inventing our future: training the next generation of surgeon innovators

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Journal of Pediatric Surgery Lecture Inventing our future: training the next generation of surgeon innovators Thomas M. Krummel Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA Received 24 September 2008; accepted 7 October 2008 President Ziegler, members and guests: I'm grateful for the privilege of presenting this Journal of Pediatric Surgery Lecture and I'm grateful to the publisher and editor-in-chief, Jay Grosfeld, as well as to APSA for this honor. In his very generous introduction, Dr Ziegler graciously omitted the many missteps, mistakes, and flat out screw ups that don't show up on one's CV. Nonetheless, they form an equally and perhaps more important component of a career. My first presentation at APSA was in 1981. At the time I felt both unqualified and nervous; 27 years later nothing has changed. Dr Ziegler has asked me to continue on the theme of innovation and so I've selected the title: Inventing Our Future: Training the Next Generation of Surgeon Innovators.1. Acknowledgments Before I get started I'd like to make several acknowl- edgements, first personal and then professional. My parents, Jim and Helen, taught me everything that is important long before I went to school. They taught me that you don't need much to have a lot, that scarcity and necessity drive innovation. My wife Susie is the love of my life; she and our 3 daughters keep it real and make everything worthwhile. These family foundations are a daily reminder of both my blessings and my responsibilities to others less fortunate. With them I believe everything is possible. I've been fortunate to have great professional colleagues at every point in the journey. The tremendous students, residents, and faculty at the Medical College of Wisconsin, Medical College of Virginia and Children's Hospital Pittsburgh, Penn State, and now Stanford and Lucile Packard Children's Hospital are a constant source of inspiration. At Penn State, John A. Waldhausen showed me the joy of coaxing a department to life and he gave me a chance. Ten years at Stanford have provided both profound opportunities and daily prods to keep going. Finally, it is our patients whose problems we are privileged to tackle who teach us so much and when we can't solve their problems those moments should engender a quiet resolve or even a quiet rage to find a better way. There's one guy who spans both the personal and professionalArnold M. Salzberg, MD, HB, and early member of APSAan icon, mentor, and friend. I'm one of Arnold's 12 disciples who were inspired to pediatric surgery. Salzberg12 disciples; he's laughing up there. True story: I'm the junior resident on pediatric surgery at MCV in 1979. It had been a lousy week. We had fixed diaphragmatic hernias on 2 beautiful 4-kg babies and then sat around and watched them die. Nothing to do. The following week, a young hotshot, Bob Bartlett, shows up and gives a research conference on a new-fangled technologyECMO. Arnie rivets me with his gaze and says Hey, Krummel, how many more kids are we going to watch die before you do something?Presented at the 39th annual meeting of the American Pediatric Surgical Association, Phoenix, AZ, May 27- June 1, 2008. Tel.: +1 650 498 4292; fax: +650 725 3918. E-mail address: [email protected]. www.elsevier.com/locate/jpedsurg 0022-3468/$ see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2008.10.005 Journal of Pediatric Surgery (2009) 44, 2135

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www.elsevier.com/locate/jpedsurg

Journal of Pediatric Surgery (2009) 44, 21–35

Journal of Pediatric Surgery Lecture

Inventing our future: training the next generation ofsurgeon innovatorsThomas M. Krummel⁎

Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA

Received 24 September 2008; accepted 7 October 2008

President Ziegler, members and guests:

I'm grateful for the privilege of presenting this Journal ofPediatric Surgery Lecture and I'm grateful to the publisherand editor-in-chief, Jay Grosfeld, as well as to APSA forthis honor.

In his very generous introduction, Dr Ziegler graciouslyomitted the many missteps, mistakes, and flat out screwups that don't show up on one's CV. Nonetheless, theyform an equally and perhaps more important component ofa career.

My first presentation at APSAwas in 1981. At the time Ifelt both unqualified and nervous; 27 years later nothinghas changed. Dr Ziegler has asked me to continue on thetheme of innovation and so I've selected the title:“Inventing Our Future: Training the Next Generation ofSurgeon Innovators.”

1. Acknowledgments

Before I get started I'd like to make several acknowl-edgements, first personal and then professional. Myparents, Jim and Helen, taught me everything that isimportant long before I went to school. They taught methat you don't need much to have a lot, that scarcity andnecessity drive innovation. My wife Susie is the love of my

Presented at the 39th annual meeting of the American Pediatric SurgicalAssociation, Phoenix, AZ, May 27- June 1, 2008.

⁎ Tel.: +1 650 498 4292; fax: +650 725 3918.E-mail address: [email protected].

0022-3468/$ – see front matter © 2009 Elsevier Inc. All rights reserved.doi:10.1016/j.jpedsurg.2008.10.005

life; she and our 3 daughters keep it real and makeeverything worthwhile. These family foundations are adaily reminder of both my blessings and my responsibilitiesto others less fortunate. With them I believe everythingis possible.

I've been fortunate to have great professional colleaguesat every point in the journey. The tremendous students,residents, and faculty at the Medical College of Wisconsin,Medical College of Virginia and Children's HospitalPittsburgh, Penn State, and now Stanford and Lucile PackardChildren's Hospital are a constant source of inspiration. AtPenn State, John A. Waldhausen showed me the joy ofcoaxing a department to life and he gave me a chance. Tenyears at Stanford have provided both profound opportunitiesand daily prods to keep going.

