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A mathematician by training, I discovered genetics in 2006 and never turned back. This blog was born to share all the fascinating things I learn about genes and DNA through my current research on viral genetics and HIV.

EE Giorgi
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  • April 11, 2017
  • 09:00 AM
  • 334 views

Looking for clues for past life on Mars

by EE Giorgi in CHIMERAS

NASA's Curiosity Mars. Credits: NASA/JPL-Caltech/MSSSOn August 6, 2012, the NASA Curiosity rover landed on Mars at the base of Mount Sharp, a mountain the size of Kilimanjaro (~19,000 feet) in the middle of Gale Crater. Nina Lanza, space scientist at the Los Alamos National Laboratory, remembers the day well. As part of the team that built ChemCam, one of the ten instruments on the rover, she spent three months at the Jet Propulsion Laboratory in California, living on “Mars time” to follow Curiosity’s first “steps.” ChemCam stands for “chemistry camera” and comprises a laser-induced breakdown spectroscopy (LIBS) instrument and a Remote Micro Imager (RMI). It was built at the Los Alamos National Laboratory in collaboration with the French space agency CNES. Nina Lanza and postdoctoral fellow Patrick Gasda are two of the Los Alamos scientists who work on the instrument. “We get to shoot a laser on Mars for a living,” Lanza says, grinning.And the laser on ChemCam is extremely powerful. When focused on a target, it vaporizes a small amount of material by heating Martian rocks to a temperature that’s roughly equivalent to that of the surface of the sun. “When we fire at a nearby target,” Gasda explains, “the elements get excited and, as they come down from that excited state, they emit light.”By looking at the light emitted by the target, scientists can analyze the composition of rocks and soils on Mars. Previous Mars missions have found ice in the near-surface at high latitudes, begging the question: was there ever water on other parts of Mars at some point? And if there was—does that mean there could have been life, too?With the very first laser shots from ChemCam, the answer was a definitive yes. “ChemCam discovered that all Martian dust is hydrated,” Lanza explains. “Given how dusty Mars is, this means that water is everywhere on the planet. We also found evidence that water was flowing in Mars’s past.” “Gale Crater was filled with water,” Gasda adds. “From the sequence of sedimentary rocks we know of flowing streams in the crater that converged to a large body of still water that likely lasted for millions of years.”“Curiosity gave us a picture of Gale Crater as an extremely habitable system,” Lanza continues. “We know that on Earth systems like this, with long-lasting neutral pH waters, would definitely support life.”But how do you go about finding evidence for life? You search for clues, in other words, unique markers that identify biological activity.“A potential marker could be manganese minerals,” Lanza says. In 2016 Curiosity found rocks rich in manganese-oxides at a location called Kimberley. “Manganese deposits in the terrestrial geological record mark the shift to higher concentrations of atmospheric oxygen due to the emergence of photosynthesis. This means that there could have been more oxygen in the Martian atmosphere in the past.” Water. Oxygen. What about other building blocks of life? How do we look for those?“Nucleic and amino acids have been found in space,” Gasda tells me. “However, ribose—the ‘R’ in RNA, one of the first building blocks of life—and other sugars have never been found in space because they are too unstable. In order to have life, you need molecules that stabilize these sugars in water. Borates are particularly promising molecules for stabilizing sugars [1].”Boron is highly soluble in water. In 2013 researchers from the University of Hawaii found boron in a meteorite from Mars [2]. That’s when Gasda became interested in this quest. “Once we knew that Gale Crater had once hosted a large body of water, it was natural to search for boron in those sediments.” ChemCam did indeed find boron on Mars in 2016. Together with the manganese oxides, this is still not sufficient evidence for life on Mars, but it shows that some of the raw ingredients were present. The scientists are primed to keep looking. Curiosity has been on Mars almost five years (or 1660 sols), and its data is helping researchers fine-tune the instruments for the next Mars rover, provisionally named Mars 2020, to be launched in July 2020. “We need to look for biosignatures,” Lanza says. “And we may not find them. But if we don’t, to me, the most striking question would be: what if there were indeed all the ingredients for life on Mars, yet life never happened? What made Earth so unique that life could happen here but nowhere else?”Gasda nods. “And if we are indeed unique, shouldn’t this make us feel more special, and make us more cautious about the way we treat our planet and our biodiversity?” I mention the current political climate, with the planned budget cuts to scientific research, and the appalling denial of any intervention to curb global warming. “These cuts to basic research are disheartening,” Lanza says. “People often think of NASA research as esoteric and out of touch. And yet almost everyone has GPS technology on their smart phones today, something we owe to space research. Take the electron as another example. I’m sure people in the nineteenth century found J. J. Thomson’s research on the electron to be highly academic, with few practical applications. Yet without his discovery we wouldn’t have electricity, and our lives today would be fundamentally different.” “The best measure for progress,” Lanza concludes, “is when you can’t imagine the knowledge you are going to gain. Let the science surprise you.” Nina Lanza is a staff scientist, and Patrick Gasda is a postdoctoral research fellow, both in the Space and Remote Sensing group at the Los Alamos National Laboratory. They are both on the science team for the Curiosity Mars rover mission. The opinions expressed here are their own and not their employer’s. Both will be speaking at the March for Science in Santa Fe, New Mexico, on April 22nd. [1] Ricardo, A. (2004). Borate Minerals Stabilize Ribose Science, 303 (5655), 196-196 DOI: 10.1126/science.1092464[2] Stephenson, J., Hallis, L., Nagashima, K., & Freeland, S. (2013). Boron Enrichment in Martian Clay PLoS ONE, 8 (6) DOI: 10.1371/journal.pone.0064624... Read more »

Ricardo, A. (2004) Borate Minerals Stabilize Ribose. Science, 303(5655), 196-196. DOI: 10.1126/science.1092464  

Stephenson, J., Hallis, L., Nagashima, K., & Freeland, S. (2013) Boron Enrichment in Martian Clay. PLoS ONE, 8(6). DOI: 10.1371/journal.pone.0064624  

  • April 3, 2017
  • 09:00 AM
  • 270 views

"Science is Under Attack." A Climate Scientist's Call to Action for the Future of our Planet.

by EE Giorgi in CHIMERAS

It’s a foggy morning in London. Meteorologist George Simpson, the director of the British Meteorological Office, sips his tea and opens a paper authored by a scientist named Guy Stewart Callendar. The last sentence of the abstract reads, “The temperature observations at 200 meteorological stations are used to show that world temperatures have actually increased at an average rate of 0.005°C per year during the past half century.”Simpson shakes his head and thinks, “Nonsense. It’s all a coincidence.”If this seems like a modern-day scene over climate change, you’ll be surprised to know that Callendar published his paper in 1938. And of course, his results, linking a global trend in temperature rises to atmospheric carbon dioxide concentrations, were received with a lot of skepticism. Almost 80 years later the debate is still ongoing.“It is disheartening,” says Todd Ringler, climate scientist currently working at Los Alamos National Laboratory. “The reality is that there is no uncertainty about the basic premise of climate change. We know that CO2 concentrations are rising, we know why they are rising, and we know that CO2 tends to warm the atmosphere.”In fact, this last effect — that CO2 warms the atmosphere — was shown by Irish physicist John Tyndall in 1859, over 150 years ago. But if the science on CO2 and its effect has been clear for so long, why does the public still have this preconception of uncertainty when it comes to global warming and climate change?“There is essentially no doubt that temperatures are rising because of CO2 concentrations,” Ringler explains. “The biggest uncertainty controlling global temperature in year 2100 is what our energy future will look like. In other words, we cannot estimate how much the temperatures will rise until we decide how dependent we want to be on fossil fuels going forward.”“Basically what you’re saying,” I interject, “is that the largest uncertainty here is human behavior, because we still haven’t made up our mind on what, if anything, we want to do about global warming.”“Exactly. I recently republished an op-ed I wrote ten years ago on the science and politics of global climate change,” Ringler says. “Unfortunately, 10 years later, the debate hasn’t changed, but all this litigation on the basic science is futile. The science is established, now we need to discuss policies.”In his op-ed, Ringler has some stern words for our leaders: “Our government was failing us 10 years ago, and it's still failing us today by moving steadily away from a position of international leadership for crafting a comprehensive policy framework.”“Why do you believe we still can’t come up with an agreement on this?” I ask.Ringler sighs. “Humans have a long history of learning by experience, by trial and error. Take vaccines, for example. When we stop vaccinating, pockets of outbreaks resurface to remind us why we invented vaccines in the first place. Climate change happens over such a long time scale and carbon stays in the atmosphere for such a long time that we don’t have the luxury of learning by trial and error here. We have to get this right the first time, and we are not good at that. Day-to-day the biggest challenge we are facing when it comes to climate change is that we cannot pin down any single event to global warming. Weather is by its own nature random, but what global warming is doing is making certain random outcomes more likely than others. It’s shifting the roll of a dice, so to speak.”And taken all together, these “random” events scattered across the globe are indeed making an impact: the ice caps have been steadily shrinking for the past 38 years of satellite records; the increasing amounts of CO2 retained by sea water are causing ocean acidification, harming marine organisms; weather patterns are becoming more severe, with stronger floods and longer droughts.“What do you see as the biggest challenge posed by the current administration?”“The current administration is ideologically opposed to regulations. But we need some rules, whatever they look like, to limit the amount of carbon in the atmosphere. Look, renewable energy is happening. Take Texas, for example, which is pioneering wind energy. Las Vegas is now mostly powered by clean energy. The very same oil companies we often think of as opposing regulations on carbon missions are actually advocating for us to take action. But the problem is global and as such it requires global agreements and global solutions. It does matter what country emits the carbon, the carbon harms everyone. All nations need to come together and share the opportunities and costs of transitioning away from fossil fuels. What the current administration needs to understand is that what they see as ‘regulations’ are in fact ‘protections’ that we need to put forward to safeguard our future and our children’s future.”“What pains me the most,” Ringler continues, “is the disconnect between science and policy. We have this disconnect between knowing something and acting accordingly. Knowledge has lost its primary role in our society, and now science is under attack. This is not healthy. A healthy society is one in which the knowledge we gather through science informs the policy making.”As Ringler wrote in his op-ed, “We owe it to ourselves and to future generations to ask the following question: What if our present understanding of global climate change is correct? What does this mean for our society? What will happen to water in the already arid West? What will happen to agriculture, both here and around the world? Can developing nations accommodate these changes? And if not, how will we deal with the climate-driven conflict that will surely follow?”Dr. Todd Ringler has 25 years of experience modeling the climate of the atmosphere and ocean. He studied at Cornell and Princeton University, then joined the research faculty at Colorado State University and is presently a scientist working at Los Alamos National Laboratory. He is member of the International CLIVAR Ocean Model Development Panel and a long-time advocate for sensible solutions to address climate change impacts. The views and opinions expressed here are Todd Ringler’s own thoughts on this subject. He will be speaking at the March for Science in Santa Fe, New Mexico on April 22nd. REFERENCES[1] Callendar, G. (1938). The artificial production of carbon dioxide and its influence on temperature Quarterly Journal of the Royal Meteorological Society, 64 (275), 223-240 DOI: 10.1002/qj.49706427503... Read more »

  • February 24, 2017
  • 11:06 AM
  • 364 views

What if black holes were not... holes? A Los Alamos physicist explains his alternative theory behind these mysterious objects.

