The Wheel: Pox, Progress, and Prosperity
Photo by iStrfry , Marcus on Unsplash
What three centuries of tension between innovation, commerce, and regulation tell us about investing in life science today.
By James Murray, ExSight Ventures
As the United States marks its 250th anniversary, it is worth stepping back from the daily information cycle to consider the environment surrounding American life science in a longer frame.
The pressures bearing down on the sector in 2026 may feel unprecedented. History suggests otherwise. The tension among scientific innovation, commerce, public investment, and regulation has existed since before there was a United States—and understanding that history offers useful perspective on where we find ourselves today.
Start in Boston, in the summer of 1721.
Smallpox is tearing through the town. A minister named Cotton Mather has learned of an unfamiliar practice—deliberately infecting a healthy person with a small dose of the disease to confer immunity—from an enslaved West African man in his household named Onesimus, who described it as commonplace where he was born.
Mather persuades a single physician, Zabdiel Boylston, to try it. The town erupts. The medical establishment condemns it as reckless folly. The newspapers savage both men. And one night, someone throws a lit grenade through Mather's window with a note attached, promising to inoculate him with it.
Boylston did something in the middle of that hysteria that turned out to matter more than the grenade: he kept records.
Of the roughly 240 people he inoculated, about 2% died. Among Bostonians who caught smallpox the ordinary way, roughly 14% died. That comparison was crude, contested, and utterly persuasive—and was also one of the first pieces of quantitative clinical evidence produced in the American colonies.
The innovation was frightening, the opposition was loud, and the data won anyway.
The seeds of a tension we continue to navigate today had been sown.
The conclusion I want to lead with is this: American prosperity in medicine has never come from choosing between commerce and regulation, or between innovation and safety.
It has come from the productive tension among three forces—entrepreneurial commerce, public investment in science, and regulation that manufactures the trust markets require.
Every durable engine of American economic power in the life sciences was built on that three-legged stool.
The distinct risk of this moment is that we are sawing at all three legs at once—retreating from public science, destabilizing the regulator that underwrites trust, and misfiring our industrial policy—precisely as a strategic competitor assembles the same stool with discipline.
The lesson of the history is not complicated. It is simply inconvenient.
Fear, Evidence, and the Nerve to Act
The inoculation wars established a pattern we still live inside: a genuine advance arrives wrapped in real uncertainty, fear rushes to fill the gap, and progress depends on two things—someone willing to marshal the evidence and someone with authority willing to act on it despite the risk.
Fifty-six years after Boylston, that someone was George Washington.
Smallpox was doing more damage to the Continental Army than the British were; the disastrous 1775–76 Quebec campaign had been gutted by it. Inoculation was legally banned in parts of the colonies and carried a real chance of killing or temporarily disabling the soldiers who received it.
Washington hesitated—the downside was vivid and the upside was statistical.
Then, from Morristown in early 1777, he ordered the mandatory inoculation of the army, carried out quietly to keep the British from learning how vulnerable his forces were.
Note what it was: a calculated bet on the best available science under conditions of deep uncertainty, made by a leader who would personally own the consequences if it went wrong.
That is not recklessness, and it is not caution. It is the disciplined acceptance of a known, quantified risk in exchange for a larger expected return—which, coincidentally or not, happens to be the entire job of an early-stage investor and the entire job of a functioning regulator.
Hamilton and the State as Catalyst
If Washington supplies the temperament, Alexander Hamilton supplies the economic doctrine.
His 1791 Report on the Subject of Manufactures argued that a nation's prosperity and security required a diversified industrial base and that government had a legitimate, active role in cultivating one—through targeted protective duties, incentives for invention, and investment in infrastructure.
Two aspects of Hamilton's argument are particularly relevant today.
First, public policy can serve as seed capital for private industry—a claim the next two centuries would repeatedly vindicate.
Second, Hamilton's tariffs were intended to be strategic and calibrated: instruments for building specific domestic capacity rather than blunt punishment applied across the board.
The distinction between industrial policy as scalpel and industrial policy as sledgehammer remains critical.
The Trust Machine: How Regulation Built the Market
We tend to narrate regulation as the tax that commerce pays—friction, cost, and the price of doing business.
