U.S. Department of Commerce, 2013
“As innovation and entrepreneurship becomes an even greater force in economic growth, U.S. universities and colleges will be in the vanguard of discovering innovation and nurturing entrepreneurs that can create products, services, economic value, and high-quality jobs.”
By Marge d’Wylde
The headline in a recent Dow Jones editorial called out, “3 technologies that could create trillion-dollar markets over the next decade.” A bold headline indeed and then you read the article and realize that research in the three technologies — CRISPR, quantum theory, and materials science — are being led by researchers at UC Berkeley’s College of Chemistry.
The numbers are heady. According to a 2018 report from the National Science Board, U.S. research and development performance totaled nearly $500 billion in 2015. The business sector accounted for more than two-thirds of the total. Academia and the federal government were the next largest performers at $50 billion. Chemistry research (including chemistry, biochemistry, and chemical engineering) is the largest single science sector funded, because it tends to produce the largest return on investment.
For academic researchers and their students, in order to get to those “trillion-dollar markets,” both time and money are needed to make their scientific breakthroughs, and then turn them into real-world products. As the cost of science research escalates (everything costs more today, from the support of Ph.D. and postdoctoral students; to state-of-the-art labs; to clinical trials), university faculty and students are looking to a more flexible range of funding, which now includes government, corporate, and private venture capital investment. They are also becoming more likely to create startups, so as to maintain control of their research and patents if the research appears promising.
According to Jeffrey Reimer, Chair of Chemical and Biomolecular Engineering (CBE), “There is definite synergy between startups and the Ph.D. research happening at the College. In recent years, a number of startups have come out of both the chemistry and CBE departments.” Some recent companies include Mosaic Materials, cofounded by Professor of Chemistry and CBE Jeff Long, Thomas McDonald (Ph.D. ’15, Chem), and Steven Kaye (Ph.D. ‘07, Chem) for developing MOFs for the oil and gas industry; Atom Computing, cofounded by Jonathan King (Ph.D. ’12, ChemE) and Benjamin Bloom (Ph.D. ’14, CU Boulder), focused on building scalable quantum computers; and Ripple Foods, cofounded by Neil Renninger (Ph.D. ChemE, ’02), who did his postdoctoral work in the lab of synthetic pioneer and CBE professor Jay Keasling, with Adam Lowry (B.S.’96; Stanford). They have developed a plant-based milk product from peas.
UC Berkeley houses a series of incubators and venture funds geared toward the University’s support of students and faculty. The University has long maintained a patent program, but its entry into the startup culture began around 1968. It is now considered one of the best university incubators for student startups, with a solid track record of success. UC Berkeley incubators can offer as much as $100K to give student startups a much-needed leg up in the beginning of their development, along with ongoing mentorship from the faculty overseeing their research.
Matthew Francis, Chair of the Department of Chemistry, notes, “Students have become more ‘mission oriented’ in the last five years. However, along with creating companies, we need them to develop a solid and ethical framework for their research. There are legal and environmental issues that should be contemplated at the beginning of any new venture. The College now offers the opportunity to take business courses as part of the degree process, to learn more about both the business and ethics behind running a startup.”
We wanted to know what it’s currently like to be involved in the College’s startup culture. So, we asked four of our faculty and alumni to share some of their experiences with us. Kevan Shokat (Ph.D. ’91, Chem), a professor of chemistry and cellular and molecular pharmacology, discusses some of the leaps needed to get research from the lab to market. Nitash Balsara, a professor of CBE and a senior scientist at Berkeley Lab, shares insights about creating startups based on scientific breakthroughs made by Ph.D. and postdocs in his lab. David Schaffer, a faculty member in the Departments of CBE, Bioengineering and the Helen Wills Neuroscience Institute, discusses how ground-breaking research has been translated from his lab to a series of startups. And Martin Mulvihill (Ph.D. ’09, Chem), who helped establish the Berkeley Center for Green Chemistry, discusses his work that is changing the way people buy chemical products, focusing on funding promising green startups.
There is a revolution happening at Berkeley’s College of Chemistry. With ground-breaking research being explored, and an increased ability to help move discoveries to market, the future is looking bright.
Kevan Shokat: Discovery science and the path to creating new drugs
Kevan Shokat — 2019
“Once you make a discovery — you’ve opened a door. Then it becomes a question of how to raise the funds to make it available to the public. If you plan to start a company, you need a really good team”
Kevan Shokat (Ph.D. ’91, Chem) is professor and vice-chair of cellular and molecular pharmacology at UCSF, professor of chemistry in the Berkeley College of Chemistry, and a Howard Hughes Medical Institute investigator. He is a pioneer in the field of chemical genetics, focusing on the development of chemical methods to decipher the role of individual kinases and their cellular signaling networks.