Finally, it is our patients whose problems we areprivileged to tackle who teach us so much and when wecan't solve their problems those moments should engender aquiet resolve or even a quiet rage to find a better way.

There's one guy who spans both the personal andprofessional—Arnold M. Salzberg, MD, HB, and earlymember of APSA—an icon, mentor, and friend. I'm one ofArnold's 12 disciples who were inspired to pediatric surgery.Salzberg—12 disciples; he's laughing up there.

True story: I'm the junior resident on pediatric surgery atMCV in 1979. It had been a lousy week. We had fixeddiaphragmatic hernias on 2 beautiful 4-kg babies and then sataround and watched them die. Nothing to do.

The following week, a young hotshot, Bob Bartlett,shows up and gives a research conference on a new-fangledtechnology—ECMO. Arnie rivets me with his gaze and says“Hey, Krummel, how many more kids are we going to watchdie before you do something?”

Fig. 2 A, Mark M. Ravitch, MD. B, What is Surgery?—Ravitch's Principles.

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With the full support of Dr Salzberg and Dr LazarGreenfield, we put together a ragtag ECMO team. Lookingback it was an insurance nightmare. That said, 18 monthsinto it we reported some real successes. Arnie says to me,“Bartlett proved ECMO could be done, Krummel provedanybody could do it.”

The AAP Surgical Section offers The Salzberg Award forMentorship—there's a good reason for that. So this one's foryou, Arnie.

2. History of surgery

The most famous painting ever depicting a physician isthis one executed by Sir Luke Fields. (Fig. 1). Appro-priately for all of us in APSA, it depicts a physicianpuzzling over a sick child. There are many interpretationsof this painting: some see the light of dusk and despair;others see the light of dawn and hope. Regardless of thoseinterpretations, no one can miss the look of care andconcern for this child's problem.

What was the state of surgical care at the time of thepainting? If this child had had an intussusception, appendi-citis or even an incarcerated hernia, death was likely.Roughly at the same time, Sir John Ericksen, the thensurgeon-extraordinaire to Queen Victoria, declared: “Theabdomen, the chest and the brain will forever be shut fromthe intrusion of the wise and humane surgeon.” Times havechanged. Why? How?

3. What is now possible?

Progress throughout the history of our field is alwaysabout innovation whether it's new tools, devices, technolo-gies, or surgical procedures. Look around your operatingroom today and you will see a dizzying array of tools andtechnologies that might bewilder the early giants in our field.

Fig. 1 “The Doctor,” 1891. Sir Luke Fildes (1844-1927). TateGallery, London.

It is important to understand that technology develop-ments specifically for children have always been a lowpriority and as such children are frequently the orphans ofinnovation. The harsh facts of small pediatric markets, poorpayer mixes, and high FDA barriers make specific andfocused pediatric innovation an area that is difficult infinancially driven markets. But children have benefitedenormously from the duality of the adult/pediatric innova-tion. Thus tools and technology for larger adult marketseventually “trickle down” to those children under our care.

In some cases, the operative solutions to pediatricproblems have had reciprocal adult benefits. Robert Gross'ligation of PDA, or the Blalock-Taussig shunt for tetralogy ofFallot were the opening wedge in the drive to surgically solvecongenital cardiac problems which ultimately demonstratedfirst the feasibility and then the evolution of adult cardiacsurgery. Tom Starzl's early experiments were focused onliver transplantation for pediatric diseases; his herculeanefforts have now benefited countless adults.

If one reflects on the tools and technologies with whichRobert E. Gross functioned and compares them to those oftoday, almost everything has changed. In the hospital,monitors, pumps, beds, transport devices, and circulatoryassist devices are all radically different. In the operatingroom, the OR table, the OR lights, tools, catheters, sutures,energy sources, scopes, staplers, ports, valves, artificialjoints, and others are all different. The diagnostic imagingstudies of his day have now given rise to the imaging studies

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of today—ultrasound, computer tomography, magneticresonance imaging, PET scans, and now functional imaging.The paltry pharmaceuticals of his day have expanded to ahost of antibiotics, antivirals, antifungals, chemotherapeu-tics, anesthetics, and next-generation biologics.

And, in point of fact, many of the operations we do areeither radically different or are done with a different set oftools and technologies. Our profession and industry can, andshould, be proud of this progress. The ability to operate onthe tiniest infant, the morbidly obese teenager, or even thefetus shows how far we have come. That said, “there is nofinish line.”

An important, and potentially disruptive, technology wasdemonstrated by Professor Jacques Marescaux and reportedin the September 27, 2001, issue of Nature [1]. Marescauxsat comfortably at a console in New York and used remotetelemanipulation, that is, surgical robotics, to remove the gallbladder of a woman in Strasbourg, France, the world's firsttransoceanic human procedure. Perhaps distance becomesirrelevant!?

