Hobart Harris, MD, MPH, chief of the Division of General Surgery, spends half his clinical time repairing incisional hernias – a common complication of open abdominal surgery in which the intestines protrude through the muscle of an incompletely healed incision.
Although most patients recover from abdominal surgery on their own, some develop disfiguring, painful hernias which can cause years of disability and unemployment. About 400,000 people require surgical repair of incisional hernias each year, costing the US health care system about $15 billion annually.
As division chief, Harris receives sales calls from industry representatives promoting many prosthetic materials designed to assist with such repairs. Out of curiosity, he began researching the history of hernia repair, and discovered that from the 1880s to the 1940s, many surgeons used wire meshes handmade from fine silver wire, termed filigrees. “The surgeons’ descriptions noted that these were very effective,” said Harris. “The body would respond to the silver filigree by depositing a fair amount of scar tissue, which would dramatically reinforce the area of the hernia.”
These meshes fell out of favor because occasionally the silver would snap – similar to a metal clothes hanger breaking if it is bent too many times – due to a change in the metal’s crystal structure called work hardening. “I thought we could exploit the body’s response to metallic silver, not to repair hernias but to actually prevent them,” said Harris. “I also thought we could avoid the work hardening problem by using small particles of silver, rather than silver mesh.”
For a year, he spent evenings and weekends reading about silver and wound healing. “The more I read, the more I was convinced that this was worth trying,” said Harris, encouraged by medical literature indicating that the body tolerates silver well, even over long exposures.
His lab conducted its first experiments on the subject. Using an established rat model of incisional hernias, his assistant sewed the abdominal muscle wall closed using rapidly dissolving sutures, sprayed on a layer of silver microparticles, then sewed the skin closed. “Our initial data showed that the intervention significantly prevented hernia formation in rats in a dose-dependent manner,” said Harris. “A little prevented it a little, and more prevented it a lot more. I’ve been doing funded scientific investigation for over 25 years, and this is the only project where something worked the first time and every time.”
Moving towards Commercialization
To take his idea to the next level, Harris took workshops sponsored by the UCSF Office of Innovation, Technology & Alliances, including the Idea to IPO and Lean LaunchPad classes. “Those courses were extraordinarily helpful for introducing me to this different world,” he said. “Beforehand, I genuinely felt that all I needed to do was prove the science, and every other obstacle would fall like a row of dominos. That was so wrong! I garnered an appreciation for the complexity of the process.” The courses taught him about the many steps required for successful commercialization, including fundraising, gaining approval from the US Food and Drug Administration (FDA), and marketing. “It’s as though you’re walking across a bridge, and every single plank has to be in place,” said Harris. “If you miss any one step, you fall.”
One major hurdle for a startup is raising funds. Although incisional hernia repair is a multibillion dollar industry, no one had ever proposed a product designed to prevent incisional hernias from developing in the first place. The good news was that Harris had no true competitors; the bad news was that no one knew they needed his product.
“Similar to how Hollywood is more interested in producing Iron Man 6 rather than a new movie with a different storyline, people are much more comfortable investing in a product similar to what they’ve seen succeed before, rather than an entirely new product,” said Harris. “When you are essentially forging a new market, there are tremendous advantages, but tremendous challenges as well.”
Pitching venture capitalists and industry professionals required Harris to enter a different cultural mindset. “Investors want venture capitalists to turn a profit,” he said. “If they do damage to someone else, or something that was marginally ethical, that’s okay. That’s a very different ethos than in medicine. I’m not suggesting that health care providers are angels and people in business are devils, but we do respond to the incentives and structure of rewards and penalties in which we operate.”
Venture capitalists only fund a tiny fraction of the ideas they hear each year. “If they’re listening to 500 pitches a year, the competition is going to be quite intense if they’re only going to pick two or three,” said Harris. “Yet they’re actually looking to invest in the lowest risk investment that still has the potential to return a significant yield.”
Harris faced other challenges as well. “There are some communities within the university that think professors should have nothing to do with commercial endeavors,” he said. “I fully appreciate examples of how industry has corrupted science, but there have also been great advances from academic-industry partnerships. We need to build in sufficient safeguards and watchdogs. For example, I did everything I could to build randomization into a recent animal study, so no one could inadvertently, even subconsciously influence the results.”
Another challenge is that entrepreneurial faculty often have a hard time receiving academic recognition for their accomplishments. “When I write papers, apply for grants, and win teaching awards, those can all be listed as supporting data for promotion,” said Harris. “But I could found a $100 billion company, and there is no currently accepted methodology for recognizing that as an advancement-worthy accomplishment, unless I can publish about it. Fortunately, at this stage of my career I’m not looking for any more accolades required for advancement, but you see the obstacle for junior faculty members.”
Overcoming a Fear of Blood
Harris grew up in Flint, Mich., where his father was a general practitioner. “I learned from both my parents that if you were fortunate enough to have the necessities of life, you needed to focus on making a positive contribution to the lives of other people,” said Harris. “I was aware of my father doing that from the way he interfaced with patients, whether they were stopping by the house or meeting him in the grocery store. That sparked the idea of medicine as a way of being a positive agent in the community.”
As a child, Harris loved science classes, but there was one problem: he was deathly afraid of the sight of blood. “There was nothing that would get a greater performance out of me than the prospect of getting a shot,” he said with a laugh. “Also, I didn’t like bugs or insects – there was very little of the naturalist in me. My father would sometimes say, ‘How are you going to be a doctor when you’re afraid to pick up a beetle?’”