by EE Giorgi in CHIMERAS

© Elena E. GiorgiThe concept of a “black hole” — a celestial body so dense and massive that not even light can escape its gravitational field — dates back to the 18th century, with the theoretical work of Pierre-Simon Laplace and John Michell. But it wasn’t until the early 20th century that these mysterious dark objects were first described mathematically by German physicist Karl Schwarzschild. Schwarzschild’s work predicted the existence of a finite distance around the black hole (called the “event horizon”) from which light cannot escape. Emil Mottola, a physicist in the Theoretical Division at Los Alamos National Laboratory, laughs as he explains this bit of history behind black holes. “Would black holes have captured the popular imagination if they were still known as Schwarzschild’s solution?” he quips. Mottola has a point. The name “black hole” was coined by the American physicist John Wheeler in the 1960s, when these objects became the subject of serious study and first entered the popular vocabulary.“And then of course, Stephen Hawking made black holes very popular with his own research and theory of black hole radiation,” Mottola adds. “To this day,” he explains, “black holes are far from being understood, and science fiction may have taken over from science fact. We can’t answer many of the most important questions without knowing what the internal states of a black hole are, but no one has ever been inside a black hole, so no one actually knows what is inside.”One particularly vexing feature of black holes is the so-called “information paradox.” In 1974, Stephen Hawking theorized that black holes emit small amounts of radiation (called Hawking radiation). However, if this is true, black holes should eventually evaporate due to the loss of mass, leaving no way—not even in principle—to recover the information that was originally enclosed in it. This question alone has generated hundreds of research papers with still no completely satisfactory resolution. In 2001, Mottola and his colleague Pawel O. Mazur proposed an alternative to Hawking’s black hole theory that eliminates the paradox. “Think of a black hole as having a physical surface,” Mottola says. He imagines this surface to be much like a soap bubble that bends and fluctuates in space. “Our idea is that quantum effects build up right at the event horizon (the bubble’s surface), leading to a phase transition. This in turn creates a gravitational repulsive force inside the “bubble” that prevents the surface from collapsing. This repulsive force is the same ‘dark energy’ force believed to cause the expansion of the universe. We call these objects Gravitational Condensate Stars or ‘Gravastars’— celestial objects that would be compact, cold and dark, and look to astrophysicists just like ‘black holes,’ although they are not ‘holes’ at all. Our hypothesis does not contradict the conservation of information because there is no infinite crushing of space and time inside a Gravastar, and information is never destroyed.”According to Mottola, the mathematical equations Hawking used to describe the temperature of a black hole are in reality describing the surface tension of a Gravastar. “If we assume that black holes have a temperature, then they need to have an enormous entropy too, but we can’t easily explain that enormous black hole entropy. In our theory, black holes don’t have a temperature, they have surface tension, like soap bubbles. In 2015 we showed that this possibility of a surface and surface tension was already inherent in Schwarzschild’s original formulation of black hole interiors in 1916, and so is consistent with both Einstein’s General Relativity and Quantum Mechanics.”As I look over my notes, I pose Dr. Mottola one final question: “Is there any way to find out who’s right, you or Stephen Hawking?”He smiles because he knows that whatever Hawking says these days carries a lot of weight, including when he proposes that black holes could be mysterious portals to other universes. “I believe we may well find out the answer in the next five to ten years,” Mottola says. “If ‘black holes’ actually are Gravastars with a surface, their surface oscillations would cause them to emit gravitational waves at certain frequencies, which is a substantially different signal than that expected from the black holes that Hawking and colleagues theorize. LIGO directly detected gravitational waves for the first time in 2015, so we have just entered a new era of gravitational wave astronomy. In a few years, we may have enough data from the gravitational waves detected by LIGO and its sister observatories to be able to resolve the conundrum.”Needless to say, the Los Alamos scientist is very excited at that prospect. References[1] Mazur, P., & Mottola, E. (2004). Gravitational vacuum condensate stars Proceedings of the National Academy of Sciences, 101 (26), 9545-9550 DOI: 10.1073/pnas.0402717101[2] Emil Mottola (2010). New Horizons in Gravity: The Trace Anomaly, Dark Energy and CondensateStars Acta Physica Polonica B (2010) Vol.41, iss.9, p.2031-2162 arXiv: 1008.5006v1[3] Mazur, P., & Mottola, E. (2015). Surface tension and negative pressure interior of a non-singular ‘black hole’ Classical and Quantum Gravity, 32 (21) DOI: 10.1088/0264-9381/32/21/215024... Read more »

Mazur, P., & Mottola, E. (2004) Gravitational vacuum condensate stars. Proceedings of the National Academy of Sciences, 101(26), 9545-9550. DOI: 10.1073/pnas.0402717101  

Emil Mottola. (2010) New Horizons in Gravity: The Trace Anomaly, Dark Energy and Condensate Stars. Acta Physica Polonica B (2010) Vol.41, iss.9, p.2031-2162. arXiv: 1008.5006v1

  • May 13, 2016
  • 09:21 AM
  • 912 views

Using Supercomputers to Probe the Early Universe

by EE Giorgi in CHIMERAS

Artist's depiction of the WMAP satellite gathering data to understand the Big Bang. Source: NASA.For decades physicists have been trying to decipher the first moments after the Big Bang. Using very large telescopes, for example, scientists scan the skies and look at how fast galaxies move. Satellites study the relic radiation left from the Big Bang, called the cosmic microwave background radiation. And finally, particle colliders, like the Large Hadron Collider at CERN, allow researchers to smash protons together and analyze the debris left behind by such collisions. Physicists at Los Alamos National Laboratory, however, are taking a different approach: they are using computers. In collaboration with colleagues at University of California San Diego, the Los Alamos researchers developed a computer code, called BURST, that can simulate a slice in the life of our young cosmos. While BURST is not the first computer code to simulate conditions during the first few minutes of cosmological evolution, it can achieve better precision by a few orders of magnitude compared to its predecessors. Furthermore, it will be the only simulation code able to match the precision of the data from the Extremely Large Telescopes currently under construction in Chile. These new telescopes will have primary mirrors that range in aperture from 20 to 40 meters, roughly three times wider than the current very large telescopes, and an overall light-collecting area up to 10 times larger. A few seconds after the Big Bang, the universe was composed of a thick, 10-billion degree "cosmic soup" of subatomic particles. As the hot universe expanded, these particles' mutual interactions caused the universe to behave as a cooling thermonuclear reactor. This reactor produced light nuclei, such as deuterium, helium, and lithium — all found in the universe today. "Our code, developed with Evan Grohs, who at the time was a graduate student at UCSD, looks at what happened when the universe was about 1/100 of a second old to a few minutes old," says Los Alamos physicist Mark Paris of the Theoretical Division. "By determining the amount of helium, lithium and deuterium at the end of those first few minutes of life, BURST will be able to shed light to some of the existing puzzles of cosmology."One such puzzle is dark matter: physicists know that such matter exists because of the way galaxies rotate, but they haven't been able to detect it because it does not radiate in any known spectrum. Physicists have theorized that dark matter is made of so-called "sterile neutrinos", which do not interact with any other particle and are responsible for these unobservable interactions. "Once we start getting data from the Extremely Large Telescopes," Paris explains, "we will model sterile neutrinos into the BURST code. If we get a good description, we will be able to prove their existence." Measurements of the cosmic microwave background radiation have led physicists to theorize "dark radiation," a speculative form of energy that may have acted in the early universe. BURST could possibly reveal whether or not dark radiation is real and caused by sterile neutrinos. "The universe is our laboratory," Paris enthusiastically concludes. "BURST will help us answer questions that are currently very difficult to address with particle colliders like the one at CERN."Ongoing support for the project is provided by the National Science Foundation at UCSD and the Laboratory Directed Research and Development program through the Center for Space and Earth Sciences at Los Alamos. BURST will be running on the supercomputing platforms at Los Alamos National Laboratory.ReferenceGrohs, E., Fuller, G., Kishimoto, C., Paris, M., & Vlasenko, A. (2016). Neutrino energy transport in weak decoupling and big bang nucleosynthesis Physical Review D, 93 (8) DOI: 10.1103/PhysRevD.93.083522... Read more »

  • April 29, 2016
  • 09:38 AM
  • 698 views

Hunting For The Signatures of Cancer

by EE Giorgi in CHIMERAS

Signatures of Mutational Processes Extracted from the Mutational Catalogs of 21 Breast Cancer Genomes. Credit:http://dx.doi.org/10.1016/j.celrep.2012.12.008Cancer is the second leading cause of death worldwide, with approximately 14 million new cases and 8.2 million cancer related deaths each year (Source: WHO). A family history of cancer typically increases a person's risk of developing the disease, yet most cancer cases have no family history at all. This suggests that a combination of both genetics and environmental exposures contribute to the etiology of cancer. In this context, "genetics" means the genetic make-up we are born with and inherited from our parents. For example, women born with specific mutations in the BRCA1 and BRCA2 genes are known to have a much higher risk of developing breast cancer later in life.However, besides the genetic make-up we carry from birth, there are many geographical and environmental factors that contribute to the risk of cancer. For example, the incidence of breast cancer is over 4 times higher in North and West Europe compared to Asia and Africa (Source: WHO). Stomach cancer, on the other hand, is much more prevalent in Asia than the US. If you think that this may be linked to the genetic differences across ethnicities, think again. The National Cancer Institute published a summary of several studies that compared the incidence of first and second generation immigrants in the US with the local population. They found that:"cancer incidence patterns among first-generation immigrants were nearly identical to those of their native country, but through subsequent generations, these patterns evolved to resemble those found in the United States. This was true especially for cancers related to hormones, such as breast, prostate, and ovarian cancer and neoplasms of the uterine corpus and cancers attributable to westernized diets, such as colorectal malignancies."According to the World Health Organization (WHO), "around one third of cancer deaths are due to the 5 leading behavioral and dietary risks: high body mass index, low fruit and vegetable intake, lack of physical activity, tobacco use, alcohol use."Cancer is the result of a series of cellular mechanisms gone awry: every time a cell divides, somatic mutations accumulate in the cell's genome. These are not mutations we are born with, inherited from our parents. Rather, these are changes that accumulate in certain cells as we grow old and are not  the same across all cells in the body. Many environmental exposures contribute to this process and affect the rate at which these mutations accumulate. However, cells have various mechanisms that are normally able to repair harmful mutations or, when the damage is beyond repair, to trigger cell death. The immune system is also "trained" to recognize cancer cells and destroy them.When all these defense mechanisms fail, cancer cells start dividing uncontrollably.As a result, all cancer cells carry a number of somatic mutations that set them apart from healthy cells, and some tend to be the same across different cancer patients: for example, specific mutational patterns found in lung cancer have been attributed to tobacco exposure and were indeed reproduced in animal models. Another set of mutations has been attributed to UV exposure and has been found in skin cancers [1, 2].This prompts the ambitious question: can we find common mutations across individuals with the same cancer? And how many of these mutational patterns that are common across individuals can we attribute to particular exposures and/or biological processes? Distinguished postdoctoral researcher Ludmil Alexandrov, from the Los Alamos National Laboratory, has been working on this problem since his he was a PhD student at the Wellcome Trust Sanger Institute."It's like lifting fingerprints," Alexandrov explains. "The mutations are the fingerprints, but now we have to do the investigative work and find the 'perpetrator', i.e., the carcinogens that caused them." During his graduate studies, under the supervision of Mike Stratton of the Wellcome Trust Sanger Institute, Alexandrov developed a mathematical model that, given the cancer genomes from a number of patients, is able to pick the "common signals" across the patients -- i.e. mutation patterns that are common across the patients -- and classify them into "signatures." "When formulated mathematically," Alexandrov explains, "the question can be expressed as the classic 'cocktail party' problem, where multiple people in a room are speaking simultaneously while several microphones placed at different locations are recording the conversations. Each microphone captures a combination of all sounds and the problem is to identify the individual conversations from all the recordings." Taking from this analogy, each cancer genome is a "recording", and the task of the mathematical model is to reconstruct each conversation, in other words, the mutational patterns. These are sets of somatic mutations that are the observed across the cancer genomes and that characterize certain types of cancers.In 2013, Alexandrov and colleagues analyzed 4,938,362 mutations from 7,042 patients, spanning 30 different cancers, and extracted more than 20 distinct mutational signatures [2]. "Some patterns were expected, like the known ones caused by tobacco and UV light," Alexandrov says. "Others were completely new."Of the new signatures found, many are involved in defective DNA repair mechanisms, suggesting that drugs targeting these specific mechanisms may benefit cancers exhibiting these signatures [3]. But the most exciting part of this research will be finding the 'perpetrator' or, as Alexandrov explains, the mutations triggered by carcinogens like tobacco, UV radiation, obesity, and so on. The challenge will be to experimentally associate these mutational patterns to the exposures that caused them. In order to do this, the scientists will have to expose cultured cells and model organisms to known carcinogens and then analyze the genomes of the experimentally induced cancers.In the meantime, the signatures found so far are only the beginning: Alexandrov and colleagues have teamed up with the Los Alamos High Performance Computing Organization in order to analyze the genomes of almost 30,000 cancer patients. "The amount of data we will have to handle for this task is enormous, on the order of petabytes," Alexandrov says. "Few places in the world have the capability to handle this many data. Under normal circumstances, it takes months to answer a question on 10 petabytes of data. The supercomputing facility at Los Alamos can provide an answer within a day." Because of his research, in 2014 Alexandrov was listed by Forbes magazine as one of the “30 brightest stars under the age of 30” in the field of Science and Healthcare. In 2015 he was awardedthe AAAS Science & SciLifeLab Prize for Young Scientists in the category Genomics and Proteomics [2] and the Weintraub Award for Graduate Research. He is now the recipient of the prestigious Oppenheimer fellowship at Los Alamos National Laboratory.Disclaimer: Elena E. Giorgi is a computational biologist in the Theoretical Division of the Los Alamos National Laboratory. She does not represent her employer’s views. LA-UR-16-xxxx.ReferencesSiegel, R., Miller, K., & Jemal, A. (2015). Cancer statistics, 2015 ... Read more »

Siegel, R., Miller, K., & Jemal, A. (2015) Cancer statistics, 2015. CA: A Cancer Journal for Clinicians, 65(1), 5-29. DOI: 10.3322/caac.21254  

Alexandrov LB. (2015) Understanding the origins of human cancer. Science (New York, N.Y.), 350(6265), 1175. PMID: 26785464  

Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Børresen-Dale AL.... (2013) Signatures of mutational processes in human cancer. Nature, 500(7463), 415-21. PMID: 23945592  

Alexandrov LB, Nik-Zainal S, Siu HC, Leung SY, & Stratton MR. (2015) A mutational signature in gastric cancer suggests therapeutic strategies. Nature communications, 8683. PMID: 26511885  