With this backdrop of progress, it is worth recalling thethoughts and comments of one of the giants in our field,Mark M. Ravitch, MD, to help frame past and presentprogress and give some framework for the future (Fig. 2A).Even in his later years, during my pediatric surgeryfellowship at Children's Hospital Pittsburgh, Dr Ravitchwas an imposing and, indeed, intimidating figure. Woe be itto the junior resident who spoke of “taking the patient tosurgery” rather than “to the operating room.” Walking DrRavitch back to his Montefiore Hospital office was aunique privilege which I relished. It was a chance to see hisincisive mind at work and his thinking has shaped mine tothis day. I recall his thoughts about the definition of“surgery” as follows:

“After all, Tom, surgery is not a place or a procedure butan intellectual discipline characterized by operativeprocedures but defined by an attitude of responsibilitytowards the care of the sick.”

He then defined a surgical operation as “an actperformed with instruments or by the hands of a surgeon.”I would further characterize and generalize a surgicaloperation to include an image and a manipulation whichnow typically goes beyond the energy of the human handto other energy sources (Fig. 2B). Early on the image thatsurgeons worked upon was that of a direct visual imagewith 2 hands directly working. We now know that a videoimage can be approached without a full open incision andperhaps using robots. We know that ultrasound, computertomography, or radioimmunoguided surgery can allow thesurgeon to see differently and to use other energy sourcesincluding heat, cold, radiofrequency energy, or photody-namic therapy. The urologists have demonstrated anincisionless approach to urinary calculi using extracorpor-eal shockwave lithotripsy (ESWL). The RET oncogenenow shows us the image of a precancerous thyroid gland

in children with MEN syndrome enabling preemptiveexcision—gene-guided surgery. What's next? The ball is inour court.

It's fair to say that a megatrend in surgical care is thebroad application of minimal access principles whileproviding the same benefit of a maximal procedure. Alooming example of what might be next incorporates severalof the previously referenced technologies melded into image-guided robotic radiosurgery or stereotactic radiosurgery.Using a robotic arm with a linear accelerator any one of anumber of extracranial tumors are now potentially amenableto radiosurgical ablation. While the vast majority of thesePhase I/Phase II clinical studies have been in adults, thepediatric application seems obvious.

In summary, discovery in emerging technologies willcontinue to shape our surgical practices—this is indeedtranslational medicine.

4. Translational medicine

Where did translational medicine originate? The rise ofintellectual capital was the key driver.

Let's look backwards for a moment. Throughout the ages,wars have had a profound impact on the development of oursurgical craft and its principles. They have had other socialimpacts. World War II was won not with brute force as hadthe previous wars, but with science and technology. Fromradar to sonar to the Manhattan Project, it was clear thatresearch, and specifically university-based research, could bean engine of military power. Shortly after the war in aseminal paper entitled “Science: The Endless Frontier” [2],Vannevar Bush predicted research as an engine not just ofmilitary but of economic power. This led to the formation ofthe NIH, the NSF, and ONR, and a surge in federal fundingfor university-based research. At the time, the prevailing lawof the land meant that federal funding = federal ownership.By 1980, the US government held over 28,000 patents.Anyone who has spent a few minutes at the Post Office, theIRS, or the DMV can imagine that commercialization wasa nightmare.

The Bayh-Dole and Small Business Patent ProceduresAct was enacted December 12, 1980; nothing has been thesame since. This law, which has been termed “the mostinspired piece of legislation to be enacted in America overthe last half century,” fundamentally altered the ownershipparadigm. Grantees, rather than the federal government(grantor), now owned the intellectual property developedwith research funding. This legislation implied a “de facto”duty to translate discoveries to reality and explicitlyencouraged academic-industry collaboration.

At present, universities now account for more than halfof all the basic research in the United States. Much, if notmost, of that resides within university schools ofengineering and medicine. It's clear that opportunity

Fig. 3 Process of “bench-to-bedside.”

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beckons—Stanford University Office of Technology andLicensing has realized more than $1 billion from its licenseinventions. The resultant philanthropy has been of evengreater value.

CL Max Nikias, provost at the University of SouthernCalifornia, puts it this way: “Universities have a fundamentalstewardship and, indeed, responsibility not just to discoverbut to ‘transfer innovation to the marketplace to truly make adifference.’”

While translational medicine has become “fashionable”as an academic buzz word, surgical research has always beentranslational. In his insightful paper [3], Francis D. Mooreasked the question: “What is Surgical Research?”

• Is it an oxymoron?• Research done by surgeons?• Research done on diseases treated by surgeons?

Dr Moore postulated that surgical research is that which“gets the surgical patient better.” As such, surgical researchhas always been and I believe will continue to betranslational. In the research laboratory, one frequentlyhears the phrase “bench-to-bedside.” In point of fact, thereis an endless cycle (Fig. 3) sometimes beginning at thebench (lasers, gene chip microarrays) and sometimes at thebedside (cardiac valves, pulse oximeters). There is no rightor wrong, no better or worse entrée into the cycle, but itinevitably requires an interplay between the clinicalproblem and the implementation of a new solution. Nomatter where the cycle is entered, the arrival of the solutionat the patient's bedside requires a commercial step. There isvirtually nothing that we use in our hospitals today that isn'tproduced by a commercial entity.

5. How do we get from bench to bedside?

Around that wheel of translational medicine are 4important and distinctly different components: discovery,invention, innovation, and entrepreneurship. Each will beconsidered in turn.

