Unusual Breadth

This quest soon led them to seek out real-world problems that could have a bigger impact on peoples lives than basic science. They moved to the West Coast, where they pursued a mix of research and development jobs in biotechincluding at Amgen and Invitrogen (acquired by Thermo Fisher)and at universities including UC Berkeley (Molokanova), UC San Diego and Stanford University (Savtchenko).

These experiences working at intersection of physics and biology coupled with decades of work across multiple scenarios in academics and industry gave the couple a unique perspective on many of the biggest problems in neuroscience and drug discovery, as well as the business processes that helped or hindered progress.

So, as they discussed whether to start their own companies, they didnt have to deliberate for long.

It was pretty clear to me that the science was coming along nicely, and that our contribution [as entrepreneurs] would be serious, meaningful, said Savtchenko.

One major challenge the pair had observed in the biotech industry involved initial testing of potential drug compoundsresults that informed whether compounds would be pursued or discarded from consideration for further development as medicines.

Savtchenko noted that biotech and pharmaceutical companies spend billions of dollars on screening drug compounds for safety and activityin vitro(in cell culture), yet the environment in plastic cell culture dishes drastically differs from the human body, especially for nerve cells (a.k.a. neurons) and heart cells (a.k.a. cardiomyocytes).

The biggest difference between neurons in the brain and neurons in a cell culture dish is whether they receive external input or not, Savtchenko explained. From the very first moment of our existence, it is normal and, in fact, necessary for our brains to be constantly bombarded by various signals (e.g., stimuli from sight, hearing, feeling, tasting)the results determine our development, define our individual personalities and, often, affect our health.

He continued, To discover drugs that can fix aberrations in brain activity and heal a patient, it is imperative to test the drug effects on functionally active, input-receiving, dynamic response-producing neurons. Otherwise, clinical studies in human patients might produce drastically different outcomes than priorin vitrostudiesresulting in failed projects, loss of multibillion dollar investments, and disappointment for millions of patients.

The development of medication that could affect the heart faces similar challenges. Testing for drug cardiotoxicity is often performed in highly artificial conditionsin an electrically insulated culture dish of human stem-cell derived cardiomyocytes, spontaneously contracting at a single frequency. In real-life, adult heart rates can vary almost two-fold over the course of a day in response to changing conditions.

Highlighting the importance of such testing, in recent decades several blockbuster drugs have been removed from the market because they were linked to irregular heartbeat, accounting for 30% of all post-approval withdrawals.

Savtchenko and Molokanova wanted to find a way to safely and reliably stimulate cells in a dish while testing their response in the presence of drug compounds so that the results of these screening studies would better predict the drugs affect in humans. Reaching this goal would mean that fewer drugs would fail at the last stages of drug discovery process, resulting in safer, more efficient, and less expensive drugs.

After her industry experience working with different materials, including semiconductor quantum dots, to stimulate cells in culture, Molokanova hit on the idea to harness the unique properties of a new two-dimensional carbon allotrope, graphene.

Graphene had been discovered by Andre GeimandKonstantin Novoselov (coincidentally fellow alumni of Savtchenkos alma mater, MIPT), who were awarded the 2010 Nobel Prize in Physics for this finding. In the Nobel announcement, the Royal Swedish Academy of Sciencesdescribedgraphene as a thin flake of ordinary carbon, just one atom thick [with] exceptional properties that originate from the remarkable world of quantum physics.

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The Explorers: A Passion for Science Leads to New Territory - University of California San Diego