Debunking myths on genetics and DNA

Saturday, December 28, 2013

Every Day Landscapes

I started a new project, called "Every Day Objects," in which I create landscapes from everyday objects I find in the house. Not sure it's going exactly where I want it to go, but it keeps my creative juices flowing. Here's the first two images, freshly uploaded to a new gallery on smugmug.

Walking on Moonlight by EEG
Spoonfuls of Me by EEG

Saturday, December 21, 2013

Happy Holidays

Happy Holidays and thank you to all my readers. Thank you for commenting, sending feedback, and participating in the discussions. I wish you all peace and joy from this holiday season and a wonderful 2014.

On a side note, if you are looking for a last-minute, tax-deductible gift, please consider donating to NOAH, a non-profit organization that supports the nearly 3 million South African kids orphaned by AIDS. NOAH has been hit hard by the economic recession and had to close many of its centers. Every penny helps.

Saturday, December 14, 2013

ASD and inflammation: more than just a correlation

There has been a lot of speculation, lately, about vaccines possibly being harmful and, in particular, causing autism. You know I work on HIV vaccine design, so there's no need to say where I stand on the need of vaccinations. No link has been found between the incidence of autism and vaccination. Of course, medicine is not an exact science. Outliers will always exist. The U.S. seem to be a special case, as the vaccination schedule in this country requires a high number of vaccine doses, yet the infant mortality rate is one of the highest among North America and European countries. However, take a close look at this graph:

The countries with low mortality rate shown in this graph have a strict vaccination schedule, just like the U.S. On the other hand, what distinguishes them from the US is affordable health care. Countries with a high infant mortality rate are countries where poor people do not have access to vaccines and good health care. For the 3-million AIDS orphans living in sub-Saharan Africa a vaccine against HIV is the only hope they have to live into adulthood. It is quite easy for those of us who have a healthy life style and have access to food, medicines, and doctors on a daily basis, to say "no, thank you" to vaccines. But please, when you make your own decision about vaccines, do remember the millions of people for whom this is not a choice. And also remember: some children who are immunodefecient really cannot be vaccinated. They cannot contract any kind of disease, either, because their immune system is not working. However, if the majority of the people continue to get vaccinated, people who really cannot be vaccinated are still protected:

found on Facebook

Back to autism. As you saw from my last post, ASD, or autism spectrum disorders, is indeed a puzzling disease and pinning down its etiology has been challenging. The genetics involve numerous genes and diverse pathways, implying that different mechanisms could potentially lead to ASD, particularly during fetal development. One thing that I recently discovered is a number of correlations found between infections in the mother during gestation and autism:
"Recent studies have highlighted a connection between infection during pregnancy and the increased risk of autism in the offspring. Parallel studies of cerebral spinal fluid, blood and postmortem brains reveal an ongoing, hyper-responsive inflammatory-like state in many young as well as adult autism subjects. There are also indications of gastrointestinal problems in at least a subset of autistic children [1]."
In his review [1], Patterson makes a good summary of the relevant studies: for example, a permanent, inflammatory-like state has been found in postmortem examination of ASD affected brains. This was found at all ages, indicating that the state was established early in the development and maintained throughout the life-span of the ASD affected individual. These abnormalities expand to the central nervous system and the peripheral immune system affecting also the gastrointestinal tract:
"These findings include immune cell infiltrates present in the colon, ileum and duodenum, as well as increased T cell activation in the intestinal mucosa. These inflammatory changes are associated with autoimmune responses that could contribute to the observations of decreased mucosal integrity, or 'leaky gut' [1]."
"Abnormal activation of the immune system may also be involved in the etiology of autism. [. . .] Family members of autistic children, particularly the mothers, show a higher incidence of allergy or autoimmune diseases. Consistent with immune involvement are findings that maternal infection is a risk factor for autism [2]."
In conclusion, there is a correlation between immune abnormalities and ASD, and the immune abnormalities propagate to the brain and the gastrointestinal tract. However, it is unclear if these abnormalities cause the behavioral symptoms of ASD or if they are a secondary effect. The health and well-being of our immune system has such deep, profound effects on the central nervous system. The two interact very closely together: stress and the general emotional status, for example, can affect immunity; vice versa, the immune system can influence behavior. Both our brain and our immune system constantly learn and readapt to the surrounding environment (for example, our immune system learns to recognize new pathogens throughout our lifetime), which makes them prone to life-long epigenetic changes induced by environmental factors such as stress and disease. It's not a coincidence that:
"Immune dysregulation has also been implicated in the etiology of a variety of neurodegenerative, psychiatric, and neurodevelopmental disorders, including Parkinson, Huntington, and Alzheimer diseases, multiple sclerosis, major depression, schizophrenia, and addiction [2]."
Hsiao et al. [2] addressed the open question of whether the immunological abnormalities cause ASD-like behaviors in a mouse model. They induced ASD in mouse offspring through "maternal immune activation" (MIA): the immune system of pregnant mice was altered and then the offsprings of the altered mice that were behaviorally abnormal was compared to the offsprings of the controls. The behaviorally abnormal MIA offsprings exhibited core behavioral symptoms of autism, including increased repetitive behaviors, decreased social interactions, and increased anxiety. Hsiao et al. found several abnormalities in the immune system of these MIA offsprings: levels of regulatory T-cells were decreased and CD4+ T-cells were hyper-responsive. These abnormalities could not be transferred to healthy mice through a bone marrow from the MIA mice. However, when irradiated and transplanted with immunologically normal bone marrow, many of the behavioral abnormalities stopped. This would suggest that the immunological dysregulation causes the ASD-like behaviors.
"It is striking that in a mouse model of an autism environmental risk factor that exhibits the cardinal behavioral and neuropathological symptoms of autism, there is also permanent peripheral immune dysregulation. This finding provides the opportunity to explore molecular mechanisms underlying the relationship between brain dysfunction and altered immunity in the manifestation of abnormal behavior. Furthermore, this finding provides a platform for investigating how prenatal challenges can program long-term postnatal immunity, health, and disease. Maternal insult-mediated epigenetic modification in HSC and progenitor cells is one possible mechanism for how effects may be established by transient environmental changes yet persist permanently into adulthood. However, the BM transplant results suggest that the peripheral environment of the MIA offspring is also critical for maintaining a permanently modified immune state [2]."
We will never be able to prove or disprove a direct causal relation between vaccines and autism: if a child develops ASD after vaccination, unfortunately, we cannot rewind time and see if the same child, without the vaccine, would've never developed ASD in his/her lifetime. ASD typically develops in infancy, which is when the bulk of vaccines are administered. The risk of ASD is much higher (see last week's post) if there's already a family member with ASD, siblings in particular. And given the deep, complex interactions and reciprocal influence between the nervous system and the immune system it is quite possible that a sudden change in the immune system could cause some level of disruption in the nervous system. However, if the immune system is primed to such risk, a virus or any other pathogen, which cause changes in the immune system just like a vaccine does, could also cause similar disruptions. On the other hand, vaccines can potentially prevent infections that, according to these studies, do increase the risk of ASD in the baby during the first trimester of gestation.

