To help guard against nefarious uses of these proteins, scientists have recently figured out a way to "watermark" them without compromising their function. A team from Google DeepMind developed this technique to better track the provenance of AI-designed proteins.
"In practice, it could help trace a design's origin, flag engineered proteins for extra biosecurity checks, and reduce misleading claims about how a protein was made," Sleator told Live Science in an email.
The unveiling of the AI program AlphaFold in 2020 was a milestone in protein engineering. The tool, which won Demis Hassabis, John Jumper and David Baker the Nobel Prize in Chemistry in 2024, can reveal the 3D structure of a protein from the sequence of its building blocks, called amino acids. Proteins fold like origami, adopting 3D shapes that dictate their function.
"Anything that can be used for good can be used for bad," said George Rose, professor emeritus of biophysics at Johns Hopkins University.
The DeepMind team has framed the watermarking effort as a "family" of related techniques they call SynthIDBio. The first member of this family is SynthIDBio-sequence, which encodes watermarks into the amino acid sequences of proteins created by a program called ProteinMPNN.
The 3D shape of a protein is largely determined by its amino acid sequence, or the order of its building blocks. In cells, these blocks are assembled by ribosomes (pictured). (Image credit: STEVEN MCDOWELL/SCIENCE PHOTO LIBRARY via Getty Images)A sister technique, called SynthIDBio-structure, instead embeds a watermark directly into the protein's structure. It does this by altering the function of AlphaFold 3, DeepMind's flagship protein prediction algorithm.
In a test, these two systems created hidden watermarks that could be detected with incredible accuracy, flagging more than 99% of watermarked proteins and correctly ignoring 99.9% of non-watermarked proteins.
How to bypass a protein watermark
The two techniques are "effective but brittle," Bruce Wittmann, a principal applied scientist at Microsoft, told Live Science in an email. That's because, as the DeepMind team also notes in their paper, the watermarks can be easily removed.
Bruce Wittmann, a principal applied scientist at Microsoft
Experts are also skeptical that watermarking would provide a long-term solution for biosecurity.
Additionally, the vast majority of software for protein prediction and generation is open-source, meaning much of the code is freely available to use and modify. That makes it far harder to bake watermarking into these programs. Wittmann warned that the field would have to shift toward closed-source models before watermarks could become an industry standard.
Exclusive to Live Science ProHe added that watermarking could act as one layer of a biosecurity defense shield, rather than offering standalone protection. Top-down regulation would be challenging to enforce. "I imagine it would be very difficult to ensure the regulations were being followed," he said.
"I'm convinced it won't work," he said. "Once there's a sweet technology that does something, government regulation to keep it under wraps has never been really successful."
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