Showing posts sorted by relevance for query bacteria. Sort by date Show all posts
Showing posts sorted by relevance for query bacteria. Sort by date Show all posts

Thursday, September 20, 2018

Secret Science Club Post Lecture Recap: Swarming Bacteria

Last night, I headed down to the beautiful Bell House, in the Gowanus section of Brooklyn, for this month's Secret Science Club lecture featuring Dr João Xavier, computational biologist and director of Sloan Kettering's X-Lab. Dr Xavier's topic was experimental evolution and swarming bacteria.

Dr Xavier began his lecture with a quote from Richard Dawkins:


My eyes are constantly wide open to the extraordinary fact of existence. Not just human existence, but the existence of life and how this breathtakingly powerful process, which is natural selection, has managed to take the very simple facts of physics and chemistry and build them up to redwood trees and humans.


He followed this up with a beautiful tribute to biodiversity, first showcasing the human diversity of New York City's populace with pictures from the subway system, then showing pictures of animal biodiversity, then expanding his focus to include plants, fungi, and bacteria. Dr Xavier then took a brief digression to note that he entered into the field of biology relatively late- he was initially more interested in math and physics, but eventually felt the call to apply his knowledge of those fields to biology. He followed up this digression with a brief overview of Darwin's theory of evolution by means of natural selection: put succinctly, successful individuals will be 'selected' by natural processes to pass on their traits to their offspring, and this selection will drive the direction in which a species will evolve. The basic mechanism of biological inheritance was formulated by Gregor Mendel, who observed the passing of traits in plant lineages. The central dogma of molecular biology, as formulated by Crick et al. is that DNA is the molecular entity behind evolution. DNA encodes genes which make proteins. DNA can be transcribed- it is copied when a cell divides, and sometimes there are errors in the copying, known as mutations. Most mutations are harmful to an organism, but occasionally they may lead to better survival outcomes. Diversity emerges through mutations, and the fittest organisms tend to propagate.

Dr Xavier then noted that everyone alive today descends from a common ancestor, then he amended this statement to note that every living organism on Earth comes from a common ancestor. He noted that this is a hard-to-grasp concept, so some people refuse to believe it. This refusal to believe led to the creation of the 'Intelligent Design' movement, which posits a director/designer in the evolution of life. The bacterial flagellum was considered the icon of Intelligent Design creationism, but Dr Xavier noted that the proteins behind the flagellum are understood- complex structures look precisely adapted to their environment, they look designed, but their evolution in incremental steps is explainable.

This talk of flagella then segued into the real topic of the lecture- the bacterium Pseudomonas aeruginosa, a human pathogen. Dr Xavier uses Pseudomonas to investigate the fundamental facts about evolution and their direct implications in medicine. Bacterial evolution can be deadly- Dr Xavier recounted a case in which a patient needed a bone marrow transplant, which involved suppressing their immune system. Ten days before the transplant, while the patient's immune system was compromised, the patient developed a Pseudomonas infection which was resistant to most antibiotics. The patient was treated with aztreonam, but the bacteria evolved resistance to this antibiotic through a mutation, sepsis set in, and the patient died. Antibiotics select for resistance against themselves- they kill off non-resistant bacteria, then the small population of resistant bacteria propagates. The evolution of antibiotic resistance is fast, and it happens all the time.

Dr Xavier then followed this cheerful news with another quote from Richard Dawkins:


“We are going to die, and that makes us the lucky ones. Most people are never going to die because they are never going to be born. The potential people who could have been here in my place but who will in fact never see the light of day outnumber the sand grains of Arabia. Certainly those unborn ghosts include greater poets than Keats, scientists greater than Newton. We know this because the set of possible people allowed by our DNA so massively exceeds the set of actual people. In the teeth of these stupefying odds it is you and I, in our ordinariness, that are here.We privileged few, who won the lottery of birth against all odds, how dare we whine at our inevitable return to that prior state from which the vast majority have never stirred?”



Bacteria evolve quickly because they reproduce quickly. The Pseudomonas bacteria form a swarming collective, they have motility due to their flagella. Dr Xavier studies this swarming behavior in petri dishes. Separate bacterial swarms in a petri dish repel each other. The bacteria need flagella to swarm, and this is the natural condition of the wild type. A non-swarming, non-flagellated form, known as flgK was developed in the lab. Dr Xavier then showed us a series of videos comparing the spread of swarming wild-type bacteria to the spread of non-swarming mutants:





Parallel experiments were conducted in different petri dishes, and they demonstrated the heritable and stable tendency to evolve into hyperswarming bacteria with multiple flagella, a new feature that evolved in the laboratory. Genome sequencing revealed the precise mutations which caused hyperswarming. Some bacteria evolved an excess of flagella, and too many 'tails' prevented swarming... the right number of flagella was needed. Hyperswarmers, though they move more quickly to exploit new resources, grow more slowly than the ancestral type bacteria- multiple tails require more resources.

Dr Xavier likened the petri dishes with different bacterial strains as to 'fighting arenas' in which the strains were pitted against each other. Different strains were stained red or green, and hyperswarmers were pitted against ancestral types. The hyperswarmers expand quickly and find nutrients, while the non-hyperswarmers are stuck in regions in which nutrients are exhausted. Faster speeds can come with a trade-off, though. Dr Xavier cited the invasive cane toad as an example of such a trade-off... in areas in which the toads are expanding their range, they evolved longer legs which enabled a faster spread. Dr Xavier joked that there was an 'Olympic village of cane toads' down under. The trade-off is that the longer legs, while enabling faster movement, also resulted in more spinal injuries among the leggy toads. In the case of Pseudomonas, hyperswarmers are not found in natural environments or in hospitals- while they can move quickly, they are bad at forming biofilms. In the fighting arena of the petri dish, the slow bacteria will eventually take over- in nature, the fast bacteria don't do well. It's difficult to evolve a change in the structure of the flagellum, the icon of the Intelligent Design movement. Dr Xavier got another dig in at the ID crowd- when the New York Times ran the headline “Watching Bacteria Evolve, with Predictable Results”, a creationist publication describing itself as 'a great tool for countering pro-Darwin propaganda' countered with the rejoinder 'They're still bacteria.' CHECK AND MATE, POINDEXTERS!!!!

Dr Xavier then went on to discuss the use of swarming bacteria to study social behavior- how do social behaviors evolve? Social behaviors can have a different impact on actors and recipients. In mutualism, everyone benefits- actors and recipients. Altruism is costly to the actor and benefits the recipients. Selfishness benefits the actor and is costly to the recipients. In the case of spite, everyone loses. Game theory uses mathematics to analyze behavioral choices. Dr Xavier cited the example of the prisoner game to illustrate game theory:





Kin selection explains many altruistic behaviors- altruism is more likely among relatives. When asked if he would lay down his life to save his brother, biologist J.B.S. Haldane was quoted as saying that he wouldn't, but that he would for two brothers or eight cousins. Altruism makes sense when it results in evolutionary fitness benefits.

Among bacteria, the whole population benefits from swarming, but swarming involves sacrifice among individuals. Non-swarming bacteria tend to consume all available nutrients in their environment until they cannot grow their population. Resources are spent to propagate a swarm, and the tiny contributions of individual bacteria can add up to an impressive spread. Alone, on-swarming bacteria cannot spread, but they can hitchhike along with swarming bacteria. In this cooperative situation, the ratio of swarming to non-swarming bacteria remains stable. Cheating is hard due to metabolic prudence- bacteria cooperate when they have excess metabolic resources to devote to swarming. Dr Xavier ended his lecture by joking that metabolic regulation of good behavior is not only found among bacteria- citing a study of judicial records which suggested that judges at parole hearings tended to become less lenient as they got hungrier, but exhibited renewed leniency after lunch.

The lecture was followed by a Q&A session. Some bastard in the audience, thinking back to Dr Paul Turner's SSC lecture on phage therapy, asked if there had been experiments to use selective pressure to 'breed' less harmful versions of pathogenic bacteria by selecting and propagating less virulent individuals. Dr Xavier replied that this hasn't been attempted, but that it would be possible for less harmful bacteria to out-compete their dangerous relatives. There's no good model for this sort of study, but it could be evolved... of course, as in the example of the introduction of the cane toad to Australia, things could go awry, as organisms don't necessarily behave in the wild as they do in the lab. The Bastard missed a bunch of questions while taking a break to micturate, but when he returned to the main auditorium, the question regarded cancer- cancer cells have an initial propagation advantage over 'normal' cells, but are an evolutionary dead end as they kill their hosts... they are successful for a while, then they fail utterly. He also mentioned the transmissable cancer that is devastating Tasmanian devil populations as a particularly horrific example of this sort of thing.

