Time for Another Human Genome Project?

The scientific charge to read a human genome started gaining traction 25 years ago. Now it may be time to think about writing one.
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The scientific charge to read a human genome started gaining traction 25 years ago. Now it may be time to think about writing one.

Conceived in the mid-1980s, launched in 1990, and completed to first draft in 2000, the Human Genome Project (HGP) was one of the largest international science collaborations in modern history. Costing approximately $3 billion, it was also one of the most expensive. The HGP was visionary, initiated even before the first bacterial genome (much smaller) had been sequenced. It transformed biology into a digital information science, yielding ongoing returns that include new insights into the molecular basis of life, cancer, and evolution, and also practical applications, like rapid genetic tests for important diseases.

That was then, this is now. Today, in 2012, reading a human genome is no big deal. It takes about a day and is approaching $1,000 in price. BGI, the Chinese DNA sequencing powerhouse in Shenzen, is out to sequence 1 million human genomes, a million animal and plant genomes, plus a million bacterial genomes for good measure. The forefront of genetics has moved on to new frontiers. One frontier is informational, massive data crunching to simply make sense of all this genetic information. The other frontier is about writing DNA code -- genetic engineering.

Genetic engineering isn't what most people imagine it to be. It still conjures up the idea of white-coated scientists surrounded by test tubes and beakers bubbling away with colorful potions. In fact, there's no lab necessary, any old coffee shop will do. This is because genetic engineering's gone digital, all done with computer software, using programs that function much like word processors. Mix and match genetic code, spell and error check, shuffle bits around -- it's drag and drop easy. When it looks good, just hit send. Companies like DNA 2.0 or IDT transform the virtual DNA into the real stuff using DNA printers called synthesizers.

It's called synthetic biology. Fast, easy, and cheap, synthetic biology is genetic engineering for the Facebook generation. Projects that once took months now take minutes; that once cost millions, a few thousand. Personal genomics following the same Moore's Law cost curve as personal computing. It's no surprise that the field's pioneers are the under-25 set, that the number of people associating themselves with synthetic biology has grown astronomically, and the potential for disruptive innovation is waking up everyone from Big Pharma to DARPA to Bill Gates, who said if he were a teenager today, he'd be hacking biology, not computers.

Activity in synthetic biology is growing across the board, with groups large and small applying the technology to specific challenges, a biofuel here, a drug there, a new diagnostic test, and so forth. With each drop in the price of DNA synthesis, or improvement in making DNA assemblies, the more projects that boot up, the more companies are launched, and the more investor money is raised. Despite this activity, outside of the scientific community, few have heard of synthetic biology, and even fewer appreciate just how powerful the technology is.

It's about time this changed. To this end, perhaps it's time to consider a new grand challenge for genetics, one that captures the public interest. I can think of none grander than an international effort to write a human genome.

I want to be absolutely clear that I'm talking only about the task of writing a complete 3 billion basepair human genome, correctly organized into 23 chromosomes, and packaged into a nucleus. A technical challenge, validated by showing the synthetic genome is functional if microinjected into a cultured cell. What I'm definitely not suggesting is growing a baby from a synthetic genome. Before we can fly, we need to be able to walk.

Here's why I believe launching an effort to write a human genome makes sense. (Think of it as HGP 2.0.)

  • It's actually commonplace to write human genomes. Every time one of our cells divide, the cell's genome must be copied. The cellular machinery for perfectly duplicating DNA and packaging it into chromosomes may be complex and currently beyond our complete understanding, but it exists. Nothing needs to be invented, per se, just harnessed and controlled.
  • Synthetic genomes have already been made. Genetic scientist Craig Venter successfully wrote and "booted" a synthetic bacterial genome in 2010. A joint U.S.-China project is now underway to write and boot a synthetic yeast genome, about 10x larger and a billion years more evolved.
  • It's affordable today and rapidly becoming more so. DNA synthesis costs fallen by about half per year on average. Today they about $0.20 cents per DNA base, or about $600 million undiscounted to synthesize a human genome. Granted, that's a lot of money. But in the next 18 months, newer synthesis technology is expected to accelerate the price drop. Next-generation DNA printers should reduce prices by a factor of 1000, or roughly $600,000. Should this reduction stay on pace, the cost of synthesizing a human genome could fall below $1,000 as early as 2020.
  • DARPA's Living Foundries synthetic biology effort is already funding breakthrough new tools and technologies for genomic engineering, and making them available to all scientists.
  • Human genome-scale engineering would allow for more rapid advancement in cancer and stem cell therapies.
  • The HGP was one of the few life science endeavors that have captured the public consciousness, resulting in massive media coverage that continues to this day. An effort to write a human genome would build on this foundation.
  • Like the first HGP, while controversial, there are obvious benefits, for example, lowering the cost of developing new drugs or producing new fuels.

Overall, a coordinated effort to write a Human Genome would likely be completed in less than a decade, cost significantly less than the first HGP, and result in countless new biotech applications. To me, it seems a no-brainer when it comes to big ideas in the genetic space. What is surprising to me is that the genomics community hasn't yet advanced such a project. Eventually, someone has to. If there's a question mark hanging over this at all, it's whether the U.S. or China will lead the scientific charge.

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