The Human Genome Project: April 15, 2018
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This week’s theme: The Human Genome Project as a great example of speculative exuberance being necessary for innovation. Plus introducing the newest member of the Social Capital family, Urban Footprint.
Over the past several weeks in Snippets, we’ve been talking about the emerging practice of Synthetic Biology, how it fits into a longer story arc of innovation in modern molecular biology, and how it’s similar but also different to the software and internet boom. As we’ve been previewing for several issues now, one of the biggest points of comparison between molecular biology and the software industry has been the plummeting costs of one of the critical inputs that we saw in both. In the IT industry we called it Moore’s Law, and in biology it’s the plummeting cost of genomic sequencing that has actually outpaced Moore’s law to a remarkable degree.
Over the last twenty years, the cost of sequencing a human genome has dropped from over $100 million to under $1,000: that’s nearly three times as fast a rate of compounding as Moore’s Laws famous doubling of performance per dollar every 1.5 to 2 years. (To put that into perspective: Moore’s Law is considered one of the modern miracles of compounding technological dividends, and anyone who understands compound interest knows what it’s like to fight for single digit percent improvements in annual gains. A 300% improvement over what is considered the canonical example? That’s ridiculous.)
Snippets readers will know that Moore’s Law didn’t just simply “happen”: it was an outcome of decades of prior investment, subsidy, and speculation, which set the stage for a combination of technological innovation and market forces that made the modern software industry possible. Last year in Snippets we did an extended series around bubbles, sustained subsidy, and other forms of “non-rational” economic investment that are typically necessary for these large-scale transformations to occur. In biology, no financial bubble was responsible; instead, it was a different kind of speculative exuberance: an enormous, coordinated investment of billions of dollars of financial capital plus an arguably even larger amount of human capital over fifteen years into an initiative called the Human Genome Project.
The goal of the Human Genome Project was considered wildly ambitious at the time: first, to sequence the entire human genetic code, which had never before been done and seemed like an overwhelming challenge to many at the time; second, to drop the costs of sequencing genetic code by a factor of ten or more, from around $4 per DNA base pair to 50 cents or less. (In hindsight, we decreased it by a factor of 100,000, to around one dollar per million base pairs; but hey, gotta start somewhere.) The main technique being used was a method called Sanger Sequencing, which was invented in 1970 and was fairly robust and reliable but very slow. Furthermore, the mindset by many at the time was that Sanger Sequencing would remain the standard method for years to come, and the main resources necessary for carrying out the Human Genome Project was more time and more equipment. So, the project was largely considered to be a “loss leader” for the future of medicine: “These sequencing machines are too expensive for researchers or private companies to purchase on their own, so by sponsoring the human genome project, we’ll both gain knowledge and be left with a lot of useful equipment that we’ll then leverage in the future.”
As you might guess, a lot of people weren’t wild about this. A representative 1990 article in the New York Times entitled “Great 15-year project to decipher genes stirs opposition” contained some unambiguous opinions from vocal opponents, including “The human genome project is bad science, it’s unthought-out science, it’s hyped science” and especially “Everybody I talk to thinks this is an incredibly bad idea.” And in retrospect, even though the effort went on to have huge lasting impact, they weren’t wrong: by just about any rational economic calculation, it was a tremendous waste of money. Biology pioneer George Church, who has been brilliantly described as ‘the Tom Brady of Genetics’ (he’s got a lot of fans, and he’s got a lot of enemies, but there’s no denying that he’s brilliant), was one of the youngest members of the decision-making council at the time and recalls with frustration that the goals were almost entirely around getting data results first, rather than focusing on costs first and data later. As he recounts, on a recent episode of After On Podcast: (lightly edited for clarity)
“I personally don’t think it was audacious enough. I felt from the very beginning in 1984, when we first proposed it, that the goal should be to reduce the price — ideally to something that was too cheap to meter, like a thousand dollars — and then start sequencing genomes. You know, maybe do some tests along the way, but not aim to spend three billion dollars, which was our original goal, a number we kind of pulled out of the air — a dollar [base pair in the human genetic code] for one genome. A full clinical genome is actually two genomes — your mother’s contribution and your father’s contribution to you. And so the thing that did for three billion dollars was one of those, which would not be useful clinically. So we didn’t actually produce a useful kind of genome, which meant we had to develop a whole new set of technologies afterwards.
I considered it crazy conservative. Cheaper and faster are two different things. You can always make something faster by just buying more machines. There were some minor improvements, but to tell you how minor they were, almost none of the improvements that we made during the genome projects persisted. There are a few things from before the Human Genome Project that persisted; like shotgun sequencing, we still do that. But all the innovations in electrophoresis, which I consider quite incremental, like changing from slab gels to copper, those are mostly gone. Next-gen sequencing [which we use today] was based on a complete redo. It comes from microscopy. So, basically that 3 billion dollars was thrown away. Neither was the genome clinical-grade, nor were the technologies preserved.”