After completing his Ph.D. in chemistry at UC Berkeley with advisor and then-faculty member Peter Schultz (who now leads Scripps Research), Shokat went to Stanford for postdoctoral research in immunology. It was there he first suggested that, rather than modify cell genetic structures to manipulate kinases, one could design small molecules that could block kinase signal paths directly. He states, “When I got to Stanford I threw myself into immunology, debating the fundamental questions of the day. I went from looking at molecules to cells.”
In 1994 he took his first faculty position, at Princeton. In a 1997 paper published in the Proceedings of the National Academy of Sciences, Shokat and three collaborators reported ground-breaking research that showed that complex proximal signaling cascades, controlled by cellular tyrosine kinases, could potentially be blocked using genetically programmed molecules.
He returned to the Bay Area in 1999, joining the faculties of both UCSF and UC Berkeley. Current research in his lab focuses on discovery of new chemical-based tools to decipher cellular signaling networks, with an emphasis on protein kinases and more recently, GTPases. The analysis of signal transduction pathways has proven challenging using the traditional tools of biochemistry, genetics, and chemistry. His lab has solved this fundamental problem for the largest family of enzymes in the human genome, protein kinases, by the development of a strategy based on a combination of protein engineering and organic synthesis.
In addition to pursuing cutting-edge research, Shokat is also committed to bringing new effective medicines to patients. He has cofounded three biotechnology companies that have taken multiple drugs through varied stages of clinical trials (including drug approval of Duvelisib in 2018), with more in development. The companies include Intellikine, established in 2007; Araxes Pharma, founded in 2012; and eFFECTOR Therapeutics, started in 2013.
Intellikine was established to focus on the development of small-molecule drugs that would specifically fight various aggressive cancers. Four years after its founding, Takeda Pharmaceuticals of Japan acquired Intellikine, boosting the odds that discoveries from the Shokat lab could make it into approved therapies that would reach patients.
Shokat notes, “It was hard to raise funds for Intellikine. Finding money is a constantly moving target in a capital environment. The early series funding was a real lesson in how to work with venture capitalists and the stock market. No matter your fundraising approach, they all have challenges. In the academic environment, you can have more control over the money you raise.”
After Intellikine was sold, Shokat and Troy Wilson (Ph.D. ’96, Biochem; J.D., NYU), who had been CEO of Intellikine, cofounded Araxes Pharma, based on additional pioneering research from the Shokat lab that uses small-molecule, covalent inhibitor approaches to develop safer, more effective ways to drug the KRAS mutant genes that cause many aggressive cancers.
According to Shokat, “Right now this is probably the mainstream approach for cancer treatment. Twenty years ago, nobody thought you could make a drug specific and potent enough to inhibit the kinases. Historically the term for this kind of discovery was ‘basic science,’ but I like to think of it as ‘discovery science’!”
He continues, “It’s very hard to plan to ‘discover a drug.’ Pharma companies have billions of dollars to invest in new drugs every year. Currently, however, there are only about 21 drugs a year making it through the FDA process to market — out of hundreds tested. It’s helpful to work inside a university research environment because you are part of a team of researchers who can support each other through the ups and downs of the process.”
In 2013, Shokat and his UCSF colleague Davide Ruggero cofounded San Diego–based eFFECTOR Therapeutics (eFFECTOR) along with CEO Steve Worland (Ph.D. ’84, Chem), focusing on the development of selective translation regulators for the treatment of cancer. To date, the company has raised multiple rounds of series funds to test drugs through FDA-approved trials. eFFECTOR recently established a partnership with Merck to evaluate the combination of eFFECTOR and Merck therapies for the treatment of patients with metastatic triple negative breast cancer.
“Once you make a discovery — you’ve opened a door,” Shokat comments. “Then it becomes a question of how to raise the funds to make it available to the public. If you plan to start a company, you need a really good team — including members with serious business acumen. It’s also special that the CEOs of these companies both received their Ph.D.s in chemistry from UC Berkeley.”
Nitash Balsara; graduates, postdocs, and the startup culture
“What has surprised me is the positive impact that startups have had on research on campus. It has made me a better academic. I feel we are doing more interesting work than ten years ago.”Nitash Balsara — 2019
Nitash Balsara, the Charles W. Tobias Professor in Electrochemistry and a senior scientist at Berkeley Lab is an internationally recognized expert in polymer materials who joined the senior faculty in the College of Chemistry in 2000. Among other innovations, his research team is responsible for the discovery of nanostructured polymer electrolyte technology, a solid electrolyte designed for use in rechargeable lithium batteries.
