🧠 Algae gave neuroscience a light switch. The Nobel committee finally flipped it.

Optogenetics, the algae protein that became neuroscience’s on-off switch, finally took the Medicine Nobel, with the usual argument about who got left in the dark. Then a cisplatin patch that skips the scalpel, a bacterial enzyme that devours bioplastic and penicillin with the same wide mouth, DeepMind’s enzymes built from almost nothing, and a pig kidney that sat glassy at minus 150 for a year and made urine on the perfusion machine when it came out. Five stories. The kidney took the longest nap.

NEWS

On October 5, the Nobel Assembly at Karolinska Institutet gave the Medicine prize to optogenetics, the algae-derived trick that lets scientists switch single neurons on and off with light. The prize went to Karl Deisseroth, Peter Hegemann, and Georg Nagel “for their discoveries concerning light-gated ion channels and optogenetics.” nobelprize Hegemann, at Humboldt University of Berlin, and Nagel, at the University of Würzburg, worked out that a pond alga uses a light-gated channel called channelrhodopsin; nobelprize Deisseroth, at Stanford, turned that protein into a switch for firing neurons in a living brain. They split 12 million Swedish kronor, about $1.2 million.

Deisseroth, a self-described night owl, missed the roughly 12:27 a.m. call, so the committee rang his wife instead. “I lost the ability to form words for about 30 seconds or so,” he told Stanford afterward.

The three-person cap did its usual damage. Science reported that Ed Boyden, first author of the landmark 2005 paper, science and Gero Miesenböck, who controlled neurons with light back in 2002, were left out; Miesenböck said it “was hard” and that the committee took “the narrowest possible view of optogenetics.”

Two days later the Chemistry prize went to Henri Kagan and Kenso Soai for non-linear effects and autocatalysis in asymmetric synthesis, the chemistry of making one mirror-image molecule instead of a 50/50 mix. The committee could not reach Kagan by phone, and Soai called it one of the most exciting days of his life. Matthew Fuchter of Oxford told Science the Soai reaction “became such a poster child because it showed it was possible,” science even if it looks nothing like biology.

The Physics prize went to Francis Halzen for neutrinos, which we will let the astrophysicists have. On optogenetics, even Nagel has said he knows of only one patient who has benefited and thought a medicine prize was early, rdworldonline as R&D World noted, which is a refreshing thing to hear from a laureate.

RESEARCH & NEWS

Privo Technologies says a chemotherapy patch cleared early oral cancer without a scalpel, and the numbers it is quoting are big. In cohort 1 of the CLN-004 trial, 21 of 22 patients hit a pathologic complete response, a 95.5% rate, after a single cycle of PRV111, a mucoadhesive cisplatin patch. The 22nd patient was downstaged from carcinoma in situ to low-grade dysplasia, and all 22 avoided the planned surgical excision.

The idea is pretty appealing. biospace Repeated oral surgery scars tissue and wrecks speech and swallowing, so a patch that delivers cisplatin locally while keeping blood levels negligible is a real quality-of-life pitch.

Now some details though. These results come from a company press release, not a peer-reviewed paper, and this is a single-arm, open-label cohort, with no control group and 22 patients, and “complete response” was judged by punch biopsy biospace rather than a resection. The registry lists CLN-004 as an adaptive phase 2/3 platform across several cisplatin formats.

The peer-reviewed evidence is older and narrower. The 2022 work was published in Nature Communications, not this carcinoma-in-situ cohort. The URL making the rounds is actually the December 2022 author correction that re-added six omitted names. nature Founder and CEO Manijeh Goldberg is the lead author, Privo is privately funded, and the program holds an FDA orphan drug designation granted in 2022 for oral carcinoma in situ. Encouraging, but hold the confetti until a journal sees the data.

RESEARCH

German researchers found a bacterial enzyme with a mouth wide enough to swallow both plastic and penicillin. Writing in the ISME Journal, a University of Konstanz team describes a family-VIII esterase whose active site is a wide-open groove rather than a narrow tunnel, giving it a “pac-man”-like shape. That is the authors’ own joke, delivered, per the university newsroom, “with a laugh.” uni-konstanz

Harry Lerner, the first author now at KU Leuven, and corresponding author David Schleheck buried bioplastic films in forest soil for a year and tracked a parallel lab experiment. All the bioplastics fully degraded in roughly 250 to 330 days, cellulose in about 80, and ordinary polyethylene barely at all, eurekalertbionity as EurekAlert summarized. Electron microscopy showed bacterium-shaped holes in the film, eurekalert as if the microbes had chewed their way in.