5.1. Discovery

The greatest advances in medicine have resulted fromunfettered, investigator-initiated inquiry and discovery—theclear result of the investigator-initiated research grantprocess. From recombinant DNA to synthetic insulinsurfactant, discovery is usually the result of basic researchinto fundamental biologic processes. While there may beawareness of clinical implications, it is really the quest fornew knowledge that drives the process. Such progress occursin an unpredictable fashion, and the costs and thus risks areconsiderable. Increasingly, it is the university laboratorywhich is best equipped to optimize and mitigate such risk.

5.2. Invention

An invention is an object, process, or technique, mentallyfabricated, with an element of novelty. It is an idea. Itfrequently builds on preexisting concepts. The Fogartyballoon catheter™ is the amalgam of 2 existing concepts, thecatheter and the balloon, but in aggregate represented a noveldevice which has had a profound impact on endovasculartherapies. An invention may not always be fully realized.Leonardo Da Vinci's helicopter invention required Sikorskyto be fully realized.

5.3. Innovation

Innovation is distinct from invention; it is the idea put intopractice. If invention is the idea, then innovation is itsapplication. The process of innovation is often moreimportant than the invention idea.

A scientist seeks understandingAn inventor seeks a solutionAn innovator seeks an application

5.4. Entrepreneurship

Finally, and in many ways, the most important concept isthat of entrepreneurship. The term is a “loaned word” coinedby an obscure Irish/Spanish economist, Richard Cantillon,living in France. Literally, it translates as “an agent who buysfactors of production at certain prices in order to combinethem, with a view to selling them at uncertain prices … in thefuture.” More specifically, it currently connotes “one whoundertakes and operates a new enterprise or venture andassumes considerable responsibility for its success.” Such an

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entrepreneur seeks independence, autonomy, and control tomaximize the likelihood of success in a risky (defined) anduncertain (ill-defined) venture. That sounds to me likea surgeon.

6. What “makes it happen”?

6.1. People, environment, and leadership

The previously described processes of discovery, inven-tion, innovation, and entrepreneurship are necessary fortranslational medicine, but are not, in and of themselves,sufficient. Enlightened leadership is an essential overlying“umbrella.” Frequently cited, but seldom understood, leader-ship according to Kotter [4] is in essence “the ability toproduce useful change.” Beyond that, it is the ability to take agroup (department, school, or university) to a place where itotherwise could not or would not go. Such leadershiprelishes the messy task of recruiting, inspiring, and retaininginquisitive (and thus occasionally prickly) thinkers anddoers. Beyond the people, leadership creates a permissiveand even celebratory environment. Is this your department?Imagine Steve Jobs as your resident—would he be

Embraced?Encouraged?Tolerated?Bludgeoned?

No department, school, or university exists in a vacuum;the surrounding environment inevitably colors the attitudesand either dampens or accelerates the process. Since WorldWar II, enlightened leadership in Silicon Valley and atStanford University has slowly but consistently produced thecurrent environment that has contributed so much to theworld. For those who want to import such a culture, severalbooks are well worth reading [5-7]. Now 60 years later, thekey currencies in Silicon Valley include:

Intellectual capitalRisk capitalVenture capital

The abundance of these capitals has produced the regional

Fig. 4 Judah Folkman, MD.

advantage [8] that has fueled discovery, invention, innova-tion, and entrepreneurship, and produced perhaps the mostfertile ground for medtech innovation in the world. Morethan 50% of the successful medical device startups are withina 50-mile radius of Stanford University.

This leads to an interesting and frequently unspokendichotomy—what we profess to believe and what weactually do. Ask anyone in our field if they are in favor ofcreativity and innovation and the answer is an overwhelmingyes. Ask the same group “who is willing to abandoneverything that got you here and makes you you?” and theharsh reality is obvious. Well characterized as the innovator's

dilemma in the book by Clayton Christensen [9] andsuccinctly explained by Judah Folkman [10] (Fig. 4):“Tom, there are no experts in the future, … only experts inthe present.” Smith-Corona was the dominant typewriter,cluttering dorm rooms when I was in college. Smith-Coronano longer exists. The experts in the present denouncedlaparoscopic cholecystectomy 20 years ago. Now many ofthose that produced the laparoscopic revolution are denoun-cing natural orifice transluminal endoscopic surgery(NOTES). The vast majority are comfortable with what weknow and what we do. Innovation through one cycle is trickyat best; serial innovation is incredibly difficult.

Conventional wisdom and experience are “state of theart” but only for today and not forever. The reality is that,in 5 years, half of what we know for sure will change. Putsuccinctly, “you can write the entire history of science inthe last 50 years, … in terms of papers rejected by Scienceand Nature” [11]. The takeaway message is innovation ishard. It runs against a gradient and frequently seems “self”-destructive and yet is essential for every advance thatmakes surgical craft and surgical care what it is today.

A simple classification for innovation in surgical care isoffered in Fig. 5. Kocher modified the existing clamps ofthe day to add a tooth to facilitate grasping of the goiterousthyroid gland. As a scrub tech, Fogarty witnessed groin toankle arteriotomies to extract emboli; failure was obviousto him as a nonexpert when he observed most of thosepatients returning a day or 2 later for an amputation. Thesurgeons relished their operation and thought it was thebest that could be done. Those same experts rejected thepublication of Fogarty's balloon catheter for nearly 3years; now it's the standard. Bill New, a Stanfordanesthesiologist, understood the simple problem of quicklyrecognizing a misplaced endotracheal tube—it was simplya matter of distinguishing between red blood and blueblood—quickly. The experts of the present plied theirexisting craft; Bill invented the pulse oximeter which hasrevolutionized the care of critically ill patients worldwide.

