The new class of protein AI design tools are amazing, and could revolutionize many areas of science, including therapeutics, diagnostics, and biosensors. Surprisingly, one important area that I haven't seen discussed too much is how these tools could impact patents. I am not a lawyer, so obviously this post is just my basic understanding, and I'd be happy to hear corrections. If there is a more expert critique I did not find it.

Patents are wordy and convoluted by design. For proteins, because a string of amino acids defines them, there are some common elements: they often include the sequence(s) being patented, and a threshold for how similar another sequence can be before infringing. That means there is a target to hit, and AI is really good at hitting targets.

There are two major categories of protein patents: biologics (usually meaning antibodies) and enzymes.

Antibodies

According to the European Patent Office, there are two main ways to patent an antibody:

• "functional" claims, usually meaning the antibody's associated antigen or epitope;
• "structural" claims, usually meaning a sequence and sequence identity threshold, along with the epitope or some other support.

Over the past few years, the "functional" claim has been going away. In the US it was killed off by the 2023 Amgen vs Sanofi ruling, which essentially said you can't patent the concept of an antibody against PCSK9. That means antibodies are now almost exclusively patented based on their structure (more specifically, a sequence plus some supporting functional information like epitope affinity.)

For antibody sequences, it used to be common for claims to cover any sequence 80%+ identical in the heavy or light chains. These days it seems like you have to be more specific, with claims only covering 100% identity to all 6 CDRs.

To take some real examples:

• Zanidatamab, a HER2 bispecific approved in 2024, claims sequences with 100% sequence identity to its CDRs;
• Epcoritamab, a CD3/CD20 bispecific approved in 2024, also has claims sequences with 100% sequence identity to its CDRs;
• Trastuzumab, the famous HER2 antibody approved in 1998 (filed in 2013), claims sequences with 85%+ sequence identity to the heavy and light chains, and does not mention CDRs at all.

The EPO says: "the slightest modification of the CDRs can affect the recognition of the target." There is a nice breakdown of the differences between the USPTO vs EPO approach to antibody patents here.

Enzymes

For enzymes, the patent landscape is more complicated, or at least more varied. Unlike antibodies, where the patents are pretty uniformly focused on the sequence that binds an epitope, enzymes can perform any number of functions. Enzyme types include enzyme replacement therapies, industrial enzymes like detergents, and molecular biology tools like CRISPR-Cas9. It is still typical for these patents to include a sequence and supporting information.

Some examples:

• this detergent patent, granted in 2018, claims sequences with 60%+ sequence identity to the reference;
• this proteinase patent, granted in 2022, claims sequences with 90%+ sequence identity to the reference;
• this novel Taq polymerase patent, granted in 2025, claims sequences with 95%+ sequence identity to the reference.

Cas9

The Cas9 patents are unusually diverse: there are hundreds of them and they mostly cover the many applications of the invention rather than the sequences. Since the 2013 ruling against Myriad Genetics, sequences from naturally occurring enzymes like Cas9 cannot be patented. Engineered sequences can be patented with other supporting functional information. You cannot take one of the thousands of unique Cas9 sequences in GenBank and use that to circumvent the CRISPR-Cas9 patents.

There are hundreds of Cas9 patents covering everything anyone could think of

AI

Given that the amino acid sequence is so important in protein patents, I am surprised that it is not bigger news that AI has effectively broken the direct connection between sequence and function.

For patents where protein sequence identity is protected, it is now relatively straightforward to generate new sequences that fold to the same structure but have 50% or lower sequence identity.

For antibody patents where the CDR sequence is protected, I believe it is also relatively straightforward to introduce a mutation that does not disrupt binding. To be honest, I am not even sure AI is required here, since a mutation scan could perform the same function. Perhaps for this reason, a recent paper called for "comprehensive CDR scanning" to protect a panel of CDR sequences instead of just one.

ProteinMPNN, published in 2022 by Baker lab, is the most prominent tool for producing a new sequence that folds to a known structure. ProteinMPNN is widely used as a step in many protein design workflows. For example, methods like RFdiffusion generate backbone coordinates only, and ProteinMPNN turns that into an amino acid sequence.

In a follow-up ProteinMPNN paper, the authors demonstrated that they could make a myoglobin and TEV protease with comparable or better function and greater stability than the natural versions, with sequence identities as low as 40%. This is below the sequence identity threshold in any patent I have seen.

ProteinMPNN can be used to produce a new sequence for a protein while maintaining its function

Sequence vs Structure

If this ability for AI to circumvent sequence-based patents is an issue, maybe the obvious change here would be to base patent protection on structure. This is a bit more complex than sequence identity, but one way to do this would be with TM-align or a similar tool. TM-align has >3k citations so it is arguably the standard in the field. A TM-score of above 0.8 indicates "the same topology"—in other words a very close structure. I think this would work well for many proteins, though it might need to be constrained to subdomains (akin to CDRs) in some cases.

Interestingly, the only literature I found on patenting 3D structure is from 20 years ago. Maybe this has been debated already and rejected for some reason. I suspect it was just easier to use sequence though.

OpenCRISPR-1

OpenCRISPR-1 was published in 2024 by the protein AI company Profluent. This is a de novo Cas9 enzyme that is substantially different in sequence to any known Cas9 (according to the abstract, "400 mutations away in sequence [from SpCas9]"—specifically 403/1380, or 71% identity).

Cas9 is a bilobed enzyme, with a REC lobe (nucleotide recognition) and a NUC lobe (DNA cleavage and PAM recognition.) Broadly speaking, the REC lobe is the first half of the enzyme (amino acids 50–700), and the NUC lobe is the second (1–50 and 700–1350.) These two lobes are connected by a "bridge helix".

