Environmental Toxins: Where Science Meets Start-Ups
Prepared by PsyMed Partner Brooks Leitner
Summertime. Lake swimming. Brain eating amoeba. How are these three things related?
If you’ve ever taken the US Medical Licensing Exam you probably already know this is referring to a Naegleria fowleri infection—A very rare, and nearly 100% fatal brain infection. This amoeba thrives in freshwater lakes and is about a third of the thickness of a human hair (15-30 microns). It enters the brain through the nose and causes this deadly brain infection called primary amebic meningoencephalitis.
Naegleria fowleri infection (taught widely in current mainstream medicine) demonstrates that nearly invisible particles from our environment can get into the brain… and have devastating effects on our health.
Not yet commonly taught in mainstream medicine are the effects of environmental toxins on our health. However within the last half year they have been published in both JAMA (microplastics found in the human brain) and the New England Journal of Medicine (microplastics found in coronary artery plaques had higher risk of stroke, heart attack, or death).
Two lessons from military veterans have further demonstrated that environmental toxic exposures lead to long term health consequences (and subsequent government intervention):
At Camp Lejeune, toxic chemicals such as trichloroethylene (TCE) and perchloroethylene (PCE) contaminated the water supply from the 1950s through the 1980s, linked to a wave of cancers, neurological disorders, and other chronic conditions among veterans and their families. This tragic exposure resulted in lasting health interventions, including government compensation and medical care for those affected.
Similarly, Agent Orange—a herbicide used extensively during the Vietnam War—contained dioxins that have been linked to cancer, birth defects, and serious illnesses. Over time, these connections led to the U.S. Department of Veterans Affairs providing long-term healthcare and disability benefits to veterans suffering from diseases tied to Agent Orange exposure, affirming the long-standing impact of environmental toxins on human health.
In a world filled with chemical products, these examples are just the tip of the iceberg.
More recently, regulatory interventions have ramped up quickly to remediate several environmental toxic exposures, including up to $9 Billion from the Biden-Harris administration to mitigate the health effects of PFAS and emerging contaminants (EPA Press Release, 2024) and tracked goals of promoting healthier environments to limit exposures as a part of Healthy People 2030.
The purpose of this report on Environmental Toxins is to advance our knowledge on this topic and share our thinking with founders, researchers, and investors. There are 4 sections:
Briefly describe what environmental toxins have been linked to health
Provide a framework to identify opportunities for environmental toxin solutions
Overview of some companies solving this problem
Identify trends, risks, and opportunities in building companies
Our understanding of toxins and their impact on health is still developing, and effective solutions remain scarce. However, with major policy shifts, increased venture capital, and rapid technological advancements, the landscape is poised for innovation. We’re optimistic that scalable technologies will emerge, addressing the growing problem of environmental toxin remediation and significantly improving public health. We’re betting on the convergence of these forces to drive breakthrough solutions.
Brief Overview on Health Effects of Environmental Toxins
Environmental Toxins refer to a subset of exposures that can influence the health of humans and beyond. Collectively they contribute to the exposome, “the environmental equivalent of the human genome” (Exposomics Consortium). The “Exposome” was first coined in 2005 by Christopher Wild.
Why is the field of exposomics emerging now?
Technological advances that have contributed to elucidation of gene-exposure-disease relationships
Advances in genome sequencing (and multi-omic measurement, e.g. RNA, Protein, Epigenetic Modifications, Metabolites, etc.)
Substantial improvements in mass spectrometry (read more)
Study designs to implicate causal relationships between exposures and disease
Biostatistical and computational methods to capture complexity
Desire for Tools and Methods to Solve problems:
Quantitative measure of exposures over the life course (prenatal and onwards)
Biomarkers combined with refined questionnaire-based approaches
It is prospective cohort study design that best suits the exposure biomarker approach (with repeat sampling), rather than retrospective
Calls upon the promise of multi-omics + behavioral questionnaires
While mass spectrometry and various chromatographic techniques remain the gold standard for quantifying and discovering small molecules, there’s a growing need for innovations in wearable, passive, and real-time sensing technologies. High-throughput methods that quantify exposures in real time offer exciting potential. Moreover, integrating high-throughput sequencing (of human or microbial DNA, RNA, and epigenetics) with actionable insights could revolutionize how we address environmental interactions. The development of advanced tools, data analytics, and study designs promises to bridge gaps in measuring previously untraceable molecules linked to human health.
