A wired baby in a neonatal intensive care unit.
I'll never forget the experience of having a child in the neonatal intensive care unit (NICU).
Now more than ever, we're working to remove the barriers between new parents and their infants.
It was another layer of uncertainty that filtered into my experience of being a first-time parent. There was so much I didn't know, and the wires attached to my son's small body for the first week of his life were a reminder of that.
I wanted to be the best mother possible. I deeply desired to bring my son home to start our lives. More than anything, I longed for a wireless baby whom I could hold and love freely without limitations.
The wires suggested my baby was fragile and it left me feeling severely unprepared, anxious, and depressed.
In recent years, research has documented the ways that NICU experiences take a toll on parents' mental health. But thankfully, medical technology is rapidly being developed to help reduce the emotional fallout of the NICU. Now more than ever, we're working to remove the barriers between new parents and their infants. The latest example is the first ever wireless monitoring system that was recently developed by a team at Northwestern University.
After listening to the needs of parents and medical staff, Debra Weese-Mayer, M.D., a professor of pediatric autonomic medicine at Feinberg School of Medicine, along with a team of materials scientists, engineers, dermatologists and pediatricians, set out to develop this potentially life-changing technology. Weese-Mayer believes wireless monitoring will have a significant impact for people on all sides of the NICU experience.
"With elimination of the cumbersome wires," she says, "the parents will find their infant more approachable/less intimidating and have improved access to their long-awaited but delivered-too-early infant, allowing them to begin skin-to-skin contact and holding with reduced concern for dislodging wires."
So how does the new system work?
Very thin "skin like" patches made of silicon rubber are placed on the surface of the skin to monitor vitals like heart rate, respiration rate, and body temperature. One patch is placed on the chest or back and the other is placed on the foot.
These patches are safer on the skin than previously used adhesives, reducing the cuts and infections associated with past methods. Finally, an antenna continuously delivers power, often from under the mattress.
The data collected from the patches stream from the body to a tablet or computer.
New wireless sensor technology is being studied to replace wired monitoring in NICUs in the coming years.
(Northwestern University)
Weese-Mayer hopes that wireless systems will be standard soon, but first they must undergo more thorough testing. "I would hope that in the next five years, wireless monitoring will be the standard in NICUs, but there are many essential validation steps before this technology will be embraced nationally," she says.
Until the new systems are ready, parents will be left struggling with the obstacles that wired monitoring presents.
Physical intimacy, for example, appears to have pain-reducing qualities -- something that is particularly important for babies who are battling serious illness. But wires make those cuddles more challenging.
There's also been minimal discussion about how wired monitoring can be particularly limiting for parents with disabilities and mobility aids, or even C-sections.
"When he was first born and I was recovering from my c-section, I couldn't deal with keeping the wires untangled while trying to sit down without hurting myself," says Rhiannon Giles, a writer from North Carolina, who delivered her son at just over 31 weeks after suffering from severe preeclampsia.
"The wires were awful," she remembers. "They fell off constantly when I shifted positions or he kicked a leg, which meant the monitors would alarm. It felt like an intrusion into the quiet little world I was trying to mentally create for us."
Over the last few years, researchers have begun to dive deeper into the literal and metaphorical challenges of wired monitoring.
For many parents, the wires prompt anxiety that worsens an already tense and vulnerable time.
I'll never forget the first time I got to hold my son without wires. It was the first time that motherhood felt manageable.
"Seeing my five-pound-babies covered in wires from head to toe rendered me completely overwhelmed," recalls Caila Smith, a mom of five from Indiana, whose NICU experience began when her twins were born pre-term. "The nurses seemed to handle them perfectly, but I was scared to touch them while they appeared so medically frail."
During the nine days it took for both twins to come home, the limited access she had to her babies started to impact her mental health. "If we would've had wireless sensors and monitors, it would've given us a much greater sense of freedom and confidence when snuggling our newborns," Smith says.
Besides enabling more natural interactions, wireless monitoring would make basic caregiving tasks much easier, like putting on a onesie.
"One thing I noticed is that many preemie outfits are made with zippers," points out Giles, "which just don't work well when your baby has wires coming off of them, head to toe."
Wired systems can pose issues for medical staff as well as parents.
"The main concern regarding wired systems is that they restrict access to the baby and often get tangled with other equipment, like IV lines," says Lamia Soghier, Medical Director of the Neonatal Intensive Care Unit at Children's National in Washington, D.C , who was also a NICU parent herself. "The nurses have to untangle the wires, which takes time, before handing the baby to the family."
I'll never forget the first time I got to hold my son without wires. It was the first time that motherhood felt manageable, and I couldn't stop myself from crying. Suddenly, anything felt possible and all the limitations from that first week of life seemed to fade away. The rise of wired-free monitoring will make some of the stressors that accompany NICU stays a thing of the past.
Today's podcast guest, Dr. Renee Wegrzyn, directs ARPA-H, a new agency formed last year to spearhead health innovations. Time will tell if ARPA-H will produce advances on the level of its fellow agency, DARPA.
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How will the agency figure out which projects to take on, especially with so many patient advocates for different diseases demanding moonshot funding for rapid progress?
