Sunday Snippet: The Elm Tree

From The Elm Tree, my contribution to the anthology The Telepath Chronicles:

Gentle, Celine thought, cracking open the ribcage—yet the procedure was far from gentle. She was breaching a sacred place, tackling the thin line between life and death, a temple that should never see the light. She forced her hands inside, her fingers prodding the softness of the tissues. 

Careful, now. This heart is young, with so many beats yet to deliver.

Come back to me, Celine pleaded, delicately compressing the heart between the flats of her fingers. Press, release, press, release, she thought, as if rehearsing a memorized prayer.

Lulled by the litany, she closed her eyes and gave in to the rhythm—press, release, press, release—until a grainy fog blanketed her eyes and the smell of burning candles filled her nostrils. 

The above is my Sunday snippet submission for the Weekend writer Warriors (you can find the Snippet Sunday group on Facebook, too). Make sure you check out all Weekend writer Warriors participants, it's a fun way to find forthcoming books -- all genres welcome, there's something for everyone's tastes.

The Elm Tree is the story of a doctor who performs a thoracotomy in a desperate attempt to save her young patient's life. I had no idea doctors could do this--crack open the rib cage and literally massage the heart to make start beat again--until I came across the true story of an ER doctor who, in a last, desperate attempt to save his patient’s life, opened the patient’s chest to manually “restart” the heart. What happened next left him completely baffled: every time the doctor compressed the heart and made it beat, the patient’s eye sprang open and stared at the ceiling. As soon as the doctor stopped, the patient closed his eyes. Imagine what this doctor must have felt, holding a dying heart in his hands, knowing that the minute he let go, the life of his patient would be lost forever.

The Elm Tree was inspired by this story and it's one of 14 science fiction stories dealing with different aspects of telepathy. Some are set in today's world, some in a future Earth, some in outer space. Each one is beautiful and enchanting in its own way. I feel honored to have my story featured with so many other talented authors.

Are we really evolving into super-humans?

© EEG

I came across an article on the Popular Science website, which, turns out, is the excerpt of a new book on evolution by Science Guy Bill Nye. From the reviews I gather that Bill Nye is an excellent writer and, being also an entertainer, he knows how to not only expose well but also infuse some good humor to what he says. That's all fantastic. But while the article starts off with some rigor, his conclusion had me roll my eyes. Because, even though he does include some speculations that he himself labels the "science fiction future of human evolution" (which of course I agree is always fun to do), by the end of the article he's doing science fiction without calling it science fiction. So I'd like to take the chance to discuss what I did not like of the excerpt from his book.

Nye starts off asks the following question:

Is there a Homo superius just around the next corner, waiting to take our place?

This is the part of the excerpt that I contest:

We cannot step away from evolution. Our genomes are always collecting mutations, and we are always making mate selections. Are humans preferentially mating with other humans who are tall? Blonde or not blonde? Are smart people actually producing significantly smarter offspring, who end up making more money and ever so slowly outcompeting other families? [. . .] I'm looking out for big changes that come from good old-fashioned Darwinian natural selection. What trait would give a future human baby such an edge that she or he will grow up to produce some amazing new kid that can do something that stands out and will attract a similarly worthy partner with whom to mate? 

I understand Nye wants to make an impact on people who love science and in particular those who don't have a technical background to understand the nuisances of a scientific theory but still appreciate the importance of scientific rigor. The purpose of his book is to make people think, "This is cool. I totally get evolution." At the same time, I do believe that anyone attempting to popularize such a debated topic should go the extra length to make sure everything he/she says is rigorous, because if it isn't, it becomes easy target for those people who, instead, want to contradict it.

My points in particular are:

1) In his book he gives examples to illustrate evolution in action that are beautiful and clear and make valid points on how evolution works. But those changes have taken tens, sometimes hundred thousands of years to take place. Yes, you can draw the same examples from viruses and bacteria, but again those organisms evolve on a much faster clock than we do. So, you can't just blatantly extrapolate those examples and speculate, based on those, what will happen in the next few decades or centuries to the human species. There aren't "big changes that come from good old-fashioned Darwinian natural selection" on the time scale he's looking at. Nothing really changes on a scale of 100 years -- that's roughly only 4 generations. On the other hand, there are other things that are changing scarily fast and will hugely impact our lives in the next 100 years: climate, for example. Food and water are likely to get scarcer. And given how fast those are changing compared to how evolution works, the sad reality is that there is no adaptation that can save us this time. If the climate were changing on a scale of tens of thousands of years we could predict a new adaptation to the rising temperatures. But on this scale? Our only hope is technology and our own good will to fix things we've badly broken.

2) Intelligence. First of all, intelligence doesn't make us any more resistant to any pathogens and in particular not to the antibiotic resistant ones. The last Ebola strain that jumped from bats to humans did not ask the target person his or her IQ before infecting them. Intelligence might prompt you to vaccinate yourself and your kids, but so long as the vast majority of the people still believe in vaccines we have herd immunity protecting even the non-vaccinated people. On the other hand, there are many social constraints that put a cap on how "intelligent" the human species can be. Social events are valued more than isolated hours of working/studying/researching, and if you look back at the lives of people who've made a difference in science, literature or medicine (just to name a few), you'll see a common pattern: they were pretty unsociable. They chose their one passion over spending time with family and friends. Those are isolated cases because again, as a species, we have social constraints that only a few outliers escape.

3) "We are always making mate selections," says Bill Nye.
No, we aren't. Single individuals make mating choices under geographical and socio-economic constraints. We, as a species, make no choice. Even though cultural and socio-economic constraints are pretty stable, interbreeding has always happened and it's not going to stop now that geographical mobility has greatly increased compared to 200 years ago. When you look at the individual level you see choices. When you zoom out and look at the species level it's all random. And of course mutations appear randomly, but those who do reach fixation through this process they do so because of random drift, not because of mating choices, especially in today's globalized world.

Rather than mating choices, we need to look at geography, as Coop et al. have done in a paper in PLoS Genetics:

It seems likely that selection in humans is generally not divergent enough to generate large frequency differences at individual loci between population pairs that are either recently separated, or regularly exchange migrants. Furthermore, populations may be too mobile, or their identities too fluid, to experience very localized pressures consistently over the several thousand years that may be required for large allele frequency changes [3].

Does that mean that selection is no longer happening?