7. “The problem”

The pulse oximeter story has an important and broadlyapplicable message. Most of us are so overcommitted that ona day-in-day-out basis simply getting through the work of the

Fig. 6 Thomas J. Fogarty, MD—“Godfather” of BiodesignInnovation Program.

Fig. 5 Classifications of Innovations in Surgical Care.

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day is a huge victory. Perhaps equally problematic isdeepening specialization. We no longer have generalsurgeons, we no longer have vascular surgeons—we havevascular surgeons who are exclusively focused on venousdisease or perhaps on endovascular approaches to abdominalaortic aneurysms. On one hand, specialization has dramati-cally improved the experience and expertise that is broughtto bear on a single clinical problem; on the other hand, weknow more and more about less and less. When was the lasttime a urologist compared notes with a neurosurgeon?Perhaps urodynamics has some overlap with the dynamics ofCSF in hydrocephalus?

An additional component of the problem is thattechnology is increasingly complex and expanding. Thedays of sewing Dacron grafts on the kitchen table andimplanting them in patients the next day are of historicinterest only. The complexities of a simple stapling device orthe bewildering requirements for a cardiac pacemaker makegarage-based breakthroughs much less common.

Together, these factors create a crisis in the pipeline ofinnovation innovators. Eight years ago, Drs Paul Yock andJosh Makower asked 2 key questions.

• Why leave innovation to chance?• Can we study, understand, and teach it?

They established the Medical Device Network and begana 10-month postgraduate program teaching team-basedinnovation. Shortly thereafter, they welcomed the participa-tion of Russell Woo, MD, a young Stanford surgical resident.Stanford Surgery has been active participants ever since. Atpresent, the mission of the Biodesign Innovation Program isthreefold:

1. Train the next generation of innovators2. Facilitate translation of new and emerging technolo-

gies to patient care3. Drive innovation based on unsolved patient problems

We regard Thomas J. Fogarty, MD (Fig. 6) as the“godfather” of this innovation program. Dr Fogarty has

authored over 100 surgical instrument patents andshepherded more than 30 successful startups to fruition,bringing great ideas to the bedside. He is the recipientof the American College of Surgeons Jacobsen Innova-tion Award, the Lemelson MIT Prize, and is aninductee into the National Inventors Hall of Fame. DrFogarty would offer the following observations about“translational medicine”.

• It is not a science fair project• It is a product in a box with a 1-800 number for salesand service

• It gets the patient better• It leverages treatment, in his case, to millions of patients

The concept of leverage is a simple, yet a profound andpowerful one. Archimedes observed “give me a lever longenough and a place to stand and I'll move the world.”Another extraordinarily creative and innovative surgeon isDr Rodney Perkins, clinical professor of surgery at Stanfordand founder of the California Ear Institute. At the FogartyLecture in 2002, he used a cartoon and several figures(Fig. 7A-C) to demonstrate leverage.

Think about how Lazar Greenfield's filter has improvedthe lives of almost a million patients. Think about howNorman Shumway's heart transplant work has shaped afield. Think about how APSA President-elect MikeHarrison has invented the entire field of fetal therapy.Think about how Jay Vacanti's work has established thescience of tissue engineering and the promise that it holds.Think about how our past president Judah Folkman's workhas affected, and will continue to affect, millions of patientseach year. That's leverage.

8. The premise

If innovation over the centuries has produced enormouspatient benefit, … then why leave it to chance? Can we studyit? Can we understand it? Can we teach it? The StanfordBiodesign Innovation Program tries to answer thesequestions.

Fig. 7 A, Leveraging Medical Knowledge—Direct Patient Care. B, Leveraging Medical Knowledge—Training Other Physicians. C, Leveraging Medical Knowledge—DevelopingNew Solutions.

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The program depends on a leadership group (Fig. 8)blending faculty from the Schools of Engineering, Medicine,and the Graduate School of Business. Roughly at theepicenter of these 3 campuses lies the James H. Clark Center,the hub of the multidisciplinary Bio-X Program and thehome of a 4000-ft2 teaching and learning facility for theInnovation Program.

The Innovation Program is clearly and unequivocallyfocused in the sphere of medtech. We tend to glibly talkabout tech transfer implying that, in the life sciences, it isgeneric. It is not. Medtech is quite different from biotechor biopharma. The disciplines of medtech are theengineering sciences intersecting with the clinical need;the innovation process is always focused on the clinicalneed. The biotech component is highly discovery drivenwith subsequent application to the clinical need andtypically leans more heavily on the fundamental sciencesand pure discovery.

At the heart of the program is a 1- or 2-year fellowshipbringing together multidisciplinary teams including a mix ofphysicians, biologists, engineers sprinkled with businessunderstanding and expertise (Fig. 9).

The first year of the fellowship actually begins 8 monthsbefore the fellows arrive. The leadership group carefullyscreens over 80 applications from around the country and,indeed, from around the world. Thirty to 35 applicants areinvited for an intensive interview day to ensure abundant and

Fig. 8 Biodesign Pro

substantial interaction between the applicants, our currentfellowship complement, and most of the key facultymembers. An agonizing selection process attempts to buildteams much like building a basketball team. Key skill sets arescrutinized, assessed, and, ultimately, invitations are offeredto the 8 top applicants. The current acceptance rate is wellover 90%.