Once again, the Secret Science Club served up a fantastic lecture. I am particularly struck by the sheer coolness of a Professor Xavier setting up clashes among mutants in a battle arena. The multiple videos of the petri dish battles were gorgeous:





Kudos to Dr Xavier, Margaret and Dorian, and the staff of the beautiful Bell House.

Thursday, June 11, 2020

Timely Secret Science Club Zoom Lecture

Tonight, while at work, I am logged into this month's Secret Science Club Zoom lecture featuring Muhammad H. Zaman of Boston University. While I miss the lovely people of the beautiful Bell House, I am currently basking in the rays of the setting sun behind the main building at my workplace.

This is going to be a bit of a liveblog. Dorian Devins just made a statement about the official SSC support for Black Lives Matter. I'm just going to say that racism is incompatible with science. PERIOD! Kudos to Dorian and Margaret for all they do.

Tonight's lecture is based on Dr Zaman's new book: Biography of Resistance: The Epic Battle Between People and Pathogens Dr Zaman began his talk by mentioning the role of systemic racism in the spread of illnesses. What can the history of antibiotic resistance tell us about future pandemics? Medical science took a fork in the road which led us to this place. Dr Zaman then shifted to the topic of the 1918 Flu, which was worldwide in scope, affecting such geographically separated individuals as Mustafa Kamal, Mohandas Ghandi, and T.S. Eliot all contracted the 1918 flu. Forty percent of the flu deaths occurred in India,

He then displayed the abstract of a paper co-written by Anthony Fauci concerning the role of bacterial pneumonia in influenza deaths. Patients who are intubated receive antibiotics, and antibiotic resistant secondary infections pose great danger to such patients.

Dr Zaman then discussed writing books in addition to research papers- books can broaden the conversation about scientific subjects. He wants to be able to discuss these subjects with neighbors, with his children's teachers, with his aunts and uncles. He also noted that books allow a holistic perspective of problems involving public health and policy.

Bacteria can be described as gram positive and gram negative according to how they react to a Gram stain developed by Hans Christian Gram, who studied pneumonia pathogens. Dr Zaman then noted that Louis Pasteur, while a titan of science, had stolen

Robert Koch formulated Koch's postulates of disease, but he also forced East Africans to take a medicine for sleeping sickness which turned out to be extremely dangerous. Dr Zaman stressed that even great scientists are humans with all of those flaws.

Dr Zaman noted that viruses can not only cause disease, but can be used to cure disease. British virologist Frederick William Twort discovered bacteriophages, viruses which harm bacteria. This research became popular with Stalin, so phage therapy was seen as 'Soviet', so the development of antibiotics was favored. Sulfa drugs were used to teat infections, but bacteria started to become less effective. Then Alexander Fleming discovered penicillin. Mary Barber was a British doctor who noted that penicillin resistance was evolving in bacteria, so new antibiotics had to be developed, such as methicillin.

There are so many different bacteria strains which produce antibiotics to provide an adaptive advantage. Bacteria have been 'waging war' since time immemorial. Dr Hazel Barton, a cave microbiologist, has been studying microbes from deep portions of the Lechuguilla cave in New Mexico. Bacteria have been competing, humans just 'put their thumbs on the scale'.

In another case, an isolated Yanomami group in Venezuela had been contacted by soldiers, and despite their isolation, fecal samples and non-invasive skin samples showed that they had resistant microbes.

There's a need to discuss overuse of antibiotics beyond talking of bad patients and bad doctors. One major factor in common outbreaks is global conflicts. In the first Gulf War, many US soldiers contracted a new, resistant bacterium, Acinetobacter baumannii. The bacterium still infects Iraqis. War kills doctors, destroys infrastructure, and contaminates soil, fostering bacterial resistance development. Similar outbreaks developed in Kabul, and Yemen is a potential source for a novel 'superbug'.

Large-scale agriculture also fosters antibiotic resistance. Citrus growers use antibiotics to affect fruit shape and color. Farm animals are given antibiotics, which get into milk and meat. Indiscriminate antibiotic use pushed by ill trained druggists is common throughout the world.

Dr Zaman posed a thought experiment: if you are a pharmaceutical executive, do you develop antibiotics which are taken for a few days or pharmaceuticals which need to be taken every day for a patient's life? Also if you develop a novel antibiotic, should it be kept 'in reserve'?
There's a 2% success rate for new antibiotics working, and most 'new' antibiotics are merely reworking old antibiotics. For gram positive bacteria, a new antibiotic hasn't been developed for thirty years, fifty years for gram negative bacteria.

Our system doesn't work because the private sector cannot sufficiently provide a public good.

The story of antibiotic resistance is a story of bad decisions, people doing things they shouldn't have done. The problem is solvable, though, if different sectors combine- public, business. People with chronic conditions are the ones most affected by resistant infections, in the United States, African-Americans are the most vulnerable. The barriers which prevent people from having decent lives must come down if we want a society in which everyone is healthy.

The lecture has now shifted into the Q&A phase. One question regarded the pace of resistance development in medicine vis-a-vis nature. The selective pressures in a lab are just more rapid in pace, so resistance evolves more quickly. Another question involved overuse of alcohol-based wipes in the current pandemic- we don't know the long-term impact because there are no good studies. They are probably less conducive to resistance than antibiotics, but they do kill beneficial bacteria as well. There could be serious concerns. What is the best thing we can do as patients to counter antibiotic resistance? Perhaps it involves forgoing immediate relief for long-term benefits. As patients and consumers, we should also push back on excessive antibiotic use in farm animals, particularly use to foster growth, rather than to treat infection. Can bacteria lose resistance to old antibiotics? Resistance is a cost to bacteria, they have to carry that gene. Antibiotics which are ineffective here in the US can still be effective in countries which have tighter controls on their use. Is humanity destined to lose the battle with bacterial resistance? Dr Zaman is an optimist. People are suffering, and socioeconomically disadvantaged people suffer the most, and our humanity is suffering. Some bastard in the audience asked: Would it be possible to use 'selective pressure' to foster bacteria which are less deleterious to human hosts? If that is done, everybody must buy in. Such bacteria would be more prone to antibiotic resistance, which is not hard to evolve. Bacteria have been around for four billion years, they are hard to 'outsmart' evolutionarily. Another question regarded the best way to combat outbreaks. Dr Zaman gave his top three: stop conflicts, which drive suffering, make sure that proper information is transmitted, and involve everyone in health decisions, not just medical professionals.

I'm going to hit 'publish' now, though the Q&A is still ongoing. Please, put your name on the Secret Science Club mailing list, because there is another lecture taking place next week.

Kudos to Dr Zaman, Dorian and Margaret for another great Secret Science Club presentation.

UPDATE: In response to a young listener, Dr Zaman stressed that the old model of a 'war on bacteria' has been discounted, and that beneficial bacteria play an important role in human health. Another good question involved a global outbreak of resistant C. difficile- while numbers have been going up, the transmission isn't as quick as a viral infection. Another question involved the danger of knocking out beneficial bacteria, which Dr Zaman noted can impact our immune systems, which are under constant pressure, upsetting the balance is bad. The follow up involved ways to restore bacterial symbionts after a course of antibiotics. Dr Zaman opined that it depends on what antibiotics are involved, but suggesting consulting a nutritionist for advice.

SECOND UPDATE: There was a question about how antibiotic resistance arises, and Dr Zaman indicated that bacteria have multiple strategies... they can evolve thicker walls, they can develop more effective efflux pumps to remove toxins, they can move genetic material to different areas to thwart antibiotics. He reiterated that bacteria have been around for billions of years, and have many survival strategems.

THIRD UPDATE: There was a question about reviving phage therapy making a comeback. Broad clinical trials are needed. We need to know how phages affect bacteria. Studies of viral mutations must be done to ensure safety. Phage therapy should supplement antibiotic and vaccine use to create a broad spectrum of therapeutic techniques.