So, as always: Read the literature, talk to your doctor, possibly to more than one, consider your family's medical history, and, whatever decision you make, make sure it is an informed decision.

[1] Patterson, PH (2011). Maternal infection and immune involvement in autism Trends in Molecular Medicine DOI: 10.1016/j.molmed.2011.03.001

[2] Hsiao EY, McBride SW, Chow J, Mazmanian SK, & Patterson PH (2012). Modeling an autism risk factor in mice leads to permanent immune dysregulation. Proceedings of the National Academy of Sciences of the United States of America, 109 (31), 12776-81 PMID: 22802640

Wednesday, December 11, 2013


Origins, by EEG

I started a new gallery on my website, titled New Beginnings, and this is the last piece I've uploaded. I hope you enjoy it!

Sunday, December 8, 2013

Autism: not one disease but a spectrum of disorders; not one gene but a network of gene coexpressions.

"Autism spectrum disorder (ASD) is a lifelong developmental condition that affects about 1 in 110 individuals, with onset before the age of three years. It is characterized by abnormalities in communication, impaired social function, repetitive behaviors and restricted interests [1]."
ASD is more common among males than females, with a 4:1 male to female ratio. Numerous studies in the literature have shown evidence for a strong genetic component of autism, with a risk up to 25 times higher among siblings compared to the general population. However, if you look at the literature, you find that these numbers change pretty dramatically from study to study. This is often the case when you look at rare disorders in conjunction with rare mutations (WARNING: the rest of the paragraph is a statistical digression, feel free to skip to the next section). The smaller the effect you are trying to measure, the more subjects you will need in your study. This is also true if you are testing many variants, as for example in GWAS studies, which investigate variants in the whole genome. If the effect is big enough, you will find statistical support for your association, however, if your sample size is not big enough, the effect you are trying to measure will vary greatly from study to study. This is because the smaller the sample size, the larger the variance, which is stat jargon to say that whatever you are trying to measure (typically an increase in risk) is likely to be different if you repeat the study.

What do we know about the genetic etiology of ASD? About 10% of people diagnosed with ASD have some underlying genetic syndrome (including mitochondrial genes). About 5% are due to rare chromosome rearrangements, for example changes in the size, shape, or number of some chromosomes. Another 5% has been associated to both inherited and de novo "copy number variations" (CNV), the presence of extra copies of some genes [1]. CNV is not rare among humans, as it accounts for approximately 0.4% of the variation between unrelated genomes. Identical twins also differ in CNV, and, even though they have identical genomes, the copy number of the genes may differ between the two. Despite this, in some families with a history of ASD the proportion of de novo CNV's has been found to be up to five times higher than in families without a history of ASD. Finally, thanks to recent advances in sequencing technology, de novo point mutations throughout hundreds of genes have been found and implicated in about 15% of ASD cases [2].

In light of the variety of mutations, genes, and phenotypes associated with ASD, two studies published in the last issue of Cell addressed the following question:
"do these genetic loci converge on specific biological processes, and where does the phenotypic specificity of ASD arise, given its genetic overlap with intellectual disability (ID)? [2]"
"if and when, in what brain regions, and in which cell types specific groups of ASD-related mutations converge during human brain development [3]" ?
Of the two papers, I've so far only read the one by Willsey et al. [3], who combined their own data with already published data and identified 144 de novo "loss-of-function (LoF)" mutations, in other words, mutations that impair the functionality of the gene (hence the corresponding protein is no longer produced). They called genes with 2 or more de novo LoF mutations "hcASD", or "high confidence" ASD because statistically they had a high probability of being truly associated with ASD. They also analyzed a less-likely set of genes with only one de novo LoF mutation, which they called "pASD genes".

Next, the researchers investigated when and where these genes are expressed during brain development. The way they did this is a bit technical, but to think about it in simple terms think of it this way: (1) they needed samples from brain tissues taken at different developmental stages; (2) they needed to look not just at one gene, but at families of genes that are likely to interact together and influence one another's likelihood of getting turned "on" and "off". When a gene is turned "on", the gene is coding a protein, and we say that the gene is "expressed."

To carry on their analysis, Willsey et al. used data published by Kang et al. (Nature, 2011) from "57 clinically unremarkable postmortem brains of diverse ancestry (31 males, 26 females) that span 15 consecutive periods of neurodevelopment and adulthood from 5.7 postconceptual weeks (PCW) to 82 years." The gene expression values were determined for each gene by brain region and by postmortem brain sample. Brain regions were grouped according to transcriptional similarity during fetal development. These data were used to generate 52 gene coexpression networks, each network composed of the hcASD genes and their top correlated genes. This coexpression network analysis is a technique that's been extensively used lately to analyze patterns of co-expressions of genes. Each gene in the network is represented by a node, and any two nodes (genes) at any given time are connected if the genes are expressed at that time.

Using this set-up, the researchers were able to link the ASD genes to particular brain regions and developmental phases.
"Our analysis identifies robust, statistically significant evidence for convergence of the input set of hcASD and pASD risk genes in glutamatergic projection neurons in layers 5 and 6 of human midfetal prefrontal and primary motor-somatosensory cortex (PFC-MSC). Given the extensive genetic and phenotypic heterogeneity underlying ASD and the small fraction of risk genes that we have examined in this study, this likely represents only one of several such points of convergence. Nonetheless, the analytic approach presented here clarifies key variables relevant for productive functional studies of specific ASD genes carrying LoF mutations, providing an important step in moving from gene discovery to an actionable understanding of ASD biology [3]."
Cortical glutamatergic projection neurons (CPNs) are a class of neocortical neurons. They are called "projection" neurons because they transmit information from the neocortex to other neocortical and central nervous system regions. During development, projection neurons are generated in the neocortical germinal zone and migrate radially to their final neocortical position. In their study, Wyllsey et al found that the development of midfetal CPNs is particularly vulnerable to ASD. Furthermore, the set of ASD genes they identified as associated to ASD are functionally diverse and encode proteins found in distinct cell compartments, confirming the theory that ASD can be caused by different and distinct pathways.
"Given recent studies suggesting that as many as 1,000 genes or more could contribute to ASD (He et al., 2013; Iossifov et al., 2012; Sanders et al., 2012), our analysis has uncovered a surprising degree of developmental convergence. Despite starting with only nine hcASD seed genes, we have identified highly significant and robust evidence for the contribution of coexpression networks relevant to L5 and L6 CPNs in two overlapping periods of midfetal human development (3–5 and 4–6) corresponding to 10–24 PCW [3]."
The importance of these studies lies in the understanding of not just the genetic association per se, but in the mechanisms that drive these associations, and, most importantly, how the numerous genes interact and when.