Table 1. Toxin Types and Effects on Health
Clearly, there are a lot of links, but what are some molecular mechanisms?
Neuronal Membrane and Neurotransmitter Modulation by PFAS: Source
Importantly, PFAS have been identified in the cerebrospinal fluid (CSF) of humans, and have been identified in brain autopsies (see review cited above for key publications). These findings provide evidence for the ability for these toxins to cross the blood brain barrier. So then, what has been shown to happen once inside the brain?
Remember, PFAS are known for their excellent surfactant properties (e.g. this allows for excellent water and oil repellant capabilities). Our cell membranes are simply lipid bilayers—and surfactants like PFAS can embed themselves in our cell (or mitochondrial) membranes to disrupt membrane fluidity, cell survival, or neurotransmitter receptor positioning. Basically, PFAS can wedge themselves into neuronal membranes to cause problems.
Some of these problems lead to impaired neurotransmitter reuptake (remember Prozac acts as a serotonin reuptake inhibitor), calcium signaling (required for neuronal function), and potentially other mechanisms related to dopamine and glutamate metabolism.
Molecular Mimicry, Cosmetics, and Autoimmune Disease: Source
2-Octynoic Acid (2OA) is a molecule in cosmetics like perfume, deodorant, lipstick etc. As a foreign molecule, if/when it enters the blood stream, our bodies (or in this study, mice) can develop antibodies against 2OA to clear it from our system.
Interestingly 2OA is structurally similar to a molecule that is a part of an enzyme in the inner mitochondrial membrane (PDC-E2 Subunit). In other words, 2OA “mimics” the natural molecule in our mitochondria. What this means is that the antibodies generated against 2OA, that were made due to exposure to this toxin, can then attack our own mitochondria, leading to autoimmune disease. The autoimmune liver disease, primary biliary cholangitis, is characterized by an elevated anti-mitochondrial antibody.
What this paper suggests, then, is that based on exposure to a toxin present in cosmetics, the organism can develop antibodies against that toxin. In some cases, these toxins look structurally similar to naturally occurring molecules in our body. In summary, an environmental toxin can trigger autoimmune disease due to a phenomenon often referred to as “molecular mimicry.”
Environmental Toxins Remediation Framework
Measuring toxins is an important step in determining their influence on health. To get a comprehensive picture, we should know from where they come, and where they go.
Just as the amount of money in your bank account does not tell you how much money you make or spend per year, simply quantifying the amount of toxin does not tell you your frequency of exposure and elimination of those toxins.
Thus, we can approach opportunities to mitigate harmful effects of toxins interacting with humans by examining the environmental toxin life cycle.
Figure 1. Environmental Toxin Life Cycle
As mentioned above, we rely heavily on the sensitive and specific measurement of toxins to determine their effects on health. While we will dive into solutions that mitigate or eliminate toxins or their interactions with us, the technologies that quantify toxins can be a space for innovation in their own right.
Table 2. Technologies to Measure Environmental Toxins
Companies Working on Solutions
Several early stage companies are focused on mitigating the effects of environmental toxins on human health:
Many early-stage companies listed above are focused on accessible and easy measurement of toxins. While at home toxin measurement is an enabling technology, we are particularly excited about mitigation solutions.
We see a major opportunity in unique biological mechanisms to degrade toxins—enzymes that only exist in certain bacteria or fungi can be employed to eat toxins that humans are not able to. Whether the enzymes are synthesized as designer proteins to chew up microplastics, or naturally occurring PFAS-eating fungi are identified, unique biology can become our friend. Bluumbio and Cambiotics fall into this category.
