, and if there were it would still depend on where you work and what your agency does. At the coroner’s office I would usually be examining victim’s clothing, typing blood (this was a while ago), running gunshot residue samples through the spectrometer and analyzing hairs and fibers. At the police department I spend 90% of my time sitting in front of a computer looking at fingerprints, and the rest photographing and processing crime scenes (usually burglaries) and evidence.

EEG:  Did you always write or was it your job that one day sparked the writing muse?

LB: I wrote first, starting in grade school, back when I wanted to be a pilot, archaeologist, ballerina or astronaut. But I always wrote mysteries.

EEG: From what I've learned about forensic sciences, you have to be very meticulous in collecting the evidence and analyzing it. Do you think this ability helps you in your writing, too?

LB: Yes. I grew up reading the classical mysteries of Ellery Queen and Agatha Christie, so it’s important to me that every last factor is realistic and fits into a pattern. There is an overwhelming amount of attention to detail in a mystery story.

EEG: How much of your heroine Theresa MacLean do you see in yourself?

LB: All of it, which is a problem. I need to let her be herself instead of what I want her to be, which is me only stronger, faster, smarter and divorced.

Well, you never know, characters do have the tendency to surprise even their authors, sometimes!

Thanks so much, Lisa, for taking the time to answer my questions. To find out more about Lisa Black and her best selling novels, visit her at

Wednesday, October 12, 2011

Are vaccines the future of cancer treatment?

The September issue of the Cancer Journal is dedicated to cancer vaccines and how they may hold the key for cancer treatment and prevention. This is not to be confused with vaccines against cancer-causing viruses, like HPV. In that case the vaccine elicits antibody responses against the virus. In the context of cancer, though, a vaccine would use the immune system's own weapons in order to destroy tumor cells. An example is the vaccine to treat advanced prostate cancer that was approved by the FDA in April 2010, after a Phase III trial showed that patients who received the treatment survived longer than the controls.

The main question in order to create a vaccine that targets cancer cells is: how do we tell the immune system which are the cells to destroy? There is a particular class of cancer cells that offers a potential candidate: cancer stem cells.

Stem cells are a class of very special cells because they are undifferentiated, which means they have the potential to generate any kind of tissue (heart, lung, skin, etc.) Seems almost a paradox, doesn't it? Stem cells can remain undifferentiated and at the same time differentiate into specialized tissue cells. This is possible through an asymmetric cell division: every time a stem cell divides, it generates two cells, an undifferentiated stem cell, and a differentiated one. This way, the differentiated cells produce the specialized tissue, while the stem cell population remains intact.

In a healthy individual, cells with this capacity are found in the bone marrow and in umbilical cords. Unfortunately, they have also been found in solid tumors, such as breast cancer, prostate cancer, and melanoma. You can immediately see the problem: if a cancer cell remains undifferentiated, it means it can preserve its population while generating new cancers in other parts of the body -- the process known as metastasis.

Therefore, one way to produce a cancer vaccine is to have it elicit immune responses against cancer stem cells [1]. How? The idea is to use proteins, or even bits of proteins (peptides) that are over-expressed on tumor cells. Vaccines that use peptides as antigens are called anticancer peptide vaccines [2], and right as I was reading about them, one of the authors of this paper [2] wrote this wonderful article on Scientific American, which describes in great detail the history and ideas behind a cancer vaccine. Quoted from the S.A. article:
"Basically, there are three elements to making a cancer vaccine. The first is to decide precisely what molecular feature, or antigen, in a malignant tumor the immune system should recognize as foreign and target for killing. The second is to decide how to deliver a triggering agent (or vaccine) to the immune system that ramps it up to attack cancer cells. And the third is to decide which cancer patients to treat and when during the course of their disease to administer the vaccine."
Mutated cancer cells arise normally (in small quantities) in the body and a healthy immune system is normally capable of recognizing them and destroying them. A vaccine would make this kind of response stronger and robust enough to wipe out all malignant cells. Unfortunately, as cancer progresses, the immune system gets severely damaged. Therefore, the key for this strategy would be to either act fast enough (when the tumor is still small), or combine it with other strategies like chemotherapy.

In the September issue of the Cancer Journal, Dhodapkar et al. [1] review what the future holds in cancer vaccine research, whereas Larocca et al. [3] discuss viral vectors, in other words, how viruses could be engineered to deliver a cancer vaccine.

[1] Dhodapkar MV, & Dhodapkar KM (2011). Vaccines targeting cancer stem cells: are they within reach? Cancer journal (Sudbury, Mass.), 17 (5), 397-402 PMID: 21952290

[2] Perez SA, von Hofe E, Kallinteris NL, Gritzapis AD, Peoples GE, Papamichail M, & Baxevanis CN (2010). A new era in anticancer peptide vaccines. Cancer, 116 (9), 2071-80 PMID: 20187092

[3] Larocca C, & Schlom J (2011). Viral vector-based therapeutic cancer vaccines. Cancer journal (Sudbury, Mass.), 17 (5), 359-71 PMID: 21952287

Photo: focal length 85mm, shutter speed 1/160, f-stop 16, ISO 400.