In the months prior to the teams' arrival, a clinical area offocused is identified for study. In the past, clinical areas haveincluded anesthesia, critical care, cardiovascular disease,neuroscience, gastrointestinal disorders, and urology. Whileit frequently aligns with 1 or 2 clinical departments, it isinevitably focused on patient problems and seeks to beagnostic as to which “trade union” treats the patient. Wemake a studied attempt to avoid congruence with clinicalexpertise on the team and the clinical topic—thus thepresence of a neurosurgeon on a team will almost certainlyguarantee that that team will not be focused in areas ofneuroscience.

At time of arrival in July, the fellows spend 7 to 8weeks in “boot camp.” This represents an intensive (50-60 h/wk) didactic, reading, self-study, and team-buildingexercise. Broad topics include the process of innovation,rules of the road in intellectual property, regulatory, andreimbursement strategies. Financial essentials of entrepre-neurship and start-ups are outlined by experts. Businessethics and law are all covered in addition to presentation

gram Leadership.

Fig. 9 Multidisciplinary teams.

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by a multitude of experts in the present outlining currenttools, technologies, problems, and solutions in theselected clinical area. A starter project is offered in thefinal week to provide a clear overview of how each pieceis essential to move a project “from scribbles on a napkinto bedside utility.” An additional week is spent inthe Design or d.school (http://www.stanford.edu/group/dschool/). Design Thinking represents an entirely newconcept to almost all team members, enticing them tothink about human factors.

8.1. Clinical immersion

A 3-month period then partners each team with aclinical discipline with extended periods of observationthroughout the hospital. Locations as diverse as anambulance, a helicopter, the emergency room, a sleeplaboratory, the GI suite, or the operating room are allselected to provide a breadth of exposure to the clinicalcare realities within the field. Functioning as a “fly on thewall,” the teams are encouraged to ask naive questions like“why does laparoscopic surgery look so contorted?” and“why does the placement of an epidural catheter sofrequently fail?” The teams are encouraged to look atprocesses from the perspective of a circulating nurse, ascrub nurse, the surgeon, the x-ray tech, or the anesthe-siologist. They are asked to observe what is said and whatis done, and equally as importantly what is not said andwhat is not done. They can take a step back and frame theproblem without focusing on the solution. As Henry Fordonce said, “If I'd listened to my customers, I'd have giventhem a faster horse.”

A database is then assembled simply listing all of thepotential needs. The target is 200; most teams find almosttwice that many problems every year. As Linus Pauling hassaid, “If I want a good idea I start with lots of ideas.” Aprocess then begins to validate the needs, answering thequestions: “Is it really a problem?” and “Who, what,where, when?”

They consult the literature to identify the scope and scaleof a problem and to whom the problem belongs: the patient,the nurse, the ambulance driver, the surgeon. They areexpected to get the facts and get the numbers.

Needs are then categorized and assessed.

• How big is the US market?• How big is the world market?• Is the impact to patients revolutionary or incremental?• What is the impact to the health care provider?• What is the financial impact—to whom?

Needs are then winnowed and culled, and hard choices

are made. It is impossible for a team of 4 to make ameaningful impact on 15 or 10 or even 5 ideas. Typically, 2or 3 are selected.

A needs specification process then evolves on the 2or 3 selected needs. The group is expected to become anexpert in the anatomy, physiology, pathophysiology,epidemiology, and market dynamics of the clinicalproblem. Current solutions, competitors, and even thoseconcepts that may be in “stealth mode” elsewhere allform the basis for a thorough understanding. Require-ments are assembled—the “must haves” and the “desir-ables.” This provides the basis for a guidance documentfor innovation.

Fig. 10 A, Protyping. B, Prototyping resources.

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Fig. 11 A, Addressed Needs: Summary of Concept Development for Need 323. B, Addressed Needs: Summary of Concept Development for Need 140. C, Addressed Needs: Summary ofConcept Development for Need 121.

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8.2. Brainstorming

Brainstorming is not BSing. Critical factors include theenvironment, the team, and a facilitator. Despite therelatively free-form nature, there are rules:

• Defer judgment• Encourage wild ideas• Build on the ideas of others• Stay focused• Be visual• Go for quantity

Concepts are then screened and selected. They areevaluated to determine whether they meet the needsspecification. Is the concept feasible? What are the risks—scientific, technical, clinical? The intellectual propertylandscape is carefully scrutinized. More than a few teamshave discovered well-protected intellectual property aroundtheir idea. That poses real-world questions.

Is there a way around existing patents?Is there a license opportunity?Are the risks too great such that funding wouldbe unlikely?

Of great important is the question: Does the team caredeeply about the problem and the solution? The conceptsare then organized on a wallpaper-sized grid called a MindMap (http://sen.stanford.edu/discover). A simple risk-reward of each approach to the central clinical problem ismade: low risk and high reward is optimal; high risk andlow reward is not.

The iterative process continues and is ultimately distilledinto a Needs Statement—what we call “the genetic code ofthe solution.” It focuses on the end point, not necessarily onthe current problem. As an example, 15 years ago the cardiacsurgeons may have suggested a needs statement: “A bettermethod to do a coronary artery bypass graft.” A much betterstatement would have been: “A better method to revascular-ize the heart.” Focus on the solution.

