In the IDF, Mintz created algorithms for sifting through reams of intelligence data to find the nuggets that have been so critical to Israel’s successes in hunting terrorist networks. When his wife, a geneticist, described the problems they had in sifting through enormous collections of genetic data, Mintz thought he might have a better way to do it.
Mintz and his partners were about to revolutionize the process of genetic sequencing. Merck bought Compugen’s first sequencer in 1994, a year after the start-up was founded and long before the human genome had been successfully mapped. But this was just the beginning. In 2005, Compugen transformed its business model and moved into the drug discovery and development arena, and did so using techniques different from those that dominate the pharmaceutical industry.
Combining mathematics, biology, computer science, and organic chemistry, Compugen has been pioneering what it calls “predictive” drug development. Rather than testing thousands of compounds, hoping to hit upon something that “works,” Compugen’s strategy is to begin at the genetic level and develop drugs based on how genes express themselves through the production of proteins.
A major aspect of Compugen’s approach is its unusual combination of “dry” (theoretical) and “wet” (biological) labs. “Imagine working with Big Pharma overseas or in another part of the country,” Alon Amit, Compugen’s VP for technology, explained. “The back and forth that you can expect is a lot slower than if you have the biologists and mathematicians literally on the same floor discussing what to test, how to test, and inform the models.”4
Though Israel’s largest company, Teva, is in pharmaceuticals, as are Compugen and a number of new Israeli companies, the more crowded field for Israeli start-ups is that of medical devices, many of them related to drug delivery. This field seems to nicely fit the Israeli penchant for multidisciplinary thinking, as well as Israelis’ characteristic lack of patience—since drugs take so long to develop.
One such mashup-based company is Aespironics, which has developed an inhaler the size and shape of a credit card that includes a breath-powered wind turbine. The problem with many inhalers is that they are tricky and expensive to manufacture. A way must be found to release the drug effectively through a wire mesh. In addition, this process must be timed perfectly with the breath of the patient to maximize and regulate the drug’s absorption in the lungs.
Aespironics seems to have solved all these problems at once. Inside the “credit card” is a fanlike propeller that is powered by the flow of air when the patient inhales from the edge of the card. As the propeller turns, it brushes against a mesh with the drug on it, thereby knocking the drug off the mesh and into the air flow in a measured manner. Since the propeller works only when the user inhales, it automatically propels the drug into the patient’s lungs.
Putting this together required an unorthodox combination of engineering skills. In addition to experts on inhalers, Aespironics’ team includes Dan Adler, whose specialty is designing gas turbines and jet engines. He was a professor at the Technion and at the U.S. Naval Graduate School and a consultant to such companies as General Dynamics, Pratt & Whitney, and McDonnell Douglas.
Mixing missiles and pills, jets and inhalers may seem strange enough, but the true mashup champion may be Yossi Gross. Born in Israel and trained in aeronautical engineering at the Technion, Gross worked at Israel Aircraft Industries for seven years before leaving to pursue more entrepreneurial endeavors.
Ruti Alon of Pitango Venture Capital, which has invested in six of Gross’s seventeen start-ups, argues that his multidisciplinary approach is the key to his success. “He has training in aeronautical engineering and electronics. He also knows a lot about physics, flow, and hemodynamics, and these things can be very helpful when thinking about devices that need to be implanted in the human body.” Plus, Alon reminded, “he knows a lot of doctors.”5
Some of Gross’s companies combine such wildly diverse technologies that they border on science fiction. Beta-O2, for example, is a start-up working on an implantable “bioreactor” to replace the defective pancreas in diabetes patients. Diabetics suffer from a disorder that causes their beta cells to cease producing insulin. Transplanted beta cells could do the trick, but even if the body didn’t reject them, they cannot survive without a supply of oxygen.
Gross’s solution was to create a self-contained micro-environment that includes oxygen-producing algae from the geysers of Yellowstone Park. Since the algae need light to survive, a fiber-optic light source is included in the pacemaker-sized device. The beta cells consume oxygen and produce carbon dioxide; the algae does just the opposite, creating a self-contained miniature ecosystem. The whole bioreactor is designed to be implanted under the skin in a fifteen-minute outpatient procedure and replaced once a year.
Combining geothermal algae, fiber optics, and beta cells to treat diabetes is typical of Gross’s cross-technology approach. Another of his start-ups, TransPharma Medical, combines two different innovations: using radio frequency (RF) pulses to create temporary microchannels through the skin, and the first powder patch ever developed. “It’s a small device,” Gross explains, “like a cell phone, that you apply to the skin for one second. It creates RF cell ablation, hundreds of microchannels in the skin. Then we apply on top a powder patch, not a regular patch. Most patches out there are gel- or adhesive-based. We print the drug on the patch, and it’s dry. When we apply the patch to the skin, the interstitial fluid comes out slowly from the microchannels and pulls the lyophilized [freeze-dried] powder from the patch under the skin.”
Gross claims that this device solves one of the most intractable problems of drug delivery: how to get large molecules, such as proteins, through the outer layer of the skin without an injection. The first products will deliver human growth hormone and a drug for osteoporosis; patches to deliver insulin and other drugs, hormones, and molecules—most of them currently delivered by injections—are in the works.
The Israeli penchant for technological mashups is more than a curiosity; it is a cultural mark that lies at the heart of what makes Israel so innovative. It is a product of the multidisciplinary backgrounds that Israelis often obtain by combining their military and civilian experiences. But it is also a way of thinking that produces particularly creative solutions and potentially opens up new industries and “disruptive” advances in technology. It is a form of free thinking that is hard to imagine in less free or more culturally rigid societies, including some that superficially seem to be on the cutting edge of commercial development.
CHAPTER 13
The Sheikh’s Dilemma
The future of the region is going to depend on our teaching our young people how to go out and create companies.
—FADI GHANDOUR
EREL MARGALIT’S BACKGROUND would not normally predict a future in venture capital. He was born on a kibbutz, fought in Lebanon in 1982 as an IDF soldier, studied math and philosophy at the Hebrew University of Jerusalem, and then pursued a doctorate in philosophy at Columbia University. He wrote his dissertation on the attributes of historical leaders—he thinks of them as “entrepreneurial leaders”—who profoundly affected the development of their nations or even civilizations (he profiled Winston Churchill and David Ben-Gurion, among others, as exemplars).