Cartoon representation of Cas9 from addgene.

The OpenCRISPR-1 enzyme is not as novel as it might seem. In fact, I found it is actually 98% identical to a sequence constructed from three Cas9's spliced together from Streptococcus cristatus, Streptococcus pyogenes and Streptococcus sanguinis (24 amino acids are unique to OpenCRISPR-1).

This raises an interesting question, which is whether you could create a "novel" Cas9 by simply stitching together the REC lobe from one species' Cas9 and the NUC lobe from another. I believe this enzyme would work, and this sequence would meet any sequence identity threshold requirements.

The Profluent paper says the OpenCRISPR-1 enzyme was released for "research and commercial applications", but there is a big caveat here. Since CRISPR-Cas9 patents post-date the Myriad decision, almost all are functional / method of use, and naturally the most protected part is the use of Cas9 in "commercial applications" like therapeutics and diagnostics.

It is commendable that Profluent tried to broaden the availability of Cas9, so I appreciate the work behind this, but as I understand it, OpenCRISPR-1 is not really more available for commercial use than any Cas9.

There is actually another "royalty-free" Cas, a "Class 2 Type V" Cas nuclease called MAD7, released by Inscripta for commercial use in 2023. I do not know how this enzyme intersects with the many Cas9 patents.

Conclusion

One upshot of all this AI work is that me-too and biosimilar antibodies will be easier to make. That saves some time and money, but does not necessarily save on the major clinical trial costs, although the probability of success could go up a lot if the antibody is functionally identical.

While many enzyme patents will be affected, patents like CRISPR-Cas9 that rely on functional or method of use claims do not seem to be impacted as much. I don't know how many enzyme patents rely on sequence identity claims vs other claims these days. It would be interesting to (get an AI to) do a proper survey.

For internal research use, it's unclear to me that using AI to reproduce a patented protein does a whole lot, since at least in drug development, the research exemption seems to allow for the use of patented material quite broadly.

I have written about protein binder design a few times now (the Adaptyv competition; a follow up). Corin Wagen recently wrote a great piece about protein–ligand binding. This purpose of this post is to review how well protein binder design is working today, and point out some interesting differences in model performance that I do not understand.

Protein design

There are two major types of protein design:

1. Design a sequence to perform some task: e.g., produce a sequence that improves upon some property of the protein
2. Design a structure to perform some task: e.g., produce a protein structure that binds another protein

There is spillover between these two classes but I think it's useful to split this way.

Sequence models

Sequence models include open-source models like the original ESM2, ProSST, SaProt, and semi-open or fully proprietary models from EvolutionaryScale (ESM3), OpenProtein (PoET-2), and Cradle Bio. The ProteinGym benchmark puts ProSST, PoET-2 and SaProt up near the top.

Many of the recent sequence-based models now also include structure information, represented as a parallel sequence, with one "structure token" per amino acid. This addition seems to improve performance quite a lot, allows sequence models to make use of the PDB, and — analogously to Vision Transformers — blurs the line between sequence and structure models.

SaProt uses a FoldSeek-derived alphabet to encode structural information

The most basic use-case for sequence models is probably improving the stability of a protein. You can take a protein sequence, make whatever edits your model deems high likelihood, and this should produce a sequence that retains the same fold, but is more "canonical", and so may have improved stability too.

An elaboration of this experiment is to find some data, e.g., thermostability for a few thousand proteins, and fine-tune the original language model to be able to predict that property. SaProtHub makes this essentially push-button.

A further elaboration is doing active learning, where you propose edits using your model, generate empirical data for these edits (e.g., binding affinity), and go back and forth, hopefully improving performance each iteration. For example, EVOLVEpro, Nabla Bio's JAM (which also uses structure), and Prescient's Lab-in-the-loop. These systems can be complex, but can also be as simple as running regressions on the output of the sequence models.

EvolvePro's learning loop

Sequence-based models are a natural fit to these kinds of problems, since you can easily edit the sequence but maintain the same fold and function. Profluent and other companies make use of this ability by producing patent-unencumbered sequences like OpenCRISPR.

This is especially enabling for the biosimilars industry. Many biologics patents protect the sequence by setting amino acid identity thresholds. For example, in the Herceptin/trastuzumab patent they protect any sequence >=85% identical to the heavy (SEQ ID NO: I) or light chain (SEQ ID NO: II).

Excerpt from the main trastuzumab patent

Patent attorneys will layer as many other protections on top of this as they can think of, but the sequence of the antibody is the primary IP. (Tangentially, it is insane how patents always give examples of numbers greater than X. Hopefully, the AIs that will soon be writing patents won't do this.)

For binder design, sequence models appear to have limits. Naively, since you do not know the positions of the atoms, then unless you are apeing known interaction motifs, you would assume binder design should be difficult?

Diego del Alamo points out apparent limits in the performance of sequence models for antibody design

Structural models

Structural models include the original RFdiffusion and the recently released antibody variant RFantibody from the Baker lab, RSO from the ColabDesign team, BindCraft, EvoBind2, foldingdiff from Microsoft, and models from startups like Generate Biomedicines (Chroma), Chai Discovery, and Diffuse Bio. (Some of these tools are available on my biomodals repo).

Structural models are trained on both sequence data (e.g., UniRef) and structure data (PDB), but they deal in atom co-ordinates instead of amino acid strings. That difference means diffusion-style models dominate here over the discrete-token–focused transformers.

