devices that could serve as bridges to transplantation andimprove patients� health to the point that they couldremain ambulatory and outpatients. Specifically, we arenow developing an implantable biohybrid device thatproduces normal portal vascular physiology, reduces por-tal hypertension, and provides hepatic synthetic function,with the potential to replace 15% to 30% of liver mass. Inaddition, we are continuing to develop an implantablepulmonary device that could provide a substantial im-provement in gas exchange for patients who are waitingfor lung transplantation or who might not be candidatesfor lung transplantation. Both of these efforts could nothave happened without the active involvement of theinvestment community.

CONFLICT OF INTEREST AND OTHER ISSUESRELATED TO THE INTERFACE OF ACADEMIAAND INDUSTRY

Conflict of interest guidelines have become an impor-tant safeguard to keep the welfare of the patient as the toppriority for the introduction of any new technology.Harvard, MIT, and MGH have very similar guidelines inthis regard. In clinical research, physicians cannot beresponsible for clinical trials and cannot have any finan-cial interest in the corporate entities that can derivefinancial benefit from the successful introduction of atechnology. These principles ensure a clear separationbetween financial incentive and the best interest of thepatient. Likewise, the patient must be protected at theinstitutional level, and similar guidelines exist for aca-demic medical centers and other academic institutions.Many other issues related to successful licensing, profitsharing, and royalty distribution are managed throughcapable technology transfer offices in university andacademic medical center settings. The importance oftransparency and disclosure remain the fundamentalunderpinnings of successful commercial application ofacademically derived new technology.

In summary, the complex world of patient care andinnovation requires multidisciplinary cooperation as wellas collaboration with industrial partners. All diagnosticand therapeutic innovation must travel through a com-mercial route before successful clinical application. In ourfield of tissue engineering and regenerative medicine,there is a 25-year track record that has led to successfulhuman applications, the development of successful com-panies, and the fueling of ongoing, original, and innova-tive work for the difficult problems that remain to besolved.

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INTELLECTUAL PROPERTY ANDROYALTY STREAMS IN ACADEMICDEPARTMENTS: MYTHS AND REALITIES

Thomas M. Krummel, MD,a Bilal M. Shafi, MD, MSE,b JamesWall, MD,c Venita Chandra, MD,a Carlos Mery, MD, MPH,d

and Michael Gertner, MS, MD,a Stanford, Calif, Philadelphia,Pa, San Francisco, Calif, and Cambridge, Mass

From the Stanford University School of Medicine Department ofSurgery, Stanford, Calif,a the University of Pennsylvania Department ofSurgery, Philadelphia, Pa,b the UCSF Department of Surgery, SanFrancisco, Calif,c and Harvard University/Brigham & Women’sHospital Department of Surgery, Cambridge, Massd

MANY OF THE PHENOMENAL BREAKTHROUGHS OF THE PAST 30YEARS were conceived and born in university laboratories.Whether in computer science, Internet technologies, orbiomedicine, the intellectual horsepower of universitylabs, the faculty, and, perhaps more important, the stu-dents is an unrivaled national—indeed world—resourceand a critical engine of economic growth. It wasn’t al-ways so. In this short review, the authors endeavor to:

d Review the historical context of the commercialization

of university research.d Dispel common myths and extract common realities

from past successes.d Outline the fundamental processes in translating

discoveries.d Emphasize the need for vigilance when conflicts of all

sorts (interest, commitment) inevitably arise.

Commercialization of university-based research hasbeen the subject of recent commentary and increasinginterest, especially in light of recent sensationalizedfinancial results. A Wall Street Journal article1 headlined‘‘More Universities Increasing Support for Campus Startups’’ highlighted several key elements—the role of thegraduate student, the value of partnerships with bothventure and industry, and the recent flourish of univer-sity economic interests in royalties, licensing, and, in-creasingly, an equity position. C.L. Max Nikias, PhD,provost of the University of Southern California empha-sized the fundamental responsibility of the university to‘‘transfer innovation to the marketplace to truly make adifference to society.’’2

Carl Schramm, CEO of the Kauffman Foundation,described ‘‘the elite of the technology transfer world’’---UC Berkeley, Caltech, Stanford, MIT, and Wisconsin---inan article entitled ‘‘Five Universities You Can Do Busi-ness With.’’3 Although this title’s grammar may be sus-pect, the ‘‘formula’’ for success at these universities isnot. How did this happen? Why? How do we ethicallypromote more?

