Leonardo da Vinci, the original Renaissance man.
Leonardo da Vinci’s name is synonymous with genius. For good reason: this illegitimate child of a well-off Florentine notary rose from obscure beginnings in a sleepy town to become the polymath who defines polymathy. A painter and draughtsman, an engineer and scientist, an anatomist and naturalist, an entertainer to courts and kings across Europe, he is the rare example of someone rightly celebrated in his own time whose reputation has not perceptibly diminished in the almost five centuries since his death.
His notebooks -- unpublished during his life -- are famously written in a mirrored cursive, indicating da Vinci’s love of puzzles. This love was, it seems hard to argue, inextricably related to his drive to plumb the deepest mysteries of nature. Now, a team of scientists, anthropologists, and art historians has taken up a challenge da Vinci himself might well have enjoyed: unlocking the man’s genome.
One of the key players in this project is Rockefeller University’s Jesse Ausubel. Ausubel -- who directs Rockefeller’s Program for the Human Environment -- is an eminent environmental scientist. He played a key role in bringing climate issues to the attention of global political leadership through the first UN Climate Conference. He served in a central capacity at the Census of Marine Life, a decade-long project undertaken by a network of researchers aimed at cataloguing and identifying life in the seas. He’s been a big thinker at the intersection of ecology and technology for more than three decades, and is one of the few humans to have a species of lobster named after him. We spoke with Ausubel about the quest to understand da Vinci’s genome and the wide array of technological and social good that might come from it.
The project has an unusual genesis, according to Ausubel. “One of my very close Italian colleagues some years ago had said to me, 'Well, of course you've delved into Leonardo.' I said, 'No, I really hadn't.' He said, 'You're really missing something.' With his encouragement, I started reading Leonardo's notebooks and reading about him. He's infinitely rich. It's just one of the great pleasures of civilization and culture, to be able to look at his work. Some time after this, we were sitting around and one of my colleagues (a physical anthropologist and an expert on bones) said, 'Jesse, you come from Rockefeller University, you're surrounded by people who do genetics and genomics, and you know people who've obtained and sequenced the DNA of neanderthals. Why don't we try it ourselves to do something serious about Leonardo and try to obtain some of his DNA and sequence it?' It was one of these moments when people say, 'Well, why don't you do this?' And we said, 'Yes, it's a great thing to do.'”
The basic idea, as Ausubel explains, is to bring to bear on the case of Leonardo the same tools that have been used to sequence the genomes of other famous individuals -- such as Christopher Columbus and England’s Richard III -- as well as our distant ancestors the Neanderthals. These tools have seen an explosive blossoming in power and affordability over the past two decades, says Ausubel. “In the early days,” he told us, “it was necessary to have quite a good sample or pool of DNA. What's happened over the last decade or two is that we've become very good at what's called single-cell genomics, working from literally one cell -- or one part of a cell in the case of mitochondria -- even if it’s been damaged.
“Now, the entire genome of a person is three billion base pairs or chemical units that we label with the letters T,C, A, and G. The genes they form cover all kinds of things, for example, whether you have blue eyes or whether you have curly hair. There are a lot of genes for olfaction and smell. Obviously lots of sequences relate to the immune system. When we started trying to assemble portions of the genome, we wanted to begin with quite long strings, say a thousand letters, and we would overlap those, put them together, to compose the larger genome. Now -- partly because of greater computational power, or let's say the use of cryptography -- we can take short segments of 30, 40, or 50 base pairs, which are much easier to grab, and build up reliable sequences from these. We can get useful DNA out of more damaged and smaller samples, and then when we get some of these letters, we've gotten better at assembling the code, or breaking the code, so to say, and putting together meaningful strings. It's become cheaper, too. Sequencing the first human genome -- depending how you do the arithmetic -- cost a couple of billion dollars. Now, you can have your entire genome beautifully sequenced for $10,000; probably for less. Obviously, if Leo’s genome were going to cost a billion or two billion dollars, it wouldn't be feasible for us to do it.”
The most obvious source for genetic material would be the man’s tomb, of course, but Ausubel cited a few problems with that. Da Vinci is buried in St. Amboise, France, where he died after serving some years in the employ of King Francis I as what Ausubel calls an “event organizer: He put on spectacles with fireworks and automata such as robotic lions and all kinds of surprising things. He was also a wonderful musician. He was the most highly paid and sought after event organizer of the era, and so the King of France, to show that he was as distinguished and as important as the Pope or the Duke of Milan, said: ‘Leonardo will come and work for me. I'll give him freedom to do his own projects, and he'll make splendid entertainments for the court and amaze the world, and I will be his patron.’ Leonardo brought prestige to Francis.” But his place of burial has been disturbed at least twice, which raises the possibility of removals and contamination.