Selection and adaptation are of course still happening, but under very particular conditions. Nye does mention a few in his article: the Spanish Flu and the Black Death. Those events inferred a selective sweep on the human genome. But you can't just mention those and forget what happens in between those selective sweeps because that actually covers the majority of our evolutionary history. Most of the mutations found in our DNA have reached fixation through random drift, yet you never hear people say that. So many evolution "experts" out there go on and on on how every single gene in our DNA has been selected and perfected through evolution. This argument, not only is simply not true, but it makes evolution an easy target for the creationists because they (rightfully) say it's wrong. Random mutations, just because they are random, can be either favorable or not depending on the environmental conditions.

The mutation that causes a disease called sickle cell anemia is an interesting example: people are affected only when they carry the mutation on both gene copies. Heterozygous people, who carry the mutation only on one gene copy, are healthy. Since the disease significantly reduces the life span of affected people, under normal conditions, you would expect a deleterious mutation like that to gradually disappear from the population. So why is it still quite prevalent, especially in sub-Saharan Africa?

A study (you can read the whole post here) compared two African populations and saw that the population where the mutation was more prevalent had a lower incidence of malaria. It's only a hypothesis, but this could possibly mean that, under particular circumstances (i.e. endemic malaria), the mutation actually confers an advantage on healthy people who carry it on one gene only -- a phenomenon called heterozygote advantage. Now, this is selection in action. However, notice that the study was conducted on isolated African populations. In fact, the smaller the population, the faster selection acts. Unfortunately, in today's world there are only few pockets left of isolated human populations.

Another study I discussed a few months ago was able to find the effect of selective sweeps caused by historically documented epidemics in the genomes of the Rroma people. This population was ideal for this kind of analysis because over the centuries they remained ethnically homogeneous and only rarely intermingled outside of their group. In fact, one can retrace the migration of ancient populations looking at the people's genome, a concept pioneered by the great population geneticist Luigi Luca Cavalli Sforza.

We can definitely retrace the past, but the question is: can we really predict the future?

What would really help the debate is to hear the voices of real scientists, but real scientists get all technical and frankly what Bill Nye is saying when he envisions a super-intelligent human walking on Mars is far more appealing to the collective imagination than the concept of a handful of random mutations accumulating in our DNA. And as a science fiction writer, I get that because I do love to push the imagination. But then let's not call it science, let's call it what it really is: science fiction.

I'm writing all this not to criticize Bill Nye who's a science enthusiast working on spreading the beauty of science. And I do reckon that he has to do put a bit of this stuff in his book or else no publishing house would accept it. But they wouldn't accept it because us, the scientists, are once again failing to communicate not just the real science but the enthusiasm for (and the value of) scientific thinking.

Thoughts?

[1] Salih NA, Hussain AA, Almugtaba IA, Elzein AM, Elhassan IM, Khalil EA, Ishag HB, Mohammed HS, Kwiatkowski D, & Ibrahim ME (2010). Loss of balancing selection in the betaS globin locus. BMC medical genetics, 11 PMID: 20128890

[2] Hafid Laayounia,1, Marije Oostingb,c,1, Pierre Luisia, Mihai Ioanab,d, Santos Alonsoe, Isis Ricaño-Poncef, Gosia Trynkaf,2, Alexandra Zhernakovaf, Theo S. Plantingab, Shih-Chin Chengb, Jos W. M. van der Meerb, Radu Poppg, Ajit Soodh, B. K. Thelmai, Cisca (2014). Convergent evolution in European and Rroma populations reveals pressure exerted by plague on Toll-like receptors PNAS DOI: 10.1073/pnas.1317723111

[3] Coop G, Pickrell JK, Novembre J, Kudaravalli S, Li J, Absher D, Myers RM, Cavalli-Sforza LL, Feldman MW, & Pritchard JK (2009). The role of geography in human adaptation. PLoS genetics, 5 (6) PMID: 19503611

The Telepath Chronicles launch party and the Winner Takes All mega-giveaway

Today's the Telepath Chronicles anthology launch day, a collection of 14 science fiction stories written by some pretty cool authors like Samuel Peralta, Susan Kaye Quinn, Autumn Kalquist, Endi Webb, Therin Knite, Vincent Trigili, and many others that I have yet to interview here on the blog.

Insecure Writer's Support Group: what's the right price for your book?

This is a monthly event started by the awesome Alex J. Cavanaugh and organized by the Insecure Writer's Support Group. Click here to find out more about the group and sign up for the next event.

My insecurity this month: what is the right price for my books?

Here's the thing: every time I run a 99 cent promotion I sell a ton of books. Both Mosaics and Gene Cards landed on a bunch of hot new releases thanks to those promotions. And then the promotion ends and sales drop. So, what's an author to do?

Incidentally (or maybe not), Amazon started a new program called KDP Pricing Support, which is still in beta, but basically takes in your book data (sales, length of the book, etc.), and tells you what the right price for your book should be. It's an interesting tool because it lets you input the hypothetical price for your book and, based on the data from similar books, it tells you how your sales and profits would change accordingly. Obviously, if you lower the price, the sales increase but the profits decrease. On the other hand, when you raise the price you see a higher profit but less sales.

One thing is for sure: if you want a ton of sales go for the lowest price. However. There's always a catch. For me, the catch is this: how many of those copies sold at 99 cents are actually read? That's a very important question to ask because if all those books end up buried in a Kindle and get never opened, all I've gained is a momentary spike in your Amazon ranking, a spike that is bound to disappear just as quickly as it appeared.

What you really want, as an author, is to engage your readers. Readers who love your book and write a review and recommend the book to their friends are priceless. Who's more likely to write a review, the impulsive buyer who forgets about your book the minute he/she sees another sale, or the reader who looks at the book description and opens a couple of reviews before clicking "Buy Now"?

There's a second consideration I make when deciding the price for my books, and it's not based on page number, like the Amazon tool does. It's based on the amount of work I put into each project. It takes me one year to produce a finished book, and that's not just because I'm a slow writer. I'm a compulsive researcher: I research everything for my story, from characters to technology, from police procedural to locations. I spend just as much time researching as I do writing. It takes time, effort, and resources to do that.

But, none of this is written in stone and I keep debating whether or not I've set the right prices, which is why this month I decided to discuss this topic as my featured insecurity. :-)

Besides, I'm not giving up 99 cent promotions. I'm still planning on having plenty of those as they help me spread the word about my books. But I think that the final price of novel-length books should be higher than $0.99. What do you think? What do you take into account when deciding the right price for your book?