  • April 22, 2016
  • 10:10 AM
  • 537 views

Digging For Clues About Climate Change

by EE Giorgi in CHIMERAS

Guest post by Rebecca McDonald, science writerPhoto Credit: LeRoy N. Sanchez While many scientists who study climate change look up to the sky for clues about the Earth’s future, one researcher has spent her career looking down—at the abundance of life in the soil below. Innumerable microorganisms such as bacteria and fungi live in harmony with plant roots, decomposing fallen leaves and dead animals. In addition to acting as the ultimate recyclers, they also stabilize the soil and help to retain water.  Cheryl Kuske, a microbiologist at Los Alamos National Laboratory, has focused the last two and a half decades on studying this microbial environment. “By decomposing organic matter,” she explains, “microorganisms help cycle carbon and nitrogen through the ecosystem.” Some of the carbon and nitrogen released from the organic matter goes into the soil and is assimilated into roots to help new plants grow—the carbon is incorporated into sugars, and the nitrogen atoms are used to build proteins. But some of these molecules are also released as CO2 and N2 gases into the atmosphere. The soil ecosystem functions in a delicate balance. Although some organisms release gases into the air, others—including certain bacteria and leafy plants—remove harmful CO2 from the atmosphere for food production. Kuske and her colleagues at Los Alamos National Laboratory have been investigating the roles of these microbes in carbon and nitrogen cycling to help make better predictions about terrestrial ecosystem responses to climate change. Using a technique called metagenomics to sequence the DNA of all the microbes at once, the team can study the organisms’ genes and the enzymes they produce. These microrganisms’ lifecycles are so intertwined that their single genomes cannot be isolated for sequencing. However, analyzed jointly, they yield important clues about their collective functions in the environment. Scientists can identify things such as which bacteria or fungi are responsible for fixing nitrogen or carbon, the ratio of bacteria to fungi in the soil, and which microbes are closely associated with root health or plant growth. The researchers can even figure out which enzymes are currently being used through a technique called meta-transcriptomics; this approach sequences only the transcripts of genomic data that are actively being made and used for protein synthesis.Photo courtesy of Cheryl KuskeBy sampling microbes from various soil environments over long periods of time, Kuske’s team and collaborators are able to understand what happens under the surface when things change aboveground. For instance, in a recent long-term study in Utah, the scientists discovered that slight changes in the summer precipitation pattern, combined with a 2°C rise in soil temperature, resulted in significant changes in the population of microbes below: the types of organisms completely changed, thus altering their overall role in the environment. For example, cyanobacteria—bacteria that create energy through photosynthesis—were no longer present. As a consequence, the new population of microbes no longer had the ability to pull carbon out of the air and had a decreased capacity for fixing nitrogen for protein synthesis. Increased nitrogen from industrial runoff or fertilizer from agriculture can also have significant effects on the composition of organisms in the soil, as nitrogen is an essential molecule for the growth of both plants and bacteria. A comparison of 15 recent field experiments where nitrogen deposition was measured showed that in an arid environment, an increase in nitrogen had a positive effect on soil health at low concentrations, but too much was toxic to the soil community [1]. In a field experiment in Nevada, higher nitrogen concentrations changed the species composition of bacteria—but not fungi—leading to a fungi-dominated community [2,3]. Although the ramifications of these changes to the microbial world are not yet completely understood, Kuske’s team is continuing their studies, both in the laboratory, under controlled conditions, as well as at various field sites in the American Southwest. What they do know is that the feedback loop is strong. Changes in the aboveground environment—such as rising temperatures, altered precipitation, and increased nitrogen runoff—lead to changes below ground that can have far-reaching consequences.“The studies being conducted at Los Alamos provide an understanding of the interactive biological processes that are inherent in all types of terrestrial ecosystems and that tightly control carbon and nitrogen fluxes to the atmosphere,” says Kuske. Climate warming and altered weather patterns will disrupt this balance. When the diversity of soil microbes change, the feedback loops that ensue could have lasting effects on the amounts of carbon and nitrogen in the soil and the atmosphere.Rebecca McDonald is a science writer at Los Alamos National Laboratory specializing in the communication of bioscience research. She has also worked as a freelance writer, and volunteers her time as a communications consultant for a science education non-profit. Disclaimer: Elena E. Giorgi is a computational biologist in the Theoretical Division of the Los Alamos National Laboratory. She does not represent her employer’s views. LA-UR-16-22406.[1] Steven B, Kuske CR, Gallegos-Graves LV, Reed SC, & Belnap J (2015). Climate change and physical disturbance manipulations result in distinct biological soil crust communities. Applied and environmental microbiology, 81 (21), 7448-59 PMID: 26276111[2] Sinsabaugh RL, Belnap J, Rudgers J, Kuske CR, Martinez N, & Sandquist D (2015). Soil microbial responses to nitrogen addition in arid ecosystems. Frontiers in microbiology, 6 PMID: 26322030[3] Mueller RC, Belnap J, & Kuske CR (2015). Soil bacterial and fungal community responses to nitrogen addition across soil depth and microhabitat in an arid shrubland. Frontiers in microbiology, 6 PMID: 26388845... Read more »

  • April 8, 2016
  • 09:56 AM
  • 762 views

The Antibacterial Resistance Threat: Are We Heading Toward a Post-Antibiotic Era?

by EE Giorgi in CHIMERAS

Source: PEW Charitable TrustsThe above graphic, from the Antibiotic Resistance Project by the PEW charitable trusts, summarizes how alarming the emergence of drug resistant bacterial strains has gotten over the past few decades. According to data from the Center for Disease Control (CDC), every year 2 million Americans acquire drug-resistant infections [1], in other words infections that do not respond to treatment with ordinary antibiotics. Not only do drug-resistant infections require much stronger drugs, but, when not deadly, they often leave patients with long-lasting complications.One of the scariest threats is carbapenem-resistant Enterobacteriaceae (CRE), bacteria that are resistant to several kinds of antibiotics. In 2001, only North Carolina, out of all 50 states had reported one CRE infection. Last year, in 2015, 48 states reported CRE infections to the CDC. And while drug-resistant strains emerge rapidly, the discovery of antimicrobial substances has stalled: in the last decade, only 9 new antibiotics were approved, compared to 29 discovered in the 1980s and 23 in the 1990s. We are fighting a new war, and we are running out of weapons.How does drug resistance emerge?Bacteria constitute an irreplaceable building block of our ecosystem: they are found in soil, water, air, and in every living organism. In humans, it's estimated that they outnumber our cells by 3:1, and numerous studies have shown that not only do they help us digest and produce enzymes that our body wouldn't otherwise be able to break down, but they can also influence gene expression and certain phenotypes (see some of my past posts for more information).They live in symbiosis with us, yet some bacteria can be highly pathogenic. The overall mortality rate from infectious diseases in the US fell by 75% over the first 15 years following the discovery of antibiotics [3], and researchers estimate that antibiotics have increased our lifespan by 2 to 10 years [4] by enabling us to fight infections that would otherwise be deadly.However, evolution has taught bacteria to fight back. Bacteria develop drug resistance through the acquisition of genetic mutations that either modify the bacteria's binding sites (and therefore the drug can no longer enter the membrane), or reduce the accumulation of the drug inside the bacterium. The latter happens through proteins called "efflux pumps", so called because their function is to pump drugs and other potentially harmful chemicals out of the cell. Once these advantageous mutations appear in the population, they spread very quickly, not only because they are selected for, but also thanks to bacteria's ability to transfer genes: the drug-resistant genes form a circular DNA unit called plasmid, and the unit is passed on to nearby bacteria so that they, too, can become drug resistant. These mechanisms are not new to bacteria, however, what's new is the increasing overuse of antibiotics and antimicrobial chemicals in our modern lifestyle. The antimicrobial agent called triclosan, for example, can be found in all antibacterial soaps, toothpaste, mouthwash, detergents, and even toys and kitchen utensils. Because of its wide use in household and hygiene products, triclosan has been found in water, both natural streams and treated wastewater, as well as human samples of blood, urine, and breast milk. As though that alone wasn't enough to alert consumers, a study published on the Proceedings of the National Academy of Sciences [5] claims that triclosan, which can be absorbed through the skin, can impair the functioning of both skeletal and cardiac muscle. The researchers confirmed these findings both in vitro and in animal models.Resistance is also spread through the use of antibiotics in industrial farming. In the US alone, the daily consumption of antibiotics amounts to 51 tons, of which around 80% is used in livestock, a little under 20% is for human use, and the rest is split between crops, pets, and aquaculture [3]. A meta-analysis published last year in PNAS [6] found that between 2000 and 2010 the global use of antibiotic drugs increased by 36%, with 76% of the increase coming from developing countries. The researchers projected that worldwide antibiotic consumption would rise by 67% by 2030 due to population growth and the increase in consumer demand.These frightening statistics prompted CDC director Tom Frieden to issue a warning: “If we are not careful, we will soon be in a post-antibiotic era.” An era when common infections are deadly again."We need to be very careful in using antimicrobial agents for everything from hand washing to toothpaste," Harshini Mukundan, microbiologist at Los Alamos National Laboratory, explains. "Increased selection of drug resistant organisms means that future generations will be helpless in fighting even the most common bacterial infections." Mukundan and her colleagues have been working on biosurveillance and tracking the emergence of drug resistant strains in high disease burden populations where emerging antibiotic resistance is a huge concern. In collaboration with the Los Alamos National Laboratory metagenomics group, and Los Alamos scientists Ben McMahon and Norman Doggett, the team is working on developing new assays for faster diagnosis of drug resistant infections. Another approach to fight drug resistance is trying to understand how bacterial efflux pumps work at excreting the drug out of the bacterium. Gnana Gnanakaran, a computational biologist at Los Alamos National Laboratory, and his team have developed mathematical models to describe the structure of these pumps [7] and find a way to deactivate them. While this research is highly promising and exciting, we all need to step up and do our part before it's too late: the CDC published a series of recommendations for patients to follow at the doctor's office, and there are smart choices we can make at home, too. In a recent report, the Food and Drug Administration (FDA) claims that there is no evidence that antibacterial soaps do a better job at preventing infections than ordinary soap, and that in fact:"New data suggest that the risks associated with long-term, daily use of antibacterial soaps may outweigh the benefits."In its 2011 policy paper, the Infectious Diseases Society of America (IDSA) recommended a substantial reduction in the use of antibiotics for growth promotion and feed efficiency in animal agriculture, and encouraged the FDA to complete and publish risk assessments of antibiotics currently approved for non-therapeutic use. Just like any other precious resource, antibiotics (and antimicrobial drugs in general) need to be used with parsimony. Resources:[1] Antibiotic Resistance Threats in the United States, 2013 (CDC)[2] PEW Antibiotic Resistance Poject[3] Armstrong GL, Conn LA, & Pinner RW (1999). Trends in infectious disease mortality in the United States during the 20th century. JAMA, 281 (1), 61-6 PMID: 9892452[4] ... Read more »

Hollis, A., & Ahmed, Z. (2013) Preserving Antibiotics, Rationally. New England Journal of Medicine, 369(26), 2474-2476. DOI: 10.1056/NEJMp1311479  

Cherednichenko, G., Zhang, R., Bannister, R., Timofeyev, V., Li, N., Fritsch, E., Feng, W., Barrientos, G., Schebb, N., Hammock, B.... (2012) Triclosan impairs excitation-contraction coupling and Ca2 dynamics in striated muscle. Proceedings of the National Academy of Sciences, 109(35), 14158-14163. DOI: 10.1073/pnas.1211314109  

Van Boeckel, T., Brower, C., Gilbert, M., Grenfell, B., Levin, S., Robinson, T., Teillant, A., & Laxminarayan, R. (2015) Global trends in antimicrobial use in food animals. Proceedings of the National Academy of Sciences, 112(18), 5649-5654. DOI: 10.1073/pnas.1503141112  

  • April 1, 2016
  • 10:12 AM
  • 754 views

Allergies: Can Too Much Hygiene Actually Harm Us?

