Encompassing more than a decade of research and a $2.7 billion investment, the Human Genome Project marked the beginning of a new era in the biological sciences. Today, little more than a decade later, all it takes is $10,000 and a blood sample to sequence and analyze anyone’s genome in a matter of days. Something big isn’t just coming, it’s already here.
“NextGen sequencing is just exploding right now,” says Tom Hays, dean of the College of Biological Sciences. “We are at a point now that we can begin to peer into large amounts of whole-genome sequence data and try to understand the genetic variation from a functional perspective. We need the public and the University to engage in conversations about the promises and challenges this technology brings.” That’s exactly what the Understand Your Genome (UYG) symposium, held earlier this spring, was all about.
Co-sponsored by the College of Biological Sciences and the U of M Medical School, UYG was a first-of-its-kind collaboration between a major research institution and the leading-edge life sciences company, Illumina. During the conference, speakers discussed the opportunities and challenges tied to increasingly cheaper and more abundant genomic data. Each of the 45 attendees also received an iPad mini with their own genome preloaded onto Illumina’s “MyGenome” application, along with a hard drive containing their genome on Broad Institute's state-of-the-art "Integrative Genome Viewer" (IGV) software.
Whereas the use of IGV is predicated upon a certain level of expertise, the MyGenome app (available on iTunes) belongs to the first generation of tools designed to make genomic data imminently accessible to the average person. With the genome of Jay Flatley (Illumina’s president) included as a reference sequence, users navigate through a sleek genome map with the swipe of a finger. They can pan out to all 23 chromosomes or zoom in to individual base pairs, peruse the results of genetic tests, learn about medical conditions associated with particular allele variants, and more.
Though this app limits its scope to personal medical applications, projects like 1000 Genomes strive to accommodate broad-scale research endeavors. Thousands of unidentified genomes are and will continue to be made freely available to the public, with major implications for modern medicine.
“We're on the verge of a whole new world in medicine,” says Bonnie LeRoy, director of the Genetic Counseling Program and co-organizer of the symposium with Hays. LeRoy believes that whole genomic information will eventually enable physicians and counselors to comprehensively assess personal health risks. The idea is to foresee and prevent disease, thereby avoiding devastating financial and health burdens. “You don't have to get that cancer,” says LeRoy. “You don't have to wait for it to happen.”
That’s a massive cultural shift to say the least, and it’s not going to be easy. First, the general public needs to realize that we’re all in this together. “Nobody’s genes are perfect,” says LeRoy. "To say ‘I’m going to have genes where nothing ever goes wrong,’ is like saying ‘I'm going to buy the car that never has an accident.’ It’s simply not true.”
Furthermore, people must be willing to approach health goals proactively rather than reactively. Simply having access to a nifty app isn’t enough to get someone on the right diet or exercise regime. “One of the most challenging and interesting areas of medicine is changing health-related behaviors,” says LeRoy.
On top of re-conceptualizing our relationship with medicine, there’s a pressing need to gather vast quantities of genomic data, and to become better at interpreting, annotating and aggregating it. “What we each got at UYG were a couple of clinical findings and a boatload of variants of unknown significance. There’s not enough data yet to say what most of those variants mean,” says Kenny Beckman, director of the Minnesota Genomics Center.
“We've learned that biology is an information science,” says Beckman. “The way to deal with biological questions is to use a big data approach.” Imagine you could navigate your genome in the same way you’d navigate the web. Beckman likens our present conundrum to the challenges of organizing information during the Internet’s infancy.
Yahoo first tackled the problem by hiring humans to manually compile hierarchical lists of related websites—a situation that’s comparable to individual researchers painstakingly annotating individual genes. Then, Google came along with sophisticated algorithms that automatically pulled search results—similar to how today’s researchers often assay entire genomic arrays and use algorithms to analyze results.
“We need to go back into the Yahoo approach,” says Beckman. “Each data set needs to be closely read and understood and manually annotated. There isn't enough data to apply that Google approach yet.”
It’s clear that today’s students must grapple with increasingly tricky sets of technical and ethical questions. With robust active-learning courses like Foundations of Biology blazing the trail, CBS is providing students with the skill set to come up with the answers.
The Understand Your Genome symposium represents a very personal active-learning opportunity,” says Hays. “It's about you, so you’re learning about genomics in a very powerful and active way.” Though the UYG symposium lasted only two days, it left attendees with a powerful impression not only of their own genetic architecture, but also of the phenomenal opportunity and need to rapidly implement more course offerings in genomics.
Last fall, David Matthes led a new freshman seminar entitled “Genome.” Students sent DNA samples to personal genomics company 23andme, and for $99, they received snippets of data and analysis regarding personal medical and ancestry information.
“From an instructional standpoint, the human genome is the perfect integrative topic, spanning topics like biochemistry, cell biology, genetics, and evolution,” says Matthes. The seminar will be offered again this fall, and Matthes plans to develop a scaled-up version of the course for CBS juniors or seniors for the 2015-16 academic year.
LeRoy and her colleagues in Genetics, Cell Biology and Development also intend to offer a UYG-like graduate-level course as soon as 2015. Required for genetic counseling students and offered as an elective for others, participants would work with either their own or a free reference genome.
According to Hays, the next couple years should also see an influx of interdepartmental classes aimed at bioinformatics analysis. These sorts of classes are both timely and necessary, considering that within a year, the cost of sequencing a full human genome should drop down to about $1,000.
As the price tag shrinks, concerns about privacy and policy are ever on the rise. “If we are paralyzed by fear, we won’t be able to take advantage of the great promise for health benefits and biomedical discoveries that this information can bring us,” says Hays. “We need to expand the dialogue to better inform citizens on the scientific and ethical challenges surrounding whole genome sequencing.”
– Colleen Smith