[1] Devlin and Schrer (2012). Genetic architecture in autism spectrum disorder Genetics & Development DOI: 10.1016/j.gde.2012.03.002

[2] Neelroop N. Parikshak, Rui Luo, Alice Zhang, Hyejung Won, Jennifer K. Lowe, Vijayendran Chandran, Steve Horvath, Daniel H. Geschwind (2013). Integrative Functional Genomic Analyses Implicate Specific Molecular Pathways and Circuits in Autism Cell DOI: 10.1016/j.cell.2013.10.031

[3] A. Jeremy Willsey, Stephan J. Sanders, Mingfeng Li, Shan Dong, Andrew T. Tebbenkamp, Rebecca A. Muhle, Steven K. Reilly, Leon Lin, Sofia Fertuzinhos, Jeremy A. Miller, Michael T. Murtha, Candace Bichsel, Wei Niu, Justin Cotney, A. Gulhan Ercan-Sencicek, J (2013). Coexpression Networks Implicate Human Midfetal Deep Cortical Projection Neurons in the Pathogenesis of Autism Cell DOI: 10.1016/j.cell.2013.10.020

Tuesday, December 3, 2013

Capturing love and fear: interview with poet, artist and radio host Lauren Camp

Some time ago I received a plea for help from a friend: "I need an author photo for my upcoming poetry book!" Of course I was willing to help. However, author photos have to abide to certain constraints, and though we did get a nice image that we both liked for her book, my friend promised me a rain check: a portrait photoshoot at her house, no limits on creativity. And I knew she meant it because her own creativity knows no limits.

My friend is award winning artist, poet, and KSFR radio host Lauren Camp, and her new book, The Dailiness is a collection of poems that just came out this month. So, a few weeks later, I load my softboxes, props, and photography gear in the car and drive to Santa Fe, where Lauren lives with her husband and cats. Their home reflects their artistic spirit: there are blues and purples in the kitchen, yellows and pinks in the living room, greens in the bedroom. It's a feast for the eyes! I start assessing natural light versus softboxes, different backgrounds, different poses. It's not until later that I notice the art on the walls and how well it blends with the colors and warmth of the rooms.

Hanging on a textured yellow wall, is a 40-inch wide portrait of Thelonious Monk sitting at the piano with his signature hat. On the adjacent wall, deep purple this time, is a mosaic of six square frames showcasing waves of interlacing patterns. As I get closer and take a better look, mesmerized by the patterns and colors, I realize I'm not staring at pictures. I'm staring at fine and detailed threadwork layered on fabric: Monk's fingers, his tie, his hat, the piano's keys--everything is carved out of tiny pieces of fabric threaded together.

In the bedroom, beside a collection of African baskets and New Mexican vases, I find one of Lauren's self-portraits, embroidered with verses from her poems. The green of her bedroom intrigues me the most, so I decide to start from there. Lauren recites poems, she tells me about her visual art, and I take pictures. That's how I learn that the Monk portrait in the living room was part of Lauren’s solo exhibit, The Fabric of Jazz: A Tribute to the Genius of American Music, which traveled to museums in ten cities from 2004 to 2007, including stops at the American Jazz Museum and the Delta Blues Museum.

So, here she is, telling me how she feels intimidated by my "probing lens," while I'm completely immersed and surrounded by her amazing artwork. How do I render the immense creativity of the person in front of me?

Lauren's poetry is as musical as her voice: words become notes and notes become melodies, like the poem "A Hum", dedicated to jazz bassist Charles Mingus:
"Notes that curve and pitch
across the room
a sound that stretches out like wings"
Lauren's words stretch, curve and pitch onto the page, her images turn into sound, and Mingus's rich, meditated tones come to live.

"Why Jazz?" I ask. I'm myself a huge Jazz fan, so I'm always intrigued by other people's reaction to my favorite music genre.

"Jazz has long been my favorite music genre. I like how complex it is, and how much history it pulls into it. But I am also very satisfied by world music -- or, better yet, by the blend of jazz, world and other sounds. That's how "Audio Saucepan" developed... because I wanted a combination that would surprise a listener. Part of my mission with the show is to segue between continents and eras and genres seamlessly."

Audio Saucepan, Lauren's radio show, airs on KSFR every Sunday evening. I ask Lauren how it all started.

"I have been a KSFR host and producer since 2003. For six years, I did a 3-hour show on Monday mornings. The format was strictly jazz, but I slipped in a poem between improvisations each week. Toward the end of that time, I also co-hosted a program called "Poetry Talk" for about a year. In 2010, I transitioned to "Audio Saucepan." I wanted several things: a) to shorten the show and make every word and sound count, b) to incorporate more poetry, and c) to widen the borders of the music beyond jazz to the full borders of the world. The show airs on Sunday evenings, 6-7PM Mountain Time. On Sunday evenings, especially, the station is nearly — if not entirely — vacant. I select the music and poems and engineer the show. It's a full hour of intense multi-tasking. Back before I started at KSFR, I was lucky to have some training at KUNM. This gave me the nuts and bolts of how sound is modulated, how to fade, how to control ambient noise — these sorts of things."

We find a blue scarf and some peacock feathers and together we arrange a somewhat unique headdress. "Your voice is so musical," I say. "Does it come natural to you or did you have some training?"

"I didn't have any voice training. In graduate school, I had one professor (I was studying oral interpretation of literature, a sideline to my main focus of advertising and public relations) who didn't approve of my New York accent, and became determined to help me rid or reduce it."

The KSFR website calls the show "Gourmet sounds for your ears and mind." Lauren herself defines it "a potluck of reason and tempo, a spicy mash of border-defying jazz, Americana, contemporary classical and world music with interpretive readings and random philosophical fragments." I suddenly realize that this blending of different senses -- flavors, sounds, visuals, music, colors, textures -- is the common denominator in all of Lauren's art.

"My materials," Lauren explains, "are cotton swatches, old portraits, an internalized map of the new freeway, threads of all weights and hues, tools for cutting, splicing, sewing. Lines of poetry (my own and words by others) enter my thoughts as lines and color. A phone call from my father. A drive home. My fingerprint on the door, on the mirror. Art and poetry are twin efforts in my world. One is always stronger, the other meeker — though who and which change regularly. I move back and forth between the creative worlds. After years of working with figures and faces, I began exploring abstraction, depth and surface texture in my art. We encounter fabric every day, either wearing it, sitting on it, opening and closing it. It is tangible — but then, the flip side — it’s unexpected as an art medium. That dichotomy pleases me: the known/unknown of it, and the chance to push it to become something else, to change it, to attempt to control it."

The Dailiness is Lauren's second poetry collection, after the This Business of Wisdom published by West End Press in 2010. Her next book? A story about her father's childhood as she rediscovers her own heritage.