BTW, if you don't want to miss my next book promotion, make sure you sign up for my newsletter. Plus, you get a free story when you sign up. :-)  (sorry, had to end with a devious plug)

The heritability of fears

Cyborg © EEG

As many of you know, one of my favorite topics here on the blog is epigenetic inheritance, i.e. the mechanisms that regulate changes in gene expression that can be passed from one generation to the next. Epigenetics has revolutionized the way we look at genetic inheritance: Darwin had taught us that the only way the environment can shape the genome of a species is through natural selection. While this is certainly still true, today we also know that:

1) Most of the mutations we see in a population have reached fixation through random drift -- the constant reshuffling from one generation to the next -- not selection.

2) The environment can induce changes in one generation that may indeed be passed on to the next generation not through actual changes in the DNA but, rather, in the way the DNA is "packaged" inside the cell nucleus (for a great explanation on how this work, see my colleague Karissa Sanbomatsu's TED talk).

 In a Nature Neuroscience paper [1], authors Dias and Ressler explored the following premise in a mouse model:

"An important, but often ignored, factor that influences adult nervous systems is exposure of parents to salient environmental stimuli before the conception of their offspring. Such information transfer would be an efficient way for parents to ‘inform’ their offspring about the importance of specific environmental features that they are likely to encounter in their future environments. However, this would necessitate the transgenerational inheritance of environmental information via the germ line by offspring not even conceived at the time."

The researchers used olfactory fear as the stimulus mostly because it's one of the best understood mechanisms, both at the neurological and the molecular biology levels. Of course, a caveat would be that humans, besides being very different from mouse models, they've evolutionarily replaced olfactory stimuli with visual ones.

The researchers used odor-naive male mice and targeted an odorant receptor (M71) whose expression in the olfactory sensory neurons has been shown to be activated by acetophenone. It is important to note that the experiment did not induce any change in the actual DNA of the mice. What they did, instead, was use acetophenone to activate the receptor so it would be expressed inside these special neurons.

As I explained in older posts, DNA is wrapped around "spools" called histones. Cells produce proteins and activate receptors depending on what genes are on the outer surface of the "histone yarn", while hidden parts of the DNA remain unexpressed (as if that gene didn't exist). A molecule like acetophenone can induce changes inside olfactory sensory neurons that cause the histones to move and expose the gene that encodes the M71 odorant receptor. Once this happens, the receptor is "activated."

 Since the mice are initially odor naive, their M71 receptor is inactivated (the gene is not expressed) prior to the exposure to acetophenone. After the receptor activation, these male mice were mated with odor naive females. So, genetically speaking, the offsprings had no reason to have the M71 receptor activated, since neither parent had it activated at birth. Yet the offsprings of the mice stimulated with acetophenone, despite not being previously exposed to any of the odors with which they were tested, were able to detect acetophenone at lower concentrations than the offsprings of mice stimulated with another molecule (propanole).

Not all offsprings were behaviorally tested. Some of the offsprings were kept naive to any exposure so that their neuroanatomy could be tested separately without risking the results to be affected by the behavioral tests. When they looked at the offsprings of the acetophenone exposed mice, the researchers found an increase in the M71 glomerular area together with a significant increase in the numbers of M71-activated olfactory sensory neurons in the main olfactory epithelium.

So, how these epigenetic changes get inherited? To address the question, Dias and Ressler examined the sperm of the acetophenone exposed mice. This part of the paper gets a little technical, but the interesting idea is that they did find molecular changes in the sperm DNA around the Olfr151 gene, which encodes the M71 receptor. They found that the 3' end of Olfr151 was significantly less methylated in the acetophenone induce mice. At the same time, they

"did not observe any histone-mediated epigenetic signatures around the M71 locus when chromatin was immunoprecipitated with antibodies that recognize histone modifications that either permit or repress to transcription."

The authors conclude:

"In summary, we have begun to explore an under-appreciated influence on adult behavior—ancestral experience before conception. From a translational perspective, our results allow us to appreciate how the experiences of a parent, before even conceiving offspring, markedly influence both structure and function in the nervous system of subsequent generations. Such a phenomenon may contribute to the etiology and potential intergenerational transmission of risk for neuropsychiatric disorders, such as phobias, anxiety and post-traumatic stress disorder."

[1] Dias, B., & Ressler, K. (2013). Parental olfactory experience influences behavior and neural structure in subsequent generations Nature Neuroscience, 17 (1), 89-96 DOI: 10.1038/nn.3594




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Ebola could mutate as rapidly as the flu

© Science Magazine

The largest genomic data collected on the Ebola virus to date has been recently published in Science [1], giving unique insights on the origin and spread of the greatest Ebola outbreak so far.

The Ebola virus was first discovered in 1976, when it caused 318 cases: until now, it was the largest outbreak.

"The current outbreak started in February 2014 in Guinea, West Africa, and spread into Liberia in March, Sierra Leone in May, and Nigeria in late July. It is the largest known EVD outbreak and is expanding exponentially [1]."

In a recent Science paper [1], researchers sequenced 99 Ebola genomes from 78 patients from Sierra Leone. By analyzing the genetic make-up of the viral population, scientists can retrace the spread of the outbreak. It's a bit like looking at the DNA of a large group of people to find out who's related to whom. In the case of Ebola, we want to know if there was only one "parent", so to speak, or if there were several animal-to-human reinsertions.

According to the paper, the event that brought the virus to Sierra Leone at the end of May was the burial of a healer from Guinea who had treated Ebola patients. Local practices at funerals include touching and kissing the corpse, and given that Ebola can survive in a dead host for up to three days, you can see how a single funeral can infect dozens of people, especially when the dead is a popular healer as in this particular case. Thirteen cases were traced back to this funeral, two of which stemmed the outbreak in Sierra Leone.

The researchers analyzed the viral genomes using phylogenetic trees, a technique that enabled them to retrace the history of the virus.

"Phylogenetic comparison to all 20 genomes from earlier outbreaks suggests that the 2014 West African virus likely spread from central Africa within the past decade [1]."

They were able to see that the "ancestor" originated from a single transmission event back in February. This finding contradicts previous hypothesis that the unprecedented spread of the outbreak was due to multiple transmission events from animal to humans. Contrary to this hypothesis, after that first transmission, in which the virus jumped from animals to human back in February, Ebola has been spreading among people alone.