Wednesday, March 25, 2015

Secret Science Club Post-Lecture Recap: Talk Dirty to Us

Last night, I headed down to the beautiful Bell House, in the Gowanus section of Brooklyn, for this month's Secret Science Club lecture, featuring Dr Christopher Mason, assistant professor of physiology & biophysics and computational biomedicine at Weill Cornell Medical College and member of the Yale Law School Information Society Project (but not, to my knowledge, a member of the Information Society). He was also named a member of the brilliant ten by Popular Science magazine. Dr Mason created quite a stir locally when the results of his NYC subway system DNA collection project were revealed earlier this year. Dr Mason gained overnight notoriety when he answered, in response to a query about germs in the subway, "You wouldn't want to lick all the poles, even though you'd probably be fine." Now THAT is one thousand varieties of awesome!

Dr Mason began his lecture by stating that he was obsessed with sequencing DNA, the molecular "recipe" present from an individual's first cells. He described development as a symphony of DNA, RNA, and proteins, a combination of processes that occur at all times.

The last ten years of microbiology have been revolutionary. To illustrate the growth of processing power in the field of genome tracking, Dr Mason brought up Moore's Law and noted that the reduction in the cost of gene sequencing has vastly outpaced the general pace of technological development. In the period from 2006-2007, the cost to sequence a genome was cut in half every five months. This reduction in cost has led to "participatory genomics", embodied by such websites as "Patients Like Me", a social media site on which individuals can share genetic data. Genome guided medicine has arrived- medicines can be tailored to a patient's genetic profile. Dr Mason noted that more data equals more power, and that organizations such as Genspace are bringing microbiology to a wider audience. One of Genspace's projects is a study of the microbiome of the ultra-polluted Gowanus Canal, mere blocks from the beautiful Bell House. Dr Mason mentioned two genes that have a great effect on the health of an individual possessing them: CCR5-Δ32 provides HIV resistance, mutations decreasing myostatin can result in larger muscle mass, and LRP5 regulates bone mass.

Dr Mason then shifted to the topic of DNA patents. Until recently, DNA, once removed from the body, could be patented. The patenting of a DNA sequence such as the BRCA1 and BRCA2 genes, which are implicated in the development of breast cancer, had the potential to stymie medicine based on these gene sequences. Dr Mason likened gene patenting to "patenting the word because and claiming to own every book". The challenge to gene patenting took place on 4/15/2013 and the Supreme Court invalidated patents on BRCA1 and BRCA2 on 6/13/2013- claims on isolated DNA were rejected. The litigation finally ended in 2015, so you now have a right to look at DNA. Dr Mason quipped, "Your genome is free!"

Dr Mason moved on to the topic of the microbiome. Every individual has more than one genome- there is the human genome and there is the genome of an individual's microbiome. Dr Mason illustrated this concept with a political analogy: "In a genetic democracy, you are the minority party." Every human being plays host to three to five pounds of bacteria, and most of the genes in your body are not "yours". Dr Mason cited the work of the Human Microbiome Project, joking "You are your bacteria." One's bacterial symbionts provide about 90% of the body's serotonin and about 50% of the body's dopamine. As Dr Mason put it, "The nearest pharmacy is your gut." The human microbiome produces about 700 "drugs". Lab studies have shown that (WARNING: NYT LINK, SAVE YOUR CLICKS) gut bacteria transplanted to fat mice can slim them.

An individual "inherits" its bacteria buddies from its mother in a Maternal Microbiome Transfer- during birth, a newborn picks up some of its mother's vaginal microbiome. Later on, this major transference is supplemented during nursing. Babies delivered through a Caesarian section tend to have a higher incidence of disease later in life. Dr Mason likened the microbiome to an anti-disease "force field", then he flashed a news report of Boeing's new "force field" patent (gotta love interdisciplinary nerdery!). He also noted that exposure to cockroaches is good for infants with asthma, and that Fecal Microbiota Transplants can harness "the power of poop" to help individuals with certain gastrointestinal problems (Dr Martin Blaser's two Secret Science Club lectures also dealt with this subject). He then cited OpenBiome as the go-to place for potential stool donors, with their "give a shit" campaign.

Dr Mason had a brief digression about bacteriophobia, quoting Bertrand Russell: "To conquer fear is the beginning of wisdom." He showed the audience a couple of photos of his adorable daughter and mentioned her habit of putting toys in her mouth. When he took her to daycare, he observed the kids all putting the same toys in their mouths and passing their microbiota around. He likened it to the whole group "making out". This was the inspiration for the big "swabbing campaign" which led to the Pathomap.

The Pathomap is a "molecular view of the city", the goal of the project, which began on 7/15/2013, was to "seek out new life, new civilizations". The project has taken place over six different seasons, with 4,342 different data points in a subway system that transports 5.5 million riders daily. Samples were swabbed, annotated, and sequenced. 50% of the DNA belonged to no known organism (though the genomes of cockroaches have not been sequenced yet). Dr Mason described the subway system as a "rainforest to explore" in an interview with the NY Times. DNA from bacteria, eukaryotes, viruses, and "ambiguous" sources) was collected. A headline in The Atlantic proclaimed: "New York City Subways Are Covered in Microscopic Pizza". Despite the discovery of minute traces of anthrax, bubonic plague causing Yersinia pestis, and dysentery-causing bacteria, 88% of the bacteria on the subway were "friendlies". Out of the deleterious 12%, the most common were Enterococcus and Shigella. Despite headlines about everything "from beetles to bubonic plague" being found, Dr Mason noted that there is zero evidence that anyone is at risk from the subway bacteria. He noted that anthrax is caused by a soil bacteria and that the "anthrax DNA" that was found could belong to an unknown relative, and there is evidence that low levels of the "bad" bacteria in the subway are okay.

The greatest genetic diversity in the subway system was found in the Bronx, with Brooklyn ranking second. Dr Mason wryly noted, "Nothing soft comes from the Bronx." High diversity is a good thing, there is a lesser risk of any one organism accumulating in a dangerous concentration. Comparing the subway system's microbiome to the human microbiome, Dr Mason stated that the subway "looks like skin" with regards to the diversity of its biome. He noted the various incidence of bacteria associated with kimchi, sauerkraut, and noted that species diversity varies by area of the city. Areas of the subway affected by superstorm Sandy were characterized by bacteria not present elsewhere, including bacteria normally associated with the Antarctic. The hourly dynamics in the subway system vary in the course of a day- the periodic cleaning of the system is like a "forest fire", followed by a repopulation of the cleaned area.

Dr Mason provided a "greatest hits" summary of his various statements to the press, including such side-splitters as "the best thing to do with newborns is roll them like sushi on the subway ground" and the bit about licking the subway poles. The man has a knack for a soundbite.

On the topic of the genetic diversity of the system, Dr Mason indicated that the presence of DNA doesn't necessarily indicate that the organism it reveals the presence of is alive. Certain bacteria can produce antibiotics in order to compete with other bacteria. Among eukaryote genes, chickpea and cucumber genes were commonly found. Cockroach genomes not being sequenced, the mighty roaches of New York have yet to take their rightful place, now they are lumped in with the "unknowns". The amount of human DNA found varied from day-to-day... Dr Mason admitted that no swabbing was done on the day of the No-Pants Subway Ride. The human DNA that was found corresponds with census data- zooming in on the different areas of the Pathomap, one can predict the census results due to DNA matches. Humanity's "molecular echo" rings throughout the Pathomap.

Noting that the bacterial "map" of the subway system looked like an ad for Uber or a full-body condom, Dr Mason tackled the question, "Should I ride the subway?" He said, "It's okay, you're all healthy." He concluded that we should ride the subway.

The final section of the talk concerned future projects. The NYC subway system, with 1.7 billion riders, is the seventh busiest subway system in the world. The swabbing and mapping of subways in other cities has already begun. Another upcoming project is a Hospital Microbiome Project. An integration of molecular and technical data would result in a "smart city" in which pathogenic microbe alerts could be issued. Nanopore sequencing, measuring DNA as it passes through pores, is making genome sequencing even more rapid, which led to a discussion of the need for BIG DATA storage, with Dr Mason musing about Yottabytes of genetic data. He also mentioned the upcoming studies of the Kelley twins to determine the effects of space travel on identical twins (obligatory shout-out to the mad genii of Riddled!)