by EE Giorgi in CHIMERAS

It's that time of the year again. You step out of the house and your eyes itch, your nose starts running and your head feels like an empty balloon. Yes, it's allergy season again. Even the resilient ones, give them enough time and eventually they will develop some form of allergic reaction. But what are allergies and why do so many people suffer from them?Allergies are a glitch in our immune system. The immune system is built to recognize and destroy pathogens -- potential threats like viruses and harmful bacteria. Unlike pathogens, allergens are substances that, despite being harmless to the body, still trigger a response from the immune system. As soon as the allergen is detected, the immune system releases a class of antibodies called IgE. These antibodies signal the cells to release histamine, a neurotransmitter that triggers all the pesky symptoms typical of an allergic reaction: wheezing, watery eyes, running nose, coughing, and all the like. Spring is a particularly dreaded time of the year for allergy sufferers because of all the pollen released in the air. Global warming has impacted the duration and spread of pollen allergies: shorter winters and warmer temperatures translate into longer pollen seasons, which in turn increase the duration and severity of symptoms for allergy sufferers. In addition, they also increase the exposure and possible sensitization of people who don't suffer from allergies ... yet [1]. Are allergies on the rise? In his 2015 review [2], Thomas Platts-Mills, of the University of Virginia School of Medicine, looks at the prevalence over the past five decades of asthma, hay fever, and peanut allergy, and reports a progressive increase in pediatric asthma, as well as a "dramatic" increase in food allergies. Allergies are more prevalent in developed countries, and particularly in urban settings, suggesting that something in the industrialized lifestyle may have triggered the increase. However, given the many drastic changes introduced in these countries over the past century, it's hard to pin-point one specific cause. Several factors have been suggested as possible explanations: changes in hygiene, for example, together with a decrease in outdoor life, smaller families and no more exposure to farm animals, have significantly reduced our exposure to bacteria; the progressive use of antibiotics and antimicrobial products have also reduced such exposure; less outdoor time also means less physical activity, more exposure to indoor allergens, and an increase in body mass. First proposed in 1989 [3], the "hygiene hypothesis" -- the theory that the rise in allergic reactions is caused by a decrease in childhood exposure to harmless bacteria -- has grown to encompass many other disorders, not just allergies. The theory originally spurred from the observation that children with a higher number of siblings had a lower risk of developing asthma, something that led researchers to think that this was due to a higher exposure to bacteria. The human microbiome is the set of all bacteria coexisting in our body. They are estimated to outnumber our cells by 3:1 and the vast majority of these organisms are not only harmless, they actually play an important role in our health. For example, by modulating the concentration of chemicals that are precursors of important neurotransmitters, they can affect our mood and mental health [4]. They can also influence our propensity to certain phenotypes such as leanness or obesity by affecting gene expression in our guts [5]. Scientists have used a mouse model to show that by transferring gut micriobiota from allergic mice to resistant mice they could actually transfer the food allergy to the latter [6], proving a correlation between the two. Tolerance to food is acquired during infancy thanks to the interaction between the immune system and the gut microbiota, and therefore, early development of the gut microbiome is believed to play a fundamental role in the predisposition to allergies and other diseases later in life. Indeed, in the industrialized countries that are experiencing an increase in allergies, scientists have observed a delayed gut colonization after birth, less biodiversity in the gut microbiome, and reduced turnover of gut bacterial strains in infants [6]. Three major factors could be responsible for this: (i) natural birth versus C-section (a C-section deprives the newborn of beneficial exposure to commensal bacteria residing in the birth canal); (ii) breast-feeding versus formula; (iii) early exposure to antibiotics. All three practices -- C-section, formula feeding, and the use of antibiotics and antimicrobial products -- have been increasingly used in developed countries, and all three affect the development of the gut microbiome of infants. While studies that have looked at possible associations between any one of them and the risk of allergies so far have not yielded conclusive results, the differences in microbiomes between healthy people and those with asthma and allergies are an indication that early exposure to bacteria may protect against these conditions [7].Is there such a thing as too much protection?These observations don't mean that we should all stop washing our hands and start living filthy. They do, however, point to a trend in overuse of antimicrobial household products (soaps, laundry detergents, kitchen cleaners, etc.). These products should be used with care and only when truly needed. In most instances, natural substitutes like vinegar to clean surfaces are a better choice, as they keep your kitchen clean without killing microorganisms that are actually beneficial to our health. As much as we strive to protect our little ones, remember that childhood exposure to pathogens makes your child's immune system grow stronger and well trained to recognize bigger dangers. (On a side note, vaccines equally stimulate the immune system without the hassle of all the symptoms.) Finally, global measures like recycling gray water can benefit both the planet and our own health, as it saves gallons of drinking water from being used in landscaping and farming, while restoring important bacteria into the soil and back into our environment. References[1] Ziska, L., Knowlton, K., Rogers, C., Dalan, D., Tierney, N., Elder, M., Filley, W., Shropshire, J., Ford, L., Hedberg, C., Fleetwood, P., Hovanky, K., Kavanaugh, T., Fulford, G., Vrtis, R., Patz, J., Portnoy, J., Coates, F., Bielory, L., & Frenz, D. (2011). Recent warming by latitude associated with increased length of ragweed pollen season in central North America Proceedings of the National Academy of Sciences, 108 (10), 4248-4251 DOI: 10.1073/pnas.1014107108[2] Platts-Mills, T. (2015). The allergy epidemics: 1870-2010 Journal of Allergy and Clinical Immunology, 136 (1), 3-13 DOI: 10.1016/j.jaci.2015.03.048[3] ... Read more »

Ziska, L., Knowlton, K., Rogers, C., Dalan, D., Tierney, N., Elder, M., Filley, W., Shropshire, J., Ford, L., Hedberg, C.... (2011) Recent warming by latitude associated with increased length of ragweed pollen season in central North America. Proceedings of the National Academy of Sciences, 108(10), 4248-4251. DOI: 10.1073/pnas.1014107108  

Platts-Mills, T. (2015) The allergy epidemics: 1870-2010. Journal of Allergy and Clinical Immunology, 136(1), 3-13. DOI: 10.1016/j.jaci.2015.03.048  

Strachan DP. (1989) Hay fever, hygiene, and household size. BMJ (Clinical research ed.), 299(6710), 1259-60. PMID: 2513902  

Molloy, J., Allen, K., Collier, F., Tang, M., Ward, A., & Vuillermin, P. (2013) The Potential Link between Gut Microbiota and IgE-Mediated Food Allergy in Early Life. International Journal of Environmental Research and Public Health, 10(12), 7235-7256. DOI: 10.3390/ijerph10127235  

  • March 23, 2016
  • 09:05 AM
  • 782 views

We Agree to Disagree: The Science of Why Your Political Posts Won’t Make Anyone Change Their Mind

by EE Giorgi in CHIMERAS

In today's heated political stage, where everyone has a soapbox thanks to outlets like Facebook, Twitter, Instagram and all the personal blogs, I've tried my best not to share my political views publicly. And I've miserably failed. I use my own Facebook page and profile to talk about science, books and photography, but then I can't resist browsing other people's posts. Most of my friends are not as shy as me about making their political views heard and that's when I fall into the trap: I comment. And then someone replies. And I comment back. And on and on it goes until one of us drops out of the conversation because clearly we're not getting anywhere. Science has taught me to be humble and rational. And yet I'm human, and every time I make a mistake in my line of work I feel something inside my brain stir and protest: "How's that possible? Surely they sent me the wrong data, or they didn't give me the correct information, or the world collapsed and my computer exploded, but there's no way I could've made that stupid mistake."Apparently, I'm not unique. We all go through this kind of mental distress whenever we encounter an inconsistency between reality and our expectations, and between other people's opinions or choices and our own. It's called "cognitive dissonance." According to Wikipedia, social psychologist Leon Festinger described four ways our brain deals with this:In an example case where a person has adopted the attitude that they will no longer eat high fat food, but eats a high-fat doughnut, the four methods of reduction are:1. Change behavior or cognition ("I will not eat any more of this doughnut")2. Justify behavior or cognition by changing the conflicting cognition ("I'm allowed to cheat every once in a while")3. Justify behavior or cognition by adding new cognitions ("I'll spend 30 extra minutes at the gym to work this off")4. Ignore or deny any information that conflicts with existing beliefs ("This doughnut is not high in fat")What determines what choice we make?In my case, I end up going back to my computer program. I typically find the bug (which I unknowingly introduced as I was coding), correct it, and rerun the analyses. Admitting my mistake costs me emotional distress, in addition to that nagging doubt at the back of my head -- will my boss still like me even though I made a stupid mistake? -- but in the long run it would cost me a lot more not to correct the error and hand the wrong analyses to our collaborators. So why can't we do the same when we are heatedly debating politics or religion? Why do some of us even resort to insults rather than admitting that our own logic is faulty? One possible reason is that there are no consequences to being disrespectful or even offensive when debating on line. After all, even when we use our real name, we are still hiding behind a shield of impersonality when typing our thoughts on an electronic device. On the other hand, if I hand out the wrong results and my collaborators publish them, there will be huge consequences for me. And frankly, trial and error is part of the scientific process: we all make mistake, we correct them, and we repeat the process over and over again until we have clean and sensible results. Only then we publish a paper. But in a political or religious debate the consequences can be far more costly if we suddenly admit that we may have been wrong all along. Changing our mind affects our self-esteem and may lead to self-blame, possibly disrupting the relationships around us. That's why our brain has a tendency to choose the easier path, which often coincides with reinvigorating present beliefs rather than shifting to new ones. As Nyhan and Reifler notice in a 2010 paper [1], there's a difference between being uninformed and being misinformed, as the latter is much harder to correct. In the paper, the authors claim that "humans are goal-directed information processors who tend to evaluate information with a directional bias toward reinforcing their pre-existing views," and conclude: "Indeed, in several cases, we find that corrections actually strengthened misperceptions among the most strongly committed subjects." This behavior of reinforcing one's beliefs the more the contrasting evidence is presented, is called the "confirmation bias". Patterson et al. [2] define this bias as the tendency to favor certain explanations that conform to our own beliefs and/or emotional response, and classify it as "cognitive" or "emotional" depending on whether it reflects the former or the latter. It's a very familiar bias, as we've all seen it everywhere around us, whether it was to defend our favorite presidential candidate or to debate climate change. A little harder is to pin it down when we are engaging in this behavior ourselves -- but rest assured, we all do it at some point, although each one of us to different extents. "Because of this mechanism," explains Robin S. Cohen, a Los Angeles based psychoanalyst, "not only are we biased to favor perceptions that are in line with our beliefs, but we are also very likely to organize our world in order to only experience things that conform to our own ideas. This makes it less likely to be confronted with alternative opinions. Our own beliefs are so thoroughly reinforced through this process that new perceptions gain very little traction." Interestingly, as Leonid Perlovsky describes in a 2013 review [3], experiments have shown that music helps abate the stressful consequences of cognitive dissonance. So, maybe I could try playing a little music in the background next time I'm trying to convince a Trump supporter to find a better presidential candidate. What do you think? Mozart or Metallica?[1] Nyhan, B., & Reifler, J. (2010). When Corrections Fail: The Persistence of Political Misperceptions Political Behavior, 32 (2), 303-330 DOI: 10.1007/s11109-010-9112-2[2] Patterson, R., Operskalski, J., & Barbey, A. (2015). Motivated explanation Frontiers in Human Neuroscience, 9 DOI: 10.3389/fnhum.2015.00559[3] Perlovsky, L. (2013). A challenge to human evolution—cognitive dissonance Frontiers in Psychology, 4 DOI: 10.3389/fpsyg.2013.00179... Read more »

Patterson, R., Operskalski, J., & Barbey, A. (2015) Motivated explanation. Frontiers in Human Neuroscience. DOI: 10.3389/fnhum.2015.00559  

  • March 16, 2016
  • 09:59 AM
  • 854 views

An open letter to all science lovers who want to defend science ... please don't.