"My father was born in Baghdad, Iraq in 1935 and emigrated to the U.S. in 1950. He was a political refugee, though he never told us that -- or, in fact, much of anything about his childhood. Imagine?! Coming to a new country all the way on the other side of the world. (He came by himself two weeks after his family because of illness and also a problem in the country... they wanted a strapping 15-year old boy to be part of their army.) But he came... and tried to become American... and leave Iraq behind.

For at least three years, I have been working on a sequence of poems about his childhood. I've had to imagine a lot of it, and to do that, I've read and studied photos, listened to the beautiful oud music that emerges like desert heat from that land. I've asked questions of relatives, and have my own memories of his culture and rituals, my own answers, too. All of this fits into the puzzle that will someday become a book called One Hundred Hungers."

We move to the living room, where a warm light filters in from tall windows and highlights a bright yellow wall. Lauren shows me a long red scarf and wears it over her head. Suddenly, I see her Middle Eastern heritage in her eyes and I feel eager to capture it.

"For more than a decade, I created two-dimensional works — many of them portraits (either of jazz musicians or self-portraits) using only fabric and thread. Lately, I have been making more sculptural, abstract works that mix fabric with other media (paint, glass, wood, found objects, and other things). The work has quieted, I believe, as my poetry has gotten more demanding. The stories I once told only in art now have another medium to emerge from, and so the art becomes a place for meditation."

As we wrap up our photoshoot, I take one last shot of the mirror by the door before packing away my things. Lauren and her husband David give me a tour of their studio, a space that exudes creativity from every wall, and then I drive off. Jazz plays on the car stereo. Our endless New Mexico horizon embraces me on my way home. As I take in the deep blue of the sky, the bright orange of the land, and the harsh light that blends them together, Lauren's words echo in my mind:
"While I’m working I consider moments of intimate precision, and chance. What happens is not entirely my doing, nor am I simply a vessel. I think, letting go through my fingertips. What I love most I capture; and what I fear — space, love — I capture that, too, if I am confident enough."

Saturday, November 23, 2013


I think Magritte would've loved to visit Ghost Towns. :-)

Latest addition to my portfolio.

Wishing everyone a great week-end!

Wednesday, November 20, 2013

Ghost Town

Three images from a recent visit to a ghost town.

Which one do you prefer?

Longing by EEG
Remembering by EEG
Mind Prisoner by EEG

Friday, November 8, 2013


Seems that the change in season brings around darker moods.

Not thrilled about these latest works, but I decided to upload them to my portfolio anyways.

Wishing everyone a wonderful week-end!

Foggy Morning by EEG

Chasing Dreams by EEG

Awesome texture by the talented Karen Waters.

Sunday, November 3, 2013

A new viral vector raises hopes for an HIV vaccine

Because I work on HIV vaccine research, I often talk about vaccines and HIV vaccine design in particular. So far, there have been several phase I HIV vaccine trials, but very few have made it into phase III. One such case was the STEP trial, which was abruptly halted in 2007 after preliminary results showed that not only the vaccine was not protecting people from getting the virus, but the rate of HIV infections was actually higher in the vaccinated subjects compared to the subjects that received a placebo. Even more alarming was that this increase in acquisition risk lasted years after vaccination.

What went wrong in the STEP trial?

Vaccines are made of a "wimpy" version of the virus: you have to use enough genetic material from the virus in order to induce antibody production, but not enough to start an infection. We call the modified virus used in a vaccine "immunogen." The immunogen is only one part of the vaccine "recipe", the other part is what we call a vector, a structure that carries the immunogen and presents it to the immune system. Viruses make excellent vectors because they are like little "boxes" that are programmed to enter cells. And of all possible viral vectors, the most often used are adenoviruses because they are very common in the human population (they cause the common cold) and are therefore considered to be safe to "hijack" into carrying vaccine immunogens.

The STEP HIV vaccine was made of an adenovirus vector (recombinant adenovirus serotype 5 or rAd5) expressing the HIV proteins gag, net, and pol. When researchers looked back at what could've possibly gone wrong they found that the rates of infections were significantly higher in subjects that had been previously infected with Ad5 and had preexisting immunity against Ad5.

The HIV community feels so baffled by the failure of the STEP vaccine trial that at a recent conference I attended, the director of the Fred Hutchinson Cancer Research Center said quite vehemently that we should all move away from vector vaccines and do DNA vaccines instead. Since DNA is naturally absorbed by cells, DNA vaccines bypass the need of a vector.

In truth there's still strong hopes for vector vaccines. The natural question to ask in light of what happened with the STEP trial is: can we use a vector that instead of worsening the immune response actually makes it better?

It turns out that there is, and it's called Cytomegalovirus, or CMV. Like adenoviruses, CMV's are also very common in the human population and typically asymptomatic unless there are other underlying conditions.

If you remember roughly how the immune system works, we have two kinds of "sentinels" looking out for invaders: B-cells, which produce antibodies, and T-cells. While antibodies bind to viral particles, thus preventing the virus to enter and infect cells, T-cells recognize infected cells and destroy them. This recognition mechanism is based on the fact that infected cells express fragments of viral proteins (epitopes) on their surface. The T-cell recognizes those proteins as foreign and as a flag of infection and thus kill the cell before it starts replicating the virus.

Eliciting antibodies able to clear the HIV virus through a vaccine has proven very challenging (I discuss why in this post). But what about T-cell vaccines? In [2] Hensen et al. showed that a CMV vector SIV vaccine was able to elicit over three times greater breadth T-cell response in rhesus monkeys and about 50% of the vaccinated animals, once challenged with SIV (the simian version of HIV) were able to clear the infection without getting sick.

The vaccine was made of a recombinant rhesus monkey cytomegalovirus (strain 68-1 RhCMV) engineered to express simian immunodeficiency virus (SIV) genes.
"The key finding of Hansen et al. is that strain 68-1 RhCMV elicited CD8+ T cell responses that target SIV epitopes that were completely different from those generated by SIV infection itself, by other virus-based vectors, or by wild-type RhCMV expressing SIV genes [1]."
Typically during an HIV infection, the immune system starts producing T-cells that attack a limited number of epitopes, in other words a limited number of viral protein fragments that infected cells express on their surface. So, the key finding in this study was that using a CMV vector increased the number and variety of epitopes that the T-cells were able to recognize.
"We conclude that RhCMV has an intrinsic ability to elicit CD8+ T cell responses to unconventional epitopes, distinct in quality and quantity from all infectious agents studied to date. [2]."
As you know, HIV's winning strategy to evade the immune system is its ability to "hide" by constantly changing its genetic structure. This is favored by the fact that under normal circumstances T-cells recognize only a limited number of epitopes. In this light you can see why increasing the magnitude and breadth of the T-cell responses is effective in defeating the virus: once primed with the CMV vector, T-cells were not only able to recognize many more epitopes, but different "versions" of such epitopes, meaning that even when the virus came up with a mutation at a certain epitope, the T-cells were still able to recognize it and kill the infected cell.

