Microcosm

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E. coli and the Elephant

p. 11.
Joshua Lederberg was only twenty-one years old when he began to work with Tatum, but he had a grand ambition: to find out whether bacteria had sex.

… Tatum was amassing a collection of mutant E. coli K-12, including double mutants – bacteria that had to be fed two compounds to survive. Lederberg reasoned that if he mixed two different double mutants together, they might be able to pick up working versions of their genes through sex.

… Twelve years later, at the ancient age of thirty-three, Lederberg would share the Nobel Prize in Medicine with Tatum and Beadle. But in 1946, when he picked up his petri dishes and noticed the spots that appeared to be the sexual colonies he had dreamed of, Lederberg allowed himself just a single word alongside the results in his notebook: “Hooray.”

p. 12.
Max Delbrück had originally studied under Niels Bohr and the other pioneers of quantum physics. … “The gene,” Delbrück proposed, “is a polymer that arises by the repetition of identical atomic structures.” To discover the laws of that polymer, he came to the United States, joining Morgan’s laboratory to breed flies.

“Phage Church”

… The ability to infect E. coli passed down from virus to virus, it became clear, had genes – genes that must be very much alike those of their host, E. coli. … scientists discovered certain kinds of viruses that could merge into E. coli, blurring their identities. These prophages, as they are called, can invade E. coli and then disappear. A prophage’s hosts behave normally, growing and dividing like their virus-free neighbors. Yet scientists found that the prophages survived within E. coli, which passed them down from one generation to the next. To rouse a prophage, the scientists needed only to expose a dish of infected E. coli to a flash of ultraviolet light. The bacteria abruptly burst open with hundreds of new prophages, which began to infect new hosts, leaving behind the clear pools of destruction. |}}

Oswald Avery는 pneumococcus를 이용한 실험에서 DNA만이 harmless strain을 deadly strain으로 바꿀 수 있다는 것을 보였다.

p. 15.
DNA was clearly important to life, because scientists could find it in just about every kind of cell they looked at. It could even be found in fly chromosomes, where genes were known to reside. But many researchers thought DNA simply offered some kind of physical support for chromosomes–it might wind around genes like cuffs. Few thought DNA had enough complexity to be the material of genes. DNA was, as Delbrück once put it, “so stupid a substance”

Avery의 실험은 DNA가 gene을 구성하는 물질임을 보였지만, Alfred Hershy와 Martha Chase의 실험이 있기 전에는 protein contamination의 가능성이 있다는 비판을 받았다.

p. 15.
Hershey and Avery searched for radioactivity and found it only within the bacteria, not the virus shells. Hershey and Chase then reversed the experiment, spiking the protein in the viruses with radioactive tracers. Once the viruses had infected E. coli, only the empty shells were radioactive. …
The structure was beautiful, simple, and eloquent. It seemed to practically speak for itself about how genes work. Each phosphate strand is studded with billions of bases, arrayed in a line like a string of text. The text can have an infinite number of meanings, depending on how the bases are arranged. By this means, DNA stores the information necessary for building any protein in any species.

The structure of DNA also suggested to Watson and Crick how it could be reproduced. They envisioned the strands being pulled apart, and a new strand being added to each. Building a new DNA strand would be simplified by the fact that each kind of base can bond to only one other kind. As a result, the new strands would be perfect counterparts.

It was a beautiful idea, but it didn’t have much hard evidence going for it. Max Delbrück worried about what he called “the untwiddling problem.” Could a double helix be teased apart and transformed into two new DNA molecules without creating a tangled mess? Delbrück tried to answer the question but failed. Success finally came in 1957, to a graduate student and a postdoc at Caltech, Matthew Meselson and Frank Stahl. With the help of E. coli, they conducted what came to be known as the most beautiful experiment in biology.