Once ideas are distilled the process of prototyping begins.In fact, it often begins as concepts are explored. Earlyprototyping begins with the simplest of materials—boxes,dowels, cardboard, duct tape. The team immediately becomesaware of realities. The following case study is illustrative.

A team observing Dr Craig Albanese, one of ourlaparoscopic gurus, observed the time wasted in toolexchange during laparoscopic surgery. Dr Albanese doubtedthe observation. Quietly, the team brought a stop watch to theoperating room. They observed consistently that at least 30%of the operative time was wasted during tool exchange—point made.

The need for a multifunctional laparoscopic tool, a SwissArmy knife if you will, evolved. The prototyping processbrought some reality to how a Swiss Army knife might be

built at the end of a laparoscopic tool. Concepts of a multi-barreled device or a tool tip that would move in and out like apump action shotgun were all studied. The concept of amultibarreled tool was discarded early based on sizeconstraints. The shotgun mechanism was discarded basedon complexity and manufacturing constraints. The lesson is:fail early, fail often, and fail cheaply (Fig. 10A). The teamhas now moved on to a clever device using a novel hingeabout the central axis. This allows the tool tip to grasp in oneorientation, to cut in another, and to coagulate when electriccurrent is delivered.

Prototyping resources are abundant throughout theStanford campus. First and most importantly, we draw onthe experience of Craig Milroy, a prototyping genius a laMacGyver. A small prototyping shop is contained within theBiodesign Innovation Program teaching facility. A shortdistance away from the Engineering campus, the StanfordProduct Realization Lab is a prototyper's playground(Fig. 10B).

An iterative process continues through the balance of theyear based on the specifics of the project. The importantsteps in the development and protection of intellectualproperty become real with a specific project. Patentability,freedom to operate, and solid documentation are developedwith the input of the Stanford Office of Technology andLicensing (OTL).

Funding is pursued in a real-world atmosphere. Our OTLoffice provides some “birdseed funding” and the NationalCollegiate Innovators and Inventors Alliance (NCIIA) hasbeen a very important source of small grants of $10,000 to$15,000. Beyond that, SBIR and STTR funding can provideconsiderable sums ($500K-$750K). The fellows learn thevalue of preserving ownership without seeking outsidefunding. Thereafter, inevitably angel funding and the venturecommunity come into play [12].

Regulatory and reimbursement strategy is another keylearning component. The team wrestles with the specificdetails and nuances of FDA strategy and approval [13].

Reimbursement strategies are similarly explored. Under-standing stakeholders, the realities of hospital purchasingdepartments, and the perspectives of CMS are learned firsthand. The inevitably dry didactic presentation from bootcamp now comes to life as the team's ideas and projectsnavigate these labyrinthine processes. Several selectedprojects and their Needs Statement are illustrated in thenext 3 figures (Fig. 11A-C).

The teams have had considerable success both atfundraising and in business plan competitions by the endof the year. While neither is the specific end goal, bothprovide external validation in the crucible of real-worldmarkets.

The surgical members of the team spend a second year on acompletely independent project. They are expected to garnerresources and bootstrap their project one way or another.They may additionally pursue a Masters in Bioengineering.The experience of JamesWall, MD, a general surgery resident

33Inventing out future

from UCSF, is illustrative (Fig. 12A). James was a fellowfrom 2006 to 2008 on loan from UCSF in the middle of hissurgical residency. James and his team addressed 4 clinicalneeds in their first year. They were finalists in the StanfordBusiness Plan competition filing 3 provisional patents and

Fig. 12 A, James Wall, MD. B, InSite Medical Techno

one utility patent. They were awarded a $20,000 NCIIA grantfor concept development.

In the second year, InSite Medical Technologies wasfounded with a $100,000 National Science Foundation(NSF) SBIR award (Fig. 12B). Five hundred thousand

logies. C, Biodesign Fellow and Student Start-Ups.

Fig. 13 The real product of Biodesign Program.

34 T.M. Krummel

dollars in angel investment was obtained, and continueddevelopment of a fundamental concept gleaned in thepediatric surgical operating room became a reality.

How did this project happen? In 2006, the team watchedan anesthesiologist spend 45 minutes trying to place anepidural catheter in a 14-year-old patient of mine who was toundergo a pectus repair. After 45 minutes of poking,prodding, and OR delay, the epidural catheter was “placed.”It never worked.

Based on this, the team explored this problem anddiscovered the huge challenge of precisely placing anepidural catheter in the epidural space. They interviewedpatients, surgeons, and anesthesiologists, and they exploredmany concepts. To this day, I remember the brainstormingsession around what came to be termed “a controlled entryinto a biologic space.” One of the engineers made theobservation that most mechanical devices requiring precisecalibration of movement use a simple 5000-year-oldmachine, … called a screw. Now 18 months later, theEpiphany™ Epidural Delivery System is well on its way tosolving the need for controlled entry into the epidural space.Simultaneously, James completed the Masters Degree inBioengineering with a focus on medical device wastemanagement—more to come on that.

Over the 8-year period of the program, a total of 10startups have resulted. In aggregate, over 10,000 patientshave been treated with these devices—that's leverage and itis only beginning.

