“By late 2015, we had cracked a lot of the challenges,” says Pardee. Then, in January, the Zika outbreak hit.
Zika is a viral disease that can stunt brain development in babies, and detecting it early it is a pain. You could look for antibodies that react to the virus, but these tend to pick up genetically similar viruses like dengue, which are found in the same places. You could sequence the virus’s genome, but that involves transporting blood samples to cities with sophisticated labs and scientific equipment. What you really want is a cheap, reliable sensor that can be taken out into the field. “Jim called Alex and me and said here’s a chance to demonstrate our tech again, and show its relevance,” says Pardee. They dropped everything else and got to work.
The team quickly developed a paper-based, color-changing Zika sensor, and incorporated it into a $250 electronic reader. It’s sensitive: It could detect very low concentrations of virus in the blood of an infected monkey. It’s specific: It doesn’t react to dengue virus. It can even tell the difference between distinct Zika strains, even if they differ by a single genetic change. And it took just six weeks to make.
The next time will be even faster. Green has now developed a computer program that will look at a virus’s genome and design toehold switches that recognize specific sequences—those that aren’t found in other viruses or in the human genome. “The algorithm really does a lot of the heavy lifting for the team,” says Pardee. “We can now put out a system for a new target in probably a week.”
In the meantime, the team has just received funding for a field trial, in which they’ll test their Zika sensor on large numbers of people in South America. And since all of this runs on the same freeze-dried, cell-free components, the sensor should work in the heat and humidity of tropical outbreaks.
The Zika sensor hints at the most exciting application of the freeze-dried extracts. At its core, it is a way of producing a colored chemical on demand. And because that works, it’s also possible to manufacture more medically useful substances, like drugs and vaccines, in hot developing countries where manufacturing facilities are scarce and access to medicine is limited by a cold chain.
For this application, Pardee’s team avoids paper. They freeze-dry DNA instructions for making the chemical of choice, the enzymes that will carry out those instructions, and liquids that provide the right conditions for the manufacturing process. The result is a “reaction pellet”—a chemical reaction on pause. To press play, just add water.
In this way, the team created a variety of medical molecules, including: antimicrobial chemicals for killing bacteria; antibodies for targeting cancer cells; and vaccines like the diphtheria vaccines, which is famously challenging to distribute because it is exquisitely sensitive to being thawed and refrozen. The products all behaved as expected: the antibodies really did attack cancer cells, and the vaccines triggered strong immune reactions in mice. “Each product has its own personality and requirements, but once you have those conditions worked out, the process is reliable,” says Pardee.