Derya Unutmaz reported that o1-pro came up with a novel idea in the domain of immunotherapy:
Introduction to the Context:
I’m working on developing innovative cancer immunotherapy approaches to address key challenges in the field. Immunotherapy is an exceptionally powerful strategy for curing cancer because it harnesses the body’s immune system—our internal army—and empowers it to recognize and eliminate cancer cells. In this effort, we are focusing on engineering T cells, the immune system’s soldiers and generals, through synthetic biology.
However, significant challenges remain, especially in treating solid tumors like breast cancer. Within the tumor microenvironment, T cells often become exhausted due to the overwhelming number of cancer cells and the suppressive environment created by the tumor. This exhaustion severely limits the effectiveness of these therapies.
To tackle this issue, we employ a cutting-edge model system using 3D bioprinted breast cancer tissue integrated with engineered human T cells. These T cells are reprogrammed through advanced synthetic biology techniques to test and develop solutions for overcoming exhaustion.
Prompt to O1-Pro:
Building on work I’ve previously done and tested with o1-Preview and GPT-4o, I posed the following prompt:
“I’d like you to focus on 3D bioprinted solid tumors as a model to address the T cell exhaustion problem. Specifically, the model should incorporate stroma, as seen in breast cancer, to replicate the tumor microenvironment and explore potential solutions. These solutions could involve technologies like T cell reprogramming, synthetic biology circuits, cytokines, transcription factors related to exhaustion, or metabolic programming. Draw inspiration from other fields, such as Battle Royale games or the immune system’s ability to clear infected cells without triggering autoimmunity. Identify potential pitfalls in developing these therapies and propose alternative approaches. Think outside the box and outline iterative goals that could evolve into full-scale projects. Focus exclusively on in vitro human systems and models.”
Why Battle Royale Games?
You might wonder why I referenced Battle Royale games. That’s precisely the point—I wanted to push the model to think beyond conventional approaches and draw from completely different systems for inspiration. While o1-Preview and GPT-4o were able to generate some interesting ideas based on this concept, but they were mostly what I could also conceive though better most PhD students. In contrast, o1-Pro came up with far more creative and innovative solutions, that left me in awe!
Idea #9: A Remarkable Paradigm
Here, I’m sharing one specific idea, which I’ll call Idea #9 based on its iteration sequence. This idea was exceptional because it proposed an extraordinary paradigm inspired by Battle Royale games but more importantly within the context of deep temporal understanding of biological processes. This was the first time any model explicitly considered the time-dependent nature of biological events—an insight that reflects a remarkably advanced and nuanced understanding!
“Adapt or Fail” Under Escalating Challenges:
Another remarkable aspect of idea #9 was that conceptually it drew from the idea of “adapt or fail” in escalating challenges, directly inspired by Battle Royale mechanics. This was the first time any model could think of it from this perspective. It also emphasized the importance of temporal intervals in reversing or eliminating exhausted T cells. Indeed, this approach mirrors the necessity for T cells to adapt dynamically under pressure and survive progressively tougher challenges, something we would love to model in in vitro systems! One particularly further striking insight was the role of stimulation intervals in preventing exhaustion. Idea #9 suggested that overly short intervals between stimuli might be a key factor driving T cell exhaustion in current therapies. This observation really amazed me with its precision and relevance—because it pinpointed a subtle but critical aspect of T cell activations and development of exhaustion mechanisms.
There's more behind the link. I have no relevant expertise that would allow me to evaluate how novel this actually was. But immunology is the author's specialty with his work having close to 30 000 citations on Google Scholar, so I'd assume him to know what he's talking about.
1. AI contributions to Erdős problems
I learned yesterday that an open problem I’d been working on for several weeks had just
been solved by Claude Opus 4.6
Claude's Cycles (Cont.) (via Bo Wang on Twitter)
The even case, which Claude couldn’t finish, was then cracked by Dr. Ho Boon Suan using GPT-5.4 Pro
Soon after, Dr. Keston Aquino-Michaels used GPT + Claude together to find simpler constructions for both odd and even m
3. A Ramsey-style Problem on Hypergraphs (FrontierMath Open Problems: Moderately Interesting)
4. anaguma: An internal model at OpenAI has just solved the unit distance problem, a major conjecture in discrete geometry.
5. OpenAI: GPT-5.6 Sol Ultra produced a proof of the 50-year-old Cycle Double Cover Conjecture using 64 subagents in just under one hour.
6. levent (Anthropic): the jacobian conjecture is false
7. 2026/07/28 | mainly GPT 5.6 Pro - David Turturean's Proof of The 2-adic Absolute Galois Group (FrontierMath Open Problems: Solid Result):
Using mostly my voice, I solved one of @EpochAIResearch's FrontierMath Open Problems: finding an explicit presentation of the 2-adic Absolute Galois Group - open for more than forty years, now with a full proof in collaboration with David Roe, the problem's proposer.