In the Q&A, some bastard in the audience asked if there was an appreciable difference between the outdoor stations, exposed as they are to UV rays and winter cold, and the sheltered underground stations. Dr Mason indicated that there was almost the same level of genetic diversity, but the outdoor stations had more plant DNA than the underground stations. Other topics addressed included probiotic deodorant sprays (the bacteria prevent the "stink producing" bacteria from proliferating, but showering washes the probiotics off). Regarding DNA sequencing and genome-based medicine, Dr Mason urged us not to run away from genetic information, but to be wary of a loss of privacy. On the "Ebola question", Dr Mason noted that Ebola is an RNA virus, and no testing for it has occurred. MRSA was found at three spots in the system. Dr Mason briefly touched on DHS pathogen detectors, using air filtration, but the feds don't typically share data. One wag, noting that Dr Mason was a charismatic, entertaining speaker, asked if he would be giving Neil Degrasse Tyson a run for his money as the great populizer of science, to which Dr Mason responded that he had met with Dr Tyson and had "exchanged microbiomes" by shaking his hand. For those of you fantasizing about hunky scientists hanging out, this isn't the first time that topic has been raised. Regarding the Gowanus, there are a lot of Archea there, talk about extremophiles!

At the end of the Q&A, Dr Mason mused about the use of bacteria to protect astronauts from radiation on long space flights, and about "microbiome synchronization" in the tight spaces astronauts would deal with. He ended by noting that the best hope for long-term human survival is space colonization. We won't be going along on to the "final frontier", we'll be travelling with trillions of our closest friends.

Once again, the Secret Science Club dished out a fantastic lecture, one that hit the "sweet spot" of imparting information, giving a look into the processes used by working scientists, a healthy dose of humor, and perhaps most important of all, a compelling local connection. Put succinctly, Dr Mason knocked it out of the park. Kudos to Dr Mason, Dorian and Margaret, and the staff of the beautiful Bell House. The ride home on the subway system was wonderful, I was able to bask in the rosy glow of knowing that I was traveling with a myriad of little buddies.

Here's a quick video featuring Dr Mason:





And, for extra measure, here's the Pathomap- be warned, though, you could spend many, many hours playing with it.

Friday, October 27, 2017

Secret Science Club Post-Lecture Recap: This Lecture's Gone Viral

On Wednesday night, I headed down to the beautiful Bell House, in the Gowanus section of Brooklyn, for this month's Secret Science Club lecture featuring evolutionary biologist and virologist Dr Paul Turner of Yale University. Dr Turner titled his lecture Viruses: Good, Bad, and Ugly, in homage to his favorite spaghetti western.

Dr Turner began his lecture by addressing the amazing biodiversity of the planet, displaying first a list of North America's 'big five' charismatic megafauna- grizzly bears, caribou, moose, bighorn sheep, and wolves, contrasting it with an invisible 'big five' of North America- the Giardia protozoan, the influenza virus, the HIV retrovirus, a bacteriophage, and the Cordyceps fungi. He posed the question, are microbes nasty? His answer was that this was not necessarily true, that microbes can benefit human health. In humans, the microbiome, the community of bacteria, fungi, and viruses within the body, outnumbers the body's own cells. The microbiome can affect one's risk of heart disease, cancer, and other illnesses- it also plays a role in an individual's weight. It is currently believed that childhood exposure to microbes may help prevent autoimmune diseases, a concept known as the hygiene hypothesis. In experimental helminthic therapy, irradiated hookworm eggs are introduced into subjects in order to reduce autoimmune diseases. Dr Turner summed up this part of the lecture by noting that we live in a microbial world.

He then posed the question: What is a virus? After repeating his theme of ugly, good, and bad viruses, he posed another question: Might a virus save your life someday? Cellular life can be divided into three broad categories- bacteria, archaea, and eukaryotes... all of which form cells enclosed by a membrane. In contrast, viruses do not form cells, they characteristically have genetic material, DNA or RNA, surrounded by proteins. Viruses come in many forms- typical bacteriophages have tail vanes (Dr Turner facetiously compared them to the lunar lander). Influenza viruses contain RNA in the center of a protein shell. Viruses have a non-cellular life cycle. In order to reproduce, a virus enters the proper cell type, injects its genetic material, the viral genetic material hijacks the cell metabolism to copy itself, and the viral offspring are released from the cell.

Viruses are biodiverse, most are sub-microscopic... an electron microscope is needed to observe them. Influenza viruses and rhabdoviruses come in many shapes. Virus size does not correlate with host size- a whale can be infected by small viruses, a bacterium by large ones.

The evolutionary origin of viruses is a mystery- viruses appeared billions of years ago. Dr Turner posed a multiple choice question. A. Did viruses evolve before bacteria, being inhabitants of an RNA-based world that existed before DNA evolved? B. Did viruses evolve as parasites within cellular organisms? C. Are viruses 'devolved' cellular information? D. Did viruses arrive to Earth from space? Dr Turner jocularly illustrated these last two options with a picture of Devo and a picture of the lunar lander juxtaposed with a bacteriophage. Dr Turner indicated that A, B, and C are the three leading ideas.

Viruses reproduce very quickly, while bacteria can reproduce rapidly through binary fission, viruses can grow even faster as their progeny are formed in the cells of other organisms. Viruses are very abundant, they thrive in all environments, and they outnumber all other organisms. They are the most numerous of Earth's inhabitants. The human global population is approximately 7.2 billion, while the global virus population is estimated to be 1031. If the genes of all of the Earth's viruses were laid end-to-end, they would stretch to the Perseus Cluster, approximately 250 million light years away.

We live in a viral world- the bad viruses make the news, they are the viruses that are researched. There is evidence of ancient viral diseases- the Pharaoh Siptah had a clubbed foot that suggests polio, which is probably depicted on an image of a priest on a stele dating to 3700BCE. The mummified remains of Ramesses V indicate that he had suffered a case of smallpox. The polio virus is common in soil, it is usually harmless to humans, but becomes extremely dangerous when it enters the human nervous system. The smallpox virus was rendered extinct in its natural environment, the human body, and exists only in labs at the CDC and in Russia.

Dr Turner then took us on a tour of deadly epidemics- the 'Ugly' viruses. The 1918 flu killed 50 million to 100 million victims, a single flu strain managed to infect approximately 500 million individuals before the advent of commercial air travel. In our modern era, where travel is common, a flu epidemic may be just as deadly if the available vaccines don't match the flu strain. The Great Plague of the 14th century, which killed approximately 40% of Europe's population, is generally blamed on the bacterium Yersinia pestis, but other pathogens may have contributed to the death toll, hygiene and sanitation being sub-par at the time. The smallpox epidemic which began in 1520 in the New World decimated the Native American populations, but there are no estimates of the death toll. The AIDS epidemic, which is generally considered to have started in 1981, has claimed 39 million lives, with 78 million likely infected.

Virus emergence is a continual process- viruses can 'jump into' humans from other organisms. Bats commonly harbor viruses, which are often transmitted to pigs, then from the pigs to humans. HIV has jumped from other primates to humans, with HIV1 originating in chimpanzees and the less lethal HIV2 originating in monkeys. The HIV strains were probably introduced to humans between the 1920s and 1940s. Flu viruses are commonly transmitted by birds, especially waterfowl. The human immune system is 'naive' to bird flus- infection is easy, and we don't have the money and time to prevent 'fires', just to put them out. The mosquito born Zika virus was first identified in a rhesus monkey, only recently emerging in humans.

After dealing with the positively ugly viruses, Dr Turner focused his attention on the merely 'bad' viruses. Some viruses make you sick but don't kill you. He repeated the 1969-vintage quip: "We can put a man on the moon but we can't cure a common cold." Colds are caused by a variety of rhinoviruses. If an individual has respiratory problems, such as asthma, a cold can be serious, but many people are healthy enough to go to work with a cold, becoming links in the chains of contagion. Rotaviruses can kill children, but generally don't kill adults. Approximately 5% of child deaths in the developing world can be attributed to rotaviruses, which cause severe, dehydrating diarrhea.

Dr Turner then posed the question, can viruses be used in biocontrol of pests? He brought up the use of myxomatosis, the dreaded 'white blindness' of Watership Down, to control the invasive rabbit population of Australia in the 1950s. While partially successful, this introduction generally failed because the virus tended to kill rabbits before they had a chance to transmit it. Dr Turner chalked this up to yet another example of the folly of introducing invasive species to Australia.

