BIOINSPIRED

A conversation with Jeff Karp, biotechnologist and entrepreneur

 

Most of us see problems as obstacles between us and what we’d rather be doing. Not Jeff Karp. He’s built a multifaceted career around tackling really tough design challenges, and his pleasure in the process is palpable.

As a kid growing up in Peterborough, Ontario, Karp figured he’d become a doctor. When he got sick at age 12, his parents took him to the Hospital for Sick Children in Toronto, where doctors conducted tons and tons of tests. The process made a deep impression. “By collecting all this data and connecting the dots, the doctors arrived at a solution,” said Karp, who was diagnosed with celiac disease. “At the time the only place you could get gluten-free food was in specialty stores in hospitals, and it was terrible.”

Karp went to McGill University in Montreal, where he started out as a biology major. But he didn’t love all the memorization, and kept thinking back to Grade 12 physics, which hadn’t come easily.“ School was always a major challenge—I was diagnosed with a learning disability when I was younger—but I loved the feeling of working really hard on difficult problems and learning something completely new.” Although the freshman had no idea what an engineer was, he gravitated towards chemical engineering because it had problem-solving elements. Chemical engineers draw on chemistry, biology, mathematics, and physics, and collaborate with engineers in disciplines like materials science and mechanical engineering—a great fit for the generalist Karp turned out to be.

By the time he applied to med school, Karp had envisioned a way to combine medicine and engineering. “I had no idea what it meant to design medical devices, but I felt that’s what I needed to do with my life.” Major glitch: the difficult courses had lowered his GPA, and he wasn’t accepted. After some self-reflection, he realized that medical training might not be necessary. “Maybe all I need to do is to learn how to talk to doctors, and then I could start designing solutions much earlier,” he reasoned. Then, sitting in a Montreal coffee shop, he overheard some acquaintances talking about bioengineering, tissue engineering, and drug delivery: the emerging field of biomedical engineering.

Entering the field meant spending a fifth year as an undergraduate taking 500-level courses with names like “Artificial Cells and Immobilization Biotechnology” and “Artificial Internal Organs.” Karp was hooked. “It was almost like coming full circle back to the biological sciences,” says Karp “and it really changed everything for me.” After getting his PhD in chemical and biomedical engineering from the University of Toronto, Karp applied to just one place: the Boston laboratory of eminent MIT biotechnologist Robert S. Langer. The subject line of his email read: “A Postdoc candidate with BIG ideas.” Langer liked the ideas but had no funding. Karp got the Canadian government to fund a two-year fellowship, Langer agreed to take him on as a post-doc, and Karp headed for Boston with his wife, Jessica.

“The basic goal is to take an idea in nature and improve upon it for your own purposes. It’s a universal tool.”

Jeff Karp

In his TEDMed talk, Karp quips that he owes his research career to Spiderman. At MIT he noticed a journal article on a colleague’s desk featuring a photo of the superhero. The article described a waterproof dry adhesive inspired by the sticky feet of the Tokay­ gecko (and Spiderman’s sticky hands). Inside the body, sutures and staples have all kinds of limitations. “Maybe we could develop a surgical patch with adhesive properties to replace them,” Karp mused. He pitched the idea to the National Science foundation, and developed a gecko-inspired patch that was fully degradable, elastic and transparent. A second-generation approach, inspired by slugs and snails, culminated in a new tissue glue that works throughout the body—including inside a beating heart, one of the harshest environments. (The glue infiltrates into tissue upon contact and cures when exposed to light, so it bonds instantly and without risk of being washed out by blood). In 2013, in collaboration with Professor Langer, Karp launched Gecko Biomedical and a parallel career as an entrepreneur.

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Surgical patches were inspired by nanostructures on gecko feet and the viscous secretions of creatures like slugs, snails, sandcastle worms that live in wet, dynamic environments.


Developing the adhesive was Karp’s introduction to bioinspiration—an emerging scientific discipline whose practitioners look to the natural world to solve industrial and medical challenges. The terms biomimicry and bioinspiration are sometimes used interchangeably, but “Bioinspiration is not imitation,” he points out.“The basic goal is to take an idea in nature and improve upon it for your own purposes. It’s a universal tool.”

 

Taking cues from nature isn’t new. Velcro was inspired by the way burrs attach to clothing.

Japan’s high-speed train is modeled in part on the super-aerodynamic beak of the kingfisher bird, which dives into the water for prey. “If there were no creatures flying through the air, would we have airplanes?” Karp wonders. Today, biomedical engineers are looking to the natural world to inform safe, sophisticated technologies that could help doctors treat patients more effectively and help patients heal faster. Why is nature such a good incubator for innovation? “Because every living thing—every plant, every animal, every creature that exists today—is here because it has solved an incredible number of challenges and evolved to tell the tale, says Karp. Evolution is the best problem-solver.”

Now director of the Laboratory for Accelerated Medical Innovation at Brigham and Women’s Hospital in Boston, he and his colleagues have invented several more creature-inspired devices.

A thumbnail-size device with tentacles made of long chains of DNA mimics the way jellyfish tentacles grab tiny prey out of the ocean: as blood flows over the device, smaller sticky DNA segments that act like hands pluck cancer cells out of the bloodstream.

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Artist’s rendering of a cancer detector sparked by jellyfish tentacles. Finding cells in the blood could help identify new drugs to stop cancers from spreading through the body.