There are two major classes of structural models:

• Diffusion models like RFdiffusion and RFantibody
• AlphaFold2-based models like BindCraft, RSO, and EvoBind2

The success rates of RFdiffusion and RFantibody are not great. For some targets they achieve a >1% success rate (if we define success as finding a <1µM binder), but in other cases they nominate thousands of designs and find no strong binder.

An example from the RFantibody paper showing a low success rate

BindCraft and RSO are two similar methods that produce minibinders (small-ish non-antibody–based proteins) and rely on inverting AlphaFold2 to turn structure into sequence. EvoBind2 produces cyclic or linear peptides, and also relies heavily on an AlphaFold confidence metric (pLDDT) as part of its loss.

BindCraft (top) and EvoBind2 (bottom) have similar loss functions that rely on AF2's pLDDT and intermolecular contacts

Even though these AF2-based models work very well, one non-obvious catch is that you cannot take a binding pose and get AlphaFold2 to evaluate it. These models can generate binders, but not discriminate binders from non-binders. In the EvoBind2 paper, they found that "No in silico metric separates true from false binders", which means the problem is a bit more complex than just "ask AF2 if it looks good".

According to the AF2Rank paper, the AF2 model has a good model of the physics of protein folding, but may not find the global minimum. The MSAs' job is to help focus that search. This was surprising to me! The protein folding/binding problem is more of a search problem than I realized, which means more compute should straightforwardly improve performance by simply doing more searching. This is also evidenced by the AlphaFold 3 paper, where re-folding antibodies 1000 times led to improved prediction quality.

Excerpt from the AF2Rank paper (top), and a tweet from Sergey Ovchinnikov (bottom) explaining the primacy of sequence data in structure prediction

RFdiffusion/RFantibody vs BindCraft/EvoBind2

The main comparison I wanted to make in this post is between RFdiffusion/RFantibody vs BindCraft and EvoBind2.

These are all recently released, state-of-the-art models from top labs. However, the difference in claimed performance is pretty striking.

While the RFdiffusion and RFantibody papers caution that you may need to test hundreds or even thousands of proteins to find one good binder, the BindCraft and EvoBind2 papers appear to show very high success rates, perhaps even as high as 50%. (EvoBind2 only shows results for one ribonuclease target but BindCraft includes multiple).

Words of caution from the RFantibody github repo (top) and BindCraft's impressive results for 10 targets (bottom)

There is no true benchmark to reference here, but I think under reasonable assumptions, BindCraft (and arguably EvoBind2) achieve a >10X greater success rate than RFdiffusion or RFantibody. The Baker lab is the leading and best resourced lab in this domain, so what accounts for this large difference in performance? I can think of a few possibilities:

• RoseTTAFold2 was not the best filter for RFantibody to use, and switching to AlphaFold3 would improve performance. This is plausible, but it is hard to believe that is a 10X improvement.
• Antibodies are just harder than minibinders or cyclic peptides. Hypervariable regions are known to be difficult to fold, since they do not have the advantage of evolutionary conservation. However, RFdiffusion also produces minibinders, so this is not a satisfactory explanation.
• BindCraft and EvoBind2 are testing on easier targets. There is likely some truth to this. Most (but not all) examples in the BindCraft paper are for proteins with known binders; EvoBind2 is only tested against a target with a known peptide binder. However, most of RFantibody's targets also have known antibodies in PDB.
• Diffusion currently just does not work as well as AlphaFold-based methods. AlphaFold2 (and its descendants, AF3, Boltz, Chai-1, etc.) have learned enough physics to recognize binding, and by leaning on this ability heavily, and filtering carefully, you get much better performance.

What comes next?

RFdiffusion and RFantibody are arguably the first examples of successful de novo binder design and antibody design, and for that reason are important papers. BindCraft and EvoBind2 have proven they can produce one-shot nanomolar binders under certain circumstances, which is technically extremely impressive.

However, if we could get another 10X improvement in performance, then I think these tools are being used in every biotech and research lab. Some ideas for future directions:

• More compute: One of the interesting things about BindCraft and EvoBind2 is how long they take to produce anything. In BindCraft's case, it generates a lot of candidates, but has a long list of criteria that must be met. One BindCraft run will screen hundreds or thousands of candidates and can easily cost $10+. Similary, EvoBind2 can run for 5+ hours before producing anything, again easily costing $10+. This approach of throwing compute at the problem may be generally applicable, and may be analogous to the recently successful LLM reasoning approaches.
• Combine diffusion and AlphaFold-based methods: I have no specific idea here, but since they are quite different approaches, maybe integrating some ideas from RFdiffusion into EvoBind2 or BindCraft could help.
• Combine sequence models and structure models: There is already a lot of work happening here, both from the sequence side and structure side. In the simplest case, the output of a sequence model like ESM2 could be an independent contributor to the loss of a structure model. At the very least, this could help filter out structures that do not fold.
• Neural Network Potentials: Neural Network Potentials are an exciting new tool for molecular dynamics (see Duignan, 2024 or Barnett, 2024). Achira just got funded to work on this, and has several of the pioneers of the field on board. Semi-open source models like orb-v2 from Orbital Materials are being actively developed too. The amount of compute required is prohibitive right now, but even a short trajectory could plausibly help with rank ordering binders, and would be independent of the AF2 metrics.

Tweet from Tim Duignan at Orbital Materials

This post is a kind of brain dump of health-related product information I have gathered over the past few years. The major themes are eliminating plastic, heavy metals, and other suspicious stuff, and using stainless steel, cast iron, silicone, and glass where possible. This post is really long, so I put a tl;dr list of all the products at the end of the article. I may update this page if I think of more!