Balsara is no stranger to bringing startups from research to market, companies that include his students as key collaborators. He co-founded Seeo in 2006 with former graduate student Hany Eitouni (Ph.D. ’04, ChemE) and former postdoctoral researcher Mohit Singh (2004-‘06, ChemE). At Seeo, what began as research to create an electro-responsive polymer for an artificial muscle became the basis for a solid dry polymer for an electrolyte battery.
In 2015, Seeo sold its technology to Bosch, a German multinational, for an undisclosed amount. It only took 12 years to progress from the original research to a functional lithium-ion battery that is safer to use than the ones currently on the market. Not only did the founders of Seeo benefit financially from this discovery, so did the University of California, which co-holds some of the patents used in the battery design. Elsie Quaite-Randall, Berkeley Lab’s chief technology transfer officer, notes, “It takes time for the Lab’s breakthrough technologies to reach this stage. It’s exciting to see the progression from fundamental science, to startup technology, to sought-after opportunity.”
Eitouni was Balsara’s first Berkeley graduate student. “Nitash was a polymer guy. I was the first student in his career to work on electrochemistry,” Eitouni says. “He has a good ability to take a problem and break it down to fundamental pursuits. His charisma is contagious, and he’s a lot of fun to work with.”
Balsara states, “In the 1980s, there were no startups on college campuses. We went to industry to develop products. Because of the increasing costs, it appears that large companies have become more risk adverse, and that kind of funding has dried up. There doesn’t seem to be the motivation now for established companies to develop new ideas, and startups have filled this void.
“Students are looking for startups today as part of their college experience. It’s really a people thing. Startups are small and comforting, akin to research groups. Also, the lead person in the startup can now be a student. The limiting steps to success are not the money, but the good ideas and execution. We have remarkable students here at Berkeley who are ambitious, talented, and grounded. They want to be successful. Undergrads are also coming with knowledge and a keen interest in research.”
In a second startup, Balsara teamed up with Joseph DeSimone of 3D Carbon and another former graduate student, Alex Teran (Ph.D. ’13, ChemE), to form Blue Current in 2014. Blue Current is now led by Kevin Wujick (Ph.D. ’16, ChemE), another former graduate student, who left the battery group at Ford to join the team. This group is also working on new lithium battery research that will take the risk out of batteries catching fire. When asked about the current status of the company Balsara states, “We are at a very interesting point in time at Blue Current.”
For Balsara, the holy grail of battery research is developing one that will last forever. “Lithium ion batteries are already a miracle,” he says. “You can recharge it over 100s of cycles. The problem about longevity is degradation of the electrolytes. The focus is to make it more stable, but then the ions don’t go fast enough. I think we will see a time fairly soon when a battery lasting 20 years is not a challenge. Lasting for a century will be next.”
In a new project, Balsara has teamed up with Steven Hetts, an M.D. and chief of interventional neuroradiology at UCSF, to work on a drug sponge to lessen the side effects of chemotherapy. Today, some chemo treatments are limited to the amount a heart can take without being either damaged or stopped by chemo toxicity. Hetts knew that chemical engineers are keenly interested in removing pollutants from the environment – and chemotherapy can be thought of as a major “pollutant.” Hetts came to Balsara with the idea that if they could “mop up” chemotherapy (the way chemical engineers determine how to mop up chemical spills) right after it transfers through the liver, this could stop the chemical from going straight on to a patient’s heart and thus permit a more effective dose.
When she read about this concept of a new type of medical drug-capture device, Xi Chelsea Chen (2012-‘16, ChemE) , a former postdoc in Balsara’s group, had a realization. She had been investigating polymer membranes which help current to flow in a fuel cell that converts hydrogen and oxygen into electricity. She realized that the benefit from the identical property in the fuel-cell material – which allows it to attract and capture certain molecules by their electric charge, while allowing other types of molecules to flow through – could be translated conceptually to the drug sponge.
“Originally, we used this material for transporting protons in a fuel cell,” Chen said. “I was really excited when I found this could be used for chemotherapy — this was branching out in a totally different direction.”
Balsara called on his long-time collaborator Joseph DeSimone, at 3D Carbon, to turn the research into a 3D printed prototype device for testing. Says Balsara, “We have been working on this research for four years now and, thanks to 3D printing, have produced working prototypes.” The team is currently in the midst of experiments to determine how much drug is absorbed when the device is implemented.
