Bits and Atoms: A Line in the Sand
By Laurence Huang (CC’22, Venture Fellow 2020–21, Director)
The global pandemic has put many things to the test, but the one key thing Covid-19 has made us question is our collective notion of control. After all, why should we have thought otherwise? The expectation of endless progress strengthened year after year, with human innovation and persistence meeting up to every challenge. Yet, hundreds and thousands of people have died, and society has been drastically altered by a single strand of RNA. Peter Thiel calls this asymmetry in progress the “Stagnation Hypothesis”. He explains that humanity has made lots of progress in “computers and the world of bits… not so much in the world of atoms.” An example he gives is a person watching videos on his phone while riding in a “19th-century subway system in New York”. However, what if we could blur the line between bits and atoms by combining advances in computation with experimental biology and the plethora of biological data readily available? Computational biology promises to synthesise these two domains of knowledge to innovate and create value in everything from disease treatment to food production, and help us address our vulnerability to contagious viruses and climate change.
The increasing allocation of capital in biotech has been building up for years, with big name VC fund Andreessen Horowitz launching its $450M bio fund in 2017. Just this July, the traditionally software-focused Charles River (CRV) closed a $600M early-stage fund, a portion of which will be dedicated to fulfilling CRV’s medtech and biotech mandate. Tech titans such as Eric Schmidt, Peter Thiel, Vinod Khosla and Bill Gates are also investing in synthetic biology, contributing to the almost $4 billion dollars collectively raised by 98 synthetic biology companies in 2018. In 1995, Bill Gates wrote, “DNA is like a computer program but far, far more advanced than any software ever created”. Recent advances in genome editing, such as CRISPR, have now opened up this computer program to the world. Jennifer Doudna, co-inventor of CRISPR, the co-founder of biotech company Mammoth Biosciences, and recent Nobel Prize winner, writes, “We have now entered into a new era of biology where it is possible to move beyond observation and towards rewriting the underlying code of living things, creating countless opportunities to improve the world we live in, from diagnosing and treating human disease to restoring the environment around us”.
What is fueling this rise in interest? Three things: DNA sequencing and synthesis, artificial intelligence and machine learning, and automation (biological data collection and manipulation in the lab). All three technologies have seen Moore’s Law-like drops in costs and increases in efficiency. This decline in barrier of entry has led to a proliferation of companies, which can be categorized into two groups: bioplatforms and specific applications. The aforementioned Mammoth Biosciences is an example of the former, utilizing bio IP, software and a central database, to create a platform that enables partners and the company itself to produce products, in a reiteratively improving process. Allowing partners to use the platform increases the number of experiments and the volume of data generated, which then increases the platform’s usefulness. Mammoth has three main product lines: diagnostics, genome editing and protein discovery. It’s protein discovery process, which is in my opinion the most exciting aspect of the business, utilizes ML algorithms to search for CRISPR systems within microbial DNA. This has already produced a growing family of proprietary Cas enzymes — the main tool in CRISPR — all of which have different properties that can then be used in genome editing and diagnostics. The application of these are endless, ranging from developing gene therapies to screening for cancer. The company has so far raised $118.12 million dollars and is currently valued at $290 million.
There are hundreds, if not thousands, of applications of computational biology, but there is one sector that I believe has the greatest potential for social value, while also being de-risked from a technological and market standpoint. The global alternative protein industry is expected to grow at a CAGR of 9.5% from 2019 to reach $17.9 billion by 2025. This growth is encouraging, given that animal agriculture is one of the largest single emitters of greenhouse gases (15% as of 2019), and according to epidemiologists, also has a high likelihood of being the primary cause of a future global pandemic. If that isn’t alarming enough, the world’s increasing population will exacerbate both issues, as well as strain existing food insecurity issues. In 2009, the Food and Agriculture Organization of the United Nations (FAO) projected that food production would have to increase 70% by 2050 to feed the world’s population. The FAO also projects global meat production to increase by 16% from 2015 to 2025.
Impossible Foods is rightfully heralded as a pioneer in synthetic biology and alternative proteins. It created a commercially successful plant-based meat alternative by fermenting genetically edited yeast to produce heme, which is what makes its burgers so meat-like. But what gets less attention is the second wave of alternative protein companies that are trying to narrow the gap between the $1.7 trillion mainstream meat market, and a plant-based future. Hoxton Farms, a company I sourced from my personal network, is trying to do just that. One of the main obstacles to widespread adoption of plant-based meats is taste. What makes a juicy piece of steak so irresistible is not that it came from a cow, but the specific amount and type of fats that are in it. Many plant-based meats use plant oils which don’t have the same taste profile and are limited in their use cases. Hoxton, founded by Max Jamilly and Ed Steele, two post-graduate students from the University of Oxford, specializing respectively in synthetic biology and mathematics, are cultivating synthetic fats derived from animal cells, using computational biology to create a digital twin of the entire bioprocess. Optimizing the cell cultivation process using mathematical modeling in tandem with biological expertise allows it to achieve production efficiency at an industrial scale, producing fat that is cheaper and higher quality; current estimates put cost reduction at 640x standard cell culture.
Innovation in this sub-sector of the alternative protein industry might hold the key to producing plant-based meat that is cheap, good for the environment, and better tasting than actual meat. But, will that be enough to make a fundamental shift in global dietary habits? Imagine the not too distant future in which plant-based meats are widely available and beat their animal-based competitors in every conceivable aspect. They are healthier, cheaper and, most importantly, do not contribute to the systematic destruction of wildlife and the environment. I suspect that, despite this, a majority of consumers in the developed world would still choose to consume animal derived meat. Part of this is the embedded nature of meat in our culture, whether it’s your favorite local dish, or misconceptions regarding the necessity of meat in a healthy diet. The plant-based movement has and will continue to face active resistance from skeptical consumers and corporations with opposing interests. The wider gene editing community has faced similar obstacles, with many people concerned with the irreversible nature of altering an organism’s genetic code.
This pattern of technology breakthrough followed by cultural resistance has happened time and time again, but what makes our current predicament unique are the ethical implications of the technology themselves, and the consequences of inaction. Which side of the in vitro gene editing debate will the public eventually fall in favor for? How do we make alternative proteins the mainstream, before it’s too late? This highlights an important aspect of innovation that is often neglected: technology’s cultural and socio-political implications. One of the most significant challenges the biotech and the broader tech industry faces is successfully navigating the narrow waterways of ethics and public opinion in order to prevent a disastrous backlash, which could lead to an exodus of much needed capital, while also working towards the solution that maximizes the greatest good.
If the line that separates bits and atoms is ever more ambiguous, the ethical line has become even more so.