Meselson and Stahl realized that they could trace the replication of DNA by raising E. coli on a special diet. E. coli needs nitrogen to grow, because the element is part of every base of DNA. Normal nitrogen contains fourteen protons and fourteen neutrons, but lighter and heavier forms of nitrogen also exist, with fewer or more neutrons. Meselson and Stahl fed E. coli ammonia laced with heavy nitrogen in which each atom carried a fifteenth neutron. After the bacteria had reproduced for many generations, they extracted some DNA and spun it in a centrifuge. By measuring how far the DNA moved as it was spun, they could calculate its weight. They could see that the DNA from E. coli raised on heavy nitrogen was, as they had expected, heavier than DNA from normal E. coli.

Meselson and Stahl then ran a second version of the experiment. They moved some of the heavy-nitrogen E. coli into a flask where they could feed on normal nitrogen, with only fourteen neutrons apiece. The bacteria had just enough time to divide once before Meselson and Stahl tossed their DNA in the centrifuge. If Watson and Crick were right about how DNA reproduced, Meselson and Stahl knew what to expect. Inside each microbe, the heavy strands would have been pulled apart, and new strands made from light nitrogen would have been added to them. The DNA in the new generation of E. coli would be half heavy, half light. It should form a band halfway between where the light and heavy forms did. And that was precisely what Meselson and Stahl saw.

Watson and Crick might have built a beautiful model. But it took a beautiful experiment on E. coli for other scientists to believe if was also true.

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p. 18.
In 1957, FrancisCrick drafted what he imagined the dictionary might look like. Each amino acid was encoded by a string of three bases, known as a codon. MarshallNirenberg and HeinrichMatthaei, … ground up E. coli with a mortar and pestle and poured its innards into a series of test tubes. To each test tube they added a different type of amino acid. Then Nirenberg and Matthaei added the same codon to each tube: three copies of uracil. They waited to see if the codon would recognize one of the amino acids. In nineteen tubes nothing happened. The twentieth tube was filled with the amino acid phenylalanine, and only in that tube did new proteins form.

… frogs, and guinea pigs … In 1967, Nirenberg and his colleagues announced they had found “an essentially universal code.”

Nirenberg would share a Nobel Prize for medicine the following year. Debrück got his the year after. Lederberg, Tatum, and many others who worked on E. coli were also summoned to Stockholm. A humble resident of the gut had led them to glory and to a new kind of science, known as molecular biology, that unified all of life. Jacques Monod, another of E. coli’s nobelists, gave AlbertKluyver’s old claim a new twist, one that many scientists still repeat today.

What is true for E. coli is true for the elephant.

p21. E.coli가 세포막을 보호하는 다양한 막과 메커니즘을 가진 반면 우리는 피부를 이용하여 세포들을 보호한다. 우리의 소화관도 결국 피부. 피부 세포들은 우리의 세포와 외부 세계사이의 장벽이므로 매우 빨리 교체되어야 하는데, 그로인해 암의 발생 위험이 높아진다.

p22.
After James Watson and Francis Crick discovered the structure of DNA, their photograph appeared in Life magazine: two scientists flanking a tall, bare sculpture. There was no picture of the scientists who collectively mapped E. coli’s metabolism. It would have been a bad photograph anyway: hundreds of people packed around a diagram crisscrossed with so many arrows that it hooked vaguely like a cat’s hairball.

… E. coli gets its energy in two ways. One is turning its membrane into a battery. The other is by capturing energy in its food.

… E. coli gives itself a negative charge in the process, attracting positively charged atoms that happen to be in its neighborhood. It draws some of them into special channels that can capture energy from their movement, like an electric version of aa waterwheel. …

ATP molecules float through E. coli like portable energy packs. … It does not unleash all the energy in a sugar molecule at once. If it did, most of that energy would be lost in heat. … E. coli makes surgical tricks, step by step, in order to release manageable burst of energy.

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p23.
E. coli has to fight for iron by building iron-stealing molecules, called siderophores, and pumping them out into iron-bearing molecules. When they do, they pry away the iron atom and then slide back into E. coli. Once iniside, the siderophores unfold to release their treasure.