by EE Giorgi in CHIMERAS

Last week I had an animated discussion on Facebook over an older post in which I describe some literature I dug out on possible (underline “possible”!) correlations with autism. True, my post is highly incomplete, but it was meant as a discussion starter to point at things that scientists have been looking at in an attempt to unravel what feels like a rise in autism. Is autism the new childhood plague of our modern society or has it always been around and we just became more aware of it? And if the rise is real, what caused it? To me the most intriguing bit is that if you type 'autism gut microbiota' into the PubMed search field (for those not familiar with PubMed, it's a repository for medical literature), you find an incredible number of studies and reviews: apparently there is an association between autism and disruptions of the gut microbiota, but whether the two are truly correlated or the correlation is spurious is still unclear. Before I go on analyzing the literature I found on this topic, let me open a parenthesis on the Facebook discussion because it's something I deeply care about. You might think that the animated discussion I got into was with anti-vaxxers who believe that vaccines cause autism. Instead, my post was criticized by pro-vaccine people who, with the same unflinching certainty typical of the anti-vaxxers, believe that the rise in autism is fiction invented by anti-vaxxers, that autism has always been around, and that any difference between gut microbiota of autistic children and non-autistic children has been disproved. "By whom?" I asked. By this one report:"Children with autism have no unique pattern of abnormal results on endoscopy or other tests for gastrointestinal (GI) disorders, compared to non-autistic children with GI symptoms, reports a study in the Journal of Pediatric Gastroenterology and Nutrition."Notice that this opening line is a bit misleading because here is the actual paper [1] whose conclusion, quoting from the abstract, are a bit more cautiously stated:"This study supports the observation that children with autism who have symptoms of gastrointestinal disorders have objective findings similar to children without autism. Neither non-invasive testing nor endoscopic findings identify gastrointestinal pathology specific to autism, but may be of benefit in identifying children with autism who have atypical symptoms."Notice also the difference from the abstract and the title of the report. You can tell which one was written by a scientist, right? Because when you do a search on PubMed using keywords autism and gut microbiota you find a long list of references and decades of research. So to me what this says is that the question is still open and we need to understand the issues better. It takes way more than one paper to disprove hypothesis-raising questions spurred from decades of research. Now here's the mother of all problems: the Internet has made everyone (EVERYONE!) an expert. Today you no longer need a medical degree to speak authoritatively about vaccines, disease, and health. This has generated movements like the anti-vaxxers, but, even more unfortunate is the rise of groups that reply to the anti-vaxxers without a scientific mind-set: these people are doing even more damage to the community than the anti-vaxxers themselves. I found myself in a conversation that had the same one-ended arguments used by anti-vaxxers except these were people who are actually in favor of vaccines: for every paper on autism and gut microbiota I brought up they would dismiss it with another one that said the opposite, demonstrating no understanding of the difference between raising hypotheses and making a claim.As a scientist, I can tell you that this behavior is the very opposite of scientific thinking. All the people who are in favor of science but DO NOT adopt a scientific attitude when counter-arguing non-scientific claims are hurting the scientific community. It's happening for vaccines, for evolution, and for global warming. For example, people who support intelligent design are mistaken about evolution because they don't understand the meaning of the word "theory" and they don't understand how scientific thinking works. We need to educate people on scientific thinking, not give bad examples of undebatable and absolute notions.So, PLEASE, all science fans, I beg of you: support us by giving us a cheer, by always citing original papers, and by keeping an open mind because that's what a real scientist would do. We are raising hypotheses, not discussing the meaning of Bible verses. And if you know you can't do any of the above, then the best support you can give us is to shut up. Let real science speak for itself. I'm fully aware that I'm preaching to the choir so I'll stop now and resume my discussion on autism and gut microbiota. As an additional side note, let me emphasize how difficult it is to discuss a topic like autism because of its extreme complexity: it's a relatively new diagnosis (first described in the early twentieth century), and even though no exact etiology has been found of date, the genetic studies conducted so far have implicated as many as 400 genes such that a malfunction in any of these genes could possibly result in autism [2]. Let's start from the facts: our body hosts more microbial cells than human cells, with the vast majority residing in the gut. These organisms, which we collectively call the "human microbiota" (and “gut microbiota” when referring to the ones residing in the gut) interact with our cells in symbiosis and in fact, some experiments have shown that they can affect our health and even gene expression (see this old post for a striking example of how genes expressed by gut bacteria can affect whether we are fat or lean). All this has been known for a long time, but it's only recently that, thanks to the advent of new DNA sequencing techniques that scientists have been able to look deeper into the composition and classification of the human microbiota. Metagenomic studies have found over 3 million distinct microbial genes (collectively called the "microbiome") in human stools, which is astonishing if you think that the human genome, in comparison, contains about 20-30 thousand genes. The gut microbiome is rich in enzymes without which our body would be unable to digest important nutrients. In fact, it's estimated that roughly 10% of our dietary energy intake comes from byproducts of fermentation from the gut bacteria. That's all fine and dandy, but what does this have to do with behavior and brain health? A lot, actually, to the point that scientists coined the phrase "gut-brain axis" to denote the deep interaction between the nervous system and the gut microbiota. A 2011 PNAS study [3] used a mouse model to demonstrate how the gut microbiota affects mammalian brain development and behavior. This can happen in a number of ways, but one interesting hypothesis is that a healthy gut microbiome can help modulate the concentration of chemicals that are important for brain development as well as important nutrients that are precursors of neurotransmitters like serotonin. Several studies done on different populations of children affected by autism spectrum disorders (ASD) have reported some form of gastro-intestinal (GI) dysfunction (such as food intolerances, abdominal pain, diarrhea and flatulence), with proportions ranging from 20-60% of the study population [4]. It's true that ASD children are often very picky eaters with drastic dietary habits, which would of course cause the GI issues. However, given the previously mentioned evidence that the gut microbiota shapes brain development since early infancy, the question of which is the cause and which is the effect at this point is legitimate. In other words, what came first, the chicken or the egg? Studies have pointed at alterations of the gut microbiota in ASD children who experience gastro-intestinal issues, and some have reported that ASD children receiving antibiotics seemed to experience behavioral improvements. Drastic changes in diet (for example adopting a gluten-free and/or casein free diet) have shown behavioral improvements in some ASD studies, but not in all (meaning that some studies still didn't observe any improvement). Some papers report a higher risk of ASD in children who have not been breast-fed or who have been weaned after the first month of life. All of these instances would cause the gut microbiota to change, including breast feeding, which plays a fundamental role in establishing a healthy bacteri... Read more »

Kushak RI, Buie TM, Murray KF, Newburg DS, Chen C, Nestoridi E, & Winter HS. (2016) Evaluation of Intestinal Function in Children with Autism and Gastrointestinal Symptoms. Journal of pediatric gastroenterology and nutrition. PMID: 26913756  

Heijtz, R., Wang, S., Anuar, F., Qian, Y., Bjorkholm, B., Samuelsson, A., Hibberd, M., Forssberg, H., & Pettersson, S. (2011) Normal gut microbiota modulates brain development and behavior. Proceedings of the National Academy of Sciences, 108(7), 3047-3052. DOI: 10.1073/pnas.1010529108  

Mulle, J., Sharp, W., & Cubells, J. (2013) The Gut Microbiome: A New Frontier in Autism Research. Current Psychiatry Reports, 15(2). DOI: 10.1007/s11920-012-0337-0  

  • February 18, 2016
  • 09:15 AM
  • 680 views

Ice caps melt, prehistoric virus escapes. No, it's not a movie.

by EE Giorgi in CHIMERAS

Last week I talked about the connection between global warming and the Zika virus. This week I'll discuss another interesting side effect we might observe in the next decade thanks to global warming. The ice caps will melt. Big deal, we already knew that. But have you ever thought of the stuff trapped in that ice that's going to thaw? What if some of that stuff isn't really dead, just dormant, waiting to come back? Sounds like fiction, but it's not.Up until a few years ago the general notion was that viruses were small. How small? Let's think in terms of genome units: viruses usually carry a handful of genes, either coded into DNA or RNA, and you can think of these as longs strings of four letters: A,C,T (or U if it's RNA), or G. The letters are called nucleotides, and the genome of most common viruses is typically in the order of tens of thousands of nucleotides long. By comparison, the human genome, with its 3 billion nucleotides, is enormous. The notion of viruses being "small" compared to living cells was turned upside down with the discovery of megaviruses in 2010 (over one million bases) and, in 2013, of the pandoraviruses, a family of viruses that can reach a staggering 2.5 million bases in genome size. Before you freak out: so far these gigantic viruses have only been found in unicellular organisms called amoebas, not in humans or any other animals. Amoebas acquire their nutrients through phagocytosis and that's also how the gigantic viruses infect them: the cell membrane forms a vesicle around the particle and engulfs it.The two specimens of pandoraviruses were found in shallow water sediments, one in Chile and the other one in Australia. They were both so big that they could be visible by optical microscopy, reaching 1 μm in length and 0.5 μm in diameter. Now to the interesting bit: the researchers found over 2,000 genes in these pandoraviruses, of which over 90% looked nothing like any other previously known gene. In fact, they appear to be unrelated to the previously discovered megaviruses. So what are they? A fourth domain of life? A completely isolated niche in the tree of life? Or could they be -- as the sci-fi writer in me wants to think -- the remnants of a completely different form of life, one that existed so long ago that these gigantic particles are all there is left of it? Ok, I thought I was original when I posed that question, but I wasn't. The researchers who'd first discovered the pandoraviruses wondered about the exact same thing and, in order to find an answer, they went digging through fossils. They found a giant virus (which they named pithovirus) in a sample of Siberian permafrost radiocarbon dated to be over 30,000 years old. And I have to say, they beat me in sci-fi imagination because they go as far as to claim that there may be more gigantic viruses frozen out there that could be released from the ice as global warming takes over. *Insert apocalyptic soundtrack here*The researchers took a sample of Siberian permafrost layer (corresponding to late Pleistocene sediments older than 30,000 years) and used it to inoculate a particular culture of amoebas (called Acanthamoeba castellanii). Lo and behold, they indeed observed particles of a prehistoric giant virus called pithovirus multiplying in the amoeba culture, making it the most ancient eukaryote-infecting DNA virus revived to date! The observed viral particles were amplified and examined through transmission electron microscopy and were found to have many similarities with the pandoraviruses, only they were even bigger. Contrary to pandoraviruses, though, these pithoviruses showed many more similarities to present-day viruses that normally infect humans and animals. This prompted the researchers to raise the alarm: "Our results further substantiate the possibility that infectious viral pathogens might be released from ancient permafrost layers exposed by thawing, mining, or drilling. Climate change in the Russian Arctic is more evident than in many other regions of the world. Whereas the average global temperature has increased by 0.7 °C during the last 100 y, the average temperatures of the surface layer of Arctic permafrost have increased by 3 °C during the same period." As the authors themselves put it, "This work is a reminder that our census of the microbial diversity is far from comprehensive and that some important clues about the fundamental nature of the relationship between the viral and the cellular world might still lie within unexplored environments."Now, if you'll excuse me, I think I just got an idea for the next bestselling post-apocalyptic thriller.Philippe, N., Legendre, M., Doutre, G., Coute, Y., Poirot, O., Lescot, M., Arslan, D., Seltzer, V., Bertaux, L., Bruley, C., Garin, J., Claverie, J., & Abergel, C. (2013). Pandoraviruses: Amoeba Viruses with Genomes Up to 2.5 Mb Reaching That of Parasitic Eukaryotes Science, 341 (6143), 281-286 DOI: 10.1126/science.1239181Legendre, M., Bartoli, J., Shmakova, L., Jeudy, S., Labadie, K., Adrait, A., Lescot, M., Poirot, O., Bertaux, L., Bruley, C., Coute, Y., Rivkina, E., Abergel, C., & Claverie, J. (2014). Thirty-thousand-year-old distant relative of giant icosahedral DNA viruses with a pandoravirus morphology Proceedings of the National Academy of Sciences, 111 (11), 4274-4279 DOI: 10.1073/pnas.1320670111... Read more »

Philippe, N., Legendre, M., Doutre, G., Coute, Y., Poirot, O., Lescot, M., Arslan, D., Seltzer, V., Bertaux, L., Bruley, C.... (2013) Pandoraviruses: Amoeba Viruses with Genomes Up to 2.5 Mb Reaching That of Parasitic Eukaryotes. Science, 341(6143), 281-286. DOI: 10.1126/science.1239181  

Legendre, M., Bartoli, J., Shmakova, L., Jeudy, S., Labadie, K., Adrait, A., Lescot, M., Poirot, O., Bertaux, L., Bruley, C.... (2014) Thirty-thousand-year-old distant relative of giant icosahedral DNA viruses with a pandoravirus morphology. Proceedings of the National Academy of Sciences, 111(11), 4274-4279. DOI: 10.1073/pnas.1320670111  

