Rapid industrial-strength nucleic acid sequencing technologies are highlighting the challenges faced by the research, medical, legal, ethical, and direct-to-consumer genetic testing communities in personalized medicine.
For example, who are the knowledgeable human beings who can explain to cancer patients—in a sensitive way—their best therapeutic option based on sequencing data from the churning genomic rubble of their life-threatening metastatic tumors? Who can confidently explain the disease risks faced by healthy couples, or their yet-to-be-conceived children, when those risks consist of an unknown summation of genetics and the myriad epigenetic effects of individual lifestyles?
Such challenges are not to be feared; we simply need to intelligently apply ourselves to understanding the benefits and limitations of such data, while discounting media reports, such as those in Science, that the National Cancer Institute has a plan to eliminate suffering and death from cancer by 2015. We need clinical reality, not the peddling of patently false hopes that mislead desperate cancer patients and their relatives who are vulnerable to such errant nonsense.
The commercial reality is that the powerhouses of semiconductor technology, pure chemistry, and raw computing power are making human genomes, their methylated derivatives (methylomes), and their RNA outputs (transcriptomes) a successful commodity. Sequencing factories are producing data at a speed that is unparalleled in the history of biology and generating a shockwave similar to the effects on the Vatican’s pigeons of the appearance of Galileo’s cat. Whether we like it or not, every one of us will ultimately be touched by sequence data and the acid test will be its usefulness, or lack thereof, in specific clinical settings.
While only a handful of sequenced human genomes were available a few years ago, by the end of 2011 American and European laboratories will likely finish sequencing 9,000 and 6,000 human genomes, respectively. In contrast, the Beijing Genomics Institute (BGI) in Shenzhen will complete somewhere between 10,000 and 20,000 genomes on its own.
Merck has signed a statement of intent to collaborate with BGI Shenzhen to explore opportunities in the healthcare space, and Twins UK and BGI Shenzhen will collaborate to sequence the methylomes of 5,000 twins to discover therapeutic targets. The U.K. government is set to examine whether an entire healthcare system is ready for genetic testing in the cancer sphere, with the National Health Service to begin mutation testing on as many as 12,000 cancer patients by 2011.
While this testing is with a very limited number of genes, it is inevitable that, as costs fall, whole-genome sequencing will become a reality throughout entire populations, and pharmaceutical and data-analysis companies will be major participants.
A proactive clinical approach to the sequencing deluge has already started at the Beth Israel Deaconess Medical Center, where clinicians, researchers, mathematicians, and software companies are creating and integrating new tools for sequence analysis and the training of next-generation molecular pathologists. While sophisticated noninvasive imaging technologies are de rigueur, it is molecular pathology enhanced by high-performance computing that will be the gateway to clinically actionable information from sequencing data.