There are a few resources that have useful information:

• Consumer Reports actually does a decent amount of health stuff. It is behind a paywall, but accessible for free online through some libraries. Usually when they look into a subject, they do a pretty thorough job. For example, they tested 126 herbs and spices for heavy metals.
• ConsumerLab's mission is "To help consumers and healthcare professionals find the best quality health and nutrition products through independent testing and evaluation." ConsumerLab tests a lot of products, but all the information is behind a paywall. I bought a subscription to test it out, and I think it's decent. They seem quite careful in their testing, but the probability they have the specific information you are looking for is low. For example, their article on protein powders is extremely rambling, but for heavy metal testing they just link to a confusing Clean Labels Project page.
• Cochrane collaboration is "a charitable organisation formed to synthesize medical research findings to facilitate evidence-based choices about health interventions". This is much broader than product reviews, but if they cover your specific topic of interest it can be very informative. The reviews are rigorous to the point of being over-cautious. If there were no clinical trial for parachute use, they would have to say the data is inconclusive. This humorous BMJ article agrees:

  Parachute use did not reduce death or major traumatic injury when jumping from aircraft in the first randomized evaluation of this intervention. However, the trial was only able to enroll participants on small stationary aircraft on the ground, suggesting cautious extrapolation to high altitude jumps.

• Elevate is a nice, short book that had some practical advice on the 80/20 of health interventions. Most memorably, the author recommends wearing natural fibers to limit skin exposure to plastics.
• plasticlist.org is a project funded by Nat Friedman where they tested ~300 foods for plastic contamination and helpfully made the results publicly available. I believe they are supposed to continue to update the list over time.
• implasticfree.com is "the easiest, fastest way to find plastic alternatives". They don't seem to do much independent testing but the information I have seen on there is quite well researched. For example, they have a good list of plastic-free kettles.

Protein powder

For various reasons — e.g., edicts from health influencer Peter Attia — many of us are eating more protein these days. Whey, collagen, and creatine are probably the three major protein supplements, and usually come in the form of concentrated powders. Anything concentrated is a concern for toxins, especially heavy metals.

When buying these, I am optimizing for these factors, in order of importance:

1. Third-party lab tests, preferably with results (since you can test and still get bad results!);
2. Price;
3. Form factor (I prefer bags to big tubs);
4. Quality, including purity (sometimes ConsumerLab has information on this).

My current favorites from each category are the following:

• AGN Roots Whey Isolate: This whey is inexpensive and their literature has some reassuring information around heavy metal testing, including providing actual numbers. Whey isolate is generally considered better than concentrate, with easier absorption and less cholesterol.

  "AGN Roots Grassfed Whey heavy-metals test results will show a Lead Concentration of < .005 mg/kg (ppm). Our grassfed whey contains up to 100 times lower concentrations of heavy metals (Mercury, Arsenic, Lead, Cadmium) than the typical "grass-fed" whey supplier."

• Natural Force Collagen: This is a reasonably priced collagen that provides some specific test results.

  "We test for Mercury (Hg), Lead (Pb), Arsenic (As), and Cadmium (Cd) on every batch. Here are some recent test results:
  Unflavored
  Mercury 0.0029 mcg/g (µg)
  Lead 0.0039 mcg/g (µg)
  Arsenic <0.001 mcg/g (µg)
  Cadmium 0.0021 mcg/g (µg)"

• It's Just! Creatine: This is one of very few creatine brands that claim to test for heavy metals. (In fairness, heavy metal contamination is not believed to be a huge concern for creatine). Naked Nutrition Creatine also claims to test for heavy metals, though neither has specifics about their testing. It's Just! Creatine comes in a bag, which I happen to prefer, so I buy that. I used to buy from bulksupplements.com but there are some concerns about their testing. Creapure is more expensive, has extensive testing (though no specific mention of heavy metals) and has also been recommended to me.

Cinnamon

Don't die guy Bryan Johnson recently tweeted about the presence of heavy metals in cinnamon. There are actually two kinds of cinnamon: Ceylon cinnamon ("true cinnamon") and Cassia cinnamon. Johnson was referencing Ceylon cinnamon, which tastes better than Cassia and has less coumarin. Coumarin is a liver toxin, so in general best avoided.

Coumarin is a flavouring substance which is contained in relatively high concentrations in cinnamon varieties collectively known as "Cassia cinnamon". In especially sensitive persons, even comparatively small quantities of coumarin can cause liver damage, although the effect is usually reversible.

In 2024, Consumer Reports tested 36 cinnamon powders for lead. 365 Whole Foods Organic Ground Cinnamon came out on top at 0.02 ppm. However — like all cinnamon that does not specifically say Ceylon — this is the cheaper Cassia variety. The best Ceylon cinnamon tested was Penzey's at 0.78 ppm. Consumer Reports rated this "ok", but it is uncomfortably close to their "don't use" rating. So, unfortunately, I do not know a great source of cinnamon. According to Consumer Reports, basil, oregano and thyme are also almost universally contaminated!

Peanut butter

Like cinnamon, peanut butter is a seemingly healthy food with some downsides. For one thing, due to their longer growing cycle, nuts can concentrate heavy metals. (Brazil nuts contain so much Selenium that you are only supposed to eat fewer than 5 per day). Also, do not eat a pound a week of peanut butter since that can cause liver damage.

The real problem peculiar to peanut butter is a mold-derived natural product called aflatoxin, a very potent toxin and carcinogen. In 2004, 125 Kenyans died from aflatoxin poisoning after eating contaminated maize, representing a fatality rate of 39%!

Compared to whole peanuts, I am told peanut butter is especially prone to aflatoxin contamination because the mold that produces it can grow on the lower quality peanut scraps and shavings used to make peanut butter. This may or may not be true — I could not find a citation.