  • February 15, 2016
  • 12:50 PM
  • 668 views

Decoding the Dark Matter of the Human Genome

by EE Giorgi in CHIMERAS

First appeared on my Huffington Post blog on February 15, 2016.  In 1994, researchers from Harvard and Stanford published a paper in which they described three mice: one was yellow and fat, one mottled and fat, and the last one was brown and lean. An ordinary image, except for one thing: despite being so different, all three mice were genetically identical. If their genes were exactly the same, what was causing such striking differences in the mice?Three genetically identical mice that do not look the same. Why?Photo credit: Nature Publishing, used with permissionAt the time, Karissa Sanbonmatsu--staff scientist at Los Alamos National Laboratory--was working on plasma physics, and she had no idea that one day she would tap into this mystery. Even though she started from a completely different field, from the very beginning she was obsessed by one question: What distinguishes life from matter? "In order to answer that question, the first place to look is the ribosome," Karissa explains. "It's the oldest molecule found in life." And for a reason: all living cells are made of proteins, and ribosomes are the "factory" inside the cell where these proteins are made. The breakthrough came in 2003, when the Q Machine, at the time the second fastest supercomputer in the world, was built at Los Alamos National Laboratory. Using the Q Machine, Karissa and colleagues were able to run the largest simulation ever performed until then in biology, allowing them to be the first team to publish an atomic structure of a ribosome in 2004. This milestone set the foundation for a deeper understanding of the ribosome. Possible future applications, for example, include making new cancer therapies based on how ribosomes differentiate in healthy versus cancerous tissue. In the meantime, a new, emerging field had been revolutionizing the way we think of genetics and inheritance: epigenetics. The three lab mice from 1994 were one example of how, by switching genes on and off, genetically identical individuals could have different observable characteristics ("phenotypes"). Epigenetics is the field that studies the mechanisms by which the environment can trigger these on/off gene patterns (called gene expression patterns), and how these modifications can be passed on to the next generation. Both animal and human studies have shown that traits acquired by the parents, such as stress responses or the ability to store fat, can be passed on to their offspring. While DNA remains unaltered, what triggers these changes in phenotype is the activation or deactivation of genes--in other words, whether certain genes produce the proteins they code for. But how are genes turned on or off? Specific factors regulate whether a gene is expressed (turned on) or silenced (turned off). These factors are recruited by RNA, the single-stranded molecule implicated in numerous cellular processes, from coding and decoding genes to protein synthesis.When they were first discovered, RNA and DNA molecules that didn't code for proteins were dubbed the "dark matter" of the genome because their function was unknown. Today we know that these molecules can affect gene expression and even change traits by turning on or off certain genes. That RNA had the power to turn genes off has been known since the early 2000s, when small RNAs were used to create mice whose cells had one particular gene silenced. Larger RNA molecules that don't code for any specific protein can also be found in different sizes inside the cell. Called long non-coding RNAs (lncRNA), they are present in great numbers in stem cells and embryos and are essential in many developmental processes."RNA could be the missing link in epigenetics," Karissa explains. "Ribosomes are made of RNA, and so, for me, the leap from ribosomes to lncRNAs was a natural one." In order to understand how lncRNAs can turn genes on and off, scientists first need to unveil their molecular structure. Can lncRNAs assume different shapes, or 3D structures, and change function accordingly, or are they bidimensional molecules? Karissa and colleagues are determined to solve the puzzle. The same techniques used to resolve the ribosome structure in 2005 can be applied to lncRNAs, but because of their larger size, the team will need faster and better computational tools than the ones they used 10 years ago.Luckily, next-generation supercomputing is underway at Los Alamos with the construction of Trinity, a machine fast enough to accommodate simulations of 3D atomic structures. This is where Karissa and colleagues are planning to run their lncRNA models. Revealing the shape of lncRNAs would be a breakthrough. But for Karissa and her team, another even more ambitious project is on the way: "Thanks to the amazing resources offered by Trinity, we will be able to run the first atomistic simulation of human chromatin, the big 'yarn' of DNA and proteins that sits inside the cell nucleus." Source: National Institutes of HealthThis means simulating the 3D structure of three billion base pairs, plus all the proteins the DNA is wrapped around! All genes reside inside the chromatin, and this is where they are activated or deactivated. Therefore, solving the 3D structure of the chromatin will shed new light on the epigenetic mechanisms that regulate gene expression. Many diseases are characterized by altered gene expression. For example, DNA-repairing genes are turned off in cancer cells, while genes that promote replication are over-expressed. Understanding the mechanisms that lead to these altered on/off patterns and how to reverse them can pave the way to new therapies and more efficient treatments--a bright future indeed for molecules once dismissed as the genome's dark matter.Elena E. Giorgi is a computational biologist in the Theoretical Division (Theoretical Biology group) at the Los Alamos National Laboratory and the author of the science fiction thrillers Chimeras, Mosaics, and Gene Cards.ReferencesKarissa Sanbonmatsu's TEDx talk "How You Know You're in Love: Epigenetics, Stress & Gender Identity."Duhl DM, Vrieling H, Miller KA, Wolff GL, & Barsh GS (1994). Neomorphic agouti mutations in obese yellow mice. Nature genetics, 8 (1), 59-65 PMID: 7987393Tung CS, & Sanbonmatsu KY (2004). Atomic model of the Thermus thermophilus 70S ribosome developed in silico. Biophysical journal, 87 (4), 2714-22 PMID: 15454463... Read more »

Duhl DM, Vrieling H, Miller KA, Wolff GL, & Barsh GS. (1994) Neomorphic agouti mutations in obese yellow mice. Nature genetics, 8(1), 59-65. PMID: 7987393  

Sanbonmatsu KY, Joseph S, & Tung CS. (2005) Simulating movement of tRNA into the ribosome during decoding. Proceedings of the National Academy of Sciences of the United States of America, 102(44), 15854-9. PMID: 16249344  

Sanbonmatsu KY. (2016) Towards structural classification of long non-coding RNAs. Biochimica et biophysica acta, 1859(1), 41-5. PMID: 26537437  

  • February 12, 2016
  • 09:20 AM
  • 843 views

The Zika outbreak: a wake-up call about climate change?

by EE Giorgi in CHIMERAS

People are still talking about the Ebola virus and its deadly outbreak in West Africa, and now a new virus is making the headlines: mostly innocuous and fairly unknown until a few weeks ago, the Zika virus is suddenly dominating the news for its putative link with a congenital birth defect that causes babies to be born with abnormally small heads and undeveloped brains. But what is the Zika virus, and how can it be harmless to most people yet cause such harm to an unborn fetus? To answer this question we have to take a step back and understand how viruses work and why some are endemic in the population, while others seem to come and go in waves. The Zika virus was first isolated in 1947 from a rhesus monkey and from a pool of mosquitos from the Zika forest, in Uganda. It belongs to the same family of viruses as dengue, yellow fever, and West Nile virus. However, unlike its close relatives, Zika was thought to be relatively harmless: most infected people will experience no symptoms and a few just a rash and mild fever. Originally confined to Africa, it started spreading to Asia in 2007. Since then the spread of the virus has been exponential.Viruses like Zika and Ebola replicate in animal reservoirs, i.e. populations where they are endemic. Ebola, for example, is usually found in bats and jumps to humans through consumption of meat from infected animals. Zika is found in monkeys and both monkeys and humans contract it through bites from mosquito carriers. In order to evade the host’s immune system, viruses evolve continuously: as organisms build immunity to fight them off, viruses accumulate genetic changes that enable them to escape the newly made defenses. Contrary to Ebola, Zika is a less spectacular virus in many ways. It’s much smaller, and most of the people who contract it don’t even realize they’ve been infected except for a pesky mosquito bite. But that pesky mosquito bite is exactly the virus’s added strength: it becomes an invisible enemy, one that hides and migrates through a tiny insect. You can stay away from infected people when you see them sniffing and sneezing, but how do you avoid a symptomless agent that spreads through a flying bug?You don’t. In areas where these mosquitos are endemic, children get infected early in life, build immunity against the virus, and don’t worry about it ever again. Why is Zika posing a threat now, then? The problem arises when the virus moves to a new geographical area and encounters a population that has never been infected before. Pregnant women are particularly at risk: unless they’ve been infected earlier in life, in which case their immune system can clear the infection before it reaches the fetus, any disease agent that has the ability to cross the placenta is a potential threat. Even a virus with normally mild symptoms like Zika, when it reaches the completely naïve immune system of a fetus in the early stages of pregnancy, can potentially cause permanent damage. Currently, the connection between microcephaly and Zika is still putative and has yet to be confirmed. The danger, however, is real. As Los Alamos National Laboratory scientist Brian Foley explains, over the last two decades, vector-borne viruses like Zika and yellow fever have spread globally at increased rate. That human behavior is once again responsible for this new spread comes as no surprise. Increased traveling between continents, an exponentially growing population and, least but not last, a rise in temperatures have created the perfect haven for mosquitos—and hence the diseases they may carry—to spread virtually unstopped. Densely populated areas that are humid and riddled with stagnant water become the ideal habitat for these bugs. The race for a vaccine has started, and several companies have already announced a time schedule to begin human trials in the near future. Zika is not a very diverse virus like HIV, for which the making of a vaccine has turned out much more challenging than originally anticipated. However, making any vaccine is regulated by strict government safety rules that require years of testing. “Under normal circumstances, it takes 10-20 years to make a vaccine,” Foley explains. “In an emergency situation, they could push it to 2-4 years. That’s still a long time in the event of an outbreak.”And it’s even longer if you think that Zika may only be the tip of the iceberg of a phenomenon we are bound to see over and over again in the near future. “The distribution, transmission, and abundance of vectors that bear and transmit diseases are being enhanced by global warming,” Foley and colleagues state in a recent publication [1]. “The mean global temperature increased approximately by 1° centigrade during the last several hundred years. However, during the next 20 years it is anticipated to increase by 2–3° centigrade.”Geographic areas that used to be too cold for mosquito-borne diseases are now seeing an increase in encephalitic viruses, dengue, and West Nile. Zimbabwe and Ethiopia are experiencing an increase in typhoid and cholera due to the same reason: combine poor hygiene with stagnant water and climate change, and you have the recipe for disaster. So yes, a vaccine can provide a solution. But if this is only the beginning, we need to think globally. It’s not just one virus we’re fighting but a global change that’s happening too fast for the natural world to adapt on its own. [1] Paul Shapshak , Charurut Somboonwit, Brian T. Foley, Sally F. Alrabaa, Todd Wills, John T. Sinnott (2015). Zika Virus. Global Virology I - Identifying and Investigating Viral Diseases Springer-Verlag... Read more »

Paul Shapshak , Charurut Somboonwit, Brian T. Foley, Sally F. Alrabaa, Todd Wills, John T. Sinnott. (2015) Zika Virus. Global Virology I - Identifying and Investigating Viral Diseases. Springer-Verlag. info:/

  • January 29, 2016
  • 10:14 AM
  • 758 views

The fossils hidden in our genome: geneticists turn into archeologists ... sort of.

by EE Giorgi in CHIMERAS

I often blog about viruses because, well, I work on viruses. Here's a quick summary of things I've blogged about that I find absolutely mind-blowing:1. About 10% of the human genome is made of genes we inherited from viruses that had replicated in our ancestors millions of years ago. 2. Viruses evolve as their hosts evolve (The Red Queen Effect), and in fact we can retrace their evolution in parallel with that of their hosts. The same is true within a single host, enabling us to retrace the evolution of a single virus in parallel with that of the host's antibodies.3. Genes expressed by viruses and bacteria in our body can affect our phenotype.4. We can use the ability of viruses to target certain cells to devise new cancer therapies. 5. We can use viruses to edit the genome of certain cells and cure genetic defects through gene therapy.So yes, viruses are cool and they play a huge role in evolution. The fact that roughly 10% of our genome is made of viral elements (called human endogenous retroviruses, or HERVs) makes our DNA a "living fossil": these are viruses that infected our ancestors millions of years ago. Retroviruses in particular insert their genome inside the cell's DNA in order to replicate. In some instances, these viral genomes got stuck inside germ line cells and that's how they got passed on to the host's offspring and became part of our DNA. Today these viruses are extinct, as they evolved into new forms, but by investigating the inactivated genes they left in our genome, researchers can find out what they looked like millions of years ago. It's like digging out fossils in our own cells. It's exactly what two scientists from The Rockefeller University did with one family of HERVs in particular, HERV-K(HML-2) believed to have replicated in human ancestors less than one million years ago (making it one of the most recent forms found in the human genome). They looked at several of these genes across different subjects and reconstructed a "consensus genome", in other words, a genetic sequence that at each DNA position had the nucleotide most frequently found across all study subjects. For example, if the samples across all subjects looked something like this, with the differences, highlighted in red (made up sequences!!):then the consensus sequence would be one of the sequences without red mutations because they represent the majority, in other words:GATACTTGGACAGGAGTTGAAGCTATAATAAGAATTCTACAACAACTGCTBack to the HERV study, which was published in PLoS Pathogens in 2007, Lee and Bieniasz recreated the HERV-K consensus from ten full-length HERV-K(HML-2) sequences and then reconstituted the virus in the laboratory. The ten sequences were selected based on their similarity to HERV-K113, a relatively young and intact HERV-K provirus. While all ten sequences had defects that made viral genes inactivated, selecting the most frequent base at each position, eliminated these defects and yielded a full genome sequence (the consensus) with intact proteins. This derived consensus sequence may not be 100% identical to the actual virus that was integrated into the human genome close to a million of years ago, but it's pretty close. This "closeness" was confirmed in the lab when the scientists saw that the virus they reconstructed based on the consensus genome was indeed able to infect T cells in vitro. All proteins of the reconstructed virus were functional and able to carry one the virus's replication cycle. It's like Jurassic Park... for viruses. :-)Lee, Y., & Bieniasz, P. (2007). Reconstitution of an Infectious Human Endogenous Retrovirus PLoS Pathogens, 3 (1) DOI: 10.1371/journal.ppat.0030010... Read more »

  • January 8, 2016
  • 11:04 AM
  • 747 views

The 2015 Dietary Guidelines for Americans are here. And Americans should read them.

