Dual use of artificial-intelligence-powered drug discovery | Nature Machine Intelligence

An international security conference explored how artificial intelligence (AI) technologies for drug discovery could be misused for de novo design of biochemical weapons. A thought experiment evolved into a computational proof.

In less than 6 hours after starting on our in-house server, our model generated 40,000 molecules that scored within our desired threshold. In the process, the AI designed not only VX, but also many other known chemical warfare agents that we identified through visual confirmation with structures in public chemistry databases.

Many new molecules were also designed that looked equally plausible. These new molecules were predicted to be more toxic, based on the predicted LD50 values, than publicly known chemical warfare agents (Fig. 1). This was unexpected because the datasets we used for training the AI did not include these nerve agents.

The virtual molecules even occupied a region of molecular property space that was entirely separate from the many thousands of molecules in the organism-specific LD50 model, which comprises mainly pesticides, environmental toxins and drugs (Fig. 1). By inverting the use of our machine learning models, we had transformed our innocuous generative model from a helpful tool of medicine to a generator of likely deadly molecules.

Our toxicity models were originally created for use in avoiding toxicity, enabling us to better virtually screen molecules (for pharmaceutical and consumer product applications) before ultimately confirming their toxicity through in vitro testing. The inverse, however, has always been true: the better we can predict toxicity, the better we can steer our generative model to design new molecules in a region of chemical space populated by predominantly lethal molecules.

We did not assess the virtual molecules for synthesizability or explore how to make them with retrosynthesis software. For both of these processes, commercial and open-source software is readily available that can be easily plugged into the de novo design process of new molecules.

We also did not physically synthesize any of the molecules; but with a global array of hundreds of commercial companies offering chemical synthesis, that is not necessarily a very big step, and this area is poorly regulated, with few if any checks to prevent the synthesis of new, extremely toxic agents that could potentially be used as chemical weapons.

Importantly, we had a human in the loop with a firm moral and ethical 'don't-go-there' voice to intervene. But what if the human were removed or replaced with a bad actor? With current breakthroughs and research into autonomous synthesis, a complete design–make–test cycle applicable to making not only drugs, but toxins, is within reach. Our proof of concept thus highlights how a nonhuman autonomous creator of a deadly chemical weapon is entirely feasible.