There is also the unfortunate fact that the smaller, higher quality peanut butter brands may actually have a higher probability of contamination than the sugar and palm oil-laden Skippys and Jifs of the world, simply because the larger players have enough scale to do frequent testing. The FDA tests for aflatoxins, so in general there should be no brands with a huge problem here.

Because of these health risks, the FDA has published action levels for aflatoxin and regularly tests foods for the presence of aflatoxins. By using modern agricultural and processing techniques, companies can reduce the possibility of contamination in their products.

There is a specific variety of peanut, Valencia peanuts, that is less prone to aflatoxin contamination. Kirkland peanut butter is currently made with US Valencia peanuts. Since we had been buying Kirkland peanut butter for a while, I actually went as far as testing it for aflatoxin with the excellent Trilogy Lab, who graciously tolerated my tiny order. Kirkland had undetectable levels of aflatoxin, so that's what we exclusively buy now.

Aflatoxin levels in Kirkland Valencia peanut butter were undetectable (results from Trilogy Lab)

Turmeric

Turmeric is a popular supplement with pretty weak evidence for any positive effects, but also weak evidence for any negative effects. However, like cinnamon, and powders in general, there are concerns around heavy metal contamination.

Despite the paucity of evidence, I do sometimes take turmeric. I buy it from BioSchwartz because (a) it's turmeric extract, which apparently removes some impurities; (b) BioSchwarz does a lot of testing and is credible enough to be used in some studies.

Interestingly, there is also evidence that curcumin may chelate heavy metals, and hence reduce the total heavy metal burden on the body. On balance I find it worthwhile to take some turmeric, but I don't think it's an obvious win.

Sunscreen

For regulatory reasons — basically, because sunscreen is regulated like a drug in the US — it is difficult to buy good sunscreen in the US. This used to be a niche concern, but is now so mainstream that even AOC talked about it.

Recently, I found a good source of sunscreen information, Lab Muffin Beauty (e.g., her Top Sunscreen Recommendations for 2024). Lab Muffin Beauty is a PhD cosmetic chemist, and seems to have a ton of expertise on the topic. One interesting point she makes is that "physical" (Zinc or Titanium-based) sunblocks are not really any safer than "chemical" sunscreens. The basic argument is that both enter your bloodstream at low concentrations, and both appear to have comparable, and negligible, health impacts. She convinced me, for what it's worth. (Note, usually "sunblock" refers to the physical kind and "sunscreen" the chemical kind.)

Lab Muffin Beauty also had an interesting video that references the cancer-causing thymine dimer formation that can happen when UV damages DNA.

Thymine dimers resulting from UV radiation. These mutations can cause cancer.

The sunscreens I currently buy are:

• Biore UV Aqua Watery Essence SPF 50: This is a great sunscreen, even (surprisingly to me) doing well when tested in water. However, there is a catch. If you live in the US, you may end up buying the US version, which is not as good. You have to either buy specific Asian-origin SKUs on Amazon (taking some risk on counterfeit or incorrect products), or buy from a non-US store like StyleVana. If you buy four or more of these from StyleVana, as I did, the shipping is not bad, and thankfully sunscreen should last three years or more.
• NIVEA SUN Protect Super Water Gel: This one is less protective (it is only SPF30 and PA+++), but it's a bit easier to buy online (though the price is all over the place), and the pump is convenient to use, especially for children.

These two sunscreens are "watery" style, which I prefer. All of the "white" sunscreens I have ever used leave white deposits everywhere. I don't have recommendations for non-watery sunscreens but Lab Muffin Beauty also has plenty of recommendations in her video.

One thing to be aware of is that lots of brands have US versions of their sunscreens where they use the exact same brand names (e.g., La Roche-Posay Anthelios), so it's tricky to know what you are buying.

Toothpaste

Toothpaste has the same problem as sunscreen in that it is regulated like a drug in the US. Again, this means US toothpastes lag in technology by years.

The most notable ingredient that is missing from US toothpaste is NovaMin, a bioactive glass found, for example, in European Sensodyne but not US Sensodyne. This is especially egregious to me because the European Sensodyne reduces sensitivity by remineralizing teeth while the US Sensodyne includes a numbing agent (potassium nitrate) that just masks sensitivity!

(1) Bioactive glass (NovaMin) alone exhibited promising remineralization capabilities compared with a combination of fluoride and bioactive glass or just fluoride; (2) bioactive glass with fluoride seemed to potentiate the effect of fluoride alone

There is actually an interesting story behind NovaMin. To summarize, GSK bought the rights to NovaMin but the US trials were too expensive given the size of the toothpaste market. Realistically, not many people care enough to look into what ingredients US Sensodyne has vs European Sensodyne.

There is good news though. I don't understand the regulatory story here — it may be because they do not claim cavity prevention effects — but Amazon now sells toothpastes containing nano-hydroxyapatite, which seems to be as good as NovaMin at remineralization. For example, Davids, which does not have fluoride, and Made by Dentists, which does. Note that fluoride also remineralizes, albeit via a different mechanism, and I believe using both is recommended.

While fluoride toothpastes work by depositing fluoride ions into your enamel, fluoride free toothpaste with hydroxyapatite works by depositing naturally beneficial materials like calcium and phosphate ions into your enamel.

So, while fluoride is renowned for its strength, hydroxyapatite stands out for its natural affinity with the teeth and its potential to excel in specific oral health aspects. That's why many people suggest that both nano hydroxyapatite and hydroxyapatite are better than fluoride.

Unlike supplements and sunscreen, the effects of NovaMin/nano-hydroxyapatite are quite visible. You can see the "dentine tubule occlusion" process with a Scanning Electron Microscope within just a few days.