Tuesday, October 11, 2011

Facebook and the unselfish gene

So I finally did it. As some of you regulars may have noticed, I put the blog on Facebook. And then I instantly became needy and sent out a bulk of emails begging people to like me. I sent out five and since they're very nice friends of mine, they all liked me. And then I thought, "Well, now, my friends' friends' will like me, and then my friends' friends' friends', and then..."

Hmm. That got me thinking. Does it work like with viruses? No, seriously, do "likes" spread like a viral infection in the body? If not, what kind of network do they resemble? Neurons? Random walks? Traffic network? Surely somebody has thought of modeling this -- does anybody know?

I really got curious about this. I logged onto PubMed and did a search under the keyword "Facebook." I got around 200 hits, none of which answered my questions, but I did find a few papers that captured my attention, so I thought I'd list them below.
  • The unselfish gene [1]. Species compete for resources. We've learned in school that natural selection is a competition among the fittest. Philosophers like Hobbes and Machiavelli have stated that humans are essentially selfish, pushing societies to promote self-interest with the use of incentives and punishments. In his review, Dr. Benkler looks at how this line of thinking has changed in the past few years. In fact, we now believe that evolution selects cooperation over competition. The evidence, according to Benkler, doesn't come from evolutionary biology only, but also from sociology, psychology, and economics. And to prove his point, Benkler points to the success of social networks like Facebook, Craigslist, and LinkedIn, which provide emotional, social, and psychological support, gratification, and a great deal of information resources. The sharing of information that goes through the Internet is an indication of cooperation. Indeed, my PubMed search yielded many results on the benefits of Facebook and social networking when it comes to health support groups, health care, and advantages of networking for medical practices. So, I completely agree, except I do find Facebook a little selfish when it comes to... self-promotion. Ahem, yes, I confess I am myself guilty of the crime, since I put my blog in there out of a selfish, egotistical need to have readers...
  • Facebook is smoking [2]. This one sounded intriguing. Does the title imply that Facebook is as addictive as smoking? Or that it's as cancerogenic as smoking? Or maybe, Facebook is smoking on your computer after so much use? Unfortunately, I couldn't find anything besides the title, not even the abstract.
  • Mirror, mirror on my Facebook wall: effects of exposure to Facebook on self-esteem [3]. Does Facebook enhance or diminish self-esteem? My intuition would be that it requires some solid self-esteem to put yourself "out there." The debate is still very much open, however, some of the literature* seems to indicate that Facebook has beneficial effects on self-esteem. So, stop hiding! Find the guts, go out there, and you'll be a better person! (Yes, yes, I am indeed preaching to myself! Again, guilty.)
* In my literature search, unfortunately, there were numerous papers I didn't have access to.

All of the above is fascinating and interesting, but what about the networking model? I still think a viral infection model might work: you need to re-define parameters such as fitness cost and effective population size. For example, you might send the request to "like you" to, say, 10 friends, but only the ones who will actually click on the like button are the ones who actually "replicate." Say you get 7 likes. Now, all the 7 friends' friends will see the likes, but how many will go ahead and click the like button in turn? That's the effective size population, how many "likes" will actually generate new "likes." In this model there's no immune pressure, but if the effective size is too small, then the infection doesn't take off.

Obviously, this is just my speculations, so I did a second PubMed search and this time I typed "Facebook viral," hoping I'd get some insight on whether Facebook "likes" spread like a virus. This is the only entry I got:
  • Using the Internet and social media to promote condom use in Turkey [4]. Not exactly what I meant in my search, but look at the bright side -- another Facebook success story.
That's all for today. Short post, I know, but hey, all those refreshing clicks on FB to check the number of likes, it's a lot of work, you know?

... Pssst. Hey. If you happen to have a spare second, would you click on the like button up there? ...

Okay, those last two statements were jokes. Seriously. Just give me a pat on the back and my self-esteem will thrive. Promise.

[1] Benkler Y (2011). The unselfish gene. Harvard business review, 89 (7-8) PMID: 21800472

[2] Mgweba L, Dlamini S, Kassim J, Planting T, & Smith D (2009). Facebook is smoking. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 99 (11) PMID: 20222194

[3] Gonzales AL, & Hancock JT (2011). Mirror, mirror on my Facebook wall: effects of exposure to Facebook on self-esteem. Cyberpsychology, behavior and social networking, 14 (1-2), 79-83 PMID: 21329447

[4] Purdy CH (2011). Using the Internet and social media to promote condom use in Turkey. Reproductive health matters, 19 (37), 157-65 PMID: 21555096

Photo: last dahlias of the season! Focal length 85mm, F-stop 20, shutter speed 1/50, ISO 100. A special thanks goes to my neighbor who does an amazing job growing these beautiful flowers and then kindly lets me photograph them.

Monday, October 10, 2011

So, how does one become a computational biologist?