Porcupine quills, which are barbed so that they penetrate easily but are hard to pull out, inspired designs for a biodegradable surgical staple that reduces leakage and bacterial infections. Other organisms or structures under observation are parasitic worms, cactus needles, and spider webs. The road from invention to product is long, expensive, and strewn with scientific, logistical, and financial hurdles. Some of these technologies are in use, others are being tested, and many others are still in the theoretical phase. Now available from a company called Skintifique, a cream to prevent nickel allergies is based on calcium carbonate particles that bind nickel and other metal allergens—“a solution already out there in nature,” Karp points out. “Phytoplankton—marine algae—are often covered by calcium carbonate shells believed to protect them from heavy metals in the ocean.”

Unlike most medical researchers, who hone in on a particular disease or set of technologies, Karp is interested in a range of medical issues where a bioengineering breakthrough could have a big impact in a relatively short time.

His lab is populated with people from different backgrounds: “every country and every expertise you can imagine—chemical engineering, biology, materials science, medicine—because innovation happens at the interface of disciplines and diversity.” Karp points out that not everyone on a team has to know all the information—“only a very small amount ends up being important, and often I’m completely unqualified”—and that only a great team makes this possible. “I like to bring people into my lab who contribute specific kinds of expertise. Then I guide the project towards maximum impact and scientific rigor.” Developing the surgical patch involved a team of clinicians working alongside experts in biomaterials, device design, and fiber optics. Not to mention inspiration from slugs, snails, and sand castle worms, whose viscous secretions stay put and repel water, just as the patch had to.

Karp points out that “it’s really hard to make progress in science unless you can look at things from different angles. Solutions are all around us in nature, staring us in the face.” The biggest challenge lies in correctly defining the problem. “Once you understand it—a big ‘if,’ because most of the time we really don’t—it’s much easier to see the connections in nature that might be relevant, and make that light bulb go off.”

every living thing—every plant, every animal, every creature that exists today—is here because it has solved an incredible number of challenges and evolved to tell the tale,

Jeff Karp

An even bigger challenge, perhaps, is to choose which problem to focus on. Instinct is key, according to Karp, who believes that we can build instincts and cultivate new ones by immersing ourselves in stimulating and challenging environments. “If you don’t feel qualified, embrace the vulnerability and the challenge,” he counsels students. “That’s how you build the killer instincts that will make you as valuable as the most experienced person on the team. Take a small risk and there’s a good chance you’ll be able to succeed, which builds confidence so you can take a bigger risk next time.”

Success and failure are not opposites, and another key element is the ability to embrace failure as a problem-solving tool.

One of Karp’s lab’s early goals was to develop a technology that could infuse stem cells into the bloodstream and control their path, like a GPS for administered cell therapy, so they would reach a specific site of disease or inflammation. The team developed a five-step process that worked in an animal model, and Karp went to a big investor for funding. “The investor said, ‘This is going to make a great academic paper, but it will never help patients in its current form, because it’s too complicated. You have to do quality control at every single step in manufacturing for medical products and you’re not going to be able to scale this up. Can you work out a simpler approach?’” The lab started the next stem cell project with scale-up in mind and “radical simplicity” as a guiding design principle. Six years later, in 2015, the single-step cell engineering technology was licensed to a pharmaceutical company.

What futuristic gizmo would Karp most like to see in the lab of his dreams? “An instrument that would allow us to peer into anywhere into the human body, non-invasively, so we could visualize biology in real-time at the single-cell level during a clinical trial.” The most common way to affect a patient’s health is to administer small-molecule drugs (which are most of the pills we take). Currently, it takes billions of dollars to develop a single drug, and clinical trials often fail because it turns out to have toxic side effects, which are difficult to engineer around. “If we could administer a drug and scan the patient a few times a day to observe the molecule’s effect on different cells on the body, we could detect side effects early on, change the dose, add other combinations of molecules, and see which conditions are required to treat a condition or kill all the cells within a tumor—with minimal systemic toxicity.”

That’s one of many medical problems looking for a solution. As Karp points out, inventors can also come at it from the opposite direction. What’s an example of a solution looking for a problem? “Recently someone figured out that when cats or dogs drink, they pull the tongue back fast, which pulls the water with it. It’s putting energy into the water, adding momentum to it so it springs back into the mouth. I look at that and say ‘How can we make use of it?’ Maybe it’s ridiculous.” Maybe not. Then there’s the orchid he bought two and a half years ago at Trader Joe's, which his wife wanted to toss once it finished blossoming. Karp kept fiddling with water and fertilizer, “and lo and behold, a year later, one day a flower comes out. And now there are seven flowers. There’s so much I don’t understand,” he says happily. A botanist could explain the underlying mechanisms, of course, but that’s only a small piece of what interests the biotechnologist. “I feel like there’s a lot in there that could help us come up with better therapies and cures, if we just understood the forces that drive that orchid.”

 

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IMAGE CREDITS
Title and background images: Compositions from Ernst Haeckel's illustrations
Surgical Patch: Courtesy Karp Laboratory
Gecko: F. Hecker/AGE Fotostock
Drug delivery system: Courtesy Karp Laboratory
Parasite Worm: Richard Kessel/Visuals Unlimited
Shark Skin: Ted Kinsman/Science Source
Sandcastle Worm: Fred Hayes/University of Utah
Namib Desert Beetle: Tierfotoagentur/AGE Fotostock
Mussel Beards: Pascal Goetgheluck/Science Source
Jumbo Squid Beak: WaterFrame/Alamy