Pre- and post-treatment with nano-hydroxyapatite

Biomin F

The strongest remineralizing agent of all appears to be "Biomin F", which deposits fluoroapatite, a bioglass claimed to be 10 times more acid resistant than hydroxyapatite. Of course, you cannot buy Biomin F in the US, despite receiving FDA clearance in 2021 (note, not "FDA approval" as it says in the article!) You can buy Biomin C, but that is very similar to regular nano-hydroxyapatite. Not only that, but stores worldwide are low on Biomin F inventory for some reason. The Biomin Canada store is out of stock until "Q2 2025". Burbel in Ireland has it for the very reasonable price of €8 per tube, but it is out of stock until "next week", and this Australian pharmacy has it but with you'll pay $30 shipping to the US.

The British Dental Journal news article on Biomin F includes this hilariously mercantile take. Dentists really get away with some things doctors would not dare say:

BioMin F delivers controlled fluoride release to strengthen teeth against acid attack and reduce dentine hypersensitivity including scaling and post-bleaching sensitivity, a problem that reduces patient acceptance of this highly profitable revenue stream.

Floss

Floss is likely a significant source of PFAS (the Teflon-related "forever chemicals" that don't break down) and microplastics. A recent NHANES report found higher PFOAs in dental floss users, but, counterintuitively, lower levels of other PFAS. (NHANES is a massive survey that forms the basis for many observational health studies.)

Flossing with Oral-B Glide, having stain-resistant carpet or furniture, and living in a city served by a PFAS-contaminated water supply were also associated with higher levels of some PFASs.

These are not great studies, and there is nothing all that concerning in these reports, but since floss is something that can directly contact blood, it still seems worth addressing. Just last month, Consumer Reports reviewed PFAS-free flosses. Of those recommended, TreeBird seems to have the best reviews, but you have to buy it directly from the manufacturer for some reason. I have been using a very similar product, Bambo Earth, and it works ok. However, it is quite thin and breaks quite easily.

Flosses tested for the presence of fluorine

Air filters

Despite the increase in awareness of air filtration due to recent forest fires (at least in the US), I think air pollution is still underappreciated as a cause of disease. In a large study published in NEJM in 2017, they found a very strong correlation between PM2.5 and all-cause mortality.

Increases of 10 μg per cubic meter in PM2.5 [was] associated with increases in all-cause mortality of 7.3%

Although this is an observational study, it was large and well-controlled. There are many cities in the USA with an average PM2.5 of 10μg/m³ or greater, and in India, some cities can even average >100μg/m³. Within cities there is also a lot of variation, with houses closer to freeways having much greater PM2.5 levels. The air filtration company IQAir publishes an interesting "most polluted cities" leaderboard.

IQAir's most polluted cities in the US

The content of the pollution matters. An estimated 30% of Bay Area pollution blows in from China, including a lot of lead from coal-fired power plants.

Thankfully, there are plenty of good air filters around these days, and the technology is very standard: essentially an air filter is just a fan and a HEPA filter (the exception is Molekule, which doesn't work well). We have BlueAir and use cheaper third-party filters. I have tested a few of these third-party filters with a particle counter, and they all appear to work fine. Coway and Winix also work fine and are cheaper than BlueAir. Winix even has its own air quality sensor built in, which is pretty amazing for a $180 device. To really go all out, IQAir will sell you a whole-house HEPA filter for around $3000 (many houses already have air filters, but these are usually around MERV 13, where HEPA is closer to MERV 17).

MERV vs HEPA ratings

Although HEPA filters are most important because they catch PM2.5 particles, you can also buy activated carbon filters. Activated carbon captures VOCs like benzene (which a gas range will emit, even when off!) Wildfires are also a major source of VOC pollution. Combination HEPA–activated carbon filters are easy to buy for BlueAir, Coway, and Winix, so I think it's worthwhile.

Nose sprays

Airborne infectious diseases mostly enter through the nose and mouth. Generally, breathing through the nose is thought to be healthier, since the nose has more active barriers than the mouth, including a mucous layer and increased nitric oxide concentration (an antimicrobial). The recent fitness influencer trend of taping your mouth shut at night to improve sleep quality and reduce sleep apnea may also prevent infection.

Studies indicate that NO may also help to reduce respiratory tract infection by inactivating viruses and inhibiting their replication in epithelial cells.

Studies indicate that individuals who snore or breathe through the mouth during sleep—conditions which are highly prevalent in males—are more likely to develop respiratory tract infections. Our anecdotal observations also suggest that favoring nasal breathing during sleep by sealing the mouth with adhesive tape reduces common colds. This phenomenon may be due to the filtration and humidifying effects of the nose on inhaled air and to increased NO levels in the airways, which may decrease viral load during sleep and allow the immune system more time to mount an effective antiviral response.

You can also potentially prevent even more infections by augmenting the nose's defenses. There are at least two products that claim to do this:

Carrageenan

Luca V-Defense is a Korean nose spray that deposits a layer of type of carrageenan on the inside of the nose. As a common food thickener, carrageenan seems to be quite safe. There are several other carrageenan-based sprays on Amazon, like Betadine. Based on the ingredients I don't think there is too much to choose between them.

Strangely, even though the putative mechanism of action is prevention, the trials I found are for treatment post-infection (e.g., for the common cold, influenza, SARS-CoV-2). This is probably because real prevention trials would have to be extremely large and expensive.

