How Human Genetics Is Changing Drug Development with Eric Green
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Table of Contents
Introduction
Guest Snapshot
From Genome Sequencing to Drug Targets
Genetic Medicines: Programming Drugs at the Molecular Level
Rethinking Clinical Trials for Severe Diseases
Lessons from COVID on Drug Development Speed
The Economics of Drug Pricing
Why Biotech Needs Contract Manufacturers
What's Next for Trace Neuroscience
Memorable Quotes
Links You Might Find Valuable
Introduction
The cybersecurity landscape has evolved from isolated hacker attacks to a professionalized criminal ecosystem operating at global scale. Jason Passwaters has spent two decades on the front lines of this evolution—first as a Marine Corps counterintelligence specialist and FBI contractor tracking cyber criminals, then as co-founder and CEO of Intel 471, a company that monitors the cyber underground for Fortune-level enterprises.
In this conversation, Jason walks through his journey from tactical interrogation work in the Marines to building a $20 million ARR cyber threat intelligence company without outside funding. He offers practical guidance on personal cybersecurity for individuals with substantial assets, explains how ransomware crews operate like legitimate SaaS companies, and shares what keeps him up at night as AI lowers the barrier for bad actors to scale their operations.
Guest Snapshot
Name: Eric Green, M.D., Ph.D.
Titles: CEO and Co-Founder, Trace Neuroscience
Credentials:
Physician-scientist with MD-PhD training
Cardiologist with a focus on translating human genetics into precision therapies
Current focus: Developing a genomic medicine to restore UNC13A protein function in people with ALS
Additional areas of expertise: Genetics-guided drug development, biotech company building, rare disease therapeutics
From Genome Sequencing to Drug Targets
The human genome was sequenced roughly 20 years ago, but the real breakthroughs in drug development are happening now. Green explained that sequencing a single genome isn't particularly useful on its own. The power comes from sequencing thousands or tens of thousands of genomes from people with and without specific diseases.
"You can start to find which genes confer added risk for a disease," Green said. "And not just that, which genes might actually lead you to have a more severe form of disease."
This approach flips traditional drug development on its head. Instead of starting with a hypothesis about what might work, researchers can identify genes that nature has already shown matter for a disease. At Trace Neuroscience, this led them to UNC13A—a gene with an unusual origin story.
The Worm Connection
Back in the 1960s, researchers were systematically mutating every gene in worms to see what happened. When they mutated the gene that would come to be known as UNC13A, the worms became uncoordinated. Scientists eventually discovered why: the protein from this gene is essential for communication between nerves and muscle cells.
Fast forward to genetic studies in ALS patients. Green's team found that people with ALS lose this same protein, leading to the paralysis characteristic of the disease. The connection was clear: restore the missing UNC13A protein, and you might be able to restore nerve-muscle communication.
"When you lose it, that communication can't happen," Green explained. "The worm becomes uncoordinated and the same thing happens in other organisms."
Genetic Medicines: Programming Drugs at the Molecular Level
Trace's approach uses antisense oligonucleotides—essentially short sequences of nucleic acids designed to find and bind to specific RNA in the nervous system. Think of it as a precision-guided system that locates the exact genetic instruction it needs to modify.
The medicine itself is a sequence of letters (A, T, C, G) programmed to recognize its target. Once it finds the RNA that makes UNC13A protein, it ensures healthy amounts of the protein get produced.
This represents a shift from small molecule drugs or biologics to medicines that work at the genetic level. Green pointed out that while manufacturing these genetic medicines requires specialized expertise, biotech companies don't need to build their own facilities. Contract manufacturing organizations specialize in producing oligonucleotides at varying scales and specifications.
"We start out doing this at small scales. We might make 100 different things with them," Green said. "And over time, we are making larger and larger quantities of one thing that are made to very exacting specifications so that we actually feel comfortable giving it to a human."
Rethinking Clinical Trials for Severe Diseases
Developing drugs for ALS comes with unique challenges. The typical life expectancy after diagnosis is two to three years, which means patients usually only have the opportunity to participate in one clinical trial.
That reality shapes every decision about trial design. Trace plans to start clinical trials directly in ALS patients next year, rather than beginning with healthy volunteers. They'll start at doses they believe will be effective, not at minimal doses just to assess safety.