Still, the problem originating in 1982 shouldn’t be taken as the sign of a major enigma. The same mathematician noted the problem was “basically attention-bottlenecked”. When submitting the problem, Roe suggested the main difficulty was that “the answer is likely to be messy”.
8. 2026/07/30 | Tencent Hy - Not sure what is the name of this thing
Tencent Hy: For a finite set of integers (A), how much faster can (|A+A|) grow than (|A-A|)?
A 1969 theorem gave an upper bound of 2 for the exponent. For more than 50 years, the best constructions barely exceeded 1.1.
With help from our research agent Hyra and the Hy3 model, we found an explicit construction showing that the optimal exponent is exactly 2.
Paper: https://arxiv.org/abs/2607.27199
Hyra blog: https://hy.tencent.ai/research/hyra
Formal proof: https://github.com/linhaowei1/sum-diff-proof
GPT‑5.6 Sol Pro can solve it too: it recovered the same explicit construction using a slightly different argument. https://chatgpt.com/share/6a6af651-8ecc-83e8-ab0f-6fe887f0cc4c
1. Part of a theorem in Terence Tao's Local Bernstein theory, and lower bounds for Lebesgue constants (via Jared Duker Lichtman on Twitter)
After some experimentation using the tool AlphaEvolve, the author was led to conjecture a proof of (1.28) by separately lower bounding each of these two factors. The first of these conjectures was then proven by ChatGPT, and the author was able to prove the second, thus giving a complete proof of Theorem 1.4.
2. 2026/07/23 - @2ap2cb2: Counterexample to Wall II Graph Conjecture 194
GPT 5.6: "It is a niche open conjecture embedded in a respectable automated-conjecturing programme"
3. 2026/07/22 | GPT 5.6 Pro - Counterexample to Goemans’ conjecture a.k.a. Dinitz-Garg-Goemans conjecture by @Dmitry Rybin
GPT 5.6: "Recent papers explicitly call it a “famous conjecture,” but that fame is local to combinatorial optimization and approximation algorithms."
1. AI guided discovery of a murine model of asymptomatic Alzheimer’s disease (via Bryan Johnson)
ChatGPT 5.5 is not impressed: "It is a Boolean implication network plus hand-designed gene signature selection and composite scoring."
I was literally just reading this before seeing your post:
https://www.techspot.com/news/106874-ai-accelerates-superbug-solution-completing-two-days-what.html
Arguably even more remarkable is the fact that the AI provided four additional hypotheses. According to Penadés, all of them made sense. The team had not even considered one of the solutions, and is now investigating it further.
I think DeepMind's FunSearch result, showing the existence of a Cap Set of size 512 for n=8, might qualify:
https://www.nature.com/articles/s41586-023-06924-6
They used an LLM which generated millions of programs as part of an evolutionary search. A few of these programs were able to generate the size-512 Cap Set. This isn't a hugely important problem, but there was preexisting interest in it. I don't think it was particularly low-hanging fruit; there have been some followup papers using alternative scaffolding and LLMs, and the 512 result is not easy to reproduce.
I've also done some work on LLM generation of programs that have solved longstanding open instances of combinatorial design problems:
https://arxiv.org/pdf/2501.17725
As noted in the paper though, these do feel a bit more like low-hanging fruit, and these designs probably could have been found by people working to optimize several methods to see if any work. Still, they were recognized open instances, and no one had previously solved before the LLM generated code that constructed the solution.
It's hard to see what a novel insight is exactly. Any example can be argued against. Can you give an example of one? Or of one you've personally had?
Various LLMs can spot issues in code bases that are not public. Do all of these count?
In a recent post, Cole Wyeth makes a bold claim:
I commented:
My question is: can anyone confirm the above rumor, or cite any other positive examples of LLMs generating insights which help with a scientific or mathematical project, with those insights not being available anywhere else (ie seemingly absent from the training data)?
Cole Wyeth predicts "no"; though LLMs are able to solve problems which they have not seen by standard methods, they are not capable of performing novel research. I (Abram Demski) find it plausible (but not certain) that the answer is "yes". This touches on AI timeline questions.
I find it plausible that LLMs can generate such insights, because I think the predictive ground layer of LLMs contains a significant "world-model" triangulated from diffuse information. This "world-model" can contain some insights not present in the training data. I think this paper has some evidence for such a conclusion:
However, the setup in this paper is obviously artificial, setting up questions that humans already know the answers to, even if they aren't present in the data. The question is whether LLMs synthesize any new knowledge in this way.