The biological effect of carrageenan appears to prevent the virus from binding to cell surfaces or penetrating the cells

The antiviral effect of iota-carrageenan was previously shown in vitro for several other viruses, e.g., influenza A virus, human rhinovirus, endemic human coronaviruses and herpes simplex virus 2

None of the claims or evidence here is amazingly strong, but a physical barrier is a pretty simple and believable mechanism of action, especially for prevention, so I am inclined to believe some efficacy. Also, a common mechanism for infection is simply dried out mucous membranes, especially on airplanes, so carrageenan could also help with that.

Low indoor [relative humidity], as experienced during winter months or inside airplanes, directly or indirectly influences several mechanisms that increase the transmission of respiratory diseases.

Nitric oxide

Enovid (aka VirX) is a nitric oxide spray that is more expensive, more difficult to buy, and arguably less safe than carrageenan. You cannot buy it on Amazon for a reasonable price. Enovid has been tested in a Phase III in India for SARS-CoV-2:

Secondary endpoint assessments demonstrated a greater proportion of patients receiving [NO nasal spray] (82.8%) cleared SARS-CoV-2 (RT-PCR negative) by [end of treatment] compared to placebo (66.7%, p = 0.046), with no virus RNA detected a median of four days earlier compared to placebo (three vs seven days; p = 0.044).

The results for treatment are pretty good, if not amazing. Like carrageenan, it is possible that the NO effect is more relevant for prevention than treatment. It's honesly unclear to me why it helps at all post-infection.

I use both of these products sometimes. In particular, for airplane trips, I generally try to use the Luca spray beforehand, a mask (3M Aura) on the plane (which also helps with the dry air), and maybe Enovid at some point after. Airplanes are a major source of infections, and anecdotally, this protocol helps.

All told, I think the carrageenan sprays are probably a better bet than the NO sprays. They are cheap, easy to buy, have decent evidence for being protective against all airborne infection, and seem very safe.

Gas and induction stoves

Gas stoves produce a lot of noxious fumes, including NO₂, benzene, and CO. Like asbestos, lead, and other once-common toxins, the ubiquity of gas stoves may hide how unhealthy they actually are. By one estimate, gas stoves cause 12% of childhood asthma cases in the US, though honestly this is a weak observational study and the claim is heavily disputed (12% is a number so high that it would require extraordinary evidence).

This increased exposure likely causes ~50,000 cases of current pediatric asthma from long-term NO₂ exposure alone. Short-term NO₂ exposure from typical gas stove use frequently exceeds both World Health Organization and U.S. Environmental Protection Agency benchmarks.

Even with the kitchen extractor hood turned on, NO₂ levels exceed health guidelines

As mentioned above, activated carbon filters can remove some of these VOC pollutants, while regular HEPA filters cannot. Indoor plants may also help a little bit!

Some plants, like snake plants, remove a small amount of VOCs from the air

Venting with an extractor fan helps a lot, but the only real solution is replacing gas with electric, which these days means induction. Consumer Reports recommends this LG Induction Stove ($2800) or the cheaper IKEA TVARSAKER stove ($1400). There are also new lithium battery-augmented stoves like the Copper Charlie and Impulse Labs (cooktop only).

These induction stoves are admittedly pretty expensive, but as a stopgap, the Wirecutter-recommended Duxtop portable induction cooktop is only around $120, and some alternatives are half as much.

Electric kettles

Microplastics and other leached chemicals appear when you add boiling water to plastic. Since I drink a lot of tea, I spent quite a bit of time looking for a kettle with no plastic parts exposed to water. The more I read the more it seemed like every kettle has some small amount of plastic somewhere, so I was not totally satisfied, but I ended up buying a Cosori gooseneck kettle, and I like it. This recent roundup from implasticfree.com recommends the Cosori, plus several other options if gooseneck does not suit.

Tea bags

Tea bags, especially the plasticky-looking ones, can also contain microplastics. We buy Republic of Tea bags, which are made from wood pulp, and sell in bulk bags of 250. The company claims no plastics are used, though this reddit thread throws some doubt on that. Apparently, "plant-based bioplastics" are commonly used to seal tea bags, and there's no doubt many companies will refer to this as "plastic free". implasticfree.com also has a list of approved tea bags. Loose leaf tea is probably safest given the confusion here, but it's too inconvenient for me.

AeroPress

I have been using an Aeropress for many years, and it always bugged me that it's plastic. As plastics go, polypropylene seems like a good one, but it's still not ideal. There have been handmade metal-and-glass versions available online for a few years, but I was never convinced that with welding etc. I wasn't trading plastic contamination for metal contamination. This year, Aeropress finally released a stainless steel and borosilicate glass version, which I bought. It costs $150 and ships in May 2025.

The new glass and stainless steel AeroPress is $150

Travel mugs

In 2024, the giant Stanley travel mugs hydration enthusiasts were buying made the news when they were found to contain lead. Since the lead is totally separated from the interior of the cup, the risk turned out to be probably pretty negligible. Separately, Lead Safe Mama, a blogger who tests household items for lead and other contaminants, investigated and noted that the interior is only recommended for use with water, which is kind of weird.

The HydroFlask equivalent is the same size as the Stanley cup and is all stainless steel, so it's a pretty straightforward swap-in. I bought a HydroFlask, and also ended up also swapping the hard plastic part of the HydroFlask straw for a silicone straw since it comes in contact with hot liquid.

The Hydroflask straw has two separate parts: silicone on top and hard plastic on the bottom

Water filtration

There are two main ways to purify water: activated carbon filters and reverse osmosis. At one point I looked into Berkey water filters, as the only stainless steel activated carbon filter I could find. I decided against Berkey because it lacks certification and leached aluminum in at least one test.

