Luke J. O'Connor

Luke J. O'Connor

At the heart of existing language model agents is a fixed orchestrator program responsible for the state transition between consecutive turns. This paper introduces self-programmed execution (SPE), an agent architecture in which the model completion is itself the orchestrator program, and the harness evaluates this program but does not impose its own orchestration policy. I formalize this idea using agentic machines: an SPE state is one from which a model completion can load any state of an embedded copy of the machine, meaning that it is subject to no fixed turn-to-turn orchestration policy. Realizing SPE in practice is nontrivial because the same data is both model context and executable program. I therefore introduce Spell, a Lisp-based language in which programs can edit and re-evaluate themselves, and effectful expressions like model invocations are structured such that re-evaluating an edited program does not replay its side effects. Experiments with existing models, not trained for SPE or Spell, show that frontier models can operate in this regime and accomplish challenging agentic tasks. These results demonstrate how an LM can act as an agent without any fixed orchestration policy, and they raise the question of what self-orchestration strategies might be learned by a model trained for self-programmed execution. Code is available at https://github.com/lukejoconnor/spell .

Luke J. O'Connor, Alkes L. Price

Genome-wide association studies (GWAS) have emerged as a rich source of genetic clues into disease biology, and they have revealed strong genetic correlations among many diseases and traits. Some of these genetic correlations may reflect causal relationships. We developed a method to quantify causal relationships between genetically correlated traits using GWAS summary association statistics. In particular, our method quantifies what part of the genetic component of trait 1 is also causal for trait 2 using mixed fourth moments $E(α_1^2α_1α_2)$ and $E(α_2^2α_1α_2)$ of the bivariate effect size distribution. If trait 1 is causal for trait 2, then SNPs affecting trait 1 (large $α_1^2$) will have correlated effects on trait 2 (large $α_1α_2$), but not vice versa. We validated this approach in extensive simulations. Across 52 traits (average $N=331$k), we identified 30 putative genetically causal relationships, many novel, including an effect of LDL cholesterol on decreased bone mineral density. More broadly, we demonstrate that it is possible to distinguish between genetic correlation and causation using genetic association data.