"Genetic similarity across the sequenced 2014 samples suggests a single transmission from the natural reservoir, followed by human-to-human transmission during the outbreak. Molecular dating places the common ancestor of all sequenced Guinea and Sierra Leone lineages around late February 2014, 3 months after the earliest suspected cases in Guinea; this coalescence would be unlikely had there been multiple transmissions from the natural reservoir [1]."

But the most interesting point (to me at least) that the paper addresses is the virus's mutation rate. Since viruses replicate quite rapidly, it's important to know how high is the chance that at every replication cycle, errors (i.e. mutations) are introduced. Rapidly mutating viruses have a greater chance to escape the immune system (see HIV, for example) and are also much harder to target with a vaccine. The Science paper claims that

"The observed substitution rate is roughly twice as high within the 2014 outbreak as between outbreaks [1]."

In fact, they estimate the mutation rate to be roughly the same as that of the seasonal flu, which, if confirmed, would greatly hamper the creation of a vaccine.

Unfortunately the odds are still against poor countries. I attended a talk this week where the speaker reported that while the mortality rate in the affected African countries is at 95%, in the Western world it drops down to 75-80%. This is due to prompt intervention, the use of serum from people who survived the infection (and hence developed good antibodies against the virus), and the use of IVs. Unfortunately, people living in the affected countries tend to be skeptical of westerners and, just like it happened with HIV, beliefs that Ebola is yet another virus introduced by Westerners to hurt the locals are rampant.

When I finished reading the Science paper, I was saddened to find this final paragraph:

"In memoriam: Tragically, five co-authors, who contributed greatly to public health and re- search efforts in Sierra Leone, contracted EVD and lost their battle with the disease before this manuscript could be published: Mohamed Fullah, Mbalu Fonnie, Alex Moigboi, Alice Kovoma, and S. Humarr Khan. We wish to honor their memory."

[1] Gire SK, Goba A, Andersen KG, Sealfon RS, Park DJ, Kanneh L, Jalloh S, Momoh M, Fullah M, Dudas G, Wohl S, Moses LM, Yozwiak NL, Winnicki S, Matranga CB, Malboeuf CM, Qu J, Gladden AD, Schaffner SF, Yang X, Jiang PP, Nekoui M, Colubri A, Coomber MR, Fonnie M, Moigboi A, Gbakie M, Kamara FK, Tucker V, Konuwa E, Saffa S, Sellu J, Jalloh AA, Kovoma A, Koninga J, Mustapha I, Kargbo K, Foday M, Yillah M, Kanneh F, Robert W, Massally JL, Chapman SB, Bochicchio J, Murphy C, Nusbaum C, Young S, Birren BW, Grant DS, Scheiffelin JS, Lander ES, Happi C, Gevao SM, Gnirke A, Rambaut A, Garry RF, Khan SH, & Sabeti PC (2014). Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science (New York, N.Y.), 345 (6202), 1369-72 PMID: 25214632

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Ten years into the making, the HIV-1 mosaic vaccine finally goes into human trial

© Bette Korber et al.

I hope you will all forgive me if this week I'm gushing over my amazing mentor Bette Korber, as last week she shared some awesome news on Facebook:

"A landmark in my life happened yesterday, a major step in a long story. A decade ago I had an idea for making an HIV vaccine that had the potential to work globally. After a struggle (in my first 2 failed proposals, reviewers declared what I proposed was impossible), I got an internal grant from Los Alamos to develop the idea (third time's a charm). With that funding I could bring together a group of computational people to work together on expressing the idea -- a talented guy named Simon Perkins wrote amazing code to make it so, with computational design suggestions from the group, particularly my husband James Theiler. Then James, Will Fischer, Tanmoy Bhattacharya, and I put it through its paces, optimizing running conditions and devising ways to compare mosaics with natural proteins, with additional help from our friends Karina Yusim, Carla Kuiken and Bob Funkhouser. We called it a mosaic vaccine.

After so many years of hard work, and with the collaboration of experimentalists at Harvard and at Duke (Drs. Haynes, Letvin, and Barouch), two weeks ago a phase I safety trial finally opened, and an HIV mosaic vaccine went into the arm of a human volunteer for the very first time. "Safety trial" means that this is just the first phase in testing the safety of the vaccine (I explained the three phases of human trials in this post). We will gather immune responses and we are hoping to see the same good results we saw in monkeys [2-5]. If all goes well, HIV mosaics are in the pipeline for 4 more human vaccine studies. I'm so excited about this study and so proud of my mentor.

When I explain to people the challenge we are facing when designing an HIV-1 vaccine, I usually make a very simplistic comparison with the flu virus. Influenza evolves from one season to the next, which is why every year we need a new flu shot. So, basically, the flu evolves into a new virus every year. Well, HIV evolves so rapidly that every person has a different virus. In our database alone we have half a million distinct HIV viral sequences: how can you vaccinate people against half a million different viruses?

In the past, successful vaccines against diseases like polio or the measles have been made by taking a real virus, inactivating it (for example, you just take one or two of its proteins, but not the whole virus, to ensure it loses its ability to infect cells), and then injecting it into the body. The immune system "sees" the viral proteins and initiates a response. The response is then "saved" into memory cells, which, next time they encounter the pathogen, will remember how to produce the right response that will promptly clear the virus before it can start an active infection.

So, as you can see, the problem with HIV is that the viral population is so diverse that no one virus found in nature will protect people from contracting the infection. How to bypass the obstacle, then? Bette's idea is to basically use a computer that mimics HIV's evolutionary mechanisms to create an in-silico virus [1], something I've discussed in this post. The algorithm takes as input a population of, say, 100 different HIV sequences, and then recombines them creating a new population of artificially constructed viral sequences. HIV viruses can naturally recombine when infecting the same cells, and what the algorithm does is mimic this mechanism making sure that after every recombination step the new sequence is still a viable and functional virus. The computer mimics this process, iterates it multiple times and then the best representative is selected as a potential vaccine.

The first caveat is: is this new, artificially constructed sequence a real virus? After all, it was never found in nature. It was created by a computer algorithm. It turns out that when reconstructed in a wet lab, the mosaic proteins are functional and viable.