Accepted for publication November 5, 2007.

Reprint requests: Thomas M. Krummel, MD, Stanford UniversitySchool of Medicine, Department of Surgery, 701B Welch Road,Suite 225, Stanford, CA 94305-5784; E-mail: tkrummel@stanford.edu.

Surgery 2008;143:183-91.

0039-6060/$ - see front matter

� 2008 Mosby, Inc. All rights reserved.

doi:10.1016/j.surg.2007.11.011

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184 Krummel et al

HISTORICAL CONTEXT

An excellent comprehensive historical review of theprocess of technology transfer is available on the Uni-versity of California Technology Transfer web site.4 Uni-versities are a critical repository of both fundamentaland applied research, often funded with federal money.In the aftermath of World War II, the success at TheManhattan Project highlighted the criticality of univer-sity research for the increasingly technical nature of na-tional defense—brute human force was no longersufficient to win wars.

Vannevar Bush’s report ‘‘Science---The Endless Fron-tier’’5 presciently predicted the future value of universityresearch as an engine of economic growth. His reportcogently argued that federal funding for research was anational priority—not just for military defense, but foreconomic offense. The National Institutes of Health(NIH), the National Science Foundation, and the Officeof Naval Research were founded and, arguably, the rest ishistory.

However, federal funding equated to federal owner-ship; by 1980 the U.S. government held title to some28,000 patents---but fewer than 5% were commercialized.It should come as no surprise to anyone that Byzantinefederal policies, including nonexclusive licenses, lackedany rational incentive for commercialization.

Modern-day technology transfer from university re-search to commercialization traces to the Bayh--Dole andSmall Business Patent Procedures Act (P.L. 96-517)enacted December 12, 1980. This legislation fundamen-tally altered the ownership paradigm of intellectual prop-erty developed with federal funding; federal ownershipwas transferred to grantees to enhance public access.6-8 Itde facto created an implied duty for government granteesto translate research discoveries and commercialize inven-tions. Furthermore, it explicitly encouraged academic–industry collaboration to this end, but without specifyingmechanisms—thus birthing conflicts of interest.

Twenty-five years later opinions vary. Bremmer com-mented in ‘‘Innovation’s Golden Goose’’9 that the Bayh–Dole act is ‘‘perhaps the most inspired piece of legisla-tion to be enacted in America over the past half century.. This unlocked all the inventions and discoveries thathad been made in laboratories throughout the UnitedStates with the help of tax payer’s money. More thananything, this simple policy measure helped reverseAmerica’s precipitous slide into industrial irrelevance.’’Although estimates vary, by 1999 some ‘‘thirty billiondollars of economic activity per year and 250,000 jobscan be attributed to technologies born in academic insti-tutions. Also, over 2200 new companies have beenformed since 1980, based on the licensing of an inven-tion from an academic institution.’’10 In the post-Googleworld, it is much larger. In fiscal 2000, American andCanadian gross licensing income was reported in theAssociation of University Technology Managers surveyat $1.26B.

On the other hand, as Cho comments in this article,‘‘the Bayh--Dole act has created opportunities for

conflict of interest for university faculty members be-cause academic--university partnerships can offer directfinancial rewards to individual faculty members in theform of consulting fees, royalties and equity in compa-nies, while simultaneously funding these faculty mem-bers’ research.’’ Others have expressed concern thatuniversity research would become skewed toward ap-plied research and its marketable products. While the-oretically possible, a study of 3,400 faculty at six research-intensive universities showed the ratio of applied to basicresearch projects unchanged from 1983 to 1999.12

Universities account for about half of all the basicresearch in the United States. In many institutions, thelargest component with broad societal impact, andhence commercial potential, resides in academic depart-ments within university schools of medicine.