We got PUR filters, which are similar to Brita, but with some minor performance improvements (when I checked 5+ years ago). I tested our PUR-filtered water with a GeneQuant, and in that test it removed a lot of impurities! The good news is that activated carbon filters work well. The bad news is they are annoying: they need to be filled manually, changed regularly, they slow down over time, and everything is plastic.

In retrospect, reverse osmosis filters are probably a better bet. They are out of sight so they require some active maintenance to avoid bacterial and mold growth, and since reverse osmosis removes minerals, they require a separate remineralization filter to taste ok. I have yet to install a reverse osmosis filter, so I don't have any particular recommendations.

The best way to test your water is probably TapScore but it's quite expensive at $200-300.

KitchenAid attachments

Many people own the classic KitchenAid stand mixer. In 2014, Lead Safe Mama found very high levels of lead in the standard KitchenAid attachments. There is a long backstory here and KitchenAid disagrees with the conclusion, but I think overall it was convincing that there was a concerning amount of lead.

The KitchenAid stand mixer and stainless steel attachments

In 2018, KitchenAid started selling stainless steel attachments in response to this finding. We own these and they work great. We had the standard enamel-coated attachments before, and these actually chipped a little bit due to misalignment, so independent of the lead problem, this is a big improvement. If you own this mixer, this is an upgrade I would highly recommend.

Food containers

Most paper and cardboard that touches food is lined with something. It's a pretty complicated zoo of plasticky materials, and I don't understand it very well. Some things are lined with PFAS (e.g., the paper in burger or sandwich wrappers, at least up until recently), some are lined with wax (e.g., the dry wax paper under pizza), some with silicone (e.g., parchment paper), some with polyethylene (e.g., paper coffee cups, butcher's paper).

There are plenty of exceptions to the above, and it's difficult to figure out exactly what is lining what, but I think it's pretty safe to say almost all paper and cardboard that could get soggy has some kind of lining. To my mind, dry wax and parchment paper are probably ok. The other random plastics are things I'd prefer to avoid, given the choice.

Since nothing is really labeled, I am pretty suspicious that there is more PFAS here than advertised, in the same way that BPA-free essentially means "contains something a lot like BPA", e.g., BPS.

The real issue is that the industry is replacing a toxic chemical with another, yet untested chemical, which will require large investments of research funds to carry out applicable studies

Despite the recent phase-outs of PFAS, Consumer Reports did a review in 2022 and found a ton of PFAS.

Identifying the exact type of PFAS in a product is complex: There are more than 9,000 known PFAS, yet common testing methods can identify only a couple dozen.

CR tested multiple samples of 118 products and calculated average organic fluorine levels for each. Overall, CR detected that element in more than half the food packaging tested. Almost a third—37 products—had organic fluorine levels above 20 ppm, and 22 were above 100 ppm.

In a 2022 paper, they found "trillions of sub-100 nm nanoparticles" being released into water from plastic-lined single-use coffee cups.

On a particle number density basis, particles released into water from a single 300 mL hot beverage cup equate to one particle for every seven cells in the human body in a size range available for cellular uptake.

Plastic-lined paper cups leach plastics

SweetGreen

One interesting example is the "fiber bowls" you get from fancier fast food like SweetGreen. Fiber bowls are those brown bowls that look like recycled cardboard, and you'd be forgiven for thinking they are healthier than the classic plastic or styrofoam containers. They used to be lined with PFAS, but in 2020 SweetGreen partnered with FootPrint International to remove PFAS from their bowls.

There is not much information online, but FootPrint have several patents, for example:

Methods and apparatus for vacuum forming and subsequently applying topical coatings fiber-based food containers. The slurry includes an embedded moisture barrier and/or vapor barrier, and the topical coating comprises an oil barrier comprising acrylate, rice bran wax, pectin, and pea protein.

As far as I can tell, acrylate (also listed as acrylic in the patent) is safer than PFAS, since it's harder and so less prone to leach. However, though it might technically not be "plastic" for some reason, it's not far off.

SweetGreen also scored very high for plastic contamination on plasticlist.org, coming in at 4th highest for DEHP out of 300 foods tested. My understanding is that this is more likely to come from the chicken than the bowl.

The plasticlist.org top 7 by DEHP content

Mass spectrometry

One common theme here is that it's really hard to tell what products are actually made from. In most cases the information does not exist, and the manufacturers have little incentive to say anything. If the product is manufactured in China, they may not even know for sure. For example, is there "plastic" in Sweet Green bowls and Republic of Tea tea bags, or just something very similar to plastic? I still don't know.

There is a technology that can detect the constituent molecules of almost anything: mass spectrometry. I really wish someone with a mass spec could review products and tell me what they are made from. Unfortunately, mass specs are pretty expensive ($100k-$1M) and finicky to keep running, and the data analysis is not all that straightforward (as evidenced by the recent study claiming massive amounts of microplastics in the brain).

A rebuttal to the study claiming very large volume of microplastics in the brain

Amazon

Even though the majority of the links above are from Amazon, and I buy from there a lot, in general I prefer not to. It's fairly common for products on Amazon to be counterfeit, mainly because random third-party sellers get mixed in with the official stores. Supplements may be especially prone to counterfeiting, since they are so easy to fake. If you are buying products specifically to avoid contaminants, then the rampant counterfeiting might defeat the purpose. Target, Costco, etc. do not appear to have this problem.

tl;dr

Recommended product list:

• Whey powder
• Collagen powder
• Creatine powder
• Peanut butter
• Turmeric
• Sunscreen
• Toothpaste
• Floss
• Air filter
• Nose spray
• Induction burner
• Electric kettle
• Tea bags
• AeroPress
• Travel mug
• Kitchenaid attachments

Thanks to Darren Zhu for comments on this post!