The second hurdle was to prove that these artificially constructed sequences are safe to be used in a vaccine and that they do elicit protective responses against not just a few HIV viruses, but many, many HIV viruses -- enough to prevent infection. So, you get an idea of why the mosaic vaccine took 10 years from concept to the first human trial.

Animal studies [2-5] demonstrated that mosaic vaccines elicit good immune responses. In one study in particular [3], compared to controls, vaccinated monkeys required many more challenges to get infected (for a risk reduction of 80%), and once infected, they were able to control the viral load and survive the infection.

So, as Bette said, we are hopeful. Hopeful and excited!

[1] Fischer W, Perkins S, Theiler J, Bhattacharya T, Yusim K, Funkhouser R, Kuiken C, Haynes B, Letvin NL, Walker BD, Hahn BH, & Korber BT (2007). Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nature medicine, 13 (1), 100-6 PMID: 17187074

[2] Nkolola JP, Bricault CA, Cheung A, Shields J, Perry J, Kovacs JM, Giorgi E, van Winsen M, Apetri A, Brinkman-van der Linden EC, Chen B, Korber B, Seaman MS, & Barouch DH (2014). Characterization and immunogenicity of a novel mosaic M HIV-1 gp140 trimer. Journal of virology, 88 (17), 9538-52 PMID: 24965452

[3] Barouch DH, Stephenson KE, Borducchi EN, Smith K, Stanley K, McNally AG, Liu J, Abbink P, Maxfield LF, Seaman MS, Dugast AS, Alter G, Ferguson M, Li W, Earl PL, Moss B, Giorgi EE, Szinger JJ, Eller LA, Billings EA, Rao M, Tovanabutra S, Sanders-Buell E, Weijtens M, Pau MG, Schuitemaker H, Robb ML, Kim JH, Korber BT, & Michael NL (2013). Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys. Cell, 155 (3), 531-9 PMID: 24243013

[4] Santra S, Muldoon M, Watson S, Buzby A, Balachandran H, Carlson KR, Mach L, Kong WP, McKee K, Yang ZY, Rao SS, Mascola JR, Nabel GJ, Korber BT, & Letvin NL (2012). Breadth of cellular and humoral immune responses elicited in rhesus monkeys by multi-valent mosaic and consensus immunogens. Virology, 428 (2), 121-7 PMID: 22521913

[5] Barouch DH, O'Brien KL, Simmons NL, King SL, Abbink P, Maxfield LF, Sun YH, La Porte A, Riggs AM, Lynch DM, Clark SL, Backus K, Perry JR, Seaman MS, Carville A, Mansfield KG, Szinger JJ, Fischer W, Muldoon M, & Korber B (2010). Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys. Nature medicine, 16 (3), 319-23 PMID: 20173752

Gene Cards release day!

Science fiction fans: my futuristic/dystopian technothriller GENE CARDS is finally here! And here's the best news: for a limited time only (i.e. one week!) it will be at the special price of $0.99 (Kindle edition, US and UK only). Please share the news, post on Facebook, tweet, send it as a gift to the sci-fi lovers in your family and circle of friends, in other words: help me spread the word.

Read the first chapter here.

Review Highlights:

"I found Gene Cards a rewarding read, one that kept me glued to the pages throughout to see what comes next. And come they did - many suspenseful and nail biting moments." -- MysterySequels.com

"Ms. Giorgi has a very unique voice, a word artist, with a vivid and descriptive vocabulary." -- Juneta Key, Amazon Review

"Packed with action from the first page to the last, the characters are engaging and flawed in a relatable way." -- C., Amazon Review

Book Blurb:
When the cure for some means death for others, how far will you go to save your own?

Yulia Szymanski is a murderer and one of the best hackers of the century. Her mission: break her brother out of a high security jail before he dies of a rare genetic condition. On her trail is Biothreat Agent Skyler Donohue, a decorated Muay Thai fighter with a strange fascination for corpses. The obstacle to overcome: an invisible, deadly disease that strikes at random and has the city of Liasis locked in a bioterrorism siege.

When the latest to fall ill is Skyler's best friend's daughter, Skyler wants to drop the Szymanski case to chase the baffling pathogen that nobody is able to isolate. What she doesn't know is that finding Yulia is the only way to stop the epidemic and save the child's life.

In a world where identities are based on gene cards, and privacy no longer exists, survival is only granted to the rich, the healthy, and those who've learned to become invisible to the system.

Is EV-D68 causing mysterious polio-like symptoms in children?

Bubble fun at the Santa Fe Renaissance Fair © EEG 

One of the twists in my latest book, Gene Cards, is an unknown pathogen threatening the fictional city of Liasis. I confess that when I came up with the idea I was a little nervous. My story is set in the future, and with all the state-of-the-art technology we already have, is it feasible to think that we will still deal with diseases without a known causative agent? The thing is, new viruses and new pathogens arise all the time. Take the flu, for example. Every time it jumps from one species to another, it has the potential to recombine in new strains and create a new virus. Influenza viruses are usually recognizable from their surface proteins, hemagglutinin and neuraminidase. But the point is that for as long as there are pathogen that thrive in animal reservoirs and then suddenly jump to humans, these pathogens could potentially lead to unknown organisms. And it's hard to test for something you don't know. Another issue with viruses is that they can "hide" in cells (like neurons) that are not accessible through standard test, making them harder to detect unless one resolves to invasive techniques.

One thing is to theorize that it's possible, and one thing is to find it's happening, as you can read in this post from TWiV:

"In February 2014 I wrote about children in California who developed a poliomyelitis-like paralysis, also called acute flaccid paralysis or AFP. However, the cause of this paralysis was not known. The CDC has released its study of these cases and concludes 'The etiology of AFP with anterior myelitis in the cases described in this report remains undetermined'."

The CDC report is available online, and perhaps the most striking quote is the following:

"Additional laboratory testing for infectious diseases conducted at the CDPH Viral and Rickettsial Disease Laboratory did not identify a causative agent to explain the observed clinical syndrome reported among the patients."

So, what is the story, here?

Acute flaccid paralysis happens when muscles become weak or limp and can no longer contract. In order to be diagnosed as AFP, the symptoms must arise spontaneously and not be caused by a trauma. A number of viruses can cause this condition, including polio. When caused by polio, the paralysis is associated with inflammation of the spinal cord, and the whole condition takes the name of "acute flaccid paralysis associated with anterior myelitis." A total of 23 cases of acute flaccid paralysis associated with anterior myelitis have been reported in California between June 2012 and May 2014.

