The Quest for Biochemical Control

“Thus the system of the world only oscillates around a mean state from which it never departs except by a very small quantity. By virtue of its constitution and the law of gravity, it enjoys a stability that can be destroyed only by foreign causes, and we are certain that their action is undetectable from the time of the most ancient observations until our own day. This stability in the system of the world, which assures its duration, is one of the most notable among all phenomena, in that it exhibits in the heavens the same intention to maintain order in the universe that nature has so admirably observed on Earth for the sake of preserving individuals and perpetuating species.”

Pierre-Simon Laplace (1786), Sur l’Equation Séculaire de la Lune

Over the past several years, there has been a steady rise in the creation of life science firms with computational technology at their core, introducing efficiencies and understanding at large scale (and is why I started KdT Ventures). A common term to define this new vertical is Synthetic Biology, which at its core, designs, develops and characterizes biological parts in order to precisely control cellular behavior. Specifically, synthetic biologists work in the development and synthesis of biological networks, circuits and devices that perform desired functions in a predictable way. A dynamic and continuous combination of in vivo and in silico analysis is required to achieve these goals. Synthetic biology can thus be regarded as a multi-disciplinary field, combining concepts of engineering, mathematics and biology. It is also important to note here that broadly defined, Synthetic Biology includes the entire “physical layer” of the world including chemicals, agriculture, and medicine.

Something common in the institutional investment community is to use analogies to efficiently describe complex processes. In this way, one can start to draw parallels to where we are today in the biological sciences to where we have been with the computational sciences. In the simplest sense, computer chips manipulate electrical signals to combinatorially perform functions that read out on applications. Cells use DNA (like the electrical signal) to encode functions (RNA and Proteins) which combinatorially read out as cellular signals, disease states, etc… (applications). Currently, we have technology to cheaply and quickly read and understand DNA (sequencing among other things), write the code (DNA synthesis), and early biological operating systems are being discovered, like CRISPR, on which applications are starting to be built; however, it is the combinatorial nature of biology that remains enigmatic and difficult to engineer, as we lack the same fundamental understanding of the pieces, particularly in combination, that we had in the computational development cycle (ie we understood the physical principals behind electrical chips allowing true engineering). In other words, a compositional approach has allowed the construction of digital circuits in electronics of great complexity to be quickly designed and implemented.

This principle is an obsessive focus at KdT Ventures, where we are actively exploring the companies that are creating data sets to enable us to understand and manipulate biological circuitry in the same ways we have seen in the electronics industry. To get even more granular, living cells process information to make complex decisions. These decision making systems commonly take the form of genetic digital and sequential logic circuits . Decision-making systems can operate on the function of the single and multi-cellular levels, where individual cells work together to process information. Decision-making circuits mediate some of the most important and powerful processes found in biology. By understanding the design principles behind these decision-making circuits, one can in principle recapitulate their function through synthetically designed genetic circuits. These synthetic decision making systems could have applications in diagnostics, therapeutics, and new developmental programs for tissue engineering.

Central to the advancement of Biology is the capacity to precisely control it. If you are working on this problem, we would love to talk with you at KdT.