Let me make a modest proposal: Seattle should commit to sequencing and interpreting the genomes of every willing member of its population and should do it within the next five years. This program would elevate Seattle to the forefront of personalized genomic medicine, leverage many advantages unique to our area, and create a vibrant and sustainable economic engine that will drive our region for decades.
I can hear the howls of protest now, especially from the halls of the City Council and the mayor’s office. Seattle faces a lot of challenges. Like most cities, Seattle is staring at revenue shortfalls, relatively flat growth projections, and a host of problems in environment, public health, education, social services, and infrastructure. These are all pressing, immediate needs.
But at the same time, focusing too narrowly on the short term and not investing in infrastructure leaves a city’s continued relevance and growth at risk. And while the planned waterfront tunnel is an example of a commitment to physical infrastructure, I’m talking about a similar commitment to infrastructure that supports, enhances and grows human capital, which I think will be at least as important for Seattle’s future. Committing to genome sequencing is that kind of infrastructure, and when combined with the business, research and health synergies that would come out of such a commitment, this path makes a lot of sense.
Next generation DNA sequencing is a paradigm shifting technology. It’s analogous to how the creation of the integrated circuit in 1958 led to the personal computer revolution via exponential growth in processing power. Biomedical research today is undergoing radical change due to Next-generation sequencing platforms that started with Roche’s 454 in 2005 and continue today with platforms like Illumina’s HiSeq, Life Technologies’ IonProton, and others.
Over the past five years the cost of DNA sequencing has dropped at a rate that betters Moore’s law. The original human genome draft sequence cost ~$2.8 billion dollars and was announced in 2001 after a decade of work. Today, a human genome sequence can be had for about $5,000 and will arrive in as few as a couple of weeks. Most experts in the field expect the cost of a genome sequence will drop below $1,000 in the next 3-5 years, and there’s no reason for the drop in cost to end there. The $100 genome will happen.
By committing to sequencing everyone, Seattle will realize several key benefits. On an immediate level, a large part of the cost can go right back into our community. I’ll admit, $100 per genome, is a bit disingenuous. The real cost of genome sequencing is not the outlay for the sequences but rather the costs of storing, analyzing, annotating and communicating the results of the raw data. A commitment to sequence everyone in Seattle would require an additional, greater outlay of funds for analysis, and that money could funnel into our local institutions.
Few places in this country have comparable skill in genome analysis as the UW Genome Sciences Department, and none is better. The UW Genome Sciences Department would be the logical and (I expect) willing partner for building and maintaining the analysis pipeline. Likewise, the Seattle area is home to several companies, including Microsoft and Amazon, that would make natural and highly interested parties for storing data, assisting in the annotation, and providing platforms to help standardize and democratize giving data back to Seattle’s residents in easy to use, easy to understand, and portable online tools. Imagine the cocktail party chatter when you whip out your genome app.
A commitment to sequencing Seattle would also provide an irresistible draw to all kinds of smart, innovative, ambitious professionals, such as bioinformaticists, genetic counselors, database and internet security specialists, clinicians, project managers, biomedical researchers, and public health administrators, as well as people who will create the occupations we don’t even know of yet, that will be needed to deal with this kind of data and infrastructure. Economies aren’t driven solely by commodities and resources. Intellectual and human capital will only grow in importance.
Seattle is already one of the more popular destinations for people looking nationally for where to live and have a career, and it’s not just because of our great weather. They come because. Seattle has a reputation as a forward looking, progressive city with a keen technological edge and an investment in the future. Sequencing Seattle will enhance our reputation and strengthen our draw for the kinds of innovative, risk-taking, technologically-savvy people that keep a city and a culture from becoming as stale as a week-old baguette.
And let’s not overlook the financial implications of a sequenced population. The incredible resource of a large population of sequenced individuals will draw in public and private funding from the government, non-profit agencies, and pharmaceutical companies. ‘Applications by our researchers to the NIH will have an incredible advantage because the groundwork will already have been done for cutting edge genomic research. Given the push for evidence based medical treatments following healthcare reform, pharmaceutical companies are under increasing pressure to tailor their new drugs towards defined responding subpopulations. They could pay to have every person in their clinical trials sequenced. Or they can choose to hold their clinical trials in a place like Seattle where that hurdle will have already been cleared.
