Going with Plan B

“I bet on jockeys, not horses,” Nicholas Negroponte, founder and chairman of the MIT Media Laboratory and an active angel investor, once told me. He was describing his strategy of placing more trust in the people who run a company than in its products and business plan, a strategy that reflects the common reality that a startup’s initial plan often fails, for any number of reasons. The product may work well but not attract a single sale, or as is often the case in high tech, the product development may not go anywhere near as well as was hoped. A founder’s ability to face down failure and rebound is a critical consideration for any investor, and virtually every successful entrepreneur has a near-death tale or two to tell. (I have several.) Conjuring up a winning Plan B when the fan is blowing brown requires a certain ineffable combination of decisiveness, perseverance, unconventionality, and plain old-fashioned luck.

Cynthia Bamdad, founder and CEO of Waltham, MA-based Minerva Biotechnologies, is still on her first startup, so she has yet to chalk up a major entrepreneurial victory, but her life is full of the lemons-to-lemonade stories that investors love to hear. At first glance, there is little remarkable about a 51-year-old scientist with a successful biochip invention behind her setting up her own startup laboratory. What is unusual is that 15 years ago she was an artist and stay-at-home mother with five school-age children, no higher-education degrees, and no scientific background whatsoever.

Bamdad explains: “I went through a sudden and traumatic divorce which left me with no child support or alimony and literally nothing in my name besides my Ferrari.” Figuring that she was effectively unemployable, Bamdad sold the Ferrari and invested the proceeds in her own skills, enrolling at Northeastern University as a freshman and completing a degree in physics in three years. Her professors at Northeastern recommended her to Harvard University, and she dashed through her biophysics PhD there in five years, creating and patenting some of the seminal work in biochip technology. All while raising five children on her own. “I used to cook dinner at five in the morning so everyone could eat when we all got home,” recalls Bamdad, “but it all wasn’t as hard as you might imagine.”

Bamdad made the leap from academia into the entrepreneurial world when Clinical Micro Sensors of Pasadena, CA, licensed the biochip technology that she had patented at Harvard and hired her as chief scientific officer. In record time, she transformed her academic work into a commercially viable biosensor that tests for the presence of specific DNA sequences and communicates the results directly to computers for analysis-invaluable for diagnosing disease and providing early warning of biological-weapons attacks. Less than two years after her arrival, the company-and her inventions-were acquired by Motorola for $280 million. As a relative latecomer to Clinical Micro Sensors, Bamdad received a payout that, while significant, was nothing near the lion’s share reaped by the founders and venture capitalists.

Like many first-time entrepreneurs, Bamdad was spurred to mount her own steed by watching someone else get extremely rich off of her work. Minerva Biotechnologies broke out of the gates on the heels of the Motorola acquisition, driven solely by Bamdad’s conviction that she could develop commercially valuable intellectual property. One of the problems with biochips like the one she had already developed is that they work very slowly. They rely on random motion to jiggle the targets-proteins or strands of DNA, for example-into position until they bind to probes attached to the chip’s surface. Bamdad and her Minerva researchers reasoned that if the probes were free to roam through the test solution in three dimensions, the binding would be orders of magnitude faster. A test that might have taken days to complete could be done in a matter of minutes.

The problem with free-roaming probes is detecting when one has successfully bound to its target. Bamdad solved that problem by attaching the probes to extremely tiny spheres of pure gold called gold nanoparticles, a feat that required her to also solve some tricky surface-chemistry problems. When the probes bind to their targets, the gold particles clump more closely together, causing the color of the solution to shift visibly from pink to blue. And by enabling the probes to interact with potential targets in three dimensions, Minerva lopped several zeroes off typical testing times.

Testing times matter greatly to pharmaceutical companies who seek to automate the screening of potential new drugs. But even more valuable to these companies is Minerva’s ability to attach several different probes to each nanoparticle-enabling the detection of pairs of molecules joined together. This ability is critical in drug development, where a key factor is identifying whether or not a candidate drug hits its desired target. Bamdad has also used her nanoparticle techniques in attempting to understand certain disease mechanisms, and she believes that she has developed a unique method of early detection for many types of common cancers, including breast cancer.

In addition to applications in drug screening and disease diagnosis, Minerva is going after the hot field of proteomics-the effort to study all 500,000 or so proteins encoded in the human genome. Identifying these proteins and understanding which bind to which should bring tremendous new power to the field of life sciences. Bamdad thinks her nanoparticle probes are ideally positioned to solve gigantic chunks of the problem because of their ability to yield information about how proteins bind together.