"Affected patients resided in diverse geographic areas throughout California with no indication of clustering. During the 30-month inquiry, no indication of seasonality or temporal trends in disease onset was established."

Twelve patients had been vaccinated against polio, two hadn't, and for the rest no information was available. Nineteen of the 23 patients had been tested for the "usual suspects" (polio, enteroviruses, West Nile virus, rabies, etc.), but only two tested positive for Enterovirus EV-D68, which in most cases actually manifests as a respiratory disease. The CDC report excludes polio as a cause of the 23 cases in the study and concludes that no common etiology could be found.

[. . .] whether these cases represent an actual increase from baseline incidence of AFP with anterior myelitis in this population is unclear. A study examining AFP in children aged 15 years in California during 1992-1998 reported an incidence of 1.4 AFP cases per 100,000 children per year, with the most common diagnoses being Guillain-Barre syndrome (23%), unspecified AFP (21%), and botulism (12%). None of the 245 reviewed cases had recognized anterior myelitis, which is characteristic of paralytic poliomyelitis.

If you do a quick search on PubMed, you'll see that the most common etiology for AFP is polio, and in those cases it's usually associated with anterior myelitis. A Korean study carried over the span of 10 years (from 2001 to 2010) found a total of 285 AFP cases, for which Guillain-Barre syndrome was the major leading causes [1]. Usually triggered by an infection, Guillain-Barre syndrome is a disorder that affects the peripheral nervous system. With prompt treatment, it is 100% curable, though if not treated promptly, it can cause life-threatening complications.

What about the two patients who tested positive for Enterovirus D68? EV-D68 was first isolated in 1962. Since then, there have been rare reports of clustered cases, particularly in summer. However, this summer, there has been an unusual increase in reported cases of severe respiratory diseases, and most of these cases tested positive for EV-D68. Here are the latest numbers from the CDC:

"From mid-August to October 8, 2014, CDC or state public health laboratories have confirmed a total of 664 people in 45 states and the District of Columbia with respiratory illness caused by EV-D68."

What makes this virus worrisome is that it affects young children (usually under the age of 10) and that currently there is no vaccine or treatment against it. And while it normally manifests as a respiratory disease, in some rare instances, the virus can affect the nervous system. In the two California AFP cases that tested positive for EV-D68, the virus was found through nasal swabs. There is a possibility that in the other cases the virus was not found because it was elsewhere, namely in the nervous system (where it would be found only through invasive procedures).

In a different report, the CDC describes

"a cluster of nine children evaluated at Children's Hospital Colorado with acute neurologic illness characterized by extremity weakness, cranial nerve dysfunction (e.g., diplopia, facial droop, dysphagia, or dysarthria), or both. Neurologic illness onsets occurred during August 8‚ September 15, 2014."

Four of eight Colorado children tested were positive for EV-D68. And even though these symptoms are not quite equivalent to AFP, they still fall within the spectrum of acute neurologic illnesses.

Bottom line: we can't quite hold EV-D68 as responsible of the mysterious AFP cases, but we can't exclude it either. Viruses tend to target specific cells in the body, and sometimes they can spread beyond their usual "hunting grounds." When a pathogen is symptomatic (or manifests certain symptoms) only in one particular subset of the population, the reported cases appear to be unrelated, making it very hard to reconstruct the etiology of the outbreak.

Yes, sometimes reality is weirder than fiction. Ad if you are curious about the premise of my new book Gene Cards, you can read the first chapter here.

[1] Kim H, Kang B, Hwang S, Lee SW, Cheon DS, Kim K, Jeong YS, & Hyeon JY (2014). Clinical and enterovirus findings associated with acute flaccid paralysis in the Republic of Korea during the recent decade. Journal of medical virology, 86 (9), 1584-9 PMID: 24114945

[2] Zangwill KM, Yeh SH, Wong EJ, Marcy SM, Eriksen E, Huff KR, Lee M, Lewis EM, Black SB, & Ward JI (2010). Paralytic syndromes in children: epidemiology and relationship to vaccination. Pediatric neurology, 42 (3), 206-12 PMID: 20159431

First Page Review Blog-Hop: Gene Cards

Today's post is part of the First Page Review bloghop. Here's how it works: if you are writer, on your own blog, post your first 1,000 words of something you're writing or have written, then sign up on this page, linking your 1,000 word post. Visit other people on the list and read theirs, then leave a comment to let them know if you liked it, what worked, what didn't, and if you'd keep reading. And if you don't have any work in progress to share... visit the First Page Review bloghop page to discover new, forthcoming books!

My excerpt is from my new book release, GENE CARDS. Here's the first 994 words:

The blue bar inched forward.
Thirty percent download.

Orange light pooled through the electrochromic windows and drew jagged lines across the walls. Outside, helicopter blades swooshed closer. Yulia waved a hand in front of the switch sensor and the glass went from opaque back to transparent. She watched the chopper—a Sikorsky quadcopter—maneuver through the sky. Thick billows of smoke enveloped it.
A red, angry sun watched with her.

Sirens blasted in the distance, a megaphone barked down the street.
Yulia’s eyes strayed back to the screen in her hand.
Forty percent download.
Nestled in the palm of her hand, the forty panels forming the screen of her Computerized Personal Assistant buzzed with activity. Bites of data rushed across firewalls, swirling through fiber-optic cables and eluding encrypted servers, slowly filling her CPA’s two terabytes of RAM.
C’mon…

“New message,” the CPA said. “Display?”
On the bottom right corner of her screen, Yulia read, Inbox(1).
She tapped the screen and said, “No.”
The blue bar inched to fifty percent. The beat of the quad skycrane hammered against the windows.
“New message,” the CPA repeated. “Display?”
Damn!

Her muscles twitched, her foot rapped the floor. She tapped the Inbox. The screen went black, a new image quickly filled it.
She saw red, at first. Red, like the sun outside.
Red’s not good.
She bit her lip, watching.
He’s sick again.
Sick, like the sun outside. 

Yulia’s fingers wavered. She peeked at the downloading bar at the bottom of the screen—sixty-eight percent—then back to the image: the rusty skeleton of a boat deck stranded on a gray beach. Ravenous ocean waves swelled around it, dark clouds looming above.
No time now.
“Close.” She tapped the screen and the image was gone.
The sirens outside wailed closer. 