I talked with Dr. Wegrzyn about the opportunities and challenges, what lessons ARPA-H is borrowing from Operation Warp Speed, how she decided on the first ARPA-H project that was announced recently, why a separate agency was needed instead of reforming HHS and the National Institutes of Health to be better at innovation, and how ARPA-H will make progress on disease prevention in addition to treatments for cancer, Alzheimer’s and diabetes, among many other health priorities.
Dr. Wegrzyn’s resume leaves no doubt of her suitability for this role. She was a program manager at DARPA where she focused on applying gene editing and synthetic biology to the goal of improving biosecurity. For her work there, she received the Superior Public Service Medal and, in case that wasn’t enough ARPA experience, she also worked at another ARPA that leads advanced projects in intelligence, called I-ARPA. Before that, she ran technical teams in the private sector working on gene therapies and disease diagnostics, among other areas. She has been a vice president of business development at Gingko Bioworks and headed innovation at Concentric by Gingko. Her training and education includes a PhD and undergraduate degree in applied biology from the Georgia Institute of Technology and she did her postdoc as an Alexander von Humboldt Fellow in Heidelberg, Germany.
Dr. Wegrzyn told me that she’s “in the hot seat.” The pressure is on for ARPA-H especially after the need and potential for health innovation was spot lit by the pandemic and the unprecedented speed of vaccine development. We'll soon find out if ARPA-H can produce gamechangers in health that are equivalent to DARPA’s creation of the internet.
Show links:
ARPA-H - https://arpa-h.gov/
Dr. Wegrzyn profile - https://arpa-h.gov/people/renee-wegrzyn/
Dr. Wegrzyn Twitter - https://twitter.com/rwegrzyn?lang=en
President Biden Announces Dr. Wegrzyn's appointment - https://www.whitehouse.gov/briefing-room/statement...
Leaps.org coverage of ARPA-H - https://leaps.org/arpa/
ARPA-H program for joints to heal themselves - https://arpa-h.gov/news/nitro/ -
ARPA-H virtual talent search - https://arpa-h.gov/news/aco-talent-search/
Dr. Renee Wegrzyn was appointed director of ARPA-H last October.
Tardigrades can completely dehydrate and later rehydrate themselves, a survival trick that scientists are harnessing to preserve medicines in hot temperatures.
Formulating biologics to withstand drying and hot temperatures has been the holy grail for pharmaceutical researchers for decades. It’s a hard feat to manage. “Biologic pharmaceuticals are highly efficacious, but many are inherently unstable,” says Thomas Boothby, assistant professor of molecular biology at University of Wyoming. Therefore, during storage and shipping, they must be refrigerated at 2 to 8 degrees Celsius (35 to 46 degrees Fahrenheit). Some must be frozen, typically at -20 degrees Celsius, but sometimes as low -90 degrees Celsius as was the case with the Pfizer Covid vaccine.
For Covid, fewer than 73 percent of the global population received even one dose. The need for refrigerated or frozen handling was partially to blame.
The costly cold chain
The logistics network that ensures those temperature requirements are met from production to administration is called the cold chain. This cold chain network is often unreliable or entirely lacking in remote, rural areas in developing nations that have malfunctioning electrical grids. “Almost all routine vaccines require a cold chain,” says Christopher Fox, senior vice president of formulations at the Access to Advanced Health Institute. But when the power goes out, so does refrigeration, putting refrigerated or frozen medical products at risk. Consequently, the mRNA vaccines developed for Covid-19 and other conditions, as well as more traditional vaccines for cholera, tetanus and other diseases, often can’t be delivered to the most remote parts of the world.
To understand the scope of the challenge, consider this: In the U.S., more than 984 million doses of Covid-19 vaccine have been distributed so far. Each one needed refrigeration that, even in the U.S., proved challenging. Now extrapolate to all vaccines and the entire world. For Covid, fewer than 73 percent of the global population received even one dose. The need for refrigerated or frozen handling was partially to blame.
Globally, the cold chain packaging market is valued at over $15 billion and is expected to exceed $60 billion by 2033.
Adobe Stock
Freeze-drying, also called lyophilization, which is common for many vaccines, isn’t always an option. Many freeze-dried vaccines still need refrigeration, and even medicines approved for storage at ambient temperatures break down in the heat of sub-Saharan Africa. “Even in a freeze-dried state, biologics often will undergo partial rehydration and dehydration, which can be extremely damaging,” Boothby explains.
The cold chain is also very expensive to maintain. The global pharmaceutical cold chain packaging market is valued at more than $15 billion, and is expected to exceed $60 billion by 2033, according to a report by Future Market Insights. This cost is only expected to grow. According to the consulting company Accenture, the number of medicines that require the cold chain are expected to grow by 48 percent, compared to only 21 percent for non-cold-chain therapies.
Tardigrades to the rescue
Tardigrades are only about a millimeter long – with four legs and claws, and they lumber around like bears, thus their nickname – but could provide a big solution. “Tardigrades are unique in the animal kingdom, in that they’re able to survive a vast array of environmental insults,” says Boothby, the Wyoming professor. “They can be dried out, frozen, heated past the boiling point of water and irradiated at levels that are thousands of times more than you or I could survive.” So, his team is gradually unlocking tardigrades’ survival secrets and applying them to biologic pharmaceuticals to make them withstand both extreme heat and desiccation without losing efficacy.
