Adopt new technologies to drive discovery
New technologies allow researchers to collect radically different kinds of data, make striking new observations, and create further technological inventions in an exponentially growing cycle of innovation.
“Every once in a while, a new technology, an old problem,
and a big idea turn into an innovation.”
– Dean Kamen
Robert Hooke had a knack for inventing and perfecting mechanical devices, and became enamored with the newly invented microscope. Upon examining a bit of cork, Hooke observed with his microscope millions of tiny monastery-like rooms in the cork material, which he named cells, the term used at the time for such monastic devotional spaces. Here was potentially the greatest breakthrough in the history of understanding the nature of living organisms — the first observation of the building blocks of living beings.
However, it was not Hooke, but the Dutch businessman Antoni van Leeuwenhoek who followed Hooke’s lead, and became the first person to discover single-cell microorganisms, and the universal importance of cells for life. Leeuwenhoek’s observations were so fantastical that they were rejected by the Royal Society, until the more established and respected Hooke graciously provided his own support for the outsider Leeuwenhoek’s observations, which were then understood to be the first descriptions of the simplest possible living things.
Deploying recently invented technologies is a powerful path to discovery. Each new technology opens up a space of inventive possibilities, like a bridge to a new land full of untapped discoveries waiting to be realized.
Time and again, it has been prudent to be aware of the latest technological breakthroughs and to be the first to explore new applications of these technologies. Most often, the person who successfully deploys new technologies to make a major discovery is not actually the person who originally invents the technology itself. Michael Faraday discovered semiconducting materials, but that it was at Bell Labs years later where these materials were used to create charge-coupled devices (CCDs), and it was even later when an engineer at Kodak, Steve Sasson, used CCDs to create the first digital camera, which was ignored by Kodak management, coinciding with the downfall of Kodak, as digital cameras took over the camera market.
This theme of the usefulness of technology not being envisioned even by its inventor has been repeated throughout history: Douglas Engelbart developed a way of selecting coordinates on a computer screen using a pair of wheels, and his invention was later modified by Xerox scientists to involve a rolling ball, but it still didn’t see widespread use until Apple introduced the computer mouse as an input device for the Macintosh personal computer.
Technology has had an unappreciated impact in advancing the arts and humanities: in 1777, the Swedish chemist Carl Wilhelm Scheele discovered the light-sensitive property of silver chloride after discovering chlorine, but failed to imagine the implications of his finding. This new technology lay fallow for 40 years, until Nicéphore Niépce made use of silver chloride to produce the first photographic images in 1816, launching the art of photography.
The Flemish painter Jan van Eyck adopted the use of the emerging technology of oil painting to advance the quality of his work. Prior to this, painters commonly used the medium of egg tempera, in which egg was mixed with water and pigments to create paints. The lecithin lipid in egg yolk acted as an emulsifier, to stabilize the mixture and prevent the pigment, egg, and water components from separating. While effective, egg tempera had its limitations, such as the speed with which it dried, preventing easy blending of colors after they had been applied to a surface, and the dull quality of the final dried product.
In the late 1300s, oil-based paint was emerging as a new medium (no pun intended), with new possibilities. Several artists began combining egg tempera with linseed oil, by first painting a layer with egg tempera, and then adding oil paint on top. Jan van Eyck was quick to adopt this emerging new medium, and became the first master of this technique, even though he didn’t invent it. The slow drying oil paint allowed van Eyck to experiment with blending of paints on the canvas, and to create glossier finished products, as well as to work with a wider range of colors, since some pigments were incompatible with the thiol compounds present in eggs. The brilliant, glossy colors characteristic of the works of van Eyck and subsequent Renaissance painters were made possible by adopting the new technology of oil-based paints.
I experienced the power of a new technology shortly after I started as a new professor at Columbia. I recall that I was sitting in the newly procured and therefore sparse office at the Columbia University Medical Center of my colleague Chris. He had been recruited to Columbia Medical Center, as one of the leading researchers studying the biology of neurons. Shortly after arriving at Columbia, He had invited me and another colleague Marie to a meeting to discuss a potential collaborative project in which we would try to develop a treatment for patients with spinal cord injuries. Marie was describing how such patients might be cured.