Dr Turner then focused his attention on the 'good'- are viruses good for ecosystems? He noted that an absence of predators tends to throw biological systems out of balance, citing the absence of the wolf in most of North America, and the resultant explosion of the deer population, as a factor in the spread of the bacteria that cause Lyme disease... fewer deer, less Lyme. Viruses indirectly regulate the photosynthetic activity of cyanobacteria in the oceans. Cyanobacteria evolved about 3.5 billion years ago, and altered Earth's atmosphere by elevating oxygen levels. Cyanophages outnumber cyanobacteria by a factor of ten to one, regulating the cyanobacteria population. The cyanophages carry the genes which code for photosynthesis. Dr Turner noted that viruses infect other organisms and continually 'churn' genes. Approximately one in twenty of a person's daily breaths contain oxygen produced by virus genes.

Dr Turner then posed us a riddle: What would you trade 36 bushels of wheat, 72 of rice, 4 oxen, 12 sheep, 8 pigs, 2 barrels of wine, 4 barrels of beer, 2 tons of butter, 1000 pounds of cheese, a bed, a suit of clothes, and a silver cup for? The answer, of course, is a tulip bulb, but not just any tulip bulb, but a bulb infected by a tulip 'breaking' virus which resulted in fantastic mixtures of colors.

Dr Turner then posed the question, can viruses solve health problems? He brought up the topic of antibiotic resistence, citing MRSA and XDRTB as worrisome diseases- the drugs used to treat them pose dangers to the body. Antibiotic resistance is a global problem, and will be implicated in hundreds of millions of deaths worldwide by 2050. Bacteriophages are viruses that only kill bacteria- they could be used as an alternative to chemical antibiotics. Bacteriophages could be used as a self-amplifying drug- they multiply, find and kill new bacteria. In the mid-twentieth century, the Russians and Poles invested more heavily in phage therapy than in antibiotics. Phage therapy was used to treat field wounds and cholera. In the case of cholera, patients were rehydrated and given anti-cholera phages. Bacteria can evolve phage resistance. Dr Turner asked, can we develop a strategy that works even with the evolution of resistance? He indicated that the best strategy would be to discover phages which attack bacteria by binding to virulence factors- by binding to these sites, the phages would force the bacteria to evolve phage resistance by compromising virulence. Resistance would be achieved by becoming more dangerous. OMK01 (PDF link),a recently discovered bacteriophage, found in a Connecticut lake, effects the efflux pumps that bacteria use to remove antibiotics. OMK01 forces bacteria to trade phage resistance for antibiotic resistance. Dr Turner referred us to the 6/3/2016 edition of NPR's Science Friday. In 2006, the USDA approved the use of phages to combat bacteria which can taint deli meats.

Dr Turner then posed the question, would you be here without viruses? He indicated that 10% of our DNA comes from viruses which entered the genetic germ line- these genes are known as endogenous retrovirus genes. Syncytin, a protein produced by endogenous retroviral genes, is crucial to the formation of the placenta- the protein is necessary for the proper reaction of the immune system, which does not treat the fetus as a parasite. All placental mammals are made possible by viral DNA, which is a really good note on which to end a lecture.

The lecture was followed by a Q&A session. Some Bastard in the audience asked if viruses could be used in gene therapy to combat genetic diseases. While viruses are good at swapping out genes, CRISPRs are better tools, simple enought to use on multicellular organisms for correcting genomes. Another member of the audience asked, are viruses alive? Viruses are often conceived as 'quasi-living', but Dr Turner considers them living because they can reproduce and they are subject to natural selection. Asked whether viruses could jump from one 'domain' of life to another, Dr Turner indicated that this is unlikely, because cross-domain protein recognition tends to be rare, though it has often been attempted in the lab. Dr Turner then brought up the topic of bacteriophage prospecting becoming a growth industry- there is an illimitable supply of viruses out there, some of which may have therapeutic value. He then pondered whether or not humans co-evolved with phages to welcome them into the body. Asked about tips in case there's another dangerous flu outbreak, he noted that people should have a home preparedness kit so they can stay home until the epidemic wanes... I guess I need to download more ebooks!

Dr Turner delivered a top-notch lecture, informative and entertaining. I'm biased toward biological subjects, so this lecture was definitely in my top tier. Dr Turner, an extremely nice guy, lingered for an 'adult beverage' afterward, and I had a brief conversation with him about OMK01, which he told me was located in Dodge Pond, a polluted body of water not far from Lyme.

Kudos to Dr Turner, Dorian and Margaret, and the staff of the beautiful Bell House for yet another fantastic lecture. Here's the first of a three-part video series on viral biology by Dr Turner:





Crack open a beverage and soak in that SCIENCE! Be sure to watch the other two videos in the series- more videos, more drinking, more learning.

Oh, and this month's lecture was the annual Lasker Foundation collaboration with the Secret Science Club. Special thanks to the good folks at the foundation for their support. The foundation was giving out these great T-shirts with the slogan: If you think research is expensive, try disease.

Wednesday, May 21, 2014

Post Lecture Recap: I Get By With a Little Help From My Friends

Last night, I headed down to the beautiful Bell House in the Gowanus section of Brooklyn, for the latest Secret Science Club lecture. This month's lecture featured the triumphant return of NYU microbiologist Dr Martin Blaser. As you may recall, Dr Blaser's last lecture focused on the bacteria which live inside the human gut, with a special spotlight on the H. pylori bacterium, which is endemic to the human stomach. This month's lecture was a companion piece to Dr Blaser's new book, Missing Microbes:How the Overuse of Antibiotics Is Fueling Our Modern Plagues.

Dr Blaser began his lecture with a discussion of the conundrum of early life antibiotic exposure. Each and every human being on the planet has a plethora of microbial symbionts. These symbionts are ancient- all animal lineages have them, which is evidence for such symbiotic relationships having existed among the first animals to evolve. These symbionts are "niche"- different microbes thrive in different regions of the body, with oral bacteria differing dramatically from gut bacteria, skin bacteria, and urogenital bacteria. These symbionts are persistent and conserved- after infancy, an individual's interior biome becomes remarkably stable throughout one's life. Finally, these symbionts are host-specific. Each individual has a unique microbiome. Humans harbor more bacterial cells in their bodies than "human" cells. 70-80 percent of the cells present in and on the human body are microbes. Even more dramatically, 99 percent of the genes present in the human body are microbial genes.

Dr Blaser then discussed the effects of microbial symbionts during pregnancy. Throughout pregnancy, the microbiome changes. In a study of germ-free mice introduced to bacteria taken from the gastrointestinal tracts of women in the third trimester of pregnancy, the mice gained weight and exhibited "diabetic" traits. The gut bacteria of pregnant individuals seems to "mobilize" calories in such a manner to benefit the developing fetus. The bacterial symbionts have co-evolved with the host... such coevolution can been likened to a dialogue between the host and its microbes. One of Dr Blasers main areas of inquiry is what happens when this relationship is perturbed.

A disappearing microbiota results in a changing human ecology- altered microbe composition affects physiology. The early microbiome affects development, with early antibiotic exposure correlating with the incidence of obesity. The geography of obesity and the geography of antibiotic use correlates in a very suggestive manner. It has long been known that subtherapeutic use of antibiotics will promote growth in farm animals. The earlier in life this antibiotic use occurs, the more efficient its results.

Studies indicated that the subtherapeutic antibiotic treatment (STAT) will result in greater muscle mass. Add fat to STAT, and the antibiotics pontentiate fat gain. A study was performed to determine if increased adiposity was durable with limited antibiotic exposure- administration of antibiotics for four weeks was sufficient to cause long-term adiposity. In subjects exposed to antibiotics from birth, the weight gain was more pronounced. Mice exposed to early antibiotic "treatments" down-regulated their immune systems. With time, the "fecal community" of microbes can revert to normal after the cessation of antibiotic exposure, but the effects on body mass are permanent. Antibiotic exposure need not be persistent- "pulse" doses of antibiotics are sufficient to affect immunity.

During development, an organism's stem cells receive signals from its microbial symbionts. In early life, there is a more diverse microbiome, which tends to stabilize as one grows into adulthood. One antibiotic dose can decrese microbial biodiversity, which can alter development. It is estimated that the population in the U.S. has lost 20% of its microbial biodiversity- antibacterial activities have "collateral damage".