These are remarkable results and I can't wait to follow this story as it moves to its next step -- human clinical trials.

[1] Nilu Goonetilleke, Andrew J. McMichael (2013). Antigen Processing Takes a New Direction Science DOI: 10.1126/science.1239649

[2] Scott G. Hansen, Jonah B. Sacha, Colette M. Hughes, Julia C. Ford, Benjamin J. Burwitz, Isabel Scholz, Roxanne M. Gilbride, Matthew S. Lewis, Awbrey N. Gilliam, Abigail B. Ventura, Daniel Malouli, Guangwu Xu, Rebecca Richards, Nathan Whizin, Jason S. Reed (2013). Cytomegalovirus Vectors Violate CD8+ T Cell Epitope Recognition Paradigms Science DOI: 10.1126/science.1237874

Tuesday, October 22, 2013

Trick or Treat

Latest additions to my portfolio, right in time for Halloween. ;-)

Trick or Treat!

Daphne by EEG

The Music Room by EEG

Friday, October 18, 2013

Time for a chimera contest!

I've participated to so many blog contests in the past years, I figure it's time to give back and hold a contest of my own. So -- insert drum roll here -- I'm giving away the above image, printed on canvas and mounted on a 11x16 frame, to one lucky winner.

Here's how to participate:
1. If you haven't already, please "like" the Chimeras FB page.
2. Leave a comment either here on the blog or on the FB page -- tell me what it is you like about this blog. Suggestions are very welcome!
3. Not mandatory, but if you invite your friends to "like" the page I'll count your entry twice (let me know in the comments). I know, sorry, trying to pull some audience my way...

That's it! One week from now I will draw one lucky winner. If you're selected, I'll ask you for a shipping address so I can send you the canvas.

Shares are not mandatory but highly appreciated. The more the merrier. :-)

Monday, October 14, 2013

Fall Colors!

Yes, the days may be getting shorter and colder, but aren't the colors just gorgeous?

And then, of course, I couldn't resist playing with textures. Different feel, definitely more painterly, but still lovely. This time the texture was provided by NM photographer Karen Waters. If you live in NM, make sure to stop by the Fuller Lodge Art Center to check out her amazing work.

Whether it's fall or spring, enjoy the seasonal colors wherever you are.

Wednesday, October 9, 2013

Breaking free

Don't you ever wish you could just ...

Breaking Free by EEG

If you are curious to know how I made this image, you can see the "behind the scene" pictures in this G+ album.

Edit: I'm thrilled to announce that this image was accepted into the 2013 Twelve: Natural Magic juried exhibit to take place from December 11 until January 4 at the Viewpoint Photographic Art Center in Sacramento, CA.

Saturday, October 5, 2013

Sex Is Always Well Worth Its Two-Fold Cost

Title borrowed from Feigel et al. [1].

Sex is costly. In an asexual population, all individuals bear offsprings, resulting in a higher growth rate than in a sexual population (two-fold cost of sex). Finding a partner is risky, costly in terms of energy and resources, and it results in sexual selection which may not always favor survival. Finally, in sexual populations each individual passes only 50% of its genetic make-up to their offsprings and, furthermore, genetic recombination could break-up alleles that are in an epitastic relationship with one another (they are advantageous when together, but once separated they may incur into fitness loss).

"The advantages of sexual reproduction stem from quite various roots. For instance, sex increases genetic variability by recombination of the parental chromosomes. It makes a population more resistant against many unpredictable threats, such as deleterious mutations, parasites, a fluctuating environment, or competing groups. It also optimizes the evolutionary search for the best gene combinations in a single individual (epistasis) [1]."
Let's try an understand this better. Different alleles in the genome are not always independent, as they may affect fitness in conjunction, a mechanism called epistasis. For example, two alleles may be beneficial together, but their benefit may be lost when separated by a recombination event. Or, it could be the other way around, that a mutation arises under certain constraints, and it's not until paired with a second mutation that it becomes beneficial. This is often observed in drug resistance, for example. A mutation that confers the organism (a virus, or a bacterium) drug resistance could potentially make it less fit (for example, if it makes the organism more "visible" to the immune system). In these cases, often one observes a new mutation arise in conjunction with the drug-resistant one, and the two together restore the organism's original fitness. These secondary mutations are called compensatory mutations because they compensate for the original loss of fitness.

Recombination of genomes can go either way: it can bring beneficial mutations together, or, it can break them apart. In a Nature Genetics review [2], the authors mention a study done on segmented viruses: in this case, "sex" is equivalent to two viruses co-infecting the same cell, as when this happens the enzyme that replicates the genes jumps back and forth between the two genomes and the resulting new genome is a reshuffle of the two parental ones. The advantage of using viruses to study the effect of sex is that you can compare the result of sexual reproduction versus asexual reproduction in the same population. In the case of the segmented virus study, it was observed that an adverse mutation was slower to get cleared in the sexual population than the asexual one.

The same review cites studies done on yeast that yielded mixed results: some showed that sex did increase the rate of adaptation of the population, and some showed the opposite. A paradox? Not quite, if you throw into the picture the size of the population.
"Two recent studies have also tested the effect of recombination on the rate of adaptation in evolving microbial populations. When populations of C. reinhardtii that initially lacked genetic variation were allowed to adapt to a novel growth medium in sexual and asexual populations of varying size, sex increased the rate of adaptation at all population sizes, but particularly in large populations [2]."
Another study done on sexual and asexual yeast strains, compared adaptation in two environments: the mouse brain, which represented a highly variable environment, and a test tube with minimal growth medium.
"When sex was induced, the sexual strain won the competition in the mouse brain but not in the test tube, despite the fact that it also showed general adaptation to this environment. These results indicate an advantage to sex during adaptation to variable or harsh environments [2]."
Despite all these studies, it is still unclear what drove the evolution of sex. Did sex prevail thanks to epistasis? Or was it just drift, the random accumulation of mutations due to pure chance? More recent studies have looked at a combination of mechanisms that may have been responsible for the rise in sexual populations. For example, other aspects to account for, besides epistasis and drift, are redundancy and genome complexity. As organisms have evolved, their genomes have increased in size and complexity. Redundancy allows for more than one gene or pathway to have same function, buffering the effect of deleterious mutations. It also maintains a reservoir of non-coding allele variants that are always available in the search for new evolutionary pathways. At the same time, sex and recombination together cause genomes to be more robust and overcome the short-term disadvantage in favor of long-term advantages like increased evolvability.