Boothby’s team is focusing on blood clotting factor VIII, which, as the name implies, causes blood to clot. Currently, Boothby is concentrating on the so-called cytoplasmic abundant heat soluble (CAHS) protein family, which is found only in tardigrades, protecting them when they dry out. “We showed we can desiccate a biologic (blood clotting factor VIII, a key clotting component) in the presence of tardigrade proteins,” he says—without losing any of its effectiveness.
The researchers mixed the tardigrade protein with the blood clotting factor and then dried and rehydrated that substance six times without damaging the latter. This suggests that biologics protected with tardigrade proteins can withstand real-world fluctuations in humidity.
Furthermore, Boothby’s team found that when the blood clotting factor was dried and stabilized with tardigrade proteins, it retained its efficacy at temperatures as high as 95 degrees Celsius. That’s over 200 degrees Fahrenheit, much hotter than the 58 degrees Celsius that the World Meteorological Organization lists as the hottest recorded air temperature on earth. In contrast, without the protein, the blood clotting factor degraded significantly. The team published their findings in the journal Nature in March.
Although tardigrades rarely live more than 2.5 years, they have survived in a desiccated state for up to two decades, according to Animal Diversity Web. This suggests that tardigrades’ CAHS protein can protect biologic pharmaceuticals nearly indefinitely without refrigeration or freezing, which makes it significantly easier to deliver them in locations where refrigeration is unreliable or doesn’t exist.
The tricks of the tardigrades
Besides the CAHS proteins, tardigrades rely on a type of sugar called trehalose and some other protectants. So, rather than drying up, their cells solidify into rigid, glass-like structures. As that happens, viscosity between cells increases, thereby slowing their biological functions so much that they all but stop.
Now Boothby is combining CAHS D, one of the proteins in the CAHS family, with trehalose. He found that CAHS D and trehalose each protected proteins through repeated drying and rehydrating cycles. They also work synergistically, which means that together they might stabilize biologics under a variety of dry storage conditions.
“We’re finding the protective effect is not just additive but actually is synergistic,” he says. “We’re keen to see if something like that also holds true with different protein combinations.” If so, combinations could possibly protect against a variety of conditions.
Commercialization outlook
Before any stabilization technology for biologics can be commercialized, it first must be approved by the appropriate regulators. In the U.S., that’s the U.S. Food and Drug Administration. Developing a new formulation would require clinical testing and vast numbers of participants. So existing vaccines and biologics likely won’t be re-formulated for dry storage. “Many were developed decades ago,” says Fox. “They‘re not going to be reformulated into thermo-stable vaccines overnight,” if ever, he predicts.
Extending stability outside the cold chain, even for a few days, can have profound health, environmental and economic benefits.
Instead, this technology is most likely to be used for the new products and formulations that are just being created. New and improved vaccines will be the first to benefit. Good candidates include the plethora of mRNA vaccines, as well as biologic pharmaceuticals for neglected diseases that affect parts of the world where reliable cold chain is difficult to maintain, Boothby says. Some examples include new, more effective vaccines for malaria and for pathogenic Escherichia coli, which causes diarrhea.
Tallying up the benefits
Extending stability outside the cold chain, even for a few days, can have profound health, environmental and economic benefits. For instance, MenAfriVac, a meningitis vaccine (without tardigrade proteins) developed for sub-Saharan Africa, can be stored at up to 40 degrees Celsius for four days before administration. “If you have a few days where you don’t need to maintain the cold chain, it’s easier to transport vaccines to remote areas,” Fox says, where refrigeration does not exist or is not reliable.
Better health is an obvious benefit. MenAfriVac reduced suspected meningitis cases by 57 percent in the overall population and more than 99 percent among vaccinated individuals.
Lower healthcare costs are another benefit. One study done in Togo found that the cold chain-related costs increased the per dose vaccine price up to 11-fold. The ability to ship the vaccines using the usual cold chain, but transporting them at ambient temperatures for the final few days cut the cost in half.
There are environmental benefits, too, such as reducing fuel consumption and greenhouse gas emissions. Cold chain transports consume 20 percent more fuel than non-cold chain shipping, due to refrigeration equipment, according to the International Trade Administration.
A study by researchers at Johns Hopkins University compared the greenhouse gas emissions of the new, oral Vaxart COVID-19 vaccine (which doesn’t require refrigeration) with four intramuscular vaccines (which require refrigeration or freezing). While the Vaxart vaccine is still in clinical trials, the study found that “up to 82.25 million kilograms of CO2 could be averted by using oral vaccines in the U.S. alone.” That is akin to taking 17,700 vehicles out of service for one year.
Although tardigrades’ protective proteins won’t be a component of biologic pharmaceutics for several years, scientists are proving that this approach is viable. They are hopeful that a day will come when vaccines and biologics can be delivered anywhere in the world without needing refrigerators or freezers en route.