An important component of what we teach centers aroundethical and evidence-based innovation. The current challengeis that new technologies are faster than our profession'sability to provide evidence-based data, before widespreadapplication. The only solution to that is to be certain that

ethics is a basic science of those whom we train. Acomprehensive discussion is outside the scope of thispresentation, but several recent reviews have been published[14,15].

The classic way to learn material is to teach it. A two-quarter graduate level class is cross-listed at Stanford in theSchools of Engineering, Medicine, and the Graduate Schoolof Business. The fellows serve as teaching assistants (TAs)for the class and their active participation forces them torelearn to teach.

Above and beyond that, a Medical Technology Career Fairis held every year. Every other year, we run the EmergingEntrepreneurs Program. Emerging Entrepreneurs is a practicalworkshop for young innovators throughout SiliconValley andthroughout the world (http://emergingentrepreneurs.org).

Every year we host a series of public lectures. The first is aseries of 4 speakers at the Innovator's Workbench (http://innovatorsworkbench.stanford.edu). Speakers have includedDean Kamen, the inventor of the Segway and Fred Moll,cofounder of Intuitive Surgical.

Now in its 10th year, the annual Fogarty Lecture isdesigned to celebrate the historic partnerships betweenStanford University, industry, and venture capital that havecreated such remarkable progress, and acknowledges thehistoric, creative, and ingenious contributions Dr Thomas J.Fogarty has made throughout his career. Past speakers are a“who's who” of contributors to newmedical technology suchas Thomas Fogarty, Robert Bartlett, William New, RodneyPerkins, Delos Cosgrove, Paul Yock, William Brody,Andrew Grove, and Casey McGlynn.

Based on our experience and the demands of both ourclass and a number of other institutions considering suchprograms, our syllabus and Source Book for the graduate

35Inventing out future

class is now expanding to a textbook expected to bepublished in early 2009.

As of this year, the program has trained 47 graduates with2 senior fellows and 8 incoming recruits. More than 50invention disclosures and patents have been filed. Multipleabstracts, posters, chapters, and manuscripts have beenpublished and/or presented. There have been real-worldfunding successes through the NCIIA, the SBIR process,angel, and venture investors. That said, our real product isour trainees (Fig. 13).

In summary

• Surgery and surgical care have evolved over the pastcenturies and will continue to evolve.

• Surgeons must be thoughtful about how they definethemselves.

• Ravitch's Principles provide a useful framework forclarity to understand and actively participate in theevolution of surgical technology.

• Surgeons ignore technologic advancement at their ownperil.

• Our early experience with an innovation trainingprogram suggests strategies for training a nextgeneration of Tom Fogarties.

I leave you with one final thought: “The art of surgery isnot yet perfect and advancements now unimaginable are stillto come. May we have the wisdom to live with this withgrace and humility.” This statement is as true in 2008 as itwas when it was penned by William Stewart Halsted almost100 years ago.

Again, my sincere thanks and gratitude to the AmericanPediatric Surgical Association for the privilege of presentingthis lecture.

References

[1] Marescaux J, Leroy J, Gagner M, et al. Transatlantic robot-assistedtelesurgery. Nature 2001;413(6854):379-80.

[2] Report to the President by Vannevar Bush. Director of the Office ofScientific Research and Development, July 1945 found at. http://www.nsf.gov/about/history/vbush1945.htm.

[3] Moore FD. What is surgical research? J Surg Res 1974;16(6):679-87.[4] Kotter JP. John P. Kotter on What Leaders Really Do. Boston (Mass):

Harvard Business Press; 1999.[5] Hiltzick M. Dealers of Lightning: Xerox PARC and the Dawn of

the Computer Age. New York, NY: HarperCollins Publishers;1999.

[6] Malone MS. Bill and Dave: How Hewlett and Packard Built theWorld's Greatest Company. London, England: Penguin Books Ltd;2007.

[7] Gillmore CS. Fred Terman at Stanford. Stanford (Calif): StanfordUniversity Press; 2004.

[8] Saxenian A. Regional Advantage. Cambridge (Mass): HarvardUniversity Press; 1995.

[9] Christensen CM. The Innovator's Dilemma—When New Technolo-gies Cause Great Firms to Fail. Boston (Mass): Harvard BusinessSchool Press; 1997.

[10] Personal communication between Judah Folkman and Tom Krummel,Fall 1981.

[11] Lauterbur, Paul C. All science is interdisciplinary - from magneticmoments to molecules to men, Nobel Lecture, Department 8,2003.

[12] Krummel TM, Shafi BM,Wall J, et al. Intellectual property and royaltystreams in academic departments: myths and realities. Surgery2008;143(2):183-91.

[13] Connor J. Making sense of the FDA. In: Krummel TM, Grosfeld JL,editors. Seminars in pediatric surgery, vol. 15(4). Philadelphia (Pa):W.B. Saunders Co.; 2006.

[14] Riskin DJ, Longaker MT, Krummel TM. The ethics of innovation inpediatric surgery. Semin Pediatr Surg 2006;15:319-23.

[15] Biffl WL, Spain DA, Reitsma AM, et al. The Society of UniversitySurgeons Surgical Innovations Project Team: responsible develop-ment and application of surgical innovations: a position statement ofthe Society of University Surgeons. J Am Coll Surg 2008;206(6):1204-9.