While iron is essential to E. coli, it’s also a poison. Once inside the microbe, a free iron atom can seize oxygen atoms from water molecules, turning them into hydrogen peroxide, which in turn will attack E. coli’s DNA. E. coli defends itself with proteins that scoop up iron as soon as it arrives and store it away in deep pockets. A single one of these proteins can safely hold 5,000 irons atoms, which it carefully dispenses, one atom at a time, as the microbe needs them.

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p24.
Life’s list grows longer. It stores information in genes. It needs barriers to stay alive. It captures energy and food to build new living matter. But if life cannot find that food, it will not survive for long. Living things nned to move … And to make sure they’re going to the right direction, most living things have to decide where to go.

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p26.
All it can do is swim in a straight line or tumble.

… An attractive molecule, … E. coli swims longer between its tumbles. This bias is enough to direct E. coli slowly but reliably toward the serine. Once it gets to the source, it stays there by switching back to its aimless wandering.

… Its array of receptors may turn out to be far more than just a microbial tongue. It may be more like a brain.

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p27.
The contrast between these two kinds of cells - sloppy and neat - seemed to stark in the mid-1900s that scientists used it to divide all of life into two great groups. All species that carried a nucleus were eukaryotes, meaning “true kernels” in Greek. All other species - including E. coli - were now prokaryotes. Before the kernel there were prokaryotes, primitive and disorganized. Only later did eukaryotes evolve, bringing order to the world.

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p28.
Only in the past few years have scientists begun to see how E. coli organizes its DNA. Their experiments suggest that it folds its chromosome into hundreds of loops, held in place by tweezerlike proteins. Each loop twists in on itself, but the tweezers prevent the coiling from spreading to the rest of the chromosome.

The system

p34.
Another similar repressor might keep the genes of prophages silent as well, Jacob thought. Perhaps these circuits are common in all living things. “I no longer feel mediocre or even mortal,” he wrote.

But when François tried to sketch out his ideas for his wife, he was disappointed. …

Jacob’s idea was so elegantly simple that it seemed obvious to anyone other than a biologist. Yet it represented a new way of thinking about life. Genes do not work in isolation. They work in circuits.

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p46.
E. coli expresses its individuality in other ways. In a colony of genetically identical clones, some will produce sticky hairs on their surface, and some will not. In a rapidly breeding colony, a few individual microbes will stop growing, entering a peculiar state of suspended animation. In a colony of E. coli, some clones like milk sugar, and other don’t.

The E. coli Watcher’s field guide

p52.
It can reach a population of 100 trillion, outnumbering the cells of our body ten to one. Scientists estimate that a thousand species of microbes can coexist in a single human gut, which means that if you were to make a list of all the genes in your body, the vast majority of them would not be a human.

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p57.
E. coli builds chemical weapons. Known as colicins, these deadly molecules kill in many ways. Some pierce the microbe’s membrane like a spear, forcing its innards to spill out. Others block E. coli from building new proteins. Others destroy DNA.

Everflux

Darwinian evolution의 증거를 보여준 실험.

p69.
The experiment would have resembled a slot machine that pays out a lot of small wins.

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p70.
The controversy did not die until JoshuaLederberg, the scientist who discovered E. coli sex, tested the jackpot hypothesis with a new experiment.

Lenski 그룹의 (long term) evolution 실험. 굴드의 생각과는 달리 독립적인 라인들은 꽤 비슷한 길을 걷는다.

p76.
Lenski and his colleagues took a close look at how the expression of genes changed in two lines of E. coli. They found fifty-nine genes, and in all fifty-nine cases, the genes had changed in the same direction in both lines. The evolutionary song remains the same

E. coli colony는 niche를 찾아서 분화한다.

p78.
Whether scientists study cichlids or E. coli or any other organism, they face the same question: Why specialize? Why don’t organisms evolve to become jacks-of-all-trades instead? There may simply be limits to how well one organism can do many things. …

Death and Kindness

Darwin at the drugstore

Open source

Palimpsest

p143.
The message you’ll actually get on your flagellum apron will be far simpler. Above the picture of the flagellum it reads, “Intelligent Design Theory.” And below: “If it looks designed, maybe it is.”

Playing nature

N Equals 1