Key differences in the ALS trial approach:
Starting in patients immediately, not healthy volunteers
Beginning at potentially effective doses
Treating patients for months, not days or weeks
Allowing patients who benefit to stay on the drug longer
"If they're going to enroll in a clinical trial, we want to have the greatest likelihood possible that they're actually not just helping us learn about our drug, but giving them the potential to benefit," Green said.
The regulatory framework supports this approach for severe, life-threatening diseases. The risk-benefit calculation changes when the alternative is a disease that has had virtually no new treatment options in 100 years.
Lessons from COVID on Drug Development Speed
The rapid development of COVID-19 vaccines and therapeutics demonstrated what's possible when regulatory processes adapt to urgent needs. Green believes the experience offers lessons for other severe diseases, particularly ultra-rare conditions.
The question comes down to balancing risk and benefit. Historically, US regulators have erred heavily on the side of minimizing risk, even if that means slowing development or missing potential benefits. But COVID showed that this balance can shift appropriately when circumstances demand it.
"Can we recognize the potential benefit in moving more quickly while realizing that we may need to take on a little bit more risk?" Green asked. "These so-called N of 1 or ultra rare disease therapies are something that we should think about differently than we should think about developing medicines for more common diseases."
A cholesterol drug that represents the fourth treatment option in a crowded market deserves different scrutiny than the first medicine for a child with a rare disease who will die without intervention. Current FDA leadership is starting to embrace this more flexible mindset.
The Economics of Drug Pricing
One of the more contentious aspects of drug development is pricing, especially when manufacturing costs drop significantly after the development phase. Green defended the current system where companies have a period of pricing protection followed by generic competition.
His perspective centers on two realities:
The massive investments required to develop new medicines carry enormous risk and take years to realize
Drugs are the only part of healthcare that eventually go generic, making them broadly affordable
"The drugs are the only part of the healthcare industry that go generic, nothing else does," Green noted. "I think that structure is one that has really incentivized innovation, but also for a lot of really life-changing medicines has now made them very broadly affordable."
The system creates incentives for investors to fund high-risk, long-timeline drug development while ultimately benefiting patients through generic access after the protection period ends.
Why Biotech Needs Contract Manufacturers
One practical insight from the conversation was how critical contract manufacturing organizations (CMOs) are to the entire biotech industry. These specialized companies handle functions that would be impractical for individual biotech firms to build in-house.
For Trace, that means partnering with organizations that spend all day, every day making oligonucleotides. They can produce compounds at different scales and purity levels, starting with small batches of 100 different candidates and eventually scaling to larger quantities of the final drug candidate made to exacting specifications.
"This, to me, is one of the biggest enablers for the whole biotech industry," Green said. "There are a huge number of functions that are essential for what we do that are impractical for us to be building on our own."
Manufacturing partnerships allow biotech companies to focus their capital and expertise on drug discovery and development rather than building out infrastructure that others can provide more efficiently.
What's Next for Trace Neuroscience
Trace Neuroscience is preparing to initiate human clinical trials in 2026. That first patient treatment will be a significant milestone—not just for the company, but for the ALS community that has been waiting for meaningful therapeutic advances.
The clinical trials will start to answer whether restoring UNC13A protein can translate into clinical benefit for people with ALS. Given that this protein is essential for nerve-muscle communication, and that people with ALS lose it, the scientific rationale is strong. But as with all drug development, the proof comes from clinical results.
For anyone who wants to follow Trace's progress, the company maintains updates at traceneuro.com and expects to share more information about trial initiation in the coming year.
Memorable Quotes
On the power of human genetics: "You can start to find which genes confer added risk for a disease. And not just that, which genes might actually lead you to have a more severe form of disease."
On UNC13A's discovery: "When you lose it, that communication can't happen. The worm becomes uncoordinated and the same thing happens in other organisms."
On clinical trial design for ALS: "The sad reality is that for most people with ALS, they only get one clinical trial. So the typical life expectancy is two to three years. And so if they're going to enroll in a clinical trial, we want to have the greatest likelihood possible that they're actually not just helping us learn about our drug, but giving them the potential to benefit."
On the drug pricing system: "The drugs are the only part of the healthcare industry that go generic, nothing else does."
On contract manufacturing: "This, to me, is one of the biggest enablers for the whole biotech industry—there are a huge number of functions that are essential for what we do that are impractical for us to be building on our own."
Links You May Find Valuable
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