Dr Blaser enumerated a plan to address the diminishing microbial biodiversity. Research about the consequences of overuse of antibiotics has to continue. Education about the risks of antibiotic overuse needs to proceed. The development of narrow-spectrum antibiotics which target deleterious microbes while doing minimal damage to helpful symbionts needs to be prioritized. Remediation of damaged internal biomes with probiotics needs to be promoted, with the reversal of the loss of biodiversity the end goal. Finally, the recovery of "lost" microbes needs to be investigated.

Once again, Dr Blaser delivered a thought-provoking lecture on a topic which has far-ranging implications on human health. In the Q&A session, he went into more depth on such subjects as fecal transplants. Some bastard in the audience asked about the implications of antibiotic overuse on autoimmune maladies. Dr Blaser indicated that a diminished internal biome has been implicated in some forms of asthma, and there are now studies concerning the role of a diminished microbiome in type one diabetes.

To get a taste of Dr Blaser's congenial lecturing style, here is the man himself being interviewed on The Daily Show:




For a more substantial interview, here is Dr Blaser's appearance on Leonard Lopate's radio show.

Needless to say, last night's lecture was yet another phenomenal presentation of the Secret Science Club. Here's a tip of the hat and a heartfelt thank-you to Dorian, Margaret, and the staff of the beautiful Bell House.

EDIT: Holy cats, I left out a crucial part of the lecture, having been rushed when I was composing this post. One of the most important items was a timeline of antibiotic development- as microbes evolved resistance to antibiotics (it's a simple matter of evolution- any bacteria not killed by an antibiotic will reproduce, and their descendents will be resistant). New antibiotics have been developed to counter microbial resistance, and the microbes would develop resistance to the new antibiotics. We are now at a stage where there are multiple-resistant strains of various microbes, with MRSA being a particularly pernicious example. Sorry about this lapse, folks!

Sunday, August 14, 2016

Science is Cool, Literally

Today was another scorcher, so I decided to take shelter from the heat in the American Museum of Natural History. In the interest of full disclosure, my primary reason for heading down to the museum was the imminent closing of the Secret World Inside You exhibit. I parked in the Bronx and took the 1 train down to 79th St, sharing the subway ride down with some revelers heading to the Dominican Day parade, felicidades, mis amigos Dominicanos.

The museum was a cool respite from the scorching environment of Manhattan, and I proceeded up to the third floor for the exhibit, previewed in this video:





The exhibit started with the topic Meet Your Microbiome, which featured a video presentation by Dr Martin Blaser, who delivered two lectures with the Secret Science Club.

The basic gist of the exhibit was that 99% of the genes in your body aren't yours, they belong to the microbes which inhabit your body. While these microbes sometimes cause illness, most of them are harmless fellow travelers and some of them are necessary for proper health. Even the harmless bacteria provide some benefits, as they crowd out hostile microbes, such as the fungi which cause athlete's foot.

The exhibit was broken down into sections detailing the various biomes of the body, the introduction to the skin's biome being a nice bit of poetic language expressing scientific truth:


Your skin is the largest organ of your body. In an average adult, this protective layer covers some 20 square feet (1.8 square meters). Think of your skin as a sprawling countryside of hills and valleys, cracks and crevices, smooth slopes and rough terrain. Some parts are cool and dry, others warm and humid, and still others oily or forested with hair. Many species of bacteria, fungi, and other microbes call this landscape home.


There was a display about microbial transfer, with an amusing report of roller derby players having more similar microbiomes after the bruising contact of a match.

Another big part of the exhibit dealt with pregnancy and childbirth- in the womb, a fetus is protected from bacteria and viruses in its amniotic sac, and during natural childbirth, the baby picks up a bit of its mother's microbiome while exiting through the birth canal. Infants born by cesarean-section do not receive this beneficial microbial slathering, so swabbing C-section delivered babies with extracts from mom's birth canal may show some promise in remedying this microbial deficit.

The section of microbes' role in the health of their host was fascinating- there were placards detailing Helicobacter pylori's mixed role in human health (described in some detail in this lecture recap). Another bacterium given accolades is Lactobacillus johnsonii, which may provide hosts with lower rates of asthma and allergies which affect the lungs. Bacteroides fragilis can reduce inflammation in colitis sufferers. One particularly funny display illustrated the use of fecal transplants to aid colitis patients infected with Clostridium difficile:




Yes, I am an overgrown eight year-old.

There was also a really funky model of a macrophage engulfing harmful staphylococci while ignoring useful bacilli and red blood cells:




The caption of the display likened the macrophage to a well-behaved dog, warding off intruders but welcoming to friends. Can you dig it?

Other sections explored other bodily biomes, such as the mouth, with a special focus on the role of acid-producing bacteria in causing tooth decay.

The exhibit featured a lot of interactive displays. One was a game called 'Build your microbiome', which simulated the development of gut bacteria through diet, stressing the importance of probiotics and vegetable matter which provides a lot of nourishment for gut bacteria. One grand interactive exhibit portrayed a woman laying on a table, surrounded by icons which, when touched, would bring up displays of the microbes inhabiting her body, from her hair to the soles of her feet.

The exhibit was really well-done, with a myriad of tiny lights to symbolize the various symbiotic microbes and a lot of buttons to push for inquisitive children. It was a charming exhibit, conveying a topic which is still a bit 'foreign' to a society raised to believe that 'germs' are bad. It was definitely worth heading out of the house in the blistering heat to attend this cool exhibit.

Friday, March 3, 2017

Secret Science Club Post-Lecture Recap:Formidable Formicidae

Last night, I headed down to the beautiful Bell House, in the Gowanus section of Brooklyn, for this month's Secret Science Club lecture featuring myrmecologist (how I love that word), evolutionary biologist, and adventurer Dr Corrie Moreau of Chicago's Field Museum of Natural History.

Dr Moreau (could there be a more perfect name for a biologist?) began her lecture with a note of gratitude toward her subjects, noting that ants have taken her around the world, and that tropical fieldwork is tough, fun, and rewarding. She learned how to do rainforest 'canopy work' in French Guiana, and her travels sometimes involved unintended consequences, such as dealing with tropical illnesses. While her collecting of specimens was typically above-board, involving extensive dealings with customs agents, she once smuggled a tick out of Uganda... in her nose (this seems to be a trend). She underscored the importance of documenting biodiversity by noting that habitat degradation is affecting many ecosystems. Dr Moreau chose to study ants because they are beautiful and diverse, with approximately thirteen-thousand species known to science, with estimates of unidentified species being twice that number. Notable ant varieties include the fungus-growinng ants, the army ants, which can be used as emergency sutures in the field, and the honeypot ants, which include two convergently-evolved lineages, one in Mesoamerica, one in Australia. Dr Moreau noted that the honeypot ants live in environments which have boom-or-bust resource cycles, so 'repletes' store liquid resources until they are needed. She offered this piece of advice- eat the golden repletes, which are filled with nectar... the dark ones are often filled with the remains of rotting carcasses. Dr Moreau then covered the Dracula ants, which feed prey items to their larvae, then poke holes in them in order to drink their hemolymph, resulting in heavily-scarred larvae.

After this introduction to some of the more outré ants, Dr Moreau then discussed the processes that generate biodiversity. Some branches of the ants' evolutionary tree have more species than others, and some regions of the globe harbor more species of ants than others. Some traits have evolved numerous times in different ant lineages. Speciation can occur due to geographic separation of populations. Determining the pace of evolution, whether fast or slow, depends on studying the fossil record. One crucial factor in evolution is symbiosis- organisms evolve together. Dr Moreau quoted her doctoral advisor, E.O. Wilson, who characterized ants and other invertebrates as "The little things that run the world." Then she amended this observation by noting that microbes are the little things which run the little things which run the world.

Dr Moreau then covered variety of symbiotic relationships which ants have with other organisms. There are ants which 'farm' scale insects for the honeydew they secrete. Other ants have a mutualistic relationship with acacia trees- the trees provide food and shelter for the ants, which defend the trees from herbivores. Also, there are ants which have symbiotic relationships with fungi, both beneficial and horrifically deleterious. Ants don't exist in isolation, when studying them, researchers need to think about other organisms as well.

