Displacement

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

Latest addition to my portfolio.

Wishing everyone a great week-end!

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

November

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.

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

Trick or Treat

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

Trick or Treat!

Daphne by EEG

The Music Room by EEG

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. :-)

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.

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.

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).

However:

"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

Fallen

Latest addition to my portfolio.

Ms. Stick Insect

Image credit: funkman.org.

 
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

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:

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

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!

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

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.

Afterthoughts

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

Doors

Two Doors by EEG

This image popped into my head last night.
Many thanks to Joel Olives for sharing his awesome textures.

Happy Friday!

Images, images, images

The show is in 4 weeks. A little less, actually.

Am I nervous?
Yes.

Am I excited?
YES!

I just ordered canvas prints for the last two images and then I'm all set to go. Let me tell you a bit about both, because, as you can tell, they are very different.

Macondo Dreams by EEG

For this image I had the model first, which almost never happens. She's a beautiful young lady visiting from Italy and as soon as I met her I thought of one of my favorite painters, Dante Gabriel Rossetti. Luckily, she didn't object when I asked her to pose for me. The title came after my mom, looking at this image, reminded me of my favorite book of all times: One Hundred Years of Solitude. Lots of favorites in this image. :-)

Down the Rabbit Hole by EEG

For this second image I had the idea first, which is not always a good thing as I often end up with something totally different than what I originally had in mind. I wanted to show a woman falling down the Rabbit's Hole. I wanted a very dramatic pose and a very dramatic dress. Adding drama over drama, she ended up looking dead. While by all means not the picture you'd want to hang in your living room, I think this is an attention grabber, so it'll go in the show. If nothing else, I'm hoping it'll draw some curiosity in a casual passer-by, enough to make them want to step inside the gallery. :-)