A tree on the street burst, sending debris and ashes drumming against the windowpanes.
A loud buzz, the electronic voice of the security system crackling to life. “Code nine-eight-nine. The system has been informed of an emergency.”
“Really?” Yulia snapped.
“Recognition failed. Please repeat.”
She bit her lip. Stay calm. You’ll get out of this. 

With its syncopated cadence, the central computer dictated its impersonal warning: “The system will proceed to shut down at seventeen-oh-five GMT on August ten, two thousand fifty-six. Shut down will complete in ninety seconds.”
Yulia locked her fingers around her CPA. She had ninety seconds to finish the download and leave. The shutdown was irreversible. She could yell some random command at the speakerphone, but the voice recognition software would reject it.
Come on! 

“Gas. Disconnected.”

Through the electrochromic windows, she could now see the plume of smoke loom over the horizon. The sky darkened, the red disk of the sun glimmered through the haze like a reversed eclipse. 

“Electricity. Disconnected. Battery life. Fifteen seconds.”

Light burst through the OLED TV screen one last time and then died. Suddenly muted, digital frames scattered on the white walls flickered and went black. The wireless power source tower faded from red to gray.
Ninety percent download.
Come on!

Down the street, barked the impersonal voice of a security drone: “Mandatory evacuation for all residents. Please evacuate. Now.”
Heedless, the central computer resumed its warning. “Q-Network. Dis—”
Another loud buzz, this time followed by sparks.
The system exhaled its last breath, Yulia thought.

Electronically controlled, all doors in the apartment closed. Sprinklers came down from recesses in the ceiling.
Yulia ducked to cover her CPA from the water.
The shelves rattled, one of the picture screens fell and crashed into a million fragments. The metal cabinet shook, its long forgotten treasures trembled: a black and white picture in an old-fashioned wood frame. A seashell. A vintage 35mm camera. 

The CPA emitted a brusque bleep.
Download complete.
Yulia exhaled. She unplugged the cat-5 cable, morphed her CPA to a cube, and slid it in her pocket.
This is all I need.
The sprinklers spit rust-smelling water on her face.
Car keys. Check. Data. Check.
My K45. 

A whiff of gunpowder emerged over the reek of fire smoke. And blood. Not much, just a trickle snaking its way on the floor. Duane stared at her with vacant eyes, an arm loosely wrapped across the back of the couch as if he’d just sat down to chat. A hint of surprise lingered in his gaze. His wet forehead was plastered with strands of ash blond hair.
Yulia brushed her fingers along the back of his hand, the same hand that yesterday had run on her breasts, teasing, caressing. 

Her two-millimeter H&K K45 lay on the cushion next to him. She picked it up, pressed the release and checked the magazine.
Twenty more rounds.
Plenty.

She snuck the handgun in her waistband and kissed Duane’s forehead—a wet kiss, lulled by the monotone hiss of the sprinklers.
“Bye, babe. Sorry you didn’t enjoy the ending.”
The acrid smell of wildfire welcomed her outside, stinging. The plume loomed and covered the sky, as if night had fallen. She heard the chopper but couldn’t locate it. Ashes prickled her face like soft raindrops. The metallic voice of the security drone sounded far away now, its distant call an unheard lullaby. 

Her Toyota SX waited on the curbside, under a layer of soot. She climbed behind the wheel, called the engine on, then the wipers.
The fifteen-year-old engine roared. Without a GPS or QNet communicator to inform it of the current emergency, the navigator’s greeting seemed surreal.
“Welcome, Alex. Where should I take you today?”
“Away,” Yulia ordered the navigator. “As fast as you can.”

Headlights on, the Toyota whipped into the street.
She saw the flash first, through the rearview mirror. Then came the blast, so strong it made the car jump and propel forward. Glass shattered and exploded. Debris washed on the windshield. 

She didn’t stop to look back. It no longer mattered.
Nothing mattered anymore.
Tires skittered on soot.
The Toyota lost ground, then gained it back.
Run.
Away.



Book Blurb:
When the cure for some means death for others, how far will you go to save your own?

Yulia Szymanski is a murderer and one of the best hackers of the century. Her mission: break her brother out of a high security jail before he dies of a rare genetic condition. On her trail is Biothreat Agent Skyler Donohue, a decorated Muay Thai fighter with a strange fascination for corpses. The obstacle to overcome: an invisible, deadly disease that strikes at random and has the city of Liasis locked in a bioterrorism siege.

When the latest to fall ill is Skyler's best friend's daughter, Skyler wants to drop the Szymanski case to chase the baffling pathogen that nobody is able to isolate. What she doesn't know is that finding Yulia is the only way to stop the epidemic and save the child's life.

In a world where identities are based on gene cards, and privacy no longer exists, survival is only granted to the rich, the healthy, and those who've learned to become invisible to the system.

Preorder GENE CARDS on Amazon (release date October 15).

Golden fall colors and a little experimentation

Gold © EEG

The aspen leaves are turning again and I feel lucky I live in an area where I can witness their splendor. As with most things when it comes to landscape photography, fall colors too are best rendered either at sunrise or at sunset. Sadly, the forest closest to where I live burnt in 2011, and the next closest one is 1 hour drive away. Did I mention I'm not much of a morning person?

Last Friday I got there at 10 am. The colors were stunning, but I knew the light wasn't the best one could get. Still, I decided to make the best out of it. I came back home with 150 shots, of which this one was my favorite:

© EEG

It's pretty, gives an idea of the gorgeous colors, but it's not a biting picture. I wanted something more, so I tried a little experiment (the result is the picture at the top). It turned out a lot more work than I had anticipated, and since many asked me how I achieved the final result, I decided to document it step by step.