[1] Alexander Feigel,, Avraham Englander,, & Assaf Engel (2009). Sex Is Always Well Worth Its Two-Fold Cost PLoS ONE DOI: 10.1371/journal.pone.0006012

[2] J. Arjan G. M. de Visser & Santiago F. Elena (2007). The evolution of sex: empirical insights into the roles of epistasis and drift Nature Genetics Review DOI: 10.1038/nrg1985

Thursday, October 3, 2013


Latest addition to my portfolio.

Tuesday, October 1, 2013

Ms. Stick Insect

Image credit:

You're looking at a stick insect, a critter I was quite used to growing up as my dad, an evolutionary biologist, used to grow them at home. I know, most households have cats, dogs, guinea pigs and rabbits; ours had cats, dogs, toads, fruit flies, and stick insects. :-)

Children have a tendency to personify everything, animals in particular, so imagine my shock when my dad told me that stick insects are all... ladies. Yup. It's Ms. Stick Insect. And the reason why I mention this is that today I'd like to talk about sex. Ha! You didn't see that coming, did you?

How does an all-female population manage to reproduce? Embryos develop from eggs using parthenogenesis, without the need to be fertilized. This doesn't mean that the offsprings will be identical to the parent. "Reshuffling" of genes is still ensured by meiosis.

In organisms that reproduce sexually, meiosis produces gametes, cells that carry half of the chromosomes and therefore, once fused with the opposite sex gamete, it will produce a cell with the full number of chromosomes. In organisms that reproduce sexually, meiosis produces gametes, cells that carry half of the chromosomes and therefore, once fused with the opposite sex gamete, it will produce a cell with the full number of chromosomes. In diploid organisms (organisms that have two copies of each chromosome), meiosis takes place in the following steps: (i) DNA replication, which creates two exact copies of each chromosome; (ii) pairing of the chromosome homologs, one maternal and one paternal; (iii) the homologs' cross-over creating a unique mix of maternal and paternal DNA; (iii) another round of cell division creates four cells, each with one set of chromosomes.

In parthenogenesis meiosis, step (i) is skipped. In order to restore the two copies of chromosomes, in some perhenogenetic animals, the cell division in step (iv) creates two cells instead of four, each with two copies of chromosomes. However, stick insects employ a different strategy: step (iv) still creates four cells, of which only one has the cytoplasm. This cell then fuses with one of the other three effectively creating and egg with two copies of chromosomes, perfectly equivalent to a fertilized egg.

Not all stick insects reproduce through parthenogenesis. Some populations do have males and mate, though usually only about 10% of offsprings come from sexual reproduction. Morgan-Richards et al. [1] compared several populations of New Zealand stick insects (C. hookeri), and found that while mated females produced male and female offsprings in equal numbers, virgin females that reproduced via parthenogenesis produced mostly females. That's right, I said "mostly".

"A single male hatched from an egg laid by a captive virgin mother. [...] This male may have arisen by the loss of an X chromosome during cell division (non-disjunction), a mechanism recorded for other stick insect species with the same XO⁄XX sex-determination mechanism seen in C. hookeri [1]."

So even in completely parthenogenetic populations, in principle sexual reproduction is not completely lost as the reshuffling provided by meiosis can, occasionally, originate a male offspring. Furthermore, the authors confirmed a geographical distribution of the parthenogenetic population of stick insects compared to the sexual ones: all female populations in New Zealand tend to be more common farther away from the equator and at higher altitudes, implying the adaptive advantage of parthenogens in certain environments but not in others.

The fact that parthenogens would have an adaptive advantage intrigued me, so I dug a bit further and found out about a concept called the two-fold cost of sex. In a sexual population, only one of the two sexes bares offsprings, while in a one-sex population all individuals bare offsprings, hence significantly increasing its growth rate. This seems to indicate that asexual populations have a higher Darwinian fitness. So, how did we end up with so many sexual species given especially that we all originated from asexual ancestors? How can sex be evolutionary successful when the odds seem to be against it?

I'll save that discussion for the next post. :-)

[1] MARY MORGAN-RICHARDS,, STEVE A. TREWICK,, & IAN A. N. STRINGER (2010). Geographic parthenogenesis and the common tea-tree stick insect of New Zealand Molecular Ecology DOI: 10.1111/j.1365-294X.2010.04542.x

Saturday, September 28, 2013

Colors of New Mexico

The opening was a big success, thank you all so much for coming, those who could come, and for sending wishes and good vibes, those who couldn't. The pictures will be up until October 10 at the Silver Sun Gallery at 656 Canyon Road, in Santa Fe, NM.

And here's a photo of me looking at me, taken by my friend Karen:

Monday, September 23, 2013

Vaccines: what is the meaning of phase I, II and III?

I'm often asked, "How long will it take to finally have an HIV vaccine? Are we close? What about this study that published good results on an HIV vaccine?"

Right now, the HIV community is generally optimistic that we will indeed have an HIV vaccine within the next decade. This is based on the relatively recent discovery of new broadly neutralizing antibodies and the mildly positive results obtained by one of the five major efficacy trials, the RV144 Thai trial, which found a 31% reduction in HIV acquisition in vaccinated subjects versus placebo [1].

I'm also often forwarded published papers on successful HIV vaccine trials, with the attached question: "Is it done, then?"

The answer is, "No, not yet."

As I explained in my earlier HPV vaccine post, once a vaccine is approved to be tested on humans, like all human health interventions, it has to be tested in three phase clinical trials, called phase I, II, and III.
"Clinical product development typically begins with phase I studies that evaluate the safety and biological activity of a drug, vaccine, or other intervention and proceeds ultimately to phase III efficacy trials that support licensure. [. . .] Phase II clinical trial evaluation affords an opportunity to discover less frequent side effects of the intervention and to provide better quantitation of the agent‚ activity and safety in a larger and more diverse participant population. [2]."
So, a successful phase I trial means that the vaccine is safe to use on humans and it does no harm. A phase I trial does not prove that the vaccine can protect against the disease. It can take up to a decade to go from a phase I to a phase III trial. Phase III, when successful, is what ultimately proves the vaccine's efficacy.

So far there have been many phase I HIV vaccine trials, but there only have been a handful phase III trials, of which the most successful one was RV144 with the mild 31% reduction in infection rate.

Vaccines like HPV that are now being offered to the public have undergone all three clinical trial phases. This is what I was trying to explain when I discussed the HPV vaccine and I said that despite the concerns raised by the Japanese government, the vaccine wouldn't have been FDA approved had it not passed all three phases of clinical trials that proved its safety first. For example, you can read the results of a phase I HPV vaccine trial here. Notice that the paper was published in 2000 and it took roughly another decade before the vaccine was distributed.
"Before the question of drug or vaccine efficacy can be answered, safety testing, validation of mechanism, and specificity issues must be addressed in preliminary studies. These studies themselves often provide unexpected information that generates new hypotheses. An efficacy trial, usually a randomized controlled trial‚ represents the ultimate test of concept that an intervention can ameliorate disease or prevent infection [2]."
Phase I and II trials are also important for hypothesis raising, not just hypothesis testing. Back to the HIV example, we still don't know why it takes so long for the human body to produce antibodies able to recognize a broad spectrum of HIV strains. We still don't know why a small percent of HIV-infected subjects, the so called "elite-controllers", are able to keep their viral load down to undetectable for decades. We still don't have biomarkers that predict the strength of an immunological response to the vaccine. People who make strong antibodies, they make them later in the infections, when it's too late to clear the virus. Elite controllers, on the other hand, have very low antibody titers.