Harris ended up majoring in biology at Harvard. To address his childhood fears, he spent a summer working with famed cardiac surgeon Michael DeBakey, MD, at the Baylor School of Medicine in Houston. Along with other high school and college students, he worked in the animal lab.
“We were supposed to take turns being the anesthesiologist, the surgeon, and the surgical assistant,” said Harris. “In my group, neither of the other two people ever wanted to be the surgeon, so I spent the entire summer as the surgeon. The very first time I operated on a dog, it was just mind-blowing. I found the entire process and the physiology just incredible. That was not only the first real test of whether I could stomach the blood-and-guts aspect of medicine, but was my initial exposure to the technical aspects of surgery, and I was hooked immediately.”
He earned his medical degree from Harvard Medical School and his master’s degree in public health from the Harvard School of Public Health, then completed his surgery internship and residency at UCSF. Harris then completed a fellowship in hepatobiliary surgery at the University of Hong Kong Queen Mary Hospital, and a fellowship at the University of Louisville in Kentucky in endoscopic retrograde cholangiopancreatography, a procedure which combines upper gastrointestinal endoscopy and X-rays to treat problems of the bile and pancreatic ducts. He joined the UCSF faculty in 1994.
As a surgical resident at UCSF, he had his first entrepreneurial idea. Harris was working in a laboratory at the San Francisco Veterans Administration Medical Center when he observed that certain types of fat droplets in the bloodstream called lipoproteins had the capacity to bind to bacterial endotoxins and neutralize them. “That hypothesis became the foundation of 25 years’ worth of NIH (National Institutes of Health) funding,” he said. “Early on, we thought we might be able to create a synthetic lipoprotein that could be administered to septic patients. Although we give a lot of antibiotics and supportive care, we still don’t have even a single drug that is specifically targeted to sepsis. That idea prompted an initial foray into, ‘Should we patent this?’ It didn’t get very far, but was the first spark of entrepreneurial thoughts around a scientific observation.”
Passion and Optimism
In the past few years, Harris has made significant progress in bringing his incisional hernia technology to market. He founded his own company, Vitruvian Medical Devices, and is collaborating with plastic surgeon David Young, MD, surgical residents Frank Primus, MD, and Victoria Lyo, MD, MTM, and business consultant Vinod Mahendroo in testing and refining the product, which he has named MYOSEAL. So far, it has been shown to reduce the incidence of incisional hernias by 90 percent in animal models.
The latest form of MYOSEAL can be used in conjunction with any commercially available tissue sealant; after closing the abdominal muscle, surgeons spray the sealant onto the incision, then spray MYOSEAL on top of it. It only takes a minute to do this at the end of an abdominal surgery, compared with other preventive measures such as sewing mesh onto the incision area – which can take up to 30 minutes and is too laborious to be practical.
“Ninety-nine percent of surgeons I’ve talked to have said, ‘If you can show me [MYOSEAL] works and that it’s not dangerous, I’m using it,’” said Harris.
He named his company after the Vitruvian Man, the famous anatomical drawing by Leonardo da Vinci inspired by the writings of Vitruvius, a Roman architect. “Vitruvius said that architecture needed to be beautiful, strong and functional, and Leonardo da Vinci was simply saying that the human body is all those things,” said Harris. “The clincher for me in selecting that as our name was that historians have recently speculated that the Vitruvian Man has a hernia – not an incisional hernia, but a small bulge in the left groin that looks like a groin hernia.”
So far, Harris has been able to balance his day job as an academic surgeon with advancing MYOSEAL. “I tend to work between 60 and 80 hours a week, and I’ve been able to keep things moving forward in both professional arenas,” he said. He did recently take a yearlong sabbatical to focus more of his time on MYOSEAL. “My entrepreneurial activity is an obsession,” said Harris. “I think about MYOSEAL every day for hours – sometimes I even dream about it. I’m intrigued and excited by this, and that’s the ultimate reward. It’s a tremendous opportunity at this stage of my career to be creative in a related but different field.”
During his sabbatical, he honed his pitch and made close to 20 presentations to potential investors. He and his team also established contact with the FDA, gaining a better understanding of how the agency will classify the product and what preclinical regulatory hurdles Vitruvian needs to meet to obtain its first-in-human data. They are working to complete the safety and toxicology package for the FDA, and hope to initiate a Phase 1A clinical trial in early 2017.
“Dr. Harris has been absolutely amazing,” said surgical resident Lyo, who worked in Harris’s lab for two years on developing MYOSEAL. “What got me excited was seeing how excited he was about it, and how he really believes in the ability of this project to affect many people.
“We’ve had lots of very honest discussions about questions like, ‘What would it take you to call this a success?’ and ‘How does device innovation fit into your career?’” she said. “Someone who is in his mid-career who has seen a lot of problems can come up with many ideas because he has wisdom and experience, whereas I’ve only been a surgery resident for five years. He’s been extremely supportive of ways that I can innovate.”
“I didn’t want to spend the remainder of my career simply fixing hernias and ignoring this bright pink elephant, which is that incisional hernias occur in about 15 to 20 percent of patients who undergo open abdominal surgery,” said Harris. “The solution is not a better repair surgery or a newfangled repair prosthetic – it’s preventing these things from happening in the first place. I’ve always been a very optimistic person, and I think that translates into the belief that a problem can be solved.”
by Elizabeth Chur