First, copy the original picture into PS as a new layer, then make a duplicate layer. Mute the top layer and on the visible copy select Blur -> Motion Blur. Set the angle to 90 degrees. The pixel field will give the amount of blur you desire. I set it at 790 and got this:

© EEG

The above has the foreground leaves blurred too, resulting in the yellow smears toward the bottom. I wanted the foreground leaves to be surrounded by dark colors, like in the original picture, so I duplicated this layer, took the bottom part only and then extended it so it now looked like this:

Next, I used the magic wand to select (from the original picture, which you can see as the hidden "Layer 1 copy" on the right) the dark colors for the branches I wanted in the foreground. When you do that, you get all browns in the picture, not just the ones you want, so you have to go back and erase the extra stuff you don't want in the background. This is what I got after that tedious process:

Same thing with the yellows this time:

And since neither the yellows or the browns got everything I wanted, I went back and manually selected everything I wanted in the next two steps:

It's tedious and it requires a lot of patience (and I'm sure the experts know of better and easier ways of doing this especially in CCS6 -- I'm only using elements here), but I really like the end result. :-)

If you're interested, I made a poster: $45, shipping included (within the US), email me at eegiorgi(at)gmail.com

Sunday Snippet: Gene Cards

From GENE CARDS, Chapter 1:

The blue bar inched forward -- thirty percent download.
Orange light pooled through the electrochromic windows and drew jagged lines across the walls. Outside, helicopter blades swooshed closer. Yulia waved a hand in front of the switch sensor and the glass went from opaque back to transparent. She watched the chopper—a Sikorsky quadcopter—maneuver through the sky. Thick billows of smoke enveloped it.
A red, angry sun watched with her.
Sirens blasted in the distance, a megaphone barked down the street.

The above is my Sunday snippet submission for the Weekend writer Warriors (you can find the Snippet Sunday group on Facebook, too). Make sure you check out all Weekend writer Warriors participants, it's a fun way to find forthcoming books -- all genres welcome, there's something for everyone's tastes.

Download the first chapter of GENE CARDS here. You can also enter the Goodreads giveaway to win one of two signed copies! Thanks for visiting!

The IWSG is making a book!!

This is a monthly event started by the awesome Alex J. Cavanaugh and organized by the Insecure Writer's Support Group. Click here to find out more about the group and sign up for the next event.

This month marks the anniversary of the IWSG website and FB group, and to celebrate the IWSG Team is putting together an eBook that will benefit all writers - The IWSG Guide to Publishing and Beyond. The eBook will be free and available for all eReaders by early December.

My post this month is also the contribution to the e-book, which is why I'm sharing my thoughts on what I learned so far on writing and publishing from my still very limited (but hopefully expanding) point of view.

To me, these are the most important things that make for a good story and a solid readership:

Research. Spend at least as much time researching as you do writing. Talk to people. Read non-fiction on the topics you deal with in your book. For example, when I started jotting down my ideas for my debut novel, CHIMERAS, I knew nothing about police procedural, and had never talked to a cop before. So I went on amazon and bought a bunch of books on forensics. I also found two true crime books written by Miles Corwin, a journalist who was embedded in the RHD for one year. Fantastic read, I can't tell you how much those books (Homicide Special in particular) have helped me shape my story and make my characters ring true.

But I needed more. So I went looking for people I could talk to. I'd met a writer online whose books where set with the LAPD. I asked her where she did her research and she introduced me to a retired LAPD cop who helped her lot. That retired LAPD cop is now one of my best friends and his memoir sits in my Favorite Books shelf. Through him I learned not only the lingo cops use, but also their modus operandi, their witty humor, their lifestyle. And it paid off: I've had readers praise my characters because they "ring true."

Writing rules. Every time the topic comes up I roll my eyes. Can you do X in writing? Are you allowed to do Y? Why is Z strictly forbidden? For me, it all boils down to this: do not be afraid to break rules. Rather, be afraid of not breaking them well. 

Build a solid and reliable readership. By that I mean a group of readers that will always buy your books, will always write reviews and will always give you valuable feedback. The group doesn't have to be large, but it does have to keep growing and it should be a steady presence in your writing career.

Provide interesting content. Now, I know a lot of fellow writers will disagree with me on what makes interesting content. When I browse people's blogs I see that most writers talk to other writers. They post about publishing, writing, and the ins and outs of the life of a writer. And mind you, I really appreciate this because as a writer, I learned a lot from other writers who generously shared their experience on writing, publishing and marketing. But you must not forget that who will ultimately read your books are readers, not just writers.

If you look at the most successful authors out there you'll notice that on their blogs they talk to their readers. Not fellow writers, not friends or family. They engage their readers in their writing process. So yes, keep the blog posts on how to format books, what platforms are best and what promos work versus the ones that don't work. But also talk about your characters and how you got inspired to write them and what you're working on next...

Be patient. Michael Bunker wrote a great post a while ago on Kindle stuffers. A lot of people stuff their Kindles. Yes, those people will likely give you a spike in rank and it will feel good. It's a high that doesn't last long, though. Many of those Kindle stuffers will keep stuffing their Kindles and your book will be buried under a pile of stuff that may or may not be read some day. You want reliable readers, readers that pick your book because they read the description and loved he reviews. Those readers are harder to get but I promise, they are here to stay with you for the long run. So work on getting those more than you are at working on your ranks. It takes more time and even more patience, but in the long run it pays off.

Make your readers part of your writing process. Create a newsletter for your upcoming ARCs. Sending out ARCs is a must in order to build that reliable readership. Don't just send them out, ask for feedback. Tell your readers you love to hear back from them and always thank them for the time they put into reading and reviewing your work. My drafts got much better thanks to the feedback of my reviewers, and many of my readers have now become great friends.

Your time is better spent writing. Yes, I know, there's a lot of books on how to publish successfully out there, a lot of blog posts, a lot of tricks, do's and dont's that people talk about. Have I read them? Some. Would I recommend going through all that stuff? Maybe. To be honest with you, I think they're just tricks, and, statistically, what works for one book/author is not likely to work for all books/authors. Yes, if you're good at marketing you may have a better time than others struggling to push their work out there. But really. Don't waste too much time on that stuff. The time you spend writing is your investment in that faithful readership that you need to build. Let your readers push your book for you while you focus on producing the best story ever written.

Final considerations. My advice will likely be the least popular you will find out there. Why? Because it's the kind advice that overlooks fast rewards in favor of hard work that takes a long time to build. And maybe I will be proven wrong. But I see a lot of writers rise fast and then just as fast fall (and this is true for both traditionally published as well as indie authors). Fire burns through hay very quickly. If that's what you want, then go for the fast reward approach, aim at those Kindle stuffers, etc. But if you want a long lasting fire, go for the slow burning coals. Your ranks won't be shocking any time soon, but your readers will follow you through time.

I want to thank everyone who will be stopping by and leaving comments today. I'm on the road today so I will publish them and reply as soon as I can.