some of the seed money to Sage, Friend says.
When I asked him how far it’s come since we first discussed the Sage vision in March, he said, “It became real.”
Like with any startup, there have been bumps. Friend’s co-founder of the new nonprofit, Eric Schadt, left Sage in May to take a job as chief scientific officer of Menlo Park, CA-based Pacific Biosciences. Schadt said this makes sense because PacBio is developing more advanced genetic analysis tools that will be needed to really enrich the Sage database in the future, and that he can benefit both the company and the Sage database of the future by building up both organizations at the same time. So far, Friend says his partner is making good on his promise to spend one day a week working on Sage, and is traveling to Seattle frequently to stay in touch.
But really, Friend wanted to spend most of our interview talking about the deeper vision of Sage, rather than these nuts-and-bolts operational details.
The vision of Sage, Friend says, is to create the first-ever accurate disease models. This is sort of like how engineers can draw up models of how a plane with certain specifications should fly, which tells them a lot of what they need to know before actual lift-off. Having that kind of underlying model to understand basic laws of physics helps scientists interpret data streams they observe later, like when a plane is flying.
The pharmaceutical business, because it is dealing with the immense complications of what’s going on in the human body in real-time, has never come close to any models with this kind of predictive value. Scientists do experiments on animals, but they’re not the same species. Medicine currently relies on lots of what Friend calls “linear measurements,” like LDL cholesterol as a marker of heart attack risk, or Her2 gene mutations to grade the type of breast cancer a woman may have.
Diseases are actually far more complicated than a matter of a single gene or protein being out of alignment, but so far, these are some of the best facts medicine has to work with, Friend says. But now that sophisticated new genetic instruments are getting better, faster, and cheaper, it opens the door to much deeper understanding of the genetic symphony of what’s going wrong in an individual patient, and what kind of treatment might give them a greater likelihood of response. These tools can do everything from sequence the entire 3 billion letters of DNA in an individual in a row, to finding slight variations in the code called SNPs, to seeing the extent to which certain genes are turned on or off in a given sample—what’s called gene expression.
The experiments at Rosetta that gave birth to Sage looked at all these measurements, many of which were published in top scientific journals. Some of the most important work showed how abnormalities in individual DNA caused faulty transcription of RNA, which caused malfunctioning proteins, and connected all that underlying biology to a clinical diagnosis of disease. This sort of holistic data package is hard to find anywhere, and it’s the way Sage wants