(Starting today, for the next two weeks, I will be guest blogging over at Scientopia, which means that the posts here will be cross-posted over there, too. As a first post, I thought I'd tell the story of how I ended up being a computational biologist. Forewarning: there are better and more linear ways to become a computational biologist. But, as we all know, life is hardly ever linear.)

I used to think genes dictate what we can be and the choices we make dictate what we end up being. Well, that's not quite true. I haven't accounted for opportunities.
When I finished college I wanted to be a mathematician. Math is pure and beautiful. It's like a Michelangelo painting, perfect all around. You follow the steps dictated by logic and you can't be wrong. It's Socratic. I got accepted into graduate school, and my husband arranged to finish his dissertation off site so we could both go. We fit all our belongings into two suitcases (that's all we had) and left. We were young, enthusiastic, and clueless.

The bus left us in the middle of nowhere in Massachusetts. The motel we'd booked was five miles away. A lady took pity on us and gave us a ride. I forgot the lady's name, but not her baby's: Timothy. He was the cutest baby.

I grew tired of doing pure math. Yes, it's beautiful and perfect. There's Banach spaces, and then Hilbert spaces, and then Banach spaces of Hilbert spaces, and Hilberts of Banachs of Hilberts... I felt lost in one of Dr. Seuss's pictures. Oh, the thinks you can think... Yes you can, but do you want to?

(My mathematician friends, please don't hate me. I'm in confession mode, so bear with me.)

So when my husband got a postdoc in Vienna, Austria, we packed again and left. By then we had four suitcases and a baby. In Vienna I started freelance writing. I wasn't paid a penny but it was fun.

Vienna is beautiful, by the way. If you have enough money to enjoy it. We didn't.

The following year we moved to Valencia, Spain. We had four suitcases, five boxes, and a baby. Two years later we moved to Pasadena, California. We had four suitcases, twenty boxes, and two babies. Gosh, it's exponential, isn't it? Not the baby part, though. We stopped at two and glad we did.

In Pasadena I started missing my job. Did I mention I felt poor in Vienna? Haha, that was nothing compared to Pasadena! That's what Southern California does to you. I looked around but as it turns out with a degree in pure math there's not much you can do besides teaching. And I wasn't much into teaching. I continued to do freelance writing, and even though by now I was getting paid a little, it definitely wasn't enough.

So I decided to go back to school.

I applied to the biomath program at UCLA, the computational biology program at USC, and the biostat program at USC. I got accepted to all three of them. At the time I was stubbornly convinced that I could survive in Southern California without ever getting on a freeway.

I got up one morning at 4 a.m., took a bus, and three hours later I was at the UCLA campus, which is a whole city within a city. Never seen a campus that huge. The commute drained me. The next day I went to downtown to check out the USC computational biology department. The faculty there is impressive--gods in the field. Now that I knew I wasn't going to be a mathematician, I really wanted to become a computational biologist. That's where all the cool stuff was happening--genetics, protein folding, sequencing. And, they even offered me a scholarship.

Unfortunately, the USC downtown campus is not in a charming part of town (to put it in mild terms). And again, the commute from where I lived was going to be a killer. 

Finally, I went to the USC medical campus, which turned out to be ten miles down Huntington Drive from where we lived (no freeway! Can you believe it? I could get somewhere in LA county without getting on the freeway!), and met another god.

There's many gods in my life.

Stan is fantastic. If you live in Pasadena, go listen to him play the piano at the Parkway Grill on Thursday nights. He's amazing.

So, anyways, I got into the biostat program. Like I said, Stan is fantastic, and the no-freeway thing sealed the deal.

Statistics is not beautiful. You know the old saying: "There's lies, there's damn lies, and then there's statistics"? Well, it's true. I set off wanting to do pure math, which is perfect and beautiful, and here I was, doing dirty and very much imperfect stuff. But it's useful. And life, the way we describe it, is very much imperfect. So there. You can't apply perfect and beautiful to real life.

I decided I wanted to be a biostatistician. Even got a job as one. By then I could handle Californian freeways. Sort of. I still screamed from time to time. And I still got off at the wrong exits and stuff like that. But hey, the adrenaline high the morning commute down the Two-Ten gives you is unbeatable! (I don't miss it, BTW).

And then my husband had us move again. This time we filled a truck. Heck, give it enough time, you start buying furniture! No, let me rephrase that: give it enough time and a close enough Ikea.

On a side note, my husband hates Ikea. He's the one who has to decipher the cryptic drawings.

We moved to a remote part of Northern New Mexico, so remote that for a while it was only known as a "mail stop." But that's another story. For now, all I will say is that it's not the desert. It's got mountains, and trees, and forests, although the forests do tend to burn down every ten years or so...

Anyways, I'm getting carried away. The point I wanted to make is that we came out here and I met yet another god, my wonderful, amazing, gracious mentor. And guess what I ended up doing? Computational biology. Yeah, where all the cool stuff is happening.

Looking back, I did choose to become a computational biologist, didn't I?

Photo: water creek, Twin Falls, WA. Canon 40D, shutter speed 1/20, focal length 85mm, ISO 400.