by EE Giorgi in CHIMERAS

Rigatoni pomodorini e tonno. Today the FDA released the updated Dietary Recommendations for the USA. The whole document is available on the Internet for free, and you should read it:http://health.gov/dietaryguidelines/2015/guidelines/People are going to hate me for this post, but I'm going to post it anyway because somebody needs to say it. When I open Facebook, half of the posts are about how women should love their bodies. What gets me is that nobody says that loving your body is not only about accepting the way you look. Overweight is not healthy. You are not loving your body unless you adopt a healthy lifestyle.From the guidelines released today:"In addition, the eating patterns of many are too high in calories. Calorie intake over time, in comparison to calorie needs, is best evaluated by measuring body weight status. The high percentage of the population that is overweight or obese suggests that many in the United States overconsume calories. As documented in the Introduction, Table I-1, more than two-thirds of all adults and nearly one-third of all children and youth in the United States are either overweight or obese."I look around and I don't see a healthy society. What's even more saddening is that I see young people getting more and more overweight. This is particularly bad because the way the body stores fat is something that is shaped during childhood. Epigenetic marks that regulate the usage and storage of nutrients are set during childhood and are highly affected by the diet. So, a diet high in fats will make a person prone to diabetes and all sorts of health problems.But this is epigenetics, not genetics. This means that these marks are reversible if you catch them in time. On the other hand, if you don't do anything about it, these epigenetic marks will be passed on to your children and, chances are, to your children's children. In fact, I believe that many of the overweight kids we see today have inherited the marks from their parents. Coupled with an unhealthy lifestyle acquired from home, you have a recipe for disaster: more health bills and a lifetime dependency on medications and their side effects. America, is this where you want to go?I grew up on a Mediterranean diet and I never had to go on a weight loss diet in my life. No carbs, are not bad unless you have an allergy to gluten. And on a side note, the growing rate of allergies is again the biproduct of unhealthy life styles. And let's face it: anything will make you fat when overconsumed. The key to health is balance.  The Mediterranean diet is one of the easiest to adopt and it's scientifically proven to provide long-term health benefits [2,3]. Below you can find two of the many papers on how adherence to the Mediterranean diet was found to lower the risk for certain cancers and circulatory diseases. You can find many more on Pubmed. Pasta makes for fast and easy recipes, and you can add proteins and vegetables for a complete meal. I shared some recipes here. The image above is another super easy one: Rigatoni Pomodorini e Tonno. All you need is a box of pasta, a can of tune fillets (I prefer the ones that come in a glass jar, they are a bit more expensive, but the taste ad quality are way better), a box of cherry tomatoes, olive oil, and oregano.  Half the cherry tomatoes and sauteed them in two tablespoons of olive oil for a few minutes. Add the tune fillets, salt, pepper and oregano, and let simmer for a few minutes. Cook the pasta al dente, drain it and toss it in the pan. Mix well and serve. Voila', a healthy meal is made. :-) ... Read more »

  • December 18, 2015
  • 10:11 AM
  • 868 views

Scientists reproduce a stress-induced phenotype in mouse pups thanks to epigenetic reprogramming

by EE Giorgi in CHIMERAS

© Elena E. GiorgiI'm excited to be blogging about science again, albeit only occasionally. Those of you who have been following the blog from its very beginnings, back in 2011, know that I've always been fascinated with epigenetics, one of my favorite topics to discuss. So much so that I've managed to include it into the plot of my detective thriller Chimeras. The thrills in the book are fictional, but the science is all real.I was talking with my colleague Karissa Sanbonmatsu last week, who's been working on RNA and epigenetics since the early 2000s, and she was telling me how the field is still riddled with controversy. There's more and more evidence that environmentally triggered traits like stress, fat storage, and the propensity to acquire certain diseases can be passed on from one generation to the next via activated epigenetic marks, yet many scientists still refuse to believe it. How can things that are not encoded in the DNA be transmitted to the new generation? Germ cells carry epigenetic signatures that have been shaped by the environmental exposures from the parents, but how are these signatures communicated across generations? A little background.Our cells carry long bits of RNA that sense molecules and their changes in concentrations. Depending on the environmental exposures they find, they recruit epigenetic factors that then activate certain genes and/or deactivate others. This happens by inducing changes in the chromatin, the big yarn of DNA that sits inside the nucleus. When a gene needs to be activated, the big yarn moves until that particular gene is exposed on the surface and then translated into proteins. On the other hand, to silence the gene, the chromosome move around again and "hide" the gene deep inside the chromatin. RNA molecule act as regulators of these mechanisms, "deciding" which genes to activate and which ones to silence.A recent study published on PNAS sheds new light on the mechanisms that communicate epigenetic marks from the germ line to the offspring, proving that epigenetic signatures acquired by the parents can be passed onto the offspring. Rodgers et al., from the University of Pennsylvania, used a mouse model to establish the following points:First, they exposed male mice to chronic stress prior to breeding, and then observed reprogramming of certain genes in the hypothalamus of the offspring;Second, they looked at the sperm of the stressed mice and compared it to the sperm of non-stressed mice; they found a change in content of micro RNAs (miRNAs), and 9 miRNA molecules in particular were found in much higher concentrations in the stressed mice's sperm [1]. Rodger et al. hypothesized that the 9 miRNAs were responsible for the genetic reprogramming induced by the chronic stress exposure and passed on through the paternal line.To prove it, they injected the 9 miRNAs into single-cell zygotes that were then implanted into normal female mice, raised with no stress exposure, and then examined to see if they presented the same stress phenotype observed in the stressed male's offspring. Indeed, expression of the target genes in the hypothalamus was reduced in the mice that originated from these zygotes, and the expression patterns observed in these mice recapitulated what they had observed in the offspring of the stressed mice. This study, published in PNAS last october [2], is a milestone in epigenetics, as it finally shows a molecular mechanism that allows genetic reprogramming in the parent to be transmitted to the offspring. As a final thought, I want to toss in my two cents on the debated rise of autism spectrum and ADHD disorders currently observed in the Western world. Of course, there's the caveat that the diagnostic methods have changed drastically in the past few decades. Still, the increase seems real and the sad truth is that there's probably more than one cause, and the causes lie not just in what the child has been exposed to, but, once you throw in epigenetics into the pictures, his/her parents and grandparents as well. My parents for example grew up at the peak use of asbestos, DDT, and lead in paint. Yes, they survived and, knock on wood, they are quite healthy in fact. But I do fear that we will carry the consequences of those exposures for a few more generations. And who knows what the current exposure to the massive use of corn syrup and antibiotics will do to future generations. Food for thought. [1] Rodgers AB, Morgan CP, Bronson SL, Revello S, & Bale TL (2013). Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation. The Journal of neuroscience : the official journal of the Society for Neuroscience, 33 (21), 9003-12 PMID: 23699511[2] Rodgers, A., Morgan, C., Leu, N., & Bale, T. (2015). Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1508347112... Read more »

Rodgers AB, Morgan CP, Bronson SL, Revello S, & Bale TL. (2013) Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation. The Journal of neuroscience : the official journal of the Society for Neuroscience, 33(21), 9003-12. PMID: 23699511  

  • December 12, 2015
  • 12:04 PM
  • 841 views

Hunting for the signatures of cancer

by EE Giorgi in CHIMERAS

Today I'm proud to introduce you to a talented postdoctoral fellow in my own group at the Los Alamos National Laboratory. No, I had nothing to do with his work, which is why I can discuss it without any competing interests. Ours is the Theoretical Biology group, and what that means is that we do biology from a purely theoretical perspective: we design analytical models and analyze data from experiments. Sounds trivial, but it's not, and it takes the joint forces of people coming from the most disparate fields to do what we do: in our group, you'll find physicists, immunologists, biologists, statisticians, mathematicians, and then more physicists. The particular research I want to discuss today involves looking at the genomes of cancer cells. Perhaps the most famous mutations associated with cancer are the ones found in the genes BRCA1 and BRCA2. These are germline mutations, i.e. mutations that are found in certain people from birth. Women who have these mutations in the BRCA1 and/or BRCA2 genes have a 60% higher chance of developing breast cancer during their lifetime than those who don't (and yet 80% of breast cancers are not associated to these mutations, see this older post for more details on that). DNA has a certain likelihood to accumulate new random mutations every time the cell divides. These are called somatic mutations, i.e. mutations that aren't present at birth, but arise as we age. Some environmental exposures like smoking and radiation can also cause somatic mutations. Cancer tissue, as you can imagine, is riddled with somatic mutations, but, as it turns out, the mutations differ from cancer to cancer, and also depending on what exposure caused the disease. For example, certain mutational patterns occur most frequently in lung cancer caused by smoking, while others in skin cancers caused by ultraviolet light. These mutational patterns become "signatures" of a particular cancer, and the question is: can we predict the prognosis of the disease based on these signatures? Can we find specific treatments that work for specific signatures?Some drugs are already in use that work only with cancer tissues that have specific receptors. Ludmil Alexandrov, a postdoc in my group, used the incredible wealth of DNA sequencing data from tumor tissues to develop a mathematical framework that analyzes the different mutational patterns of each single cell genomes and explore how these signatures developed over time. As Alexandrov wrote in his recent article [1] in Science:"I curated the majority of publicly available data and compiled a data set encompassing ~5 million somatic mutations from the mutational catalogs of 7042 primary cancers of 30 different classes. These data revealed the existence of 21 distinct mutational signatures in human cancer. Some were present in many cancer types, [. . .] others were confined to a single cancer class." Because of this work, which he developed during his graduate research at the Wellcome Trust Sanger Institute, Ludmil won the Science and SciLifeLab prize for young scientists (awarded by the American Association for the Advancement of Science and Science Magazine) and the 2015 Weintraub Award for Graduate Research. In his own words,"In summary, my Ph.D. thesis provided a basis for deciphering mutational signatures from cancer genomics data and developed the first comprehensive census of mutational signatures in human cancer. The results reveal the diversity of mutational processes underlying the development of cancer and have far-reaching implications for understanding cancer etiology, as well as for developing cancer prevention strategies and novel targeted cancer therapies." Congratulations, Ludmil, well deserved![1] Alexandrov, L. (2015). Understanding the origins of human cancer Science, 350 (6265), 1175-1177 DOI: 10.1126/science.aad7363... Read more »

  • November 1, 2015
  • 12:00 PM
  • 717 views

How one vaccine can protect you from more than one disease

by EE Giorgi in CHIMERAS

The paper I'm discussing today came out last May in Science but, as you probably noticed, I've been busy posting about other things and neglected the science aspect of the CHIMERAS blog. Apologies to my science readers.Viruses are pesky little things that have the innate ability of inserting genetic material into our cells. As such, they are capable of permanently changing our immune system: for one thing, our immune system learns to recognize the pathogen and that "memory" will be used to prevent future infections. Viruses can also alter the expression of certain genes within the infected cells, shutting off the production of proteins that would otherwise prevent the virus from replicating. Viruses that infect preferentially cells from the immune system are particularly nasty. HIV, for example, gradually depletes the host's reservoir of T-cells (the "sentinels" of the immune system) until patients die of a common infection simply because their body can no longer fight pathogens. HIV is not the only virus that attacks the immune system. Measles is another one. The virus enters cells through a receptor that's expressed on the surface of many immune cells such as dendritic cells, macrophages, and lymphocytes. All of these cells have a very important function: they retain "immune memory." What does it mean? Every time the immune system encounters a new pathogen (a virus, a bacterium, etc.), bits of proteins from the pathogens are presented to the immune cells. The immune cells create an "impression" of these proteins so that they can bind to them and destroy them. using a metaphor, they create a "mold", a special receptor that binds to the pathogen. Lots of cells with the special "mold" are created, so they can bind to the pathogen, capture it, and destroy it. A whole army of cells needs to be created in order to get rid of the million viral particles in the body, but once the infection is over and the full army is no longer needed, only a few of these cells with the special "mold" are saved. These few are the ones that preserve the memory of the specific pathogen, so that next time it enters the body it is recognized immediately and destroyed before it can start the infection. Back to the measles virus. This nasty pathogen has a special receptor that allows it to enter the cell membrane of "mature" immune cells [1], i.e. cells that carry that special "mold" for a particular pathogen. By infecting and killing those cells, the measles virus effectively erases immune memory, making the host prone to be reinfected by pathogens it has already encountered. So, on the one hand, the virus stimulates immune responses that will protect from future measles infections. On the other hand, however, it erases some of the existing defenses against other pathogens. It's called the "measles paradox." Immune memory of previous pathogens is eared and replaced by measles-specific immune responses. [2]A study published in Science last May [3] corroborated this finding by looking at child mortality data from England, Wales, the United States, and Denmark during the decades immediately preceding and following the introduction of the measles vaccine. The researchers showed that immune memory loss caused by measles infection lasted from 6 months to several years, and that vaccination against measles significantly reduced child mortality caused by non measles infections. To further corroborate their analysis, the researchers applied the same techniques to pertussis, which is also known to cause immunosuppression. This time they found no correlation with the incidence of pertussis and non-pertussis infectious disease mortality, corroborating the hypothesis that it was the measles vaccine to cause the drop in mortality. "MV infection and vaccination produce strong and durable herd immunity against subsequent epidemics. Our results thus suggest an extra dynamical twist: MV infections could also reduce population immunity against other infections in which MV immunomodulation could be envisioned as a measles-induced immune amnesia; hence, measles vaccination might also be preserving herd protection against nonmeasles infections [3]."<\blockquote>[1] Tahara, M., Takeda, M., Shirogane, Y., Hashiguchi, T., Ohno, S., & Yanagi, Y. (2008). Measles Virus Infects both Polarized Epithelial and Immune Cells by Using Distinctive Receptor-Binding Sites on Its Hemagglutinin Journal of Virology, 82 (9), 4630-4637 DOI: 10.1128/JVI.02691-07[2] de Vries, R., & de Swart, R. (2014). Measles Immune Suppression: Functional Impairment or Numbers Game? PLoS Pathogens, 10 (12) DOI: 10.1371/journal.ppat.1004482[3] Mina MJ, Metcalf CJ, de Swart RL, Osterhaus AD, & Grenfell BT (2015). Long-term measles-induced immunomodulation increases overall childhood infectious disease mortality. Science (New York, N.Y.), 348 (6235), 694-9 PMID: 25954009... Read more »