Balsara states, “We are doing research in some very exciting fields here at Berkeley. One of the reasons I work with startups is because my students are interested in it. I think of it as a component of their education. In addition to students having compelling ideas for technology that can generate a startup, I also think it’s a human endeavor. I value the opportunity to contribute to their advancement, well after they graduate.”
David Schaffer: putting research to work for the public good
“The campus really recognizes that translating research to clinical use is central to its mission to have an impact on society. It’s also a potential source of funds for the campus.”David Schaffer — 2015
Professor David Schaffer is a luminary in the chemical engineering field. He is the Hubbard Howe Jr. Distinguished Professor of Biochemical Engineering in the CBE department of the College of Chemistry. He is also a member of the faculties of Bioengineering and the Helen Wills Neuroscience Institute, and director of the Berkeley Stem Cell Center. Schaffer has accumulated more than 20 years of research experience in this span of disciplines, developing specific expertise in the molecular engineering of biologic therapeutics, resulting in over 50 patents to date.
His first introduction to bioresearch was during his undergraduate studies at Stanford. “I was working on an early recombinant DNA research project in the lab of Charles Goochee, which resulted in my first published authorship in 1994. It was a great experience because we did the research in conjunction with Genentech.”
He went on to earn his Ph.D. in chemical engineering at MIT (1993-98). While there, he became interested in epidermal growth factor receptor-mediated gene delivery. In a recent interview he noted, “Gene therapy was a new concept at the time. The idea of using DNA as a medicine was exciting.” His time at MIT was followed by a year of postdoctoral research at the Salk Institute with Fred Gage.
Armed with a new view on the use of chemical engineering principles in working with stem cells, Schaffer joined the CBE faculty at Berkeley in 1999. His research is focused on engineering stem cell and gene therapeutics approaches for neuroregeneration. His research includes the mechanistic investigation of stem cell control, as well as molecular evolution and the engineering of viral gene delivery vehicles. One of his major research outcomes has been the development of delivery vehicles based on the adeno-associated virus, an approach which has achieved success in clinical trials for several rare diseases, including hemophilia.
Schaffer has developed exceptional skill in the art of successful translational science, guiding his lab’s research into beneficial applications. In an astoundingly short time, he has created three startups that create a bridge from his lab’s research to the market place. He observes, “My goal is to have a positive impact on health. These companies can create and run trials that allow the research to be useful.”
In 2010, he co-founded his first company, Valitor, with fellow UC Berkeley professor Kevin Healy, to develop a new generation of biotechnology drugs to precisely target diseased tissue. Two years later, he co-founded 4D Molecular Therapeutics (4DMT) with David Kirn (B.A. ’85, Physiology; M.D. ’90, UCSF), Theresa Janke (B.S., ‘96, UCSB), and Melissa Kotterman (Ph.D. ’13, ChemE). Last fall, 4DMT raised $90M in Series B financing. The company intends to use the funds to advance its Therapeutic Vector Evolution platform and a pipeline of next-generation AAV gene therapeutics. Kirn, who is chairman and CEO of 4DMT, says, “The Therapeutic Vector Evolution platform has the potential to overcome the delivery and immunology challenges that currently face the field of gene therapy. The platform could ultimately unlock the full potential of gene therapy.”
Schaffer met Kirn during an event at QB3, the UC Berkeley hub for innovation and entrepreneurship in the life sciences. Getting to know each other, they determined they had a lot in common. Kirn, a biotechnology entrepreneur and physician-scientist, had already generated a number of startups along with doing consulting on clinical development programs. Schaffer comments, “Working with David has been wonderful. I’ve been able to come up-to-speed on the business side of developing startups along with working with him on clinical trials.”
Melissa Kotterman, 4DMT’s first hire and current V.P. of Discovery and Engineering, had prior experience with Schaffer as a graduate student in his lab. She had worked on the company’s gene therapy technology while in the Schaffer group. She says, “I think it is very rare for a graduate student to have a direct opportunity, so quickly out of graduate school, to see their research really be translated, able to help patients in a really, really, rapid way.”
In 2016, Schaffer, Kirn, Janke, Kotterman and others created a third startup, IGNITE Immunotherapy. IGNITE’s focus is to further the discovery, engineering, and optimization of proprietary oncolytic vaccine products for IV administration. IGNITE has established a promising partnership with Pfizer in the area of intravenous oncolytic cancer vaccines. The companies are currently working together on cancer immunotherapy combination studies.
