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."
Jessica Fitzjohn, a postdoctoral fellow at the University of Canterbury, demonstrates the novel breast cancer screening device.
Researchers at the University of Canterbury and startup Tiro Medical in Christchurch, New Zealand are hoping their new device—which doesn’t involve any radiation or compression of the breasts—could increase the accuracy of breast cancer screening, broaden access and encourage more women to get checked. They’re digging into clues from the way buildings move in an earthquake to help detect more cases of this disease.
Earthquake engineering inspires new breast cancer screening tech
What’s underneath a surface affects how it vibrates. Earthquake engineers look at the vibrations of swaying buildings to identify the underlying soil and tissue properties. “As the vibration wave travels, it reflects the stiffness of the material between that wave and the surface,” says Geoff Chase, professor of engineering at the University of Canterbury in Christchurch, New Zealand.
Chase is applying this same concept to breasts. Analyzing the surface motion of the breast as it vibrates could reveal the stiffness of the tissues underneath. Regions of high stiffness could point to cancer, given that cancerous breast tissue can be up to 20 times stiffer than normal tissue. “If in essence every woman’s breast is soft soil, then if you have some granite rocks in there, we’re going to see that on the surface,” explains Chase.
The earthquake-inspired device exceeds the 87 percent sensitivity of a 3D mammogram.
That notion underpins a new breast screening device, the brainchild of Chase. Women lie face down, with their breast being screened inside a circular hole and the nipple resting on a small disc called an actuator. The actuator moves up and down, between one and two millimeters, so there’s a small vibration, “almost like having your phone vibrate on your nipple,” says Jessica Fitzjohn, a postdoctoral fellow at the University of Canterbury who collaborated on the device design with Chase.
Cameras surrounding the device take photos of the breast surface motion as it vibrates. The photos are fed into image processing algorithms that convert them into data points. Then, diagnostic algorithms analyze those data points to find any differences in the breast tissue. “We’re looking for that stiffness contrast which could indicate a tumor,” Fitzjohn says.
A nascent yet promising technology
The device has been tested in a clinical trial of 14 women: one with healthy breasts and 13 with a tumor in one breast. The cohort was small but diverse, varying in age, breast volume and tumor size.
Results from the trial yielded a sensitivity rate, or the likelihood of correctly detecting breast cancer, of 85 percent. Meanwhile, the device’s specificity rate, or the probability of diagnosing healthy breasts, was 77 percent. By combining and optimizing certain diagnostic algorithms, the device reached between 92 and 100 percent sensitivity and between 80 and 86 percent specificity, which is comparable to the latest 3D mammogram technology. Called tomosynthesis, these 3D mammograms take a number of sharper, clearer and more detailed 3D images compared to the single 2D image of a conventional mammogram, and have a specificity score of 92 percent. Although the earthquake-inspired device’s specificity is lower, it exceeds the 87 percent sensitivity of a 3D mammogram.
The team hopes that cameras with better resolution can help improve the numbers. And with a limited amount of data in the first trial, the researchers are looking into funding for another clinical trial to validate their results on a larger cohort size.
Additionally, during the trial, the device correctly identified one woman’s breast as healthy, while her prior mammogram gave a false positive. The device correctly identified it as being healthy tissue. It was also able to capture the tiniest tumor at 7 millimeters—around a third of an inch or half as long as an aspirin tablet.
Diagnostic findings from the device are immediate.
When using the earthquake-inspired device, women lie face down, with their breast being screened inside circular holes.
University of Canterbury.
But more testing is needed to “prove the device’s ability to pick up small breast cancers less than 10 to 15 millimeters in size, as we know that finding cancers when they are small is the best way of improving outcomes,” says Richard Annand, a radiologist at Pacific Radiology in New Zealand. He explains that mammography already detects most precancerous lesions, so if the device will only be able to find large masses or lumps it won’t be particularly useful. While not directly involved in administering the clinical trial for the device, Annand was a director at the time for Canterbury Breastcare, where the trial occurred.
Meanwhile, Monique Gary, a breast surgical oncologist and medical director of the Grand View Health Cancer program in Pennsylvania, U.S., is excited to see new technologies advancing breast cancer screening and early detection. But she notes that the device may be challenging for “patients who are unable to lay prone, such as pregnant women as well as those who are differently abled, and this machine might exclude them.” She adds that it would also be interesting to explore how breast implants would impact the device’s vibrational frequency.
Diagnostic findings from the device are immediate, with the results available “before you put your clothes back on,” Chase says. The absence of any radiation is another benefit, though Annand considers it a minor edge “as we know the radiation dose used in mammography is minimal, and the advantages of having a mammogram far outweigh the potential risk of radiation.”
The researchers also conducted a separate ergonomic trial with 40 women to assess the device’s comfort, safety and ease of use. Angela was part of that trial and described the experience as “easy, quick, painless and required no manual intervention from an operator.” And if a person is uncomfortable being topless or having their breasts touched by someone else, “this type of device would make them more comfortable and less exposed,” she says.
While mammograms remain “the ‘gold standard’ in breast imaging, particularly screening, physicians need an option that can be used in combination with mammography.
Fitzjohn acknowledges that “at the moment, it’s quite a crude prototype—it’s just a block that you lie on.” The team prioritized function over form initially, but they’re now planning a few design improvements, including more cushioning for the breasts and the surface where the women lie on.
While mammograms remains “the ‘gold standard’ in breast imaging, particularly screening, physicians need an option that is good at excluding breast cancer when used in combination with mammography, has good availability, is easy to use and is affordable. There is the possibility that the device could fill this role,” Annand says.
Indeed, the researchers envision their new breast screening device as complementary to mammograms—a prescreening tool that could make breast cancer checks widely available. As the device is portable and doesn’t require specialized knowledge to operate, it can be used in clinics, pop-up screening facilities and rural communities. “If it was easily accessible, particularly as part of a checkup with a [general practitioner] or done in a practice the patient is familiar with, it may encourage more women to access this service,” Angela says. For those who find regular mammograms uncomfortable or can’t afford them, the earthquake-inspired device may be an option—and an even better one.
Broadening access could prompt more women to go for screenings, particularly younger women at higher risk of getting breast cancer because of a family history of the disease or specific gene mutations. “If we can provide an option for them then we can catch those cancers earlier,” Fitzjohn syas. “By taking screening to people, we’re increasing patient-centric care.”
With the team aiming to lower the device’s cost to somewhere between five and eight times less than mammography equipment, it would also be valuable for low-to-middle-income nations that are challenged to afford the infrastructure for mammograms or may not have enough skilled radiologists.
For Fitzjohn, the ultimate goal is to “increase equity in breast screening and catch cancer early so we have better outcomes for women who are diagnosed with breast cancer.”