Here’s another benefit: cost savings for diagnostic and preventive medicine. No one needs to be told how health care costs are rising. Seattle can be on the forefront of taking genomic information and doing prospective studies on how that information can help guide medication, treatment, diagnosis, prognosis. We have one of the strongest concentrations in public health knowledge in the nation and can leverage that expertise to learn how genome information will make people healthier in the coming century. In addition, in just one area, oncology, we are already seeing the benefits of rapid tumor genome sequencing to identify cancer-promoting mutations. In this form of treatment, the baseline genome is compared to the tumor genome to look for changes. Having the baseline genome already in the database speeds analysis and amortizes the cost.
Seattle can also be on the forefront of figuring out how can genome data be best used ethically and effectively. This year the Presidential Commission for the Study of Bioethical Issues delivered their report on “Privacy and Progress in Whole Genome Sequencing.” We can play a key role in leading and shaping the ethics of genome sequencing.
Last, I want to touch on what could possibly be the most amazing outcome: citizen science, in which people are able to create their own research programs on the fly to answer questions. Imagine that all participants are in a database with their own preferences on what kinds of queries (health, phenotype, behavior, etc.) that they’d be willing to participate in. Someone comes up with a query and broadcasts it to the group: “Is there a genetic element to coffee preferences?” Anyone interested gets a text, chooses yes or no to participate, provides their feeling about vanilla lattes, and immediately the cohort is assembled, curated and QC’d by hard-coded heuristics developed by UW Genome Sciences and hosted on Amazon’s Web Services.
Within minutes, specific findings are reported back in whatever way you’ve selected. At the same time, ghostwriting software automatically generates an academic paper that is immediately submitted to an open-source journal and posted online. Maybe everyone contributes a dollar when they join in, to defray processing costs. And that’s how you empower people to use this infrastructure to do novel science.
These might seem like great benefits, but I’ve already pointed out the real and immediate demands on Seattle’s budget. How can a multimillion dollar project like this get off the ground? Let’s break it down.
As I mentioned, I fully believe the sequencing of a human genome will drop to between $1,000 and $100 over the next few years. For purposes of making some back of the envelope calculations, let’s go for the middle point and say the average genome over the next five years will cost $500 per individual. Seattle has a population of approximately 616,000 people. But, we’re sequencing only those who want to have their genomes sequenced, so let’s say initial uptake is 25 percent. That means about 150,000 people, multiplied by $500, for a total cost of $75 million, just for the sequencing. The entire city budget for 2013 is $951 million. Seems like a non-starter.
But. This is where creative thinking comes in. Today globally we have a few major providers of genome sequencing services. Ask them: what can you do for us? Remember, prices are going down faster than Moore’s law. BGI or Illumina might be willing to cut a low deal, not just for the business, but for the privilege of being involved. Or maybe a new player gets involved. The promise of having hundreds of thousands of genomes to process might spur a Covance or other outfit to make a huge investment in these technologies.
What if the genome sequencing is backloaded like a bad ARod contract, so the bulk happens in years 3-5, with the first couple of years devoted to pilots and infrastructure? Maybe the budget for the first year is just a few million to assess the possibilities, find vendors, build a business case and line up stakeholders. Maybe the second year is just $5-10 million, which by then will buy 10,000 genomes to start.
Go to Amazon and Microsoft and Google and pitch them on being involved. They know how to handle and analyze data, and might be willing to cut a deal in order to work with this kind of resource. Prioritize diversity and outreach in the initial cohorts and use that as a lever to attract the Bill & Melinda Gates Foundation and PATH and Seattle Biomed and other public health institutions that are trying to help people in underdeveloped countries. Information we learn about the impact of different ethnic backgrounds on health can be applied back to the populations from which our local groups originated. Indeed, one of the main drawbacks of current genomics research is the overwhelming emphasis on European-derived (*cough* white *cough*) populations.
To Sum It Up
Think of this as laying fiberoptic cables in India. As Thomas Friedman described in The World is Flat, the vast investment in infrastructure in developing countries during the dotcom boom is why you can now outsource reading your X-rays or putting together that patent application to professionals in India for a fraction of the cost of doing it locally. Sequencing in and of itself is not the point; building a vast reservoir of data and encouraging a culture of innovation to do something with it is. And doing it now. This idea is already being talked up with larger organizations, such as the United Kingdom’s NICE (even if they may not be going about it the right way). Seattle has the opportunity to do it the right way, and if we wait until everyone else is also doing it, there’s not much advantage to that.
Think of this also as a call to arms. I see sequencing as the logical tool to keep our area vibrant and growing, but that’s because I’m a genome scientist. Ask someone in 3D printing and she might say Seattle should buy everyone a 3D printer (hey!…) The point is, the future of a city, more than ever, depends not on its natural resources and history, but rather on the quality and creativity of the thinking that happens there. What gets quality and creativity going are visions of the future that inspire.
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