Marie was explaining that her work over the preceding decade had revealed that the myelin coating around the nerves in the spinal cord contained proteins that inhibit regeneration after spinal cord injury. I had always assumed that the problem with repairing spinal cord damage was that the nerves had to be stimulated to regrow across the damaged region. Marie was explaining that myelin actively suppressed nerve regrowth, and that one might be able to counteract this inhibitory effect of myelin to enable nerve regrowth, potentially curing spinal cord injuries.
Marie and Chris proposed that we perform a vast screen of thousands of chemicals for ones that might turn off this myelin-blocking effect, allowing motor neurons in the spinal cord to naturally regenerate. Now I understood the reason for the meeting: I had become skilled at using robotic systems to screen thousands of chemicals for a few that might exhibit a desired effect — Marie and Chris were hoping to realize their goal of finding chemicals that turned off myelin’s regeneration-blocking effects, allowing spinal motor neurons to regenerate and repair spinal cord injuries.
The challenge was to come up with an assay — a rapid and miniaturized test that would allow us to quickly screen thousands of chemicals for ones that could unlock a regenerative effect in spinal motor neurons. This was a daunting challenge. I had performed many robotic screens in which I measured cell death or cell growth. But measuring whether any of thousands of chemicals could cause neurons to send out projections, in the form of axons or neurites, as a first step to making neurons with regenerating axons seemed like a difficult assay. How would we measure whether axons had grown?
Chris had the answer. He had helped to develop a new instrument that could be used to test the effects of thousands of chemicals on the shape of cells. The instrument would snap a photo of each group of cells that had been treated with different chemicals in an extremely miniaturized petri dish, and then analyze the cells in the photo to see whether they had longer extensions than were found in cells that had not been treated with any chemicals. In this way, Chris proposed that we could identify drug candidates that might stimulate regeneration of motor neurons, the crucial types of cells damaged during spinal cord injury.
We launched this project with funding from New York State, and we made a surprising discovery: that a class of already approved drugs called statins potently stimulated the growth of neurites in motor neurons. These statin drugs are widely used to treat patients who had too much LDL cholesterol, as a means of preventing heart disease and decreasing the risk of heart attack.
Statins had no known use for promoting recovery after spinal cord injury, but our photographic assay showed that statin drugs had a potent activity in causing motor neurons to extend projections needed for repairing spinal cord injuries. Indeed, we wondered if the millions of patients taking statins to lower their cholesterol levels would be more resistant to spinal cord injury, or would recover faster. This discovery raised the prospect that a relatively safe and widely used class of drugs could be repurposed for treating the tragedy of spinal cord damage.
The key was the use of robotic imaging. This was an exciting new technology — the ability to quickly visualize the changes in cells after treatment with thousands of different drugs. This instrument allowed us to collect a new kind of data.
I was grateful to Marie and Chris for involving me in this study. Both were excellent colleagues and collaborators. They were, to paraphrase Gilbert and Sullivan, very well acquainted, too, with matters neurobiological, as they understood such problems, both those that were simple, and seemingly paradoxical.
Marie was not only deeply insightful about motor neuron and glial biology, but was also a passionate advocate for spinal cord research, as she tried to ensure sufficient funding to create cures that would make a difference in the lives of these patients. As Jim Ashe and Jane Roskams later noted, “Marie was the very antithesis of a ‘‘stuffy’’ scientist — she lived her life with flair and style, infectious charm, great (and occasionally irreverent) good humor, passion for her work, devotion to her friends and family, and was a remarkable mentor to her students.” She successfully lobbied to overturn a deportation order for one of her students. Sadly, Marie was not able to see the final results of our collaboration, as she passed away in 2014 after a long battle with cancer. Still, in our work together, she taught me the importance of taking advantage of exciting new technologies to solve big problems.