  • March 2, 2015
  • 09:52 AM
  • 923 views

Extinction Edge: a new thriller on how epigenetic changes induced by viruses could kill us all

by EE Giorgi in CHIMERAS

Today my friend Nicholas Sansbury Smith releases Extinction Edge, the sequel to Extinction Horizon, a sci-fi thriller where humanity is driven to extinction by a lethal virus. I posted an interview with Nick for the release of his first book, but today I wanted to talk about the science behind his premise: can a virus induce epigenetic changes?In a way, Nick's premise is similar to the premise I used in Chimeras: a large part of our DNA is made of pseudogenes, which are ancient genes that are no longer coding for proteins. They are "fossils" in a way, remnants of our evolutionary history. In very layman terms: new species evolve from old ones not because old genes are replaced, rather, new gene copies arise, then mutations accumulate and differentiate the new genes from the old ones, until the old genes are silenced and the new ones take over. (There. Millions of years of evolution in one sentence.)The part that tickles a writer's imagination is the following: if we still have all these ancient genes that once made our ancestors predators and hunters, could we possibly activate them and have people regress back to those ancient states?If you've read Chimeras, you know how I made it happen in my detective Track Presius, and if you've read Extinction Horizon you know how Nick answered the question in his book. We both use a virus, though not the same one. A virus that "awakens" non-coding genes... is that completely far-fetched?Turns out, it's not. Of course, it highly depends on what genes we want to awaken.Epigenetics studies the mechanisms that turn genes "on" and "off" (i.e. expressed or not), how they are affected by the environment, and how they can be inherited from one generation to the next without being encoded in the DNA itself. One of such mechanisms that alters gene expression is DNA methylation, the addition of a methyl group to one of the A or C nucleotides in the DNA. Several studies have looked at how viruses can alter our epigenome, some in a permanent way.Viruses insert their genes inside the host cell and hijack the cell's own proteins in order to replicate. The cell, on the other hand, defends itself by trying to silence the viral genes through a series of epigenetic mechanisms. So of course viral infections and epigenetic changes go hand in hand. I'm sure that these virally induced epigenetic changes can affect us in many subtle ways, and the vast majority of these changes leave us unharmed. However, when you search the literature, you find mostly studies that have looked at viruses that are associated with tumorigenesis because clearly that's of great interest to the medical field: viruses are much easier to detect early than tumors, and if we can understand the mechanisms they use to trigger cancer, then we can also prevent them from establishing the disease.For example, the Epstein-Barr virus causes mononucleosis but it's also associated to some types of cancers, especially in immuno-suppressed individuals such as AIDS patients. As it turns out, the virus alters genome-wide gene expression in infected cells and these alterations can be pre-cancerous [1] (meaning the affected cells have a higher chance to accumulate tumorigenic mutations). Another virus that induces pre-cancerous epigenetic changes in liver cells is hepatitis, both the B and C kind [2, 3], which lead to liver carcinoma in about 10% of the infected individuals.Epigenetic changes have been studied in HIV infected cells, too. People infected with HIV have to take a cocktail of antiretroviral medications for life and, despite the regimen, they never completely get rid of the virus. This is because the virus inserts its genome inside cells and then some of these cells become latently infected. They do not produce virions for months, sometimes years. However, as soon as the patient stops the antiretroviral therapy, the virus suddenly "awakens" and starts spreading throughout the body. These latently infected cells form a "reservoir" and how to get rid of it has been the focus of many studies lately as it is one of the major obstacles preventing us from finding a cure for AIDS. In this review [4], Mbonye and Karn explain how provirions (the HIV genes inserted inside the host cell genome) become latent through epigenetic mechanisms that silence them.Studying epigenetic changes induced by viral infections is a relatively new field, but one that is very promising because contrary to genetic changes, epigenetic alterations are reversible. So, if we can find the viral triggers that lead to pathogenesis we have a potential preventive therapy by reversing those mechanisms.Extinction Edge by Nicholas Sansbury Smith: Survivors call them Variants. Irreversible epigenetic changes have transformed them into predators unlike any the human race has ever seen. And they are evolving. A bioweapon designed to save the world, a scientific discovery that will alter human history, and a new threat that will bring humanity to the edge of extinction. Chimeras by E.E. Giorgi: Haunted by the girl he couldn't save in his youth, and the murder he committed to avenge her, Detective Track Presius has a unique gift: the vision and sense of smell of a predator. When a series of apparently unrelated murders reel him into the depths of genetic research, Track feels more than a call to duty. For Track, saving the innocent becomes a quest for redemption. The only way he can come to terms with his dark past is to understand his true nature.[1] Birdwell CE, Queen KJ, Kilgore PC, Rollyson P, Trutschl M, Cvek U, & Scott RS (2014). Genome-wide DNA methylation as an epigenetic consequence of Epstein-Barr virus infection of immortalized keratinocytes. Journal of virology, 88 (19), 11442-58 PMID: 25056883[2] Tian Y, Yang W, Song J, Wu Y, & Ni B (2013). Hepatitis B virus X protein-induced aberrant epigenetic modifications contributing to human hepatocellular carcinoma pathogenesis. Molecular and cellular biology, 33 (15), 2810-6 PMID: 23716588[3] ... Read more »

  • February 23, 2015
  • 12:38 AM
  • 835 views

Yes, autism is on the rise. Read this before blaming vaccines.

by EE Giorgi in CHIMERAS

Waiting for the rain, © EEGBecause I work on HIV vaccine design, lately I've often been involved in debates concerning the safety of vaccines. I have the greatest respect for parents who struggle with disabilities of any kind, especially in children. I'm a parent too and can't even imagine what life is like when your child has a permanent disability. But I'm also a scientist, and I believe in the good cause of my work. My boss has been working day and night for thirty years on a vaccine against HIV because her best friend died of AIDS. We have pictures of AIDS orphans on our desks. We are not monsters, we are not part of a conspiracy, we are not paid by companies to fool people.In fact, because we do basic research, our salary will be paid whether or not we do succeed in finding a vaccine. It's just our job, and we have no financial gain in this. If you want to point fingers, do it at companies who do make a profit out of health care, or out of selling plastic (and hence bypassing necessary health testing), or out of selling food. As a parent, I am the first to be concerned about the health of our children. I don't accept anything blindly without doing research, be it a vaccine or a drug or a type of food.I've discussed aluminum in vaccines and why it's a good idea to spread out the shots during the first year of life; I've also discussed why I decided to wait before letting my daughter have the HPV shot. At the same time, parents concerned about autism are right to be alarmed: if you look at the latest numbers published by the CDC, the prevalence of autism in children has doubled. However, this trend has supposedly started in the last two decades whereas vaccines have been around much longer than that [1]. It's true that the US have an aggressive vaccine schedule for infants and I suspect it's tailored to reduce the number of office visits as copays are expensive and insurance companies need to make their profits. So yes, just like other parents, I am bitter at the system. I am bitter at companies profiting out of the health of my own children, not at researchers working hard at finding a cure for deadly diseases. My plea today is to separate the two: the cure, which, just like any other cure, should be used wisely and with good measure and balance, and the people making profits out of the cure.    For example, nobody argues that antibiotics save lives. Unfortunately, today you find antibacterial stuff in soaps, detergent, even toothpaste. Doctors overprescribe antibiotics all the time. And then of course, poultry, beef and pork come loaded with antibiotics. This has led to extremely aggressive, antibiotic resistant superbugs like CRE. Yet nobody dreams of refusing antibiotics when they are really needed. That's because we all know that if you don't take them you might in fact lose your life.What our society needs is stop pointing fingers, quit all the conspiracy crap, and instead sit at the table and discuss better health practices that don't put profits first but health and good care instead.How should we address the rise in autism cases? I don't have an answer to this, but I did find a bunch of papers that got me thinking. I list them below.DISCLAIMER: I'm not discussing these papers to point at a cause of autism. In fact, I believe that we will never find a cause, just like we will never find a cause of cancer. Like I stated in my post last week, we need to think of our lives as a complex orchestra where DNA, RNA, proteins and the environment all play together to create the beautiful symphony of our life. There never is one such thing as a direct cause. Often it's just genetics. Even more often is a genetic predisposition combined with multiple sets of environmental exposures, lifestyle, and diet. If your child has autism, please focus your energy in taking care of that child rather than trying to find a cause.1) This study [1] looked into the raising numbers of autism cases:"Diagnosed autism prevalence has risen dramatically in the U.S over the last several decades and continued to trend upward as of birth year 2005. The increase is mainly real and has occurred mostly since the late 1980s. In contrast, children's exposure to most of the top ten toxic compounds has remained flat or decreased over this same time frame. Environmental factors with increasing temporal trends can help suggest hypotheses for drivers of autism that merit further investigation [1]." So the threat is real. Yet vaccines have been around much longer than the 1980s.2) Studies have found a higher incidence of autism in California, in higher educated families. This may be biased by the fact that people with a higher education will be more inclined to have their children tested for autism. But one study in particular [2] found another possible association:"Our study adds to previous work in California showing a relation between traffic-related air pollution and autism, and adds similar findings in an eastern US state, with results consistent with increased susceptibility in the third-trimester [2]." The researchers monitored the air particulate at the birth address of the child starting from preconception through the child's first birthday.  3) Breast feeding may play a protective role against autism spectrum disorders [3].4) Inflammation may play a role. Le Belle et al. [4] used a mouse model to test the following hypothesis:"A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function [4]."What they found supports the idea that, paired with genetic susceptibility, an infection in the pregnant mother could indeed higher the risk of developing autism in the child.5) But one of the most fascinating associations I found is between gut microbiome and autism. Newborns are born without any bacteria in their guts and colonization begins right after birth. Vaginal birth vs. cesarean, breast fed vs. formula seem to be factors associated to the gut microbiota found in infants."Over the first years of life the gut microbiome is changing and remodeling, ultimately resembling an adult gut microbiome by year 3. This suggests there is a “core microbiome” that is the hallmark of a healthy individual [5]." This is particularly important because the microbiota community carries millions of genes whose expression affects our own physiology. The type and number of bacteria in our guts can influence the health and good functioning of our immune system.Now, here's the worrisome bit:"Broad-spectrum antibiotics are often prescribed to infants in the Western world in an attempt to protect the developing child from disease. In addition to conferring antibiotic resistance in infancy, antibiotic over usage can significantly disrupt the overall ecology of the gut microbiota, alter the abundances of resident gut bacteria, and potentially bias the child toward certain diseases [6]."I'm not making a case that antibiotics are bad, just like I will never say that vaccines are bad. I'm just raising a flag that, like in all things, a good measure should be practiced. Antibiotics are a great means to fight infections. But is it safe to use them routinely to prevent infection?The following study [7] is from 2000, so maybe a bit outdated, and the sample number is awfully low. Still, this is what it had to say:"In most cases symptoms of autism begin in early infancy. However, a subset of children appears to develop normally until a clear deterioration is observed. Many parents of children with "regressive"-onset autism have noted antecedent antibiotic exposure followed by chronic diarrhea. We speculated that, in a subgroup of children, disruption of indigenous gut flora might promote colonization by one or more neurotoxin-producing bacteria, contributing, at least in part, to their autistic symptomatology [7]."The study has a huge limit: they tested their hypothesis on 11 child... Read more »

Kalkbrenner AE, Windham GC, Serre ML, Akita Y, Wang X, Hoffman K, Thayer BP, & Daniels JL. (2015) Particulate matter exposure, prenatal and postnatal windows of susceptibility, and autism spectrum disorders. Epidemiology (Cambridge, Mass.), 26(1), 30-42. PMID: 25286049  

Al-Farsi YM, Al-Sharbati MM, Waly MI, Al-Farsi OA, Al-Shafaee MA, Al-Khaduri MM, Trivedi MS, & Deth RC. (2012) Effect of suboptimal breast-feeding on occurrence of autism: a case-control study. Nutrition (Burbank, Los Angeles County, Calif.), 28(7-8). PMID: 22541054  

Mulle, J., Sharp, W., & Cubells, J. (2013) The Gut Microbiome: A New Frontier in Autism Research. Current Psychiatry Reports, 15(2). DOI: 10.1007/s11920-012-0337-0  

Arrieta, M., Stiemsma, L., Amenyogbe, N., Brown, E., & Finlay, B. (2014) The Intestinal Microbiome in Early Life: Health and Disease. Frontiers in Immunology. DOI: 10.3389/fimmu.2014.00427  

Sandler RH, Finegold SM, Bolte ER, Buchanan CP, Maxwell AP, Väisänen ML, Nelson MN, & Wexler HM. (2000) Short-term benefit from oral vancomycin treatment of regressive-onset autism. Journal of child neurology, 15(7), 429-35. PMID: 10921511  

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