Human cells are complicated machines, and scientists have recently gathered lots of detail about their sub-elements. But “nobody studies how these entities function as complex systems, and how they interact to determine cellular behaviors. Instead, people focus on just a small, manageable part,” says biologist Rick Horwitz. This is mostly because of the way academic labs are structured (to support deep dives on narrow slices of a problem) and the way government research money is distributed (only to very tightly defined projects, not for exhaustive, boundary-breaking macro-examinations).
To understand the astonishing ways that cells transform themselves, signal each other, migrate, and take various kinds of “action,” however, microstudies of proteins and genes and chemicals are not enough. One must watch the whole sprawling “movie” of what the cell does over time, and identify patterns. That essentially is what former Microsoft co-founder and current multibillion-dollar philanthropist Paul Allen created a new cell-science institute to accomplish. He donated $100 million to start the work, and personally recruited Rick Horwitz from the University of Virginia to direct the effort.
The institute’s 70 researchers work as one interdisciplinary team rather than as independent investigators. They use induced pluripotent stem cells—a new creation that allows a common skin cell, for instance, to be converted into a stem cell after scientists use chemicals and other stimulations to turn off certain genetic switches. A stem cell is capable of growing into any other more specialized cell (bone, muscle, blood, etc.), depending on what the body needs. By taking long, complete sequences of microscope images of those stem cells transforming themselves into more specialized cells, the Allen Institute scientists believe they will gather tremendous amounts of big-picture information about cellular machinery.
The institute will advance the field by releasing to all interested researchers both the original “movies” and any conclusions the Allen investigators draw from them. This is a classic example of unconventional, highly speculative science that is almost never funded through traditional university and government channels, yet can be a forte of philanthropy.
In 2017 Paul Allen created another new center, at the University of Washington, to map the development of cells using a different fresh technology. Every creature starts as a single cell, yet ends up with (in the case of humans) trillions of cells doing very different things. How do subsequent generations of cells grow and specialize over time?
Allen’s Center for Cell Lineage Tracing will insert “recorders” into the cells of mice and zebrafish that will trace their lineage from ancestor cells, and show how they mutated to take on specific tasks. Using this information and lots of computing power, the Allen teams will map the development of organisms from one zygote to a working body made up of hundreds of billions of special-purpose cells. This work—which Paul Allen funded with an initial $10 million gift, expandable to $30 million over eight years if it is successful—could produce valuable insights into human development, cancer, cellular repair, and other fields.
- 2016 Annual Report of the Allen Institute, alleninstitute.org/news-press/articles/2016-annual-report-multiscale-approaches-move-science-forward
- 2017 announcement of cell lineage center, alleninstitute.org/what-we-do/frontiers-group/news-press/press-resources/press-releases/paul-g-allen-frontiers-group-announces-allen-discovery-center-uw-medicine