In advance of the Cheltenham Science Festival session on the race for the $1,000 genome this Wednesday, panel participant Clive Brown agreed to write a guest post on the importance of advances in genomic technology. Clive is Chief Technology Officer at Oxford Nanopore Technologies, where he leads the specification and design of the Company’s nanopore based sensing platform, including strand DNA/RNA sequencing and protein sensing applications, which we’ve written about previously here at Genomes Unzipped.
Incidentally, the other panel members will be Adam Rutherford, presenter of the excellent recent genetics documentary series The Gene Code, and Genomes Unzipped’s very own Caroline Wright, and the session will be chaired by Times Science Editor Mark Henderson – so if you’re anywhere near Cheltenham, you should definitely check it out.
When the final Human Genome Project publication was published in 2004, hundreds of scientists from 18 different institutions from the UK to the US, China and Japan authored the paper. The cost of this phenomenal collaborative project has been estimated at more than $3 billion from its initiation, a ‘moon-shot’ that was necessary to step onto the path of improving the process of obtaining and understanding genetic information. In 2004 the cost of sequencing a whole (haploid) human genome was still in the region of tens of millions of dollars. In 2008 this dropped through $1 million, in 2009 through $100k and in 2011 the cost is approaching $10k.
Many people have criticised the fact that the Human Genome Project did not in itself deliver a new era of personalised medicine, without realising that the project was just the first hurdle which facilitated major steps forward in the basic scientific understanding of genomics – for example, understanding the basic structure of the genome or mapping the variation between different peoples’ genomes. Importantly, the foundations were laid for understanding the very complex mechanisms behind how the genetic code relates to the expression of a protein and therefore the ‘phenotype’ – how those genetic differences are manifested whether it is a trait or disease-causing malfunction.
This knowledge is needed as a foundation for the current and future crop of ambitious projects that aim to understand human diseases like cancer and how to use that knowledge to inform treatment strategies or new drug development. There is also much to learn about the genetics of infectious organisms: how do they mutate, become treatment-resistant, spread? Beyond human disease the world of agriculture is also adopting these technologies fast.
So how is technology making a difference? In the 1990s, the Harvard Business School author Clayton Christiansen coined the phrase ‘disruptive technologies’ to describe technology shifts that completely change a market, fundamentally altering the behaviour of a group of users. If you are old enough to remember life before laptops/smartphones (mainframe computers), mobile phones (land lines) and digital cameras (dropping your camera film at the chemist and paying ten pounds for 24 prints), think about how dramatically your computer, phone or photo use has changed.
It is not just the cost and simplicity of the technology that is key – it is the power of the users, developing critical mass and exploiting and evolving the use of new technologies in sometimes unpredictable ways that create markets. For example, text messages were initially intended to support mobile phone upgrades but in the time it has taken you to read these paragraphs about 100,000 texts will have been send in the UK. Now that iPhones are so broadly used, the business and user communities have developed nearly 400,000 apps independently of Apple.
This magic combination of improved costs, simplicity and power has been driving a similar revolution in genomics in recent years. A few years ago only a handful of labs had access to DNA sequencing technologies, but today there are many thousands, mostly using technology that was developed by a core team, including me, at the UK company Solexa. In a similar manner to the famous (but perhaps wrongly attributed) quote from IBM’s Thomas J Watson “There is a world market for maybe five computers“, in those days we were hearing arguments that there was no need for more advanced sequencing technologies. However, a thriving scientific community is confounding this, growing with this increased ability to analyse genetic data. As soon as basic questions are answered, more complex ones emerge and the capacity to answer those questions accelerates.
So why has genomics been disrupted by DNA sequencing technologies? A multitude of new application and scientific opportunities has opened up, many not foreseen either by the technology developers nor even the scientific community that is being further fostered by these developments. It is a highly networked group of researchers, where many research projects cross borders and the pace of new knowledge currently outpaces the ability to apply that knowledge. If you are considering further education, the world of genomics and bioinformatics will have amazing opportunities in coming years.
The idea of a ‘$1,000 human genome’ has been discussed since at least 2004. While the metric has no intrinsic significance, it became a symbol of a distant point of technology development where DNA sequencing would become accessible to mass-market science. In 2007 the US National Human Genome Research Institute (NHGRI) announced a series of technology grants to reach and exceed this target. In reality the $1000 genome is simply a point we will pass through in 2011/2012 on our way to a $100 genome and a $10 genome and finally to the point where the value of the information generated is far more important, scientifically and commercially, than the cost of generation. In 2007 the goal seemed almost impossible but it is now tantalisingly close.
However, as with all disruptive technologies, simplicity is as important as cost. Sequencing technologies have an increasingly lower entry point – you no longer need to be a large scientific institution with an army of scientists and informaticians to run these experiments. As well as the staggering power of large research centres, individual scientists are starting to write grants for DNA sequencing experiments that will be run from the benchtop, with lower waiting times for data and greater power to individuals. It’s something that we are very focused on at Oxford Nanopore.
What will this mean? Of course, many more higher-power research studies can be performed, faster. Healthcare professionals will become more versed in the language of DNA and healthcare systems will adapt to evaluate and integrate this new information. DNA/RNA data will be used at your medical appointments, whether to predict your response to a drug or to determine your best treatment path for a cancer. Cancers will no longer be categorised by the organ of origin or crude morphology, but by their genetic mutations. Tumours will be sequenced and compared to your healthy DNA while you are under consultation.
Ethical challenges will emerge more quickly that we can evaluate them. For example, non-invasive tests to sequence foetal DNA circulating in the maternal bloodstream will soon be applicable for disease testing. Will parents request information on gender or other characteristics? It will also be possible to analyse fragments of DNA/RNA that are floating in your bloodstream to diagnose disease early.
Crop scientists will not only have greater power to understand and influence breeding but the capacity to sequences entire fields of GM crops and the peripheral ecosystem – will this change the political climate for GM? As viruses could be sequenced immediately in the field and large scale screening becomes possible, could public health strategies be sophisticated enough to eliminate the risk of pandemics?
Let your imagination run wild – could genomics be used to design organisms to solve the energy crisis? Hundreds of millions of dollars are already being invested in research in this area.
Or alternatively, could the mass sequencing of vulnerable organisms be exploited to allow us to engineer or select them artificially to resist the effects of climate change? Some might argue that this may be a more expedient route than attempting to alter the individual lifestyles or imposing socio-economic limitations on 10 billion people?
In 2007 Nature Genetics asked its readers what they would do with a $1,000 genome. One respondent, Francis Collins who now advises president Obama on Science, asked back “what wouldn’t we do?”