In our recent interview, Schaffer discussed how he manages both his lab and multiple startups: “My lab is always going to be my priority, but that said, being able to work with companies has really benefited the lab in a couple of ways. It has taught me about the next steps of drug development, and that has helped the way that I shape the research in our lab. And it has also really motivated the people in the lab — I can say that, for the first time, something a graduate student created a few years ago is in a human clinical trial.”
When asked what advice he has for up-and-coming young entrepreneurial scientists, he is thoughtful, “It’s important to learn across fields. You need to figure out how to ‘speak’ both science and business. You can consider a multi-disciplinary approach, which could mean taking classes outside your major or doing research across fields. UC Berkeley recognizes the need for such training and now offers simultaneous degree programs that allow students to study both science and business, but nothing can replace the hands-on experience of starting a new company.”
Martin Mulvehill: the green entrepreneur
Healthy chemistry is California’s future. Consumers are demanding products that are safe for families and for the environment.”— Martin Mulvihill, 2019
Martin Mulvihill (Ph.D. ’09, Chem) is co-founder of Safer Made, a seed-stage venture capital fund he started with Adrian Horotan in 2016, focusing on green chemistry startups. Safer Made invests in companies and technologies that reduce people’s exposure to toxic chemicals. Mulvihill has also directly developed technologies that help provide access to clean drinking water via the detection of arsenic.
In a recent editorial on CALmatters, Mulvihill and co-author Gina Solomon proclaimed, “Healthy chemistry is California’s future. Consumers are demanding products that are safe for families and for the environment. Retailers and product manufacturers are asking their suppliers tough questions about chemical ingredients.”
Mulvihill has always followed his passion, although it wasn’t clear at first that it was chemistry. “I hated chemistry in high school,” he says with energy. “It wasn’t until I went to Reed College that I discovered I really loved chemistry! I have alumna Maggie Geselbracht (Ph.D. ’91, Chem) to thank. She introduced me to the magic of inorganic chemistry. What I found compelling was that basic learning and research is really fun. It’s a way of seeing the world with a molecular set of rules that lends insight into our day-to-day lives. To not know about chemistry is like seeing coffee, but not the caffeine.”
He decided to pursue his Ph.D. at Berkeley with professors of chemistry John Arnold and Peidong Yang. He notes, “I was very fortunate to have them as advisors. John provided me freedom and support, while Peidong gave me structure and opportunity.
“A major opportunity that opened for me at Berkeley was my introduction to green chemistry. I had invited John Warner, considered the father of the green chemistry movement, to come and lecture. We went to dinner afterwards with professors Rich Mathies (who was dean at the time), Matt Francis, and John Arnold. The UC Berkeley green chemistry program was born that evening. Berkeley was the first ‘Tier 1’ university in the country to start such a program.”
In 2010, the Center for Green Chemistry at Berkeley became a reality, with a focus on education. Mulvihill recalls, “Originally we called the program ‘Chemists for Peace.’ We even had cups made with blended peace and atom symbols. There were four or five members,” he laughs. “The name just wasn’t capturing the purpose. In a fundamental shift of focus, we changed it to the ‘Berkeley Center for Green Chemistry’ (BCGC) because it was more accessible. It was still the same concept: connecting chemistry to society, inspired by John Warner’s principles of preventing pollution, designing safer chemicals and using better energy management.”
He continues, “I learned some very important things about raising funds while working on writing grants for the BCGC. For one, early grants are intended to be catalysts. Generally, the expectation is that the dollars you receive will generate more dollars toward a project. You often need to find matching funds from other sources, so you wind up writing multiple grants to fund one project or program.”
Thus, it wasn’t much of a leap for Mulvihill to go from executive director of the green chemistry program at Berkeley to founding Safer Made in order to give fledgling green startups their first funds and make a wider commercial impact. Says Mulvihill, “The proof is in the direction the markets are moving. Consumer brands that differentiate as green are winning in the market place, and not in small numbers. If you take the organic food business as an example, over the last ten years there have been $42 billion in acquisitions of organic startups, much of it by mainstream companies.”
Consumer trends are driving change in how chemistry research is working with the market place. Mulvihill notes that some key trends currently include:
- Clean product labels — consumers are now preferentially buying products that have the fewest items listed and are “pronounceable.”
- Differentiated packaging — packages that are compostable and truly recyclable are winning the war for shelf space in stores.
- Bacteria — about 100 trillion good bacteria live in and on our bodies. Many of these bacteria reside in our gut, helping our bodies break down food and absorb nutrients. Consumers are looking for new and better ways to live in harmony with bacteria and thrive.
Mulvihill’s message is an exciting one. Future-thinking chemistry and smart product design can really change what happens to our planet and to us. So next time you are in the store, be sure to flip over the package and read the label!