The contraption looks and sounds like a washing machine: a rumbling box with a circular window near the floor.
But if you look inside, you won’t see a whir of clothes; instead you’ll see a ring of crystalline ice. This device is called the Freezemobile, and it isn’t your standard household appliance. By hooking up a few test tubes to its metal piping, chemists have used the Freezemobile to make drug ingredients designed to be transported into the remotest corners of the developing world.
That might sound like overkill when you could just send blister packs of pills. Yet for some medicines and vaccines, pills don’t do the trick. That’s because those types of drugs are often harvested from living cells — and just like your leftover lasagna, they probably won’t still be good after days in a hot car.
On Thursday, researchers at Harvard’s Wyss Institute, the Massachusetts Institute of Technology, and University of Toronto published a possible solution, spearheaded by medical engineer James Collins. Instead of making the drugs and then trying to keep them refrigerated over thousands of miles, they want to give people the ingredients. These components don’t require refrigeration, and the instructions are as simple as they come: Just add water.
“It’s essentially how you make ramen,” said Peter Nguyen, a research fellow at the Wyss, and one of the first authors on the paper.
But creating those tiny make-your-own-drug kits is hard.
Usually, to produce biologics — as these drugs are called — a company uses living cells as their factories, often turning to bacteria like E. coli. By injecting new bits of DNA into the bacteria, the researchers modify them to produce proteins that prevent or beat back disease.
These proteins, however, can be delicate things, destroyed by deep freezing or temperatures warmer than a refrigerated chill.
So Nguyen and other members of the Collins lab set about extracting cells’ innards to create what amounts to cellular machinery in powder form. To break open the cell membranes, they used a needle vibrating at supersonic frequencies. The metal moves so fast that it can cause test tubes to shatter or melt. “It feels like a tuning fork times a hundred,” said Nguyen.
With a centrifuge, they separated out the molecules important for protein production from all the other gunk, such as baubles of fat and the cell’s own DNA.
Sprinkle in some fuel and preservative, put into the Freezemobile, and voila — a speck comes out, looking like cotton candy, which could potentially be shipped out to some remote location. Tip in a pinch of freeze-dried DNA and a bit of sterile water, and a chemical reaction would begin, with the genetic material programming the cell innards to make the desired protein. The more different kinds of DNA you take with you, the more different kinds of drugs and vaccines you can make.
“It’s no longer living, but all of its internal components are still there, the ribosomes, all of the machinery that makes that protein,” said Nguyen.
The project was partly funded by Department of Defense. As Nguyen explained, with a little tweaking, these technologies could allow soldiers to carry a whole arsenal of drug ingredients into the field so they are ready for all kinds of medical needs.
To prove that this technology works, the team made and tested four different categories of biologics, including a diphtheria vaccine, an antimicrobial peptide, and a bacteria-fighting antibody. Their results were published in Cell.
To other scientists, the prospect is exciting. Bradley Bundy, an engineer at Brigham Young University, had already used similar technology to produce what may be a cancer-fighting protein. “Instead of stockpiling a whole bunch of vaccines and therapeutics, this allows us to stockpile the machinery that makes them,” he explained. That would “be more cost-effective and a little bit more versatile.”
Yet there is still a ways to go. For the diphtheria vaccine, the scientists had to filter out the active proteins from the cellular factories before they could inject them into mice — and they still don’t know exactly how that purification would happen, say, in a village with no electricity, or behind enemy lines.
David Shoultz, a drug development specialist at the global health nonprofit PATH, said that while he loves that these labs are thinking about using their technologies in the developing world, this kind of gizmo is not about to solve vaccine and medication shortages in one fell swoop.
“In two or three years, will we be able to ship these freeze-dried materials and have an instant vaccine, or an instant drug?” he asked. “Probably not. It’ll probably be more like 10 to 12 years. And we’re still going to need facilities, know-how, and people to implement them.”