Ant evolution and the evolution of the flowering plants are inextricably linked- although ants aren't pollinators, some groups of ants exploded evolutionarily with the spread of the angiosperms. Many ants shifted from predation to plant-based diets. Ants play an important role in seed distribution, with certain plants having evolved structures called elaiosomes, protein-rich and fatty tissues which are attractive to ants. After eating the elaiosomes, the ants discard the rest of the seeds in their nitrogen-rich middens, far from the mother plant.

With thirteen thousand ant species known to science, a phylogeny of ants is needed to understand evolutionary relationships and dispersal. Fossil ants are not uncommon- ant fossils are typically of insects trapped in amber and insects being compressed in fine sediment. To form a decent paleontological record, at least forty-three fossils are needed for minimum calibration points. The are extant ant fossils from one-hundred million years ago on, but there seems to be an explosive radiation of ant genera in a narrow window, about thirty million years ago- this ant invasion explosion occurred when the ants rode the wave of flowering plants.

There is a latitudinal gradient in ant species richness, with the tropics harboring more species than colder regions. Dr Moreau indicated that there are two models to explain the biodiversity of the tropics- the cradle model and the museum model. The cradle model posits that evolution occurs more quickly in the tropics, that new species evolve in the tropics more frequently than in higher latitudes. The museum model posits that older evolutionary lineages tend to survive better in the tropics, that ancient forms persist. Put succinctly, in the cradle model, the tropics are species pumps, in the museum model, they are stable places in which species can hold out for a long time. The first ants evolved about one-hundred and forty million years ago. The configuration of Earth's continents was different then- subsequent plate tectonics affected the distribution of ants. The greatest diversity among the ants, the most endemic genera and the most species, is in the Neotropics. With evidence of the survival of older forms and the diversity of novel forms, it would be safe to characterize the tropics as both cradle and museum.

Ants are efficient at exploiting novel ecological niches. With the evolution and spread of flowering trees, ants were able to spread into the forest canopy (conifers aren't a rich source of exploitable resources). The evolution of herbivory among the ants coincided with the co-evolution of ants and endosymbiotic bacteria. Ants provide an excellent opportunity to study the diversity, distribution, and influence of gut bacteria. While ants harbor diverse bacterial communities, the nitrogen-fixing Rhizobiales are common among plant-eating ants, which feed at low trophic levels. The highly predatory army ants do not need nitrogen-fixing symbionts. Herbivory necessitated bacterial symbionts, which are not distributed equally throughout the ants' evolutionary tree. In the co-evolutionary process, more closely related ants have more closely related bacterial symbionts.

Dr Moreau then gave us an overview of the gastrointestinal anatomy of an ant, with an emphasis on the locations in which bacterial symbionts are found. Dissections of ants were conducted, and the bacteria in the mouth, the crop (from which ants can regurgitate liquid for other ants), the midgut, and the hindgut (the leg was also sampled as a 'control'). All of the dissected individuals had similar bacterial flora in their midguts and hindguts. The bacterial communities of the ants were dictated by what the ants ate. The herbivorous turtle ants have co-evolved with their gut bacteria for over forty-five million years. The bacterial communities of various ants- the herbivorous ants, the highly predatory army ants, the not-entirely predatory bullet ants- have to be compared and contrasted. In one particular project, Costa Rican bullet ants were collected, and their gut bacteria were studied.

After this fantastic overview of ants and their bacterial symbionts, Dr Moreau shifted the topic of the talk to the importance of science outreach, and the diverse tools needed to share scientific knowledge. Commitment to science necessitates outreach and popularization. Scientists have to convey to people how important science is to their lives. In order to combat the stereotypical view people have of scientists, scientists have to meet with people. Dr Moreau put together an exhibit called The Romance of Ants to chronicle her life and career in graphic novel form. The theme of the exhibit is that everyone is a scientist at heart.

The lecture was followed by a Q&A session. The first question involved the evolution of eusociality in the hymenoptera- eusociality evolved several times among the different branches of the hymenoptera- there are non-eusocial bees and wasps as well as eusocial ones. Here's an overview of eusociality and genetics (ants, bees, and wasps are haplodiploid- males are born from unfertilized eggs, so sisters are more closely related to each other than they are to the mothers or to any potential offspring). Some bastard in the audience asked about the antibiotic properties of ants- ants have a metaplueral gland which produces an antibiotic fluid which protects against bacterial or fungal pathogens- ants have a lot of associated bacteria and fungi. Dr Moreau then pointed out that the bastard had attended all-but-one of the Secret Science Club lectures, which caused said bastard to blush in a most incandescent fashion, luckily the beacon-like effect wasn't so apparent in the darkened Bell House. The bastard then asked Dr Moreau a hypothetical about using ants to treat a cut in the field- while ant, uh, antibiotics aren't a panacea, the use of army ant heads as sutures would definitely be in the tropical pharmacopeia. Another attendee asked about the ant population of New York- after a joke about hipster ants in Brooklyn, Dr Moreau noted that fungus-growing ants survive on Long Island, tending to build their colonies under power lines. Another question concerned invasive ants- out of the one-hundred worst invasive species worldwide(PDF), five are ants. Invasive ant species can devastate ecosystems and outcompete native species. They thrive in locations disturbed by humans. Ants have many characteristics which make them good invaders, such as the ability to exploit novel ecological niches. In the case of the Argentine ant, the insects form mega-colonies which do not compete- offspring of different queens will interact cooperatively, probably due to the ants passing through a narrow genetic bottleneck, so all of them are closely related. Another questioner asked when eusociality first appeared in the Tree of Life- the termites, which can be likened to eusocial cockroaches, were the first eusocial insects to evolve and there are even fungus-farming termites. How do ants communicate? Ants communicate through scent- they have glands which produce pheromones, which are chemical signals to other ants. How do researchers determine fossil ant affinities? Some fossil ants have unique morphologies, but many fossil ants are similar to modern genera- younger specimens look more similar to modern ants than older ones. Regarding behavior, every ant colony acts as an individual, each worker ant can be likened to a cell in a multicellular animal. This breaks down in the case of the invasive Argentine ant supercolonies, in which neighboring colonies are not recognized as different from each other. Regarding dissection, ant specimens are handled with jewelers' forceps, though Dr Moreau joked that a common refrain in the lab is, "Don't talk to me on dissection day!" Dr Moreau noted that there is ant-specific citizen-science- volunteers can catch ants in their backyards and send them to the lab. Dr Moreau then discussed the various body forms among ant species, and while most ants produce small workers and big soldiers, there are about ten species which produce super-soldiers, and that the 'super-soldier' gene can be switched on in individuals to produce these oversized soldiers... super-soldiers can be produced in the lab. Regarding the acquisition of gut bacteria, every time an insect sheds its exoskeleton, it sheds its respiratory and digestive invaginations, and loses gut bacteria. New bacteria are obtained from other ants through oral/anal trophallaxis.

Dr Moreau ended her lecture by stating that she is unwilling to let go of field research... She is a typical field biologist, she likes looking at live things as much as studying dead ones. She joked that some of her keenest observations were picked up lying on the ground picking up chiggers and ticks while studying her subjects.

As an individual who tends to prefer biology to the other sciences, I have to say that Dr Moreau really hit a grand slam with this lecture. She imparted important knowledge about some of our most interesting fellow denizens of Earth with passion, she outlined a model for communicating scientific knowledge to the general public, and she was very entertaining. I like to talk about the 'Secret Science Sweet Spot'- that combination of hard-science lecture, adventure narrative, and advocacy that characterize the best of the lectures, and this lecture hit on all of those cylinders. Also, Dr Moreau was in town for a conference, and all-around good-guy Dr Simon Garnier was the person who told her about the SSC, inspiring her to lecture in Gowanus. Dr Garnier attended with a bunch of students from his lab, and there were a gaggle of entomologists hanging out in the beautiful Bell House. In an informal discussion over beers, I had a talk with a young entmologist about haplodiploploidy and eusociality, and he mentioned that the thrips, which are haplodiploid, also have some eusocial species. Surrounded by entomologists, I made a joke about these entomologists forming a 'hymenoptera gang' and zooming along the highways and byways on Vespas. Good times, nerding out with great people!

Kudos to Dr Moreau, Dorian and Margaret, and the staff of the beautiful Bell House. Also, high fives to all of the assorted biologists in attendance, you are all doing great work.