A few examples of fundamental discoveries success-fully translated to phenomenal clinical utility and enor-mous patient benefit include:

1. Recombinant DNA—University of California and

Stanford University;

2. Synthetic human insulin—City of Hope National

Medical Center;

3. Synthetic surfactant—University of California;

4. Neupogen—Memorial Sloan Kettering Cancer

Institute.

These huge ‘‘blockbuster’’ drugs/technologies arehousehold names. However, the vast majority of devices,drugs, and hybrid devices are neither as lucrative nor asdirectly linked to the discovering institution, but, inaggregate, they are at least as pervasive and profound.

The world regards Silicon Valley as an epicenter ofstartup activity in engineering, computer science, bio-technology, and medtech fields in large part because ofthe Stanford community---and the data support theseperceptions. ‘‘Stanford startups’’ are most often createdby alumni graduates who become successful entrepre-neurs; many other companies have been spun out of theuniversity by its faculty and students. More than 150successful medical device companies have their originsin Stanford people and technologies.

Over the past 35 years, the Stanford University Officeof Technology Licensing (OTL) has received greaterthan $1 billion of income from licensing inventionsdeveloped at Stanford.13 Additionally, OTL has taken eq-uity positions in hundreds of companies and has receivedenormous liquidated equity, most notably from Google($336 million). Such equity is managed by the StanfordManagement Company and is usually sold as soon as apublic market exists. Finally, the University has realizedhundreds of millions of dollars in philanthropic supportfrom successful entrepreneur graduates, usually in grati-tude for the very supportive environment that not onlypermits, but even celebrates, entrepreneurial success.The recent book Bill & Dave: How Hewlett and PackardBuilt the World’s Greatest Company14 chronicles the role ofStanford in the career of Bill Hewlett and Dave Packard,both of whom as individuals, through their family and

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now through their foundations, have been enormousbenefactors to the university. Royalties, equity, and phi-lanthropy are all based on innovation and all have a pow-erful impact on modern universities.

There are many ways to categorize the size, scope,and scale of commercialization. For example, in aca-demic 2005 to 2006, Stanford received $61.3 million ingross royalty revenue from 470 technologies, with royal-ties ranging from $12.38 to $29.297 million. Fifty of the470 inventions generated $100,000 or more in royalties.Seven inventions generated $1 million or greater.Stanford’s OTL will evaluate more than 450 new inven-tion disclosures each calendar year. Approximately $6million in legal expenses were incurred to concludemore than 100 new licenses. Of the new licenses, 68 werenonexclusive, 27 were exclusive, and 14 were optionagreements. This is based on annual research funding ofbetween $900 and $1000 million.15 What are the com-mon realities of these successes and what are the myths?What are the worries?

Patterns of success. For those looking for a ‘‘secretsauce’’ please consult Julia Child’s cookbooks; there isno such thing as a simple recipe for the successfultranslation of research, especially biomedical research,to improvements in patient care. As we consider patternsof success, several definitions along the sequence fromdiscovery to implementation are in order.

Discovery: The greatest advances in medicine havebeen the result of scientific inquiry and discovery (seeexamples above). Discovery occurs daily at a rapid pace;translation to patient care via invention, innovation, andentrepreneurship is both highly desirable (NIH Road-map) and highly fickle. It is poorly understood andseldom taught.

Invention: An invention is an object, process, or tech-nique that has an element of novelty. An invention isusually based on a previous development or idea. Theprocess of invention requires an awareness that existingconcepts or methods could be modified or transformedinto an invention (Fogarty’s balloon catheter, Starr Ed-wards first heart valve). Some inventions represent a rad-ical breakthrough in science or technology that extendthe boundaries of human knowledge (LASERS). Anoriginal idea may never be fully realized as a working in-vention of the idea when it

a) Violates the laws of physics (perpetual motion

machines);

b) Solves problems for which there is either no

economic incentive or no utility; or

c) Lacks a contemporaneous engineering or technol-

ogy capability (da Vinci’s conceptual helicopter).

Innovation: Although an invention is merelytheoretical, an innovation is an invention put into practice.Simply put, an invention is an idea, and an innovation is apractical application. Harold Evans and colleagues, inthe book They Made America16 (required reading forwould-be surgeon-innovators) comment ‘‘A scientist seeks

understanding, an inventor a solution, and an innovatorseeks a universal application by whatever means.’’ Evansconcretely clarifies: ‘‘Thomas Edison is thought of asAmerica’s foremost inventor with 1,093 patents in hisname, but his most important work was translating theinsights of invention into the practical reality ofinnovation through the long process of developmentand commercialization.’’ In most cases, the process of in-novation is usually more important than the idea of aninvention.

What about surgeons? As Gertner explains (in Ref. 17)‘‘Many surgeons have ideas, often great ideas related toimprovements in patient care; unfortunately many ofthese potentially great ideas are never translated to im-provements in patient care because of a lack of under-standing of the �next step.�’’17

Entrepreneur: A loaned word, entrepreneur was firstborrowed from the French by an obscure economist, Ri-chard Cantillon (1680-1734), an Irishman with a Spanishname who lived in France (shades of the global economyto come). Literally translated, an entrepreneur is ‘‘anagent who buys factors of production at certain pricesin order to combine them with a view to selling at uncer-tain prices in the future.’’18 More specifically, an entre-preneur is a person who undertakes and operatesa new enterprise or venture and assumes considerableresponsibility for its success. The entrepreneur seeks in-dependence, autonomy, and control to maximize thelikelihood of success in a risky (defined) and uncertain(ill-defined) venture (author’s note: note the similaritiesto surgeon’s traits).

Although there is no secret sauce, there are com-monalities of path finding to success. For an in-depthanalysis and synthesis of the process of innovation, thereader is directed to the following comprehensivebooks:

1. Innovation and Entrepreneurship by Peter Drucker19;

2. The Art of Innovation by Tom Kelley20;

3. The Ten Faces of Innovation by Tom Kelley21;

4. The Myths of Innovation by Scott Berkum.22

PEOPLE, ENVIRONMENT, AND LEADERSHIP

To create value for patients and the consequent pos-sibility of revenue streams to a department for theirinnovation, all 4 of these processes, discovery, inven-tion, innovation, and entrepreneurship, are necessary insome combination. Creative, successful innovation almostalways requires both inquisitive people (note plural) anda permissive, if not celebratory, environment/organiza-tion. Imagine Steve Jobs, the co-founder of Apple Com-puters and arguably one of the most creative andingenious talents of our age in your department ofsurgery. Would he be tolerated? Encouraged? Embraced?. Bludgeoned? Today, most organizations, universities,and regions aspire to an instant culture of creativity andinnovation. The current successful culture in SiliconValley really had its roots in Fred Terman’s tenure as a

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faculty member, chair, dean, and provost at Stanfordalmost 60 years ago.23

At the beginning and at the end of the quest forinnovation is the recruitment, inspiration, and retentionof creative people. Although this sounds axiomatic, de-partment chairs and leaders should consider the chal-lenges and the consequences. One of Henry T. Bahnson’sgreatest leadership contributions at the University ofPittsburgh (of many) was the housing, care, and encour-agement of two creative surgeons, Drs Mark Ravitch andThomas Starzl. Based on personal observations (TMK), DrBahnson gracefully ‘‘took the heat’’ to permit and facili-tate the accomplishments of these two ‘‘prickly’’ geniussurgeons. Are you and your department ready for thediscomfort of such creators?

Despite our professed love of creativity, we typicallycling to our treasured expertise in the present. As DrJudah Folkman is fond of saying, ‘‘There are no experts inthe future, only experts in the present’’ (personal com-munication, 1982). Famously recounted, and always witha twinkle in his eye, Dr Norman E. Shumway was ‘‘tempo-rarily’’ appointed as Chief of Cardiothoracic Surgery atStanford University until the then chair, Garrett Allen,could recruit a ‘‘big name’’ heart surgeon. This was wellbefore the profound consequences of cardiac transplan-tation were fully appreciated. Paul Lauterbur, Nobellaureate for co-inventing magnetic resonance imagingobserves that ‘‘You can write the entire history of sciencein the last 50 years in terms of papers rejected by Science orNature.’’24

This isn’t to deny the value of rational discourse anddisagreement, but the presence of the ubiquitous‘‘devil’s advocate’’ with no intentional counterbalancecrushes the next surgical Steve Jobs. If one considers thetrack record of the elite of the technology transferworld,2 clear commonalities exist—curious and inquisi-tive students and faculty and an environment that en-courages risk taking and occasionally wild ideas.

The myth of the lone inventor (or surgeon) battlingsolo against all odds in her garage is convenient,seductive, pervasive, and almost always wrong. GuyKawasaki debunks the concept arguing that two ormore innovators, often with balancing and complemen-tary skills, are far more effective.25 ‘‘Successful compa-nies are started and made successful by at least two,and usually more, founders. After the fact, one personmay come to be recognized as �the innovator,� but it al-ways takes a team of good people to make any venturework.’’ Consider such innovative duos as Watson andCrick, Hewlett and Packard, Jobs and Wozniak, Gatesand Allen, and Page and Brin.

The myth of the epiphany. When an amazinginnovation appears, it is easy to believe in a magicalmoment of insight. Unlike Archimedes, fresh from thebath running through the streets of Athens shouting eu-reka, seldom is there a single moment of epiphany. Ber-kum22 explains: ‘‘The best way to think about epiphanyis to imagine working on a jigsaw puzzle. When youput the last piece into place is there anything specialabout that last piece or what you were wearing when

you put it in? The only reason the last piece is significantis because of the other pieces you’ve already put intoplace. If you jumbled up the pieces a second time anyone of them could turn out to be the last magical piece.Epiphany works much the same way: . it’s the work be-fore and after.’’

Gordon Gould, a primary inventor of the laser, hadthis to say about his own epiphany: ‘‘In the middle ofone Saturday night . the whole thing . suddenlypopped into my head . but that flash of insightrequired 20 years of work I’d done in physics and opticsto put all the bricks of that invention in there.’’22

It’s fair to say that no grand invention anywhere inhistory has escaped long tedious hours required to takean insight and create it into something of utility for theworld. It’s the hard work, however unglamorous thatmay be, that matters. Epiphany is largely irrelevant, abyproduct of the former.

SO YOU HAVE A GREAT IDEA, NOW WHAT?

The following is a summary of an extensive review ofthe process presented in the monograph ‘‘Advanced andEmerging Technologies in Pediatric Surgery and theProcess of Innovation’’17 as well as in a forthcoming chap-ter ‘‘From Idea to Bedside: The Process of Surgical Inven-tion and Innovation’’ in the textbook Key Topics in SurgicalResearch.26

Many physicians have great ideas; few of these areever translated to improvements in patient care becauseof a failure to understand ‘‘the next step.’’ In almostevery case, the next step is actually a step backwards tounderstand the real clinical problem, ‘‘the clinicalneed.’’ Once the clinical need is really understood,that is, the genetic code of the solution, an effectivepath forward can then be derived. This pathway involvesan appreciation of many issues, including intellectualproperty ownership, regulatory pathways, finance, andclinical trial strategies. The understanding and applica-tion of these issues underlie successful innovation inbiomedical technology transfer.

The clinical need. ‘‘If I had asked my customers whatthey wanted, they’d have said a faster horse,’’ said HenryFord.20 A need to prevent charring of the electrocautery whilecauterizing tissue is an example of the statement of a clini-cal need from the 2005 to 2006 surgical innovation fellow-ship at Stanford. It is the simple statement of a clinicalproblem and it is nonspecific with regard to a solution.It, thus, is a starting point, a reason to innovate. The nat-ural surgical tendency is to jump to a solution before fullyunderstanding the problem (we need to use Teflon to preventcharring of the electrocautery tip). This might be one solution,but is not necessarily the best solution.

A well-characterized need or problem statement ispowerful because it delineates the characteristics of theproblem so that many solutions may be entertained(Fig 1). As this figure indicates, the needs characteriza-tion process is nonlinear and iterative. It extends froma deep understanding of the real clinical need and re-quires interpretation, not just of what surgeons or

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patients say, but often what they don’t say or what theydo in unguarded moments. This iterative process con-tinues through prototyping, with early crude mockupsconstructed to serve as ‘‘feels like’’ versions of the device.There’s a very pragmatic and yet artful exploration thatcharacterizes success in this process and produces

Fig 1. A proposed schematic of the initial innovationprocess for a medical device.

products and devices that improve patient care and, inthe end, have the indirect consequence of producingrevenue streams to the inventor, the department, andthe university.

Idea generation. ‘‘The best way to get a good idea isto get a lot of ideas,’’ said Linus Pauling. What isimportant is to generate a maximum number of needsin an uninhibited process. A day in the hospital inevita-bly reveals a large number of needs (snorkeling) andvalidates the message that needs are relatively easy tofind and all can look appealing. It’s only by a rigorousand disciplined process (the deep dive) that the realimportance of a need can be assessed. Only then is itworth investing the intellectual capital and other re-sources needed to pursue a solution. By the end of thedeep dive phase, the innovators should have becomeexperts on the problem with a detailed specification ofthe need, including anatomy, pathophysiology, epidemi-ology, market dynamics, competitors and their currentsolutions, and customer requirements---‘‘must haves’’and ‘‘desirables.’’ This culminates in a needs statementthat is a single sentence that focuses on the goal or theendpoint, not the problem and not the medical tradeunion that might deliver the solution. This can bethought of as ‘‘the genetic code of the solution.’’ Atthis point, it is not possible to understand the optimalsolution. The process is then driven forward by brain-storming sessions. Such 60- to 90-minute focused ses-sions involving people from different disciplines shouldproduce a wide range of possible solutions. This conceptoriginates with Alex Osborn,27 whose observations aboutcreativity led to four brainstorming rules:

1. Produce as many ideas as possible;

2. Produce ideas as wild as possible;

3. Build on each others’ ideas;

4. Avoid passing judgment.

Ideally, several brainstorming sessions build on oneanother and can involve technical experts, productdevelopment specialists, clinical experts, or experiencedentrepreneurs.

Now begins the winnowing process to rank solutions.Ranking hierarchy depends on such factors as feasibility,novelty, the regulatory process, development costs, andthe burden of proof as to efficacy. Some experiencedinnovators follow their instincts; others follow rigorousscoring schemes and others still a simple 4-square risk/reward grid.

THE ROLE OF INTELLECTUAL PROPERTYPROTECTION

This represents another path-finding skill. The bestapproach is pragmatic, and tempered by reality. Com-plete secrecy usually creates an uninformed solution. Anaı̈ve, nonsecretive approach may lead to idea theft.

Patent law defines an inventor of a patentable inven-tion as someone who conceives of an original, useful,and nonobvious idea. An inventor must have conceived

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(a mental act) an essential element of the invention. Aperson who actually made a physical embodiment of theinvention, however, may not be an inventor, no matterhow difficult the reduction to practice was. A person whocontributed only labor, but did not contribute to theconcept of one of the embodiments of the claimedinvention, similarly is not considered an inventor. Ques-tions of inventorship can arise when faculty and studentswork on a project. Often an invention is co-invented by afaculty and a student