Journal of Pediatric Surgery Lecture
Surgeon Innovators.can't solve their problems those moments should engender a
Hey, Krummel, how many more kids are we going to watch
Journal of Pediatric Surgery (2009) 44, 2135Association, Phoenix, AZ, May 27- June 1, 2008. Tel.: +1 650 498 4292; fax: +650 725 3918.1. 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
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 earlymember of APSAan icon, mentor, and friend. I'm one ofArnold'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 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-fangledtechnologyECMO. Arnie rivets me with his gaze and saysPresented at the 39th annual meeting of the American Pediatric SurgicalPresident 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 ofInventing our future: traininsurgeon innovatorsThomas M. Krummel
Department of Surgery, Stanford University School of Medic
Received 24 September 2008; accepted 7 October 2008E-mail address: firstname.lastname@example.org.
0022-3468/$ see front matter 2009 Elsevier Inc. All rights reserved.doi:10.1016/j.jpedsurg.2008.10.005the next generation of
Stanford, CA, USA
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 we
www.elsevier.com/locate/jpedsurgdie before you do something?
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 forMentorshipthere'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 and
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
22 T.M. Krummelconcern for this child's problem.What was the state of surgical care at the time of the
painting? 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-
Fig. 2 A, Mark M. Ravitch, MD. B, What is Surgery?Ravitch's Principles.
of todayultrasound, computer tomography, magnetic
thou eld,Mar ent
in children with MEN syndrome enabling preemptive
By 1980, the US government held over 28,000 patents.Anyone who has spent a few minutes at the Post Office, the
23Inventing out futureprogress 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 ofsurgery 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 glandsoceanic human procedure. Perhaps distance becomevant!?ith this backdrop of progress, it is worth recallingghts and comments of one of the giants in our fik M. Ravitch, MD, to help frame past and presresonance 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 . 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 firsttran esIRS, 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 factoduty 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 opportunityexcisiongene-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 practicesthis 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 ,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.
24 T.M. KrummelbeckonsStanford 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 fashionableas an academic buzz word, surgical research has always been
Fig. 3 Process of bench-to-bedside.translational. In his insightful paper , 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 whichgets 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 entre 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.
The greatest advances in medicine have resulted fromunfettered, investigator-initiated inquiry and discoverytheclear 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.
An invention is an object, process, or t...