Finally, to make things even more complicated, the animal models used to test vaccines are not good predictors of the human immune system. For examples, vaccinated macaques have been challenged with SIV, the simian immunodeficiency virus, which is a much older virus than HIV. There are ways to "humanize" the monkeys, but they can never 100% predict the human trial. And that's why we've been eagerly waiting for phase I of the mosaic vaccine... unfortunately, we are still waiting. I should have an update soon, though, as I'm heading out to see our collaborators later this week. Stay tuned!

[1] Supachai Rerks-Ngarm, et al. (2009). Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand N Engl J Med DOI: 10.1783/147118910790291082

[2] Lawrence Corey, Gary J. Nabel, Carl Dieffenbach, Peter Gilbert, Barton F. Haynes, Margaret Johnston, James Kublin, H. Clifford Lane, Giuseppe Pantaleo, Louis J. Picker and Anthony S. Fauci (2011). HIV-1 Vaccines and Adaptive Trial Designs Sci Transl Med DOI: 10.1126/scitranslmed.3001863

Friday, September 20, 2013

The Departure

Just uploaded to my portfolio. Texture this time courtesy of the incredibly talented fine art photographer Brooke Shaden. Thanks for being such a great inspiration, Brooke!

Sunday, September 15, 2013

Bacteria to the rescue!

Last month I talked about a cancer killing virus. Well, guess what comes next? A cancer killing bacterium, of course! :-) Our hero is once again, the one and only E. coli, a bacteria that normally resides in our guts and that is much beloved by experimentalists because it's cheap and easy to grow.

In 2011, a group from Nanyang Technological University, in Singapore, genetically modified a strain of E. coli so it would sense and kill the human pathogen Pseudomonas aeruginosa[1], a bacterium responsible for infections that can be lethal in immunochallenged subjects. Pseudomonas aeruginosa is resistant to many currently available antibiotics. On the other hand, therapies that do succeed in killing the bacterium also kill other bacteria that are part of a healthy microbiome.

How to eradicate a Pseudomonas aeruginosa infection without harming the "good" bacteria, then?

When in highly competitive environments, bacteria produce toxins, called bacteriocins, that kill closely related, competing strains. The bacteriocin that Pseudomonas aeruginosa produces is a toxic peptide called pyocin. The advantage of using such toxins instead of antibiotics is that, while resistance to antibiotics appears relatively early after therapy thanks to lateral transfer, no toxin-resistant strains have been observed so far.
"Given the stalled development of new antibiotics and the increasing emergence of multidrug-resistant pathogens, using synthetic biology to design new treatment regimens for infectious disease could address an urgent need [1]."
So, how does the bioengineered E. coli kill the pathogens? In order to "communicate" with one another, bacteria release a number of chemicals whose concentrations are proportional to the population density. These exchanges are called "intercellular quorum communication", or quorum sensing, and enable bacteria to turn "on" or "off" gene expression depending on the surrounding cell density of the population (i.e. when the concentration of molecules signaling a certain status reach a specific threshold). One of such mechanisms regulates the production of pyocin. Saeidi et al. [1] reproduced this regulatory mechanisms to enable their bioengineered E. coli to "sense" the presence of Pseudomonas aeruginosa, release the toxin, and kill it.
"Upon reaching a threshold concentration, the lysis E7 protein perforates membrane of the E. coli host and releases the accumulated pyocin S5. Pyocin S5, which is a soluble protein, then diffuses toward the target pathogen and damages its cellular integrity, thereby killing it [1]."
But wait, what about cancer? Eradicating cancer faces similar issues: you need to kill all the "sick" cells without harming the healthy ones. Chemotherapy drugs often end up damaging healthy cells too, hence the need of "targeted" drugs, drugs that can be delivered exclusively to the cancer cells.

A group from the University of Maryland used the quorum sensing mechanisms intrinsic in the bacterium to make it sense cancer cells. And while it doesn't quite kill the cancer cells, this research is important because the bacterium could become a means to transport specific drugs to the cancer tissues, while leaving the healthy cells untouched.
"By altering their quorum sensing genetic circuits, we engineered bacteria to find cells of interest (diseased or otherwise), dock on associated surface receptors or biomarkers (‘features’), integrate surface feature density, and also decide whether or not to initiate gene expression. This ‘smart’ bacterium reinforces the notion of an expanded synthetic biology umbrella that confers new capabilities on the individual cell. The resultant cell has capabilities that could be viewed as analogous to a dirigible—a transport vehicle that autonomously navigates and carries or deploys important cargo [2]."
The principle is the following: 1. find a biomarker that can "flag" the target cell and distinguish them from the healthy cells; 2. using the biomarkers as flags, deploy "nanofactories" to the target cell and have them produce the "quorum sensing" chemicals; 3. once quorum sensing is triggered, the bioengineered E. coli "swim" to the target cells.

Nanofactories are made of an antibody motif for binding to the cell and a fusion protein that produces quorum molecules when bound to the targeted bacterium [3]. In [2], Wu et al. used squamous cancer cells of the head and neck as target cells. These express EGFR, epidermal growth factor receptor, at a high threshold, which was used as biomarker. The nanofactories bound to EGFR and synthesized AI-2, the quorum sensing molecule that stimulated E. coli motility.
"In summary, the docking of anti-EGFR-NF onto mammalian cell surfaces was specifically controlled by EGFR surface density which, in turn, controlled subsequent AI-2 synthesis, bacteria migration, and the switching response phenotype. The signal generating and cell recruiting design shown here provides a tractable means to ensure site-specific gene initiation, providing a focused and predicted phenotype."
In the future, the cancer-sensing E. coli could become an efficient transporter of drugs aimed at destroying cancer cells while leaving the healthy cells intact.

[1] Nazanin Saeidi, Choon Kit Wong, Tat-Ming Lo, Hung Xuan Nguyen, Hua Ling, Susanna Su Jan Leong, Chueh Loo Poh & Matthew Wook Chang (2011). Engineering microbes to sense and eradicate Pseudomonas aeruginosa, a human pathogen Molecular Systems Biology DOI: 10.1038/msb.2011.55

[2] Hsuan-Chen Wu, Chen-Yu Tsao, David N Quan, Yi Cheng, Matthew D Servinsky, Karen K Carter, Kathleen J Jee, Jessica L Terrell, Amin Zargar, Gary W Rubloff, Gregory F Payne, James J Valdes & William E Bentley (2013). Autonomous bacterial localization and gene expression based on nearby cell receptor density Molecular Systems Biology DOI: 10.1038/msb.2012.71

[3] Rohan Fernandes, Varnika Roy, Hsuan-Chen Wu & William E. Bentley (2010). Engineered biological nanofactories trigger quorum sensing response in targeted bacteria nature nanotechnology DOI: 10.1038/nnano.2009.457

Saturday, September 14, 2013

Save the date!