Closed-loop detection and mitigation systems would be particularly exciting. A major translational risk is understanding whether the toxin remediation strategy actually influenced our health. For example, numerous supplements have an uncertain effect on health (because we rarely have a method to measure its efficacy). If we could measure the toxins real time in response to a remediation intervention, we would gain significantly more conviction that the novel solutions are effective.
Ideally all aspects of the environmental toxin life cycle are covered—from source, to mediators, to measurement, to elimination. Integration of these solutions would be even more powerful.
Trends, Risks, and Opportunities
The good news is entrepreneurs are building. There are more pools of funding, academic and industry innovation, and convergence of computational, biotech, and hard tech innovation than ever before. International trends are showing that the future is bright for innovative builds.
Trends
Regulatory momentum: Governments are committing billions to environmental toxin remediation. Seizing this opportunity can accelerate innovation and market growth.
Real-time toxin monitoring: Emerging compact devices, like personal “toxin” detectors, are revolutionizing early intervention, similar to how smoke detectors transformed public safety.
Nature-inspired biotech: Leveraging natural systems (e.g., bacteria and fungi) to engineer novel enzymes that degrade ‘forever chemicals,’ following the CRISPR-Cas9 revolution.
Risks
Market fragmentation: Companies must choose between consumer health and the more rigorous FDA pathways, which can make market entry challenging.
Efficacy challenges: Establishing clear links between toxins and disease is complex, given the intricate interactions between toxins and individual biology. Proving solutions work is difficult.
Opportunities
Comprehensive measurement: Untargeted mass spectrometry can detect an immense range of harmful molecules, paving the way for broad-spectrum exposure solutions.
Personalization: Advances in data analytics offer tailored interventions. Early entrants with robust data may gain a first-mover advantage.
Differentiation
Integrated solutions: Just as diagnostics are paired with therapeutics (see: Alto Neuroscience), combining detection with toxin mitigation enhances long-term value.
Vulnerable populations: Focusing on high-exposure groups like veterans or firefighters, and leveraging policy (e.g., PACT Act), presents a strategic market entry point.
We are bullish about the potential to improve public health through the mitigation of environmental toxins. The convergence of technology, regulatory action, and recognition within academic medicine suggests we’re only at the beginning of this journey. Historically, toxins like lead and arsenic have been treated reactively, but now there’s an opportunity to proactively eliminate chronic exposures.
At PsyMed, we thrive on investing at the cusp of technical validation—where novel mechanisms and testable scientific theories show initial signs of success. If your company is here, we’re excited to see what you’re building.
Also, what companies did we leave out? Start the conversation in the comments.
How to learn more:
Podcasts/Videos
Business Trip Podcast (PsyMed Ventures & MBX Capital): Environmental Toxins and Mental Health
Mayo Clinic Video: Tomorrow’s Cure: How a lifetime of exposures impact health – exposome explained (Executive Director for Mayo Clinic's Center for Individualized Medicine & director of the Center for Innovative Exposomics at Columbia University)
Bloomberg Originals Documentary: The Poison in Us All
Key Exposome Papers:
The exposome and health: Where chemistry meets biology Science 2020 (Gary Miller Sr. Author)
Emphasis on technical improvements in mass spectrometry and network science to understand the integrated multi-omic effects of exposures on health
The Exposome in the Era of the Quantified Self Ann. Rev. Bio. Data Science 2021 (Mike Snyder Sr. Author)
Emphasis on techniques and methods to quantify
Wearables, digital health, mass spectrometry, to genome sequencing
The Exposome and Toxicology: A Win–Win Collaboration Tox Sciences 2022 (Robert Barouki Corr. Author)
Conceptual framework linking toxicology and exposomics
Original Research (Helix Database formation study): Multi-omics signatures of the human early life exposome Nature Communications 2022 (Martine Vrijheid Sr. Author)
Exposome-Wide Association Study Database: HELIX
Academic Centers on Exposomics
Downloadable version of this report:
