Biomedical engineer Kevin Zhao has a sensor in his arm and his chest that monitors his oxygen level in those tissues in real time.
Last month, at a conference celebrating DARPA, the research arm of the Defense Department, FBI Special Agent Edward You declared, "The 21st century will be the revolution of the life sciences."
Biomedical engineer Kevin Zhao has a sensor in his arm and chest that monitors his oxygen level in real time.
Indeed, four years ago, the agency dedicated a new office solely to advancing biotechnology. Its primary goal is to combat bioterrorism, protect U.S. forces, and promote warfighter readiness. But its research could also carry over to improve health care for the general public.
With an annual budget of about $3 billion, DARPA's employees oversee about 250 research and development programs, working with contractors from corporations, universities, and government labs to bring new technologies to life.
Check out these three current programs:
1) IMPLANTABLE SENSORS TO MEASURE OXYGEN, LACTATE, AND GLUCOSE LEVELS IN REAL TIME
Biomedical engineer Kevin Zhao has a sensor in his arm and his chest that monitors his oxygen level in those tissues in real time. With funding from DARPA for the program "In Vivo Nanoplatforms," he developed soft, flexible hydrogels that are injected just beneath the skin to perform the monitoring and that sync to a smartphone app to give the user immediate health insights.
A first-in-man trial for the glucose sensor is now underway in Europe for monitoring diabetics, according to Zhao. Volunteers eat sugary food to spike their glucose levels and prompt the monitor to register the changes.
"If this pans out, with approval from FDA, then consumers could get the sensors implanted in their core to measure their levels of glucose, oxygen, and lactate," Zhao said.
Lactate, especially, interests DARPA because it's a first responder molecule to the onset of trauma, sepsis, and potentially infection.
"The sensor could potentially detect rise of these [body chemistry numbers] and alert the user to prevent onset of dangerous illness."
2) NEAR INSTANTANEOUS VACCINE PROTECTION DURING A PANDEMIC
Traditional vaccines can take months or years to develop, then weeks to become effective once you get it. But when an unknown virus emerges, there's no time to waste.
This program, called P3, envisions a much more ambitious approach to stop a pandemic in its tracks.
"We want to confer near instantaneous protection by doing it a different way – enlist the body as a bioreactor to produce therapeutics," said Col. Matthew Hepburn, the program manager.
So how would it work?
To fight a pandemic, we will need 20,000 doses of a vaccine in 60 days.
If you have antibodies against a certain infection, you'll be protected against that infection. This idea is to discover the genetic code for the antibody to a specific pathogen, manufacture those pieces of DNA and RNA, and then inject the code into a person's arm so the muscle cells will begin producing the required antibodies.
"The amazing thing is that it actually works, at least in animal models," said Hepburn. "The mouse muscles made enough protective antibodies so that the mice were protected."
The next step is to test the approach in humans, which the program will do over the next two years.
But the hard part is actually not discovering the genetic code for highly potent antibodies, according to Hepburn. In fact, researchers already have been able to do so in two to four weeks' time.
"The hard part is once I have an antibody, a large pharma company will say in 2 years, I can make 100-200 doses. Give us 4 years to get to 20,000 doses. That's not good enough," Hepburn said.
To fight a pandemic, we will need 20,000 doses of a vaccine in 60 days.
"We have to fundamentally change the idea that it takes a billion dollars and ten years to make a drug," he concluded. "We're going to do something radically different."
3) RAPID DIAGNOSING OF PATHOGEN EXPOSURE THROUGH EPIGENETICS
Imagine that you come down with a mysterious illness. It could be caused by a virus, bacteria, or in the most extreme catastrophe, a biological agent from a weapon of mass destruction.
What if a portable device existed that could identify--within 30 minutes—which pathogen you have been exposed to and when? It would be pretty remarkable for soldiers in the field, but also for civilians seeking medical treatment.
This is the lofty ambition of a DARPA program called Epigenetic Characterization and Observation, or ECHO.
Its success depends on a biological phenomenon known as the epigenome. While your DNA is relatively immutable, your environment can modify how your DNA is expressed, leaving marks of exposure that register within seconds to minutes; these marks can persist for decades. It's thanks to the epigenome that identical twins – who share identical DNA – can differ in health, temperament, and appearance.
These three mice are genetically identical. Epigenetic differences, however, result in vastly different observed characteristics.
Reading your epigenetic marks could theoretically reveal a time-stamped history of your body's environmental exposures.
Researchers in the ECHO program plan to create a database of signatures for exposure events, so that their envisioned device will be able to quickly scan someone's epigenome and refer to the database to sort out a diagnosis.
"One difficult part is to put a timestamp on this result, in addition to the sign of which exposure it was -- to tell us when this exposure happened," says Thomas Thomou, a contract scientist who is providing technical assistance to the ECHO program manager.
