How we're using AI to discover new antibiotics

So how are we going to beat
this novel coronavirus?

By using our best tools:

our science and our technology.

In my lab, we're using
the tools of artificial intelligence

and synthetic biology

to speed up the fight
against this pandemic.

Our work was originally designed

to tackle the antibiotic
resistance crisis.

Our project seeks to harness
the power of machine learning

to replenish our antibiotic arsenal

and avoid a globally devastating
post-antibiotic era.

Importantly, the same technology
can be used to search

for antiviral compounds

that could help us fight
the current pandemic.

Machine learning is turning
the traditional model of drug discovery

on its head.

With this approach,

instead of painstakingly testing
thousands of existing molecules

one by one in a lab
for their effectiveness,

we can train a computer

to explore the exponentially larger space

of essentially all possible molecules
that could be synthesized,

and thus instead of looking
for a needle in a haystack,

we can use the giant magnet
of computing power

to find many needles
in multiple haystacks simultaneously.

We've already had some early success.

Recently, we used machine learning

to discover new antibiotics
that can help us fight off

the bacterial infections that can occur
alongside SARS-CoV-2 infections.

Two months ago, TED's Audacious Project

approved funding for us
to massively scale up our work

with the goal of discovering
seven new classes of antibiotics

against seven of the world's
deadly bacterial pathogens

over the next seven years.

For context,

the number of new class of antibiotics

that have been discovered
over the last three decades is zero.

While the quest for new antibiotics
is for our medium-term future,

the novel coronavirus
poses an immediate deadly threat,

and I'm excited to share that we think
we can use the same technology

to search for therapeutics
to fight this virus.

So how are we going to do it?

Well, we're creating
a compound training library,

and with collaborators
applying these molecules

to SARS-CoV-2-infected cells

to see which of them exhibit
effective activity.

These data will be use to train
a machine learning model

that will be applied to a [?]
library of over a billion molecules

to search for potential
novel antiviral compounds.

We will synthesize and test
the top predictions

and advance the most promising
candidates into the clinic.

Sound too good to be true?

Well, it shouldn't.

The Antibiotics AI Project is founded
on our proof of concept research

that led to the discovery
of a novel broad spectrum antibiotic

called Halocin.

Halocin has potent antibacterial activity

against almost all antibiotic-resistant
bacterial pathogens,

including untreatable
pan-resistant infections.

Importantly, in contrast
to current antibiotics,

the frequency at which bacteria
develop resistance against Halocin

is remarkably low.

We tested the ability of bacteria
to evolve resistance against Halocin

as well as Cipro in the lab.

In the case of Cipro,

after just one day, we saw resistance.

In the case of Halocin,

after one day we didn't
see any resistance.

Amazingly, after even 30 days,

we didn't see any
resistance against Halocin.

In this pilot project, we first tested
roughly 2,500 compounds against E. coli.

This training set included
known antibiotics,

such as Cipro and penicillin,

as well as many drugs
that are not antibiotics.

These data we used to train a model

to learn molecular features
associated with antibacterial activity.

We then applied this model
to a drug repurposing library

consisting of several thousand molecules,

and asked the model to identify molecules

that are predicted
to have antibacterial properties

but don't look like existing antibiotics.

Interestingly, only one molecule
in that library fit these criteria,

and that molecule
turned out to be Halocin.

Given that Halocin does not look
like any existing antibiotic,

it would have been impossible for a human,
including an antibiotic expert,

to identify Halocin in this manner.

Imagine now what we could do
with this technology

against SARS-CoV-2.

And that's not all.

We're also using the tools
of synthetic biology,

tinkering with DNA and other cellular machinery, to serve human purposes like combating COVID-19 [??] we are working to develop a protective mask that can also serve as a rapid diagnostic test. How does that work? Well, we recently showed that you can take the cellular machinery out of a living cell and freeze-dry it along with RNA sensors onto paper in order to create low-cost diagnostics for Ebola and Zika. The sensors are activated when they're rehydrated by a patient sample that could consist of blood or saliva, for example. It turns out this technology is not limited to paper and can be applied to other materials, including cloth. For the COVID-19 pandemic, we're designing RNA sensors to detect the virus and freeze-drying these along with the needed cellular machinery into the fabric of a face mask, where the simple act of breathing, along with the water vapor that comes with it, can activate the test. Now, if the patient is infected with SARS-CoV-2, the mask will produce a fluorescent signal that can be detected by a simple, inexpensive handheld device. In one or two hours, a patient could those be diagnosed safely, remotely and accurately. We're also using synthetic biology to design a candidate vaccine for COVID-19. We are repurposing the BCG vaccine, which has been used against TB for almost a century. It's a live attenuated vaccine, and we're engineering it to express SARS-CoV-2 antigens, which should trigger the production of protective antibodies by the immune system. Importantly, BCG is massively scalable and has a safety profile that's among the best of any reported vaccine. With the tools of synthetic biology and artificial intelligence, we can win the fight against this novel coronavirus. This work is in its very early stages, but the promise is real. Science and technology can give us an important advantage in the battle of human wits versus the genes of superbugs, a battle we can win. Thank you.