August 29, 2025
In the summer of 1983, Kary Mullis had an idea that would win him the Nobel Prize in Chemistry and would transform biology forever. The polymerase chain reaction (PCR) was elegant in concept but demanded exacting precision in practice. Today, that same protocol governs DNA amplification in labs from Beijing to Baltimore, a testament to something we rarely consider: how the most profound human discoveries depend not just on flashes of insight, but on the painstaking construction of reliable, repeatable procedures.
Protocols are the invisible architecture of modern knowledge. They are the reason a cancer researcher in Boston can build directly on work done in Tokyo, why archaeological findings in Peru can be validated using methods developed in Oxford. Consider the CONSORT guidelines, which since 1996 have governed how clinical trials must be reported. These aren't merely bureaucratic requirements—they are the difference between medicine and guesswork, between treatments that save lives and those that merely seem to. When researchers follow CONSORT protocols, they create a common language that allows the global medical community to distinguish genuine breakthroughs from statistical noise.
The social sciences face a different challenge: how do you systematize the study of beings who are themselves capable of systematic thought? Bronisław Malinowski grappled with this paradox in the Trobriand Islands a century ago, developing ethnographic protocols that remain influential today. His insight was that studying human culture required its own rigorous methodology; not the detached observation of laboratory science, but immersive participation governed by careful rules about documentation, interpretation, and ethical responsibility. Later, the Institutional Review Board system would codify these ethical concerns, ensuring that the study of human behavior never again trampled on human dignity.
Now we live in an age where protocols govern not just research methods but the very infrastructure of knowledge itself. The Internet Protocol Suite (TCP/IP) transforms the chaotic potential of global connectivity into ordered, reliable communication. Meanwhile, computational social scientists like Matthew Salganik are developing new protocols for the ethical analysis of big data, recognizing that unprecedented access to human behavior data requires unprecedented responsibility in its use. These digital protocols don't just enable new forms of research, they come to define the boundaries of what we can know about ourselves.
What emerges from this long view is a striking paradox: Protocols are simultaneously conservative and revolutionary—they preserve the accumulated wisdom of communities while enabling radical departures from conventional thinking. In an era when expertise itself is under assault, when the very idea of authoritative knowledge faces skepticism, protocols offer something invaluable: a transparent pathway from question to answer, from hypothesis to conclusion. They remind us that knowledge is not a collection of facts but a set of practices, and that the difference between wisdom and opinion often lies not in what we discover, but in how we go about discovering it.
– Geoffrey W. Smith
First Five
First Five is our curated list of articles, studies, and publications for the month.
1/ How to lose twice as much weight
“People eating minimally processed foods lost twice as much weight as those on ultra-processed diets, even though both diets were nutritionally balanced and participants could eat freely. This real-world, long-term study revealed that food processing itself—not just nutrients—plays a significant role in shaping body weight and health outcomes.” Read more here >
2/ Brain erosion?
“Air pollution isn't just bad for your lungs—it may be eroding your brain. In a sweeping review covering nearly 30 million people, researchers found that common pollutants like PM2.5, nitrogen dioxide, and soot are all linked to a significantly higher risk of dementia. The most dangerous? PM2.5—tiny particles from traffic and industry that can lodge deep in your lungs and reach your brain.” Read more here >
3/ 7K is the new 10K
“Walking 7,000 steps a day may be just as powerful as hitting the much-hyped 10,000-step goal when it comes to reducing the risk of early death and disease. A sweeping global review of 57 studies shows that 7,000 steps per day slashes the risk of dying early by nearly half—and brings major benefits across heart health, dementia, depression, and more. The bonus? Even walking from 2000 to 4000 steps per day brings measurable improvements. For millions of people, this study redefines what it means to "move enough.”” Read more here >
4/ Foundations of human intelligence
“A study has demonstrated how neurons in the human brain generate memories and establish narratives. Contrary to previous beliefs, individual neurons represent the concepts we learn, regardless of the context in which we encounter them. This allows humans, unlike other animals, to establish higher and more abstract relationships, which lays the foundation of human intelligence.” Read more here >
5/ Nuclear spin microscopy
“Researchers have invented an entirely new field of microscopy—nuclear spin microscopy. The team can visualize magnetic signals of nuclear magnetic resonance with a microscope. Quantum sensors convert the signals into light, enabling extremely high-resolution optical imaging.” Read more here >
Did You Know?
In this section of our newsletter, we seek to demystify common terms and practices in our work as investors.
Cash Runway / Burn Rate
Burn rate is the rate at which a company uses up its available cash, while runway refers to how long a company can operate before it runs out of cash.
Burn rate is a necessary consideration for unprofitable companies (including pre-revenue) companies as is defines the pace at which the company consumes its cash reserves (venture capital funding). Gross burn is the total amount of operating costs incurred each month, while net burn is the total cash that a company loses on a monthly basis. The burn rate affects the company's cash runway which is how much time the company has before it depletes its cash reserves.
Cash runway defines the amount of time that a company can continue to operate before its cash reserves are depleted. There are two ways to calculate cash runway, which is typically measured in months. The first is to divide cash on hand by the company's net burn, which is the difference between incoming cash and outgoing cash. The second formula is to divide the company's cash on hand by the future expected monthly burn rate. Founder must consider their company's projected runway in order to time fundraising efforts for additional financing rounds.
– Haiming Chen & Dylan Henderson
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