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.