Metagenomics flagged one enriched esterase gene, and the purified enzyme did two things in a tube: it cut the polyester into monomers and it cleaved penicillin eurekalert and ampicillin, hinting at a link between plastic diets and antibiotic resistance, as Phys.org noted.

The caveats matter here. The plastic is long-chain aliphatic polyester, a compostable material, not the PET in bottles or the HDPE in bags, so this is not a rival to PETase or LCC. The structure is an AlphaFold3 model, the docking is in silico, and the tube tests used a soluble version of the enzyme, as the authors report in the ISME paper. The resistance angle is a hypothesis, not a bacterium behaving badly. Still, a wide-open active site that is bad at being picky is a useful place to start

RESEARCH

DeepMind says it built working enzymes from scratch, and for once the branding undersells the caveat: AlphaProtein Novo shares the Alpha name but is its own diffusion pipeline, Substack using an AlphaFold 3 variant only as a filter, not AlphaFold itself. The October 5 preprint is a collaboration with Frances Arnold’s lab x at Caltech and Peng Liu’s at Pittsburgh, and it is not peer-reviewed.

The pipeline designed Kemp eliminases, serine esterases, a nitrene transferase that makes the drug building block piperidine, and an esterase that chews the plasticizer DEHP. x Its best from-scratch Kemp eliminase hit a kcat/KM of 14,600 per molar per second, roughly 70 times prior de novo designs. The piperidine enzyme made one ring over the other at 99 to 1 with 94% enantiomeric excess, cbirt while screening 188 natural proteins turned up nothing better than 30 to 70.

Read the claim carefully. “Match or surpass naturally occurring activity and selectivity” is about product selectivity and surviving harsh conditions, like the DEHP design working 14 times better at 90 degrees, not about raw speed, where the designs still trail evolved enzymes by orders of magnitude. cbirt

Outside reaction is thin, since no big protein-design lab is on record yet, and the commentary so far lives on blogs. Christopher Gannatti, WisdomTree’s global head of research, notes the system picks designs by where atoms sit, not what the reaction costs in energy, and bioinformatician Daniel Buchan calls it a major advance while the hard part stays the motif. After Claude’s ART enzyme, this is a suspiciously enzyme-heavy autumn.

RESEARCH

A pig kidney spent 366 days in deep storage and then made urine on a perfusion machine, which is the kind of sentence that needs quotation marks around “frozen.” The organ was vitrified, not frozen, meaning cooled into a glass-like, ice-free state at minus 150 degrees Celsius, technologyreview as MIT Technology Review reported. The University of Minnesota team, co-led by surgeon Erik Finger and bioengineer John Bischof, technologyreview posted the work as a bioRxiv preprint in October, with Zonghu Han as first author. biorxiv

The trick is rewarming. The team perfused the kidney with iron oxide nanoparticles technologyreview and a new cryoprotectant called PEZ42, then flipped the particles with a radiofrequency field to heat the organ evenly from the inside, technologyreview warming it in under six minutes. These pig kidneys weigh about 100 grams, roughly 100 times the rat kidneys the group technologyreview vitrified back in 2023, and Bischof says adapting the cocktail took three years. technologyreview

“Brought back to life” means transplanted into pigs for two-hour, non-survival experiments and run on perfusion machines; the kidneys pinked up and made urine, but no animal was kept alive long term. Urine ran about two-thirds of normal, technologyreview and creatinine clearance landed well below fresh organs. yahoo The paper is more modest than the headline: Greg Fahy, chief scientific officer of 21st Century Medicine, told MIT that regaining blood flow is important but “we can’t tell from these experiments whether these kidneys might have supported life or not.” technologyreview

The payoff would be enormous, since banking organs for a year could reshape matching, cut discard, and support pig-organ xenotransplantation. The field, funded through the NSF center ATP-Bio, now has to prove a rewarmed kidney can keep an animal alive.

Time was a common variable in all five this time. The optogenetics Nobel landed about two decades after the channelrhodopsin papers and forty years after Kagan’s first non-linear effect. Privo’s fresh numbers lean on a proof of concept from 2022. The Konstanz team watched bacteria chew through bioplastic for most of a year, faster than microbiologists expected. eurekalert DeepMind compressed enzyme discovery from eons of evolution into a few rounds of diffusion and filtering. And a pig kidney sat vitrified for 366 days before producing a drop. The science that looks sudden in a headline is almost always the slow kind finally paying out.

Which of these will still matter in a decade? Hit reply, we read everything. And if you know someone who still thinks de novo enzyme design is science fiction, forward this along.

Keep questioning everything (especially any press release that leads with a percentage),

Prateek & Jere

P.S. We timed how long it took to read this edition. Still faster than rewarming a kidney, but only just.