Here's a short video of Dr Moreau lecturing on the evolution of ant gut bacteria:





Here's a longer video featuring Dr Moreau lecturing on biodiversity and the evolution of ants:





Dr Moreau also has several videos on the Field Museum's Brain Scoop YouTube channel. If you are going to get stuck in a time-sink, I can think of few better ones than the Brain Scoop.

Wednesday, February 13, 2013

Post Lecture Recap: The World in Your Guts

Last night, I headed down to the beautiful Bell House in the Gowanus section of Brooklyn for this month's Secret Science Club lecture by Dr. Martin Blaser, director of NYU’s Human Microbiome Program. Dr Blaser's title for the lecture was: "While Babies Sleep and Dream, their Microbiome Never Rests"- a very sweet, poetic title.

After a brief overview of the topics he would cover, Dr Blaser opened his lecture with a slide of the changes in the Greenland ice sheets due to global warming. Just as global warming is a change in the macroenvironment, there are changes occurring in the microenvironment inside our bodies.

The lecture then proceeded to the topic of the three "Kingdoms" of life, the Bacteria, the Archaea, and the Eukarya. To put our place in the scheme of things into perspective, Dr Blaser showed a slide of the "Tree of Life" and informed us that, in comparison to the distantly related bacteria Escherichia coli and Clostridium sp., humans can count as close relatives corn and fungi.

The microbiome is ancient, niche-specific, persistent, conserved, and host specific. Ever since animals evolved, they have had microbial symbionts. In a typical human body, there are 23,000 "human" genes present, and 8 million microbial genes. Put bluntly, 99% of the genes present in your body are bacterial. Different sites around the human body have different microbial populations. The diversity of an individual's microbiomes levels out with age, with the "adult" microbiome typically being established by the age of three. The host and the symbiotic microbes co-evolve- host and symbiont send "signals" to each other.

The next topic in Dr Blaser's lecture was the stomach bacterium Helicobacter pylori. H. pylori us the dominant microorganism in the human stomach, and has been around for at least 100,000 years and has a worldwide distribution. Approximately half of the world's population plays host to H. pylori. The bacteria adhere to the stomach epithelia and form "pedestals". The bacteria produce a protein called CagA which they inject into the epithelial cells by means of molecular "syringes". As an aside, I wish to note that molecular syringes may have formed a precursor to the bacterial flagellum, a finding which torpedoed the foolish "irreducible complexity" argument posited by "Intelligent Design" creationists.

Recently, H. pylori has been rapidly disappearing in many regions of the world- this graph shows the precipitous decline in the U.S. over eighty years. Currently, only about 6% of children in the U.S. possess H. pylori symbionts.

H. pylori has been implicated in gastric cancer as well as stomach and duodenal ulcers. Men with H. pylori are more likely to develop stomach cancer than men without H. pylori. As H. pylori disappears, the incidence of gastric cancer has decreased. There's a downside, though- as H. pylori disappears, the incidence of gastric "reflux" and esophageal adenocarcinoma has increased. Reflux, which makes esophageal cancer more prevalent, was rare in the 1930s, but the incidence has been increasing with the wane of H. pylori. H. pylori is bad for the stomach, but good for the esophagus. As Dr Blaser bluntly put it, you can't win.

The next topic of the lecture involved other health effects of H. pylori. The stomach produces the hormone ghrelin, which stimulates appetite. H. pylori affects ghrelin levels. Ghrelin levels are typically high in the morning, which triggers hunger, and decrease as one is satiated. If H. pylori is eradicated, ghrelin levels tend to remain high. The elimination of H. pylori has also been implicated in increased asthma rates and may play a role in the increased incidence of food allergies. In children under fifteen, there is an inverse association between asthma and the presence of H. pylori, but there is no such association in children over the age of fifteen. Asthma rates tend to rise with courses of antibiotics administered to infants- early H. pylori infection could possibly prevent asthma. Wheezing is caused by metacholine. H. pylori makes wheezing less prevalent in infants. the bacteria in the stomach protect the lungs. H. pylori can also cause increased skin sensitization. The disappearance of H. pylori may be related to T-cell depletion and increased gastric acidity. H. pylori is good for the upper regions of the gastrointestinal tract and bad for the lower reaches of the GI tract. It's good for us early in life, but bad for us later in life. Once again, you can't win.

The next topic of the lecture was an overview of the disappearing microbiota hypothesis. A changing human ecology since the 19th century has affected the transmission and maintenance of the indigenous microbiota, and the microorganismal composition changes have an effect on health. Since the 19th century, each generation of mothers has passed fewer microbes to its children. In a cross-cultural study, the diversity of microbiota in the U.S. has been found to be lower than that in the Malawian and South American indigenous populations.

One major factor in the transmission of microbiota is the method of birth. Mothers pass their microbiota to their children through the birthing process (vaginal birth transfers a more diverse microbiota than birth by Caesarian section), through the mastication of food for their infants, through nursing, and through skin contact.

Dr Blaser then went on a slight tangent about the overuse of antimicrobials, and injected a moment of bizarre hilarity by showing an ad for an antimicrobial stapler (as an aside, I wonder if that's why Milton was so upset at losing his red Swingline). He emphatically stated that less bacteria do not equal better health.

The "antimicrobials" discussion turned to the use of antibiotics. Out of the top eight prescriptions given to children, five are for antibiotics. 41 million courses of antibiotics are administered to children yearly. This may be a factor in the rise of obesity throughout the developing world for the last thirty years. The administration of low doses of antibiotics (STAT: sub-therapeutic antibiotic treatment) promotes growth in farm animals. The earlier the antibiotics are applied, the greater the increase in growth. Studies involving mice showed no difference in weight between mice given "STAT", but the mice given antibiotics had a greater fat mass. Not only does STAT create a greater fat mass, but it also changes the host's microbiota. The microbiota change precedes the development of obesity. Liver adiposity also increases with STAT. STAT also affects lipid metabolic processes and fatty acid metabolism. The antibiotics change the composition of microbiota through Natural Selection (microbes not killed by the antibiotics proliferate when "weaker" microbes die off) The application of antibiotics also decreases the activation of the immune system's T-cells, and changes genes which regulate obesity in early life.

Besides STAT, sub-therapeutic antibiotic treatment, studies were made of PAT, pulse antibiotic therapy, the administration of antibiotics as if an infection were being treated. In these studies, it was found that three "pulses" of antibiotics were sufficient to accelerate weight gain and resulted in bigger bones with a higher mineral content. It's possible that PAT could be resulting in increases in average height.

The administration of antibiotics reduces the diversity of microbiota- with each "pulse" there is a permanent reduction in microbiota species. If an ecosystem is perturbed once, it can recover, additional perturbations cause permanent change. Perturbed equilibrium changes all "pathways" in an ecosystem. This has an implication in the development of stem cells because microbiota create a context for development. By perturbing microbiota, we could be changing metabolic, cognitive, and developmental processes. A changing microbiota also has allergic and autimmune implications- a rise in allergies and autoimmune disorders could be "collateral damage" resulting from changing microbiota.

In the Q&A session, some bastard in the audience asked Dr Blaser if the various "probiotics" on the market were of any value. He indicated that most of the probiotics on the shelf were more triumphs of marketing rather than paragons of therapeutic value. He also asserted that more narrow spectrum antibiotics were needed to prevent large scale disruptions of microbiota. In a response to a question about Fecal Transplant Therapy, he indicated that the clinical trial showed that fecal transplants are useful in treating persistent Clostridium difficile infections. As an aside, I think I could become a regular POOP donor... I'm full of the stuff! Diet can change the microbiome somewhat, but the fundamental (heh heh) "fingerprint" of the microbiome doesn't change much.

Once again, this was a top-notch lecture in a top-flight series. It was also an appropriate lecture for the Valentine's Day season, because it was a celebration of the fact that no-one is alone, ever. So... love the little buddies who travel with you wherever you go. Special thanks to Dr Blaser, Secret Science Goddesses Dorian Devins and Margaret Mittelbach, and the staff of the beautiful Bell House. They are even better than my beloved gut-buddies, and I never have to worry about them giving me ulcers.

POSTSCRIPT: Me being me, I couldn't finish this post without putting up the video for Germfree Adolescents by the late great Poly Styrene and the X-Ray Spex: