World’s Most Wired
Erez Lieberman Aiden
Erez Lieberman Aiden wants to make a point about the fractal topology of chromosomes, so he’s sitting on the floor of a CVS grocery aisle in Harvard Square, looking for the right kind of ramen noodle.
Ramen noodles, it turns out, bear a certain resemblance to the stuff of life, though not any ramen will do. None of the fancy brands, nothing pre-cooked, just undergraduate dietary staple Nissin Top Ramen (Oodles of Noodles™) in an orange plastic wrapper.
An hour later, over a simmering pot, Aiden explains that ramen comes in an unentangled state: Drop a block into hot water, let it soften, and you can fork out strands without disturbing other noodles. Bring the water to a boil, though, let the noodles churn, and you can’t take a forkful without dragging along the whole mass.
“Being unentangled is entropically unfavorable,” he says. “Equilibrium for a long chain is to be knotted.” Practical enough to complain that a packet of noodles now costs 67 cents, Aiden can’t help talking like the 32-year-old wunderkind computational biophysicist he is.
Put another way, the noodles want to be tangled. It’s their natural, default state, the path of least resistance. Given the chance, they knot up. This is what your chromosomes, those long noodly spools of DNA and protein coiled inside every cell — so often depicted in X-shaped neatness by biology textbooks and commercial iconography — should do, too. But somehow they don’t.
Instead, chromosomes take what’s called a “fractal globule” form, twisting and looping into a state that’s extraordinarily dense, yet completely unentangled. With a small enough fork, you could pull part of one chromosome out without disturbing the rest.
It’s a marvelous shape, this fractal globule, and may even prove integral to life. Yet until 2009, when Aiden and colleagues unveiled Hi-C, a new technique for reverse-engineering the structure of entire chromosomes, the form had only been glimpsed in shadowy pieces.
With support from the National Institutes of Health, Aiden is now studying chromosome structure at even higher resolution. He wants to learn how genomic form relates to function, perhaps helping to explain central questions of disease and development that remain largely unanswered.
“There’s been this humongous black box: What exactly is the role that structure plays in the genome?” Aiden said. “Now we can start looking at that.”
“There’s been this humongous black box: ‘What exactly is the role that
structure plays in the genome?’ Now we can start looking.”
— Lieberman Aiden
Still just a graduate student when Hi-C and his fractal globule graced the prestigious cover of Science, Aiden is now a fellow at Harvard. In the intervening years, dozens of researchers have used Hi-C and its methodological descendants to open that genomic black box for themselves. In a way, Aiden’s legacy is as much about the method, the big-picture technique, as what he found.
That’s only appropriate. Aiden has always been a big-picture thinker; raised in the Midwood section of Brooklyn, it’s hard not to hear him without thinking of the protagonist of Pi, Darren Aronofsky’s film about a Brooklyn mathematician’s search for life’s underlying pattern, albeit without the character’s angst and pathologies.
“I enjoyed mathematics from a very young age,” he said. “At the beginning of college, I had this illusion, which was kind of silly in retrospect, that if I just understood math and physics and philosophy, I could figure out everything else from first principles.”
To be fair, neither does Aiden share the Pi protagonist’s archetypal scrawniness. A sturdy six feet tall, he has the slight paunch and strong back of a man who works long desk hours and spends a lot of time carrying infants. In June, his 2-year-old son was joined by a newborn daughter.
Aiden attended Princeton University, where his attentions ranged from the mathematics of linguistic development to the implications of German philosopher Ludwig Wittgenstein’s later statements on the nature of knowledge. “I had a wonderful time,” Aiden recalled.
Amidst these heady pleasures, however, he realized that “abstraction was not what I wanted to be doing. I wanted to do things with a tangible impact on people in my lifetime.” After graduating in 2002, Aiden spent a year at Yeshiva University — his extended family are Hasidic Jews — with the intent of describing historical change with mathematical equations, but his heart had already taken a comparatively pragmatic turn.
In fall 2003 he started a Ph.D. at Harvard and MIT, jointly supervised by evolutionary dynamicist Martin Nowak and geneticist Eric Lander. Both are famous in their fields: Nowak for research on evolution’s basic rules and the non-biological evolution of culture, and Lander as a Human Genome Project leader and interpreter of genomes. In their new student, their thinking cross-pollinated.
“It wasn’t totally unnatural to think about cultural evolution, and once I started, it became natural to say, ‘What’s going to be really transformative in this space?'” Aiden said. “It would be the ability to bring massive quantities of information to bear, based on the genomic model.”
- A 3-D genome map of chromosome 14. Each pixel represents the similarity between the spatial neighborhoods of a pair of megabases. (One megabase equals one million letters of DNA.) Position on the x- and y- axes represent their position on the chromosome. (Credit: Erez Lieberman Aiden)
- A streamlined three-dimensional rendering of a Hilbert curve, the fractal space-filling curve into which chromosomes fold without tangling. (Credit: Miriam Huntley, Rob Scharein and Erez Lieberman Aiden.)
orking with fellow Harvard polymath Jean-Baptiste Michel, a systems biologist and psychologist who also studied under Nowak, Aiden scanned hundreds of library books, building up a massive, millennium-spanning database of the English language. Out of this came a high-profile Nature paper on the evolution of verb conjugation, the seeming dryness of which belies its landmark status. For decades, the idea of cultural evolution had intrigued scientists, but never had it been studied in such exhaustive, quantitative detail.
The research was also exhausting. The researchers might have stopped altogether, but for a curious observation made during their 18 long months of book-scanning: Especially for old, obscure titles, the last person to take the book out often wasn’t a person at all, but Google, which had just started its Google Books project.
7 Favorite Paradoxes
Berry’s Paradox: ‘The smallest number that can’t be defined in 12 words or less’ (is a
definition in 12 words or less)
Braess’ Paradox: It is possible to build a new road in such a way that it takes longer
for everyone to get where they want to go.
Arrow’s Paradox: It is hard to design a good voting system!
Banach-Tarski Paradox: ‘A ball can be chopped up and reassembled into two balls.’
Exchange Paradox: There are two identical envelopes, one of which contains twice as much money as they other. You pick one at random, but before you open it, you are given the opportunity to switch. Should you? If so, should you switch twice?
Raven Paradox: ‘All ravens are black’ is logically equivalent to ‘all non-black objects are not ravens.’ So if you see a pink elephant (it’s not black and not a raven), is this evidence that ‘all ravens are black’?
Goodman’s Paradox: An object is called grue (resp. bleen) if it is green (resp. blue) before 2020 and blue (resp. green) afterward. [Of course, an object is called blue (resp. green) if it is bleen (resp. grue) before 2020 and grue (resp. bleen) afterward.] Is it just as logical to expect that grue objects will remain grue on Jan. 1, 2020 as to expect that green objects will remain green?
World’s Most Wired
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