My first "solo" show is in two weeks! I will be at the Silver Sun Gallery at 656, Canyon Road, in Santa Fe, NM, for the opening reception on Friday September 27 from 5 p.m. to 7 p.m.

Hope to see you there!

For a preview of what you'll see at the show, please visit my portfolio.

Sunday, September 8, 2013


As always, prints are available here.

The HPV vaccine: a few things you should know

If you are a young woman under 25 years of age, or if you have a teenager at home, chances are, your doctor told you about the HPV vaccine. HPV, or Human Papillomavirus is a DNA virus that infects keratinocytes, cells found in the epidermis and in mucous membranes. Though in some cases the virus causes painful warts, HPV infections are often asymptomatic. So why bother screening an asymptomatic virus? Because while the majority of the infected people clear the virus within 1-2 years, in less than 10% of the cases the infection persists and can, eventually, lead to cancer.

Studies have shown that cancer is linked to persistent infections, and that on average it takes around 5 years to reach a pre-cancer state [1]:
"Persistent infections and precancer are established, typically within 5-10 years, from less than 10% of new infections. Invasive cancer arises over many years, even decades, in a minority of women with precancer, with a peak or plateau in risk at about 35-55 years of age [1]."
Unfortunately, there are no screenings currently available for HPV in men or infections that do not pertain the cervix. For cervical cancer in women, the current recommendation is to get a pap smear every 2-3 years, which has been highly effective in reducing the incidence of HPV-caused cervical cancers.

Like HIV, HPV has a highly diverse subpopulation: there are over one hundred different types of HPV strains, of which, only a small subset (less than 20) are carcinogenic. According to the CDC, about 26,000 cancers every year in the United States are caused by HPV, which is why the CDC recommends teenagers to be vaccinated, girls in particular:
"There are two [FDA-approved] HPV vaccines available (Gardasil and Cervarix) which protect against the types of HPV infection that cause most cervical cancers (HPV types 16 and 18). Both vaccines should be given as a three-shot series. Clinical trials and post-licensure monitoring data show that both vaccines are safe."
Types 16 and 18 are associated with slower viral clearance [1] and have been linked to about 70% of cervical cancers and 85% of anal cancers [2]. Because the vaccines are most effective prior to any exposure to the virus, the current recommendation is to administer the shots within the 13-25 age bracket.

So then the vaccine seems a good idea, right?

I certainly thought so until my friend Alex brought up the news that last June Japan withdrew HPV vaccine reccomendations.
"According to a report in the Japan Times, 8.29 million people had received the HPV vaccine as of December 2012, and there were 1968 cases of concerning adverse events reported as of March 2013. Of these adverse events, 106 were described as "serious cases of pains or body convulsions, pains in joints, or difficulty in walking."
And while all vaccines bring some risks, but the risks are outnumbered by the lives they save, if you do the math you'll find that
"Those numbers translate to a rate of 12.8 serious cases of adverse events per 1 million inoculations, according to the report. This compares unfavorably with the 0.9 serious adverse events per million influenza inoculations in Japan and the 2.1 serious adverse events per million inoculations of inactivated polio vaccine."
So I went back to the CDC page, found that nothing had changed in their recommendations, however, I found a transcript of a CDC press briefing from June 2012, in which a CDC employee claimed that they had found about a dozen US reports similar to the adverse cases reported in Japan, but that no causality had been established.

In the literature, I found a report that advocates for reforms in the Japanese vaccination program:
"This directive [to stop recommending the HPV vaccine] was issued due to fears of adverse events, especially complex regional pain syndrome. However, the present system of reporting adverse events does not follow a systematic process for identifying causality; a rigorous scientific approach is needed to investigate adverse events associated with HPV vaccines. [...] Japan's vaccination system suffers from a failure of governance—also reflected in other aspects of the vaccination schedule. Mumps, adult pneumococcal, rotavirus, and hepatitis B vaccines have yet to be introduced in the routine schedule, even though they are recommended by WHO."
What's the take home message out of all this?

You know I work on HIV vaccine design and I'm a long-time advocate for vaccines. If you look back in time, vaccines have saved far more lives than the supposed adverse effects. Our immune system is a brilliant machinery designed to recognize self from non-self and destroy whatever falls in the latter category. It's built on both genetics (native immunity) and experience (acquired immunity), as it constantly retunes to allow the body to adapt to a changing environment. Messing up with the immune system can have unforeseen, permanent consequences.

It takes decades for a vaccine to go from design to marketing. It needs to be tested on animals before it is tested on humans. The first phase I trials on humans have the sole "safety" objective, in other words, even before we know whether the vaccine is effective in preventive a certain disease, we need to prove it is safe to use and causes non harm. Neither vaccine would have been FDA approved had they not passed all the safety requirements.

This means that if you search the literature, you will find published studies on the safety of for either the Gardasil or the Cervarix HPV vaccines. For example, I found a pooled analysis of 11 cohorts published by Landes Bioscience, in which you can find all statistics of adverse effects, from a common headache to more serious ones. In their discussion, the authors (affiliated with GlaxoSmithKline Biologicals) bring up the fact that there could be a correlation between underlying auto-immune disorders and the reported adverse effects, and that a direct causality with the HPV vaccine, once again, could not be established.

At the end of the day, we are individuals, not statistics. It's fine to read that a certain condition or side effect is so rare it happens once in a billion cases, yet we don't want to be that one in a billion case. HPV is more likely to cause cancer in smokers. Maintaining a healthy life should be our foremost priority. For cervical cancer in particular (which covers the vast majority of HPV-caused cancers), given how long it takes for the virus to establish a persistent infection, doing the pap test every other year will likely catch the infection before it gets to a precancer stage.

Do your homework. Read. Exercise. Eat healthy. Then do more homework. It's your life, make informed decisions.

[1] Helen Trottier, Salaheddin Mahmud, José Carlos M Prado3, Joao S Sobrinho, Maria C Costa, Thomas E Rohan, Luisa L Villa and Eduardo L Franco (2008). Type-Specific Duration of Human Papillomavirus Infection: Implications for Human Papillomavirus Screening and Vaccination Infectious Diseases DOI: 10.1086/587698

[2] Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, & Wacholder S (2007). Human papillomavirus and cervical cancer. Lancet, 370 (9590), 890-907 PMID: 17826171