Other questions that remain up in the air for now: Do all humans have the same epigenetic response to the same exposure events? Is it possible to distinguish viral from bacterial exposures? Does dose and duration of exposure affect the signature of epigenome modification?
The program will kick off in January 2019 and is planned to last four years, as long as certain milestones of development are reached along the way. The desired prototype would be a simple device that any untrained person could operate by taking a swab or a fingerprick.
"In an outbreak," says Dr. Thomou, "it will help everyone on the ground immediately to have a rapidly deployable machine that will give you very quick answers to issues that could have far-reaching ramifications for public health safety."
Silkworm silk is fragile, which limits its uses, but a few extra genes can help.
Today, biomimetics is everywhere. Shark-inspired swimming trunks, gecko-inspired adhesives, and lotus-inspired water-repellents are all taken from observing the natural world. After millions of years of evolution, nature has quite a few tricks up its sleeve. They are tricks we can learn from. And now, thanks to some spider DNA and clever genetic engineering, we have another one to add to the list.
The elusive spider silk
We’ve known for a long time that spider silk is remarkable, in ways that synthetic fibers can’t emulate. Nylon is incredibly strong (it can support a lot of force), and Kevlar is incredibly tough (it can absorb a lot of force). But neither is both strong and tough. In all artificial polymeric fibers, strength and toughness are mutually exclusive, and so we pick the material best for the job and make do.
Spider silk, a natural polymeric fiber, breaks this rule. It is somehow both strong and tough. No surprise, then, that spider silk is a source of much study.The problem, though, is that spiders are incredibly hard to cultivate — let alone farm. If you put them together, they will attack and kill each other until only one or a few survive. If you put 100 spiders in an enclosed space, they will go about an aggressive, arachnocidal Hunger Games. You need to give each its own space and boundaries, and a spider hotel is hard and costly. Silkworms, on the other hand, are peaceful and productive. They’ll hang around all day to make the silk that has been used in textiles for centuries. But silkworm silk is fragile. It has very limited use.
The elusive – and lucrative – trick, then, would be to genetically engineer a silkworm to produce spider-quality silk. So far, efforts have been fruitless. That is, until now.
We can have silkworms creating silk six times as tough as Kevlar and ten times as strong as nylon.
Spider-silkworms
Junpeng Mi and his colleagues working at Donghua University, China, used CRISPR gene-editing technology to recode the silk-creating properties of a silkworm. First, they took genes from Araneus ventricosus, an East Asian orb-weaving spider known for its strong silk. Then they placed these complex genes – genes that involve more than 100 amino acids – into silkworm egg cells. (This description fails to capture how time-consuming, technical, and laborious this was; it’s a procedure that requires hundreds of thousands of microinjections.)
This had all been done before, and this had failed before. Where Mi and his team succeeded was using a concept called “localization.” Localization involves narrowing in on a very specific location in a genome. For this experiment, the team from Donghua University developed a “minimal basic structure model” of silkworm silk, which guided the genetic modifications. They wanted to make sure they had the exactly right transgenic spider silk proteins. Mi said that combining localization with this basic structure model “represents a significant departure from previous research.” And, judging only from the results, he might be right. Their “fibers exhibited impressive tensile strength (1,299 MPa) and toughness (319 MJ/m3), surpassing Kevlar’s toughness 6-fold.”
A world of super-materials
Mi’s research represents the bursting of a barrier. It opens up hugely important avenues for future biomimetic materials. As Mi puts it, “This groundbreaking achievement effectively resolves the scientific, technical, and engineering challenges that have hindered the commercialization of spider silk, positioning it as a viable alternative to commercially synthesized fibers like nylon and contributing to the advancement of ecological civilization.”
Around 60 percent of our clothing is made from synthetic fibers like nylon, polyester, and acrylic. These plastics are useful, but often bad for the environment. They shed into our waterways and sometimes damage wildlife. The production of these fibers is a source of greenhouse gas emissions. Now, we have a “sustainable, eco-friendly high-strength and ultra-tough alternative.” We can have silkworms creating silk six times as tough as Kevlar and ten times as strong as nylon.
We shouldn’t get carried away. This isn’t going to transform the textiles industry overnight. Gene-edited silkworms are still only going to produce a comparatively small amount of silk – even if farmed in the millions. But, as Mi himself concedes, this is only the beginning. If Mi’s localization and structure-model techniques are as remarkable as they seem, then this opens up the door to a great many supermaterials.
Nature continues to inspire. We had the bird, the gecko, and the shark. Now we have the spider-silkworm. What new secrets will we unravel in the future? And in what exciting ways will it change the world?
This article originally appeared on Freethink, home of the brightest minds and biggest ideas of all time.