Eighteen years later, we now see clearly that both the data generated through the project and the equipment that was left behind both ended up being largely squandered, but we got something far more valuable instead. As Church calls it, the project created an ‘overhang’ of nascent science and technology which led to Next Generation Sequencing (which uses light instead of chemical reactions as a data transfer mechanism and can sequence DNA orders of magnitude faster than the older methods, at fractions of the cost), which thereby led to the plummeting costs and explosion of data that left the original project’s output in the dust. So, in retrospect, we did things absolutely inefficiently. But could it have happened any other way? Maybe not; we’ll never know. It’s not so different than many of the other enthusiastic bubbles that have led to bursts of wasteful infrastructure investment, much of which ultimately got ripped up and replaced, but which expanded the industry so rapidly that it created an entire new generation of technological progress that far outpaced the first. It’s not so different than Manifest Destiny giving us the railroad giants, the DOD giving us Silicon Valley, or the dot com bubble giving us high-speed internet. And the future of biology, of health care, of agriculture, and much more has that wasteful investment to thank.
The US Department of Agriculture rules that CRISPR-modified plants won’t be regulated as strongly as transgenic GMOs:
These are not your father’s GMOs | Antonio Regalado, MIT Technology Review
Scams worth knowing about:
Synthetic fraud: chasing ghosts in the credit system | Brett Johnson
The dots do matter: how to scam a Gmail user | James Fisher
Perspectives on transportation economics:
Analyzing 1.1 million NYC Taxi and Uber trips, with a vengeance | Todd W. Schneider
Understanding how Uber & Lyft grow in markets | Kevin Kwok
The Ben & Jerry’s crash course in transportation economics | Joe Cortright, City Observatory
Land, housing and cities:
The Dow of Cities | Joe Cortright, City Observatory
Exclusive interview: why Zillow is becoming an iBuyer | Inman
Other reading from around the Internet:
How to pick a career (that actually fits you) | Tim Urban, Wait But Why
Glass: humankind’s most important material | Douglass Main, The Atlantic
Fake news flourishes when partisan audiences crave it | The Economist
Chatbots: what happened? | Dave Feldman
Nikon versus Canon: a story of technology change | Steven Sinofsky
The evolving pharmaceutical benefits market | Kevin Schulman & Barak Richman, JAMA
Interface hall of shame: the Quicktime 4.0 player | Iarchitect
And finally, the Information 2018 Diversity Index (formerly the ‘Future List’), done every year in partnership with Social Capital, is now out:
2018 VC Diversity Index | The Information
Silicon Valley’s most and least diverse investors | Serena Saitto, The Information
In this week’s news and notes from the Social Capital family, we have a new company joining the Social Capital family that we’re very excited to share with you: UrbanFootprint.
In a world that’s becoming more urban ever year, we at Social Capital believe that cities, their citizenry and their governments are some of the most important areas where we should be paying attention. Cities and municipal governments are critically important for how our society works, but until recently they’ve been relatively ignored by the software industry — until technology like mobile phones and ridesharing suddenly put the next decade of disruption into clear focus, but without clear solutions. Fortunately, the deep, institutional knowledge and perspective required for cities to evolve harmoniously with software and 21st century urban development already exists. It exists in the minds and collective experiences of civil servants, urban planners, developers, and stakeholders in every part of the urban fabric. But without tools to bring those ideas together, and without the ability to uncover consensus between all of these different stakeholders, we’ll see more conflict, not less; more reinforcing inequality, not less; and more anger and resentment from citizens and voters, not less.
That’s why we’re so excited for the opportunity in front of UrbanFootprint:
Reviving our original social networks: cities | Jay Zaveri, Social Capital
In his blog post accompanying the announcement, Social Capital partner Jay Zaveri writes:
“On our journey to learn about city development, we met Peter Calthorpe and Joe Distefano — two brilliant and world-renowned urban planners who have worked on improving cities over the past few decades. They’ve helped cities ranging from Chongqing in China to Columbus in Ohio, one city at a time for 30 years. They’ve packaged this knowledge into a technology product over the last three years, including the planning best practices, data, models and insights, so that city officials, planning firms and even citizens can build sustainable, safe and resilient cities. They’ve tested the platform in a few cities over the last couple of months, including Los Angeles, Madison and Columbus.
Today, UrbanFootprint is coming out of stealth, and announcing a major partnership with the State of California, which is making UrbanFootprint available to urban planners in all its 440 municipalities. We’re excited to be an investor in and a partner of UrbanFootprint as it launches its product to empower planning at a parcel, neighborhood, city or region scale, simulating unlimited scenarios for development with an unprecedented understanding of outcomes.”
Later on this spring, we’ll do a larger feature in Snippets on cities, how they’re organized, how they interact and benefit from technology, and where we see unanticipated consequences that backfire for society. Most of all, we’ll spend time talking about how cities are unbelievably resilient systems — we can even call them ‘organisms’ — that represent one of humanity’s single best shots at getting the future right. If you’re an optimist, cities and the urban future are a great place to go looking for ways to make a positive impact. Welcome to the team to everyone at UrbanFootprint, and if you’d like to join, they’re currently hiring for engineering positions in Berkeley.
Have a great week,
Alex & the team from Social Capital