History suggests something closer to the opposite: in medicine, regulation is part of the infrastructure that made the market possible at all.
By the turn of the twentieth century, the American drug and food supply was a caveat-emptor free-for-all of adulterated products, secret formulas, and lethal patent medicines. The Pure Food and Drug Act of 1906 began creating the framework that would ultimately become the FDA.
Industry's reputable players learned something important: the trust that regulation manufactured could be worth more than the freedom it took away.
A consumer who can believe the label will buy the product. A market flooded with adulterators punishes the honest producer; a credible regulator protects it.
That does not mean regulation is self-justifying. Rules can ossify, compliance costs are real, and those costs can fall hardest on smaller companies. A regulator that says "no" reflexively can destroy value as surely as one that says "yes" carelessly.
The case is not for more regulation.
It is for calibrated regulation—the scalpel again, not the sledgehammer, and not the absence of the instrument altogether.
The Human Genome Project: Public Science as Seed Capital
Between 1990 and 2003, the federal government spent roughly $3.8 billion sequencing the human genome—an international public effort complemented and pressured by private enterprise.
The Human Genome Project did what public science does at its best: it de-risked an entire field so private capital could build on top of it.
It helped make the genomic medicine economy possible and is a direct ancestor of the gene therapies, cell therapies, and precision diagnostics that are now reality—including areas in which ExSight invests.
When we invest in an ocular gene therapy, we are standing on a foundation that no single company could have afforded to pour.
That foundation was a public good, produced by exactly the Hamiltonian instinct—the state as catalyst—that helped build American industry in the first place.
So: three legs.
Commerce. Public science. Trust-making regulation.
That is the machine that helped make the United States the unrivaled center of biomedical innovation.
The Present Tension
The threats facing the life sciences sector in 2026 touch each of those three legs.
Changes in federal support for scientific research raise questions about the future of public science. Turnover and uncertainty at the FDA directly affect the predictability upon which biotechnology investment depends. And shifts in pharmaceutical trade and industrial policy are forcing companies and investors to reconsider manufacturing, supply chains, capital formation, and long-term strategy.
At the same time, China has emerged as an increasingly formidable competitor in biotechnology, supported by sustained investment, regulatory modernization, and an expanding life-sciences ecosystem.
For investors, these are not abstract policy debates. They are inputs into the risk-adjusted returns we model when deciding which companies, technologies, and modalities to back.
What the History Teaches
Four lessons stand out.
One: the antidote to anti-science is not counter-rhetoric. It is evidence, and the nerve to act on it.
Boylston did not win the argument by out-shouting the mob. He counted, compared, and documented. Our industry must continue producing undeniable data while doing a better job communicating scientific and medical breakthroughs to the public.
Two: do not saw off the legs of the stool—and never all three at once.
Commerce, public science, and calibrated regulation are not competing goods. They are complements.
Three: regulation, done with competence, is a competitive asset—not simply a competitive drag.
The FDA's credibility is part of the valuation of every American drug. The goal should be a regulator that is fast, predictable, and rigorous—not one that is merely permissive and not one that is absent.
Four: public science may be some of the cheapest seed capital a nation can deploy.
No private balance sheet was going to fund the Human Genome Project alone. Yet its returns accrued broadly, including to the private companies that subsequently built the genomic-medicine economy.
Where This Leaves ExSight
We cannot pretend today's tensions will resolve neatly or soon.
For early-stage life-science investors, the answer is not to predict every turn in the environment. It is to prepare for uncertainty and become more deliberate within it.
Our posture remains unchanged and hardened by history.
We invest early, on domain conviction others lack. We prize capital efficiency and clear regulatory paths—attributes that become even more valuable when the path itself is shifting. We lean deliberately toward modalities where foundational public investment and research spending from years past are now coming to fruition.
And we take genuine, rather than naïve, comfort from perhaps the plainest lesson of all:
The wheel turns.
Fear over evidence, then evidence over fear.
Ignorance has reared its head in the United States before, more than once, and innovators kept building through it. We must continue to champion the scientific inquiry, evidence, entrepreneurship, and innovation that have helped build one of the world's most dynamic life-sciences ecosystems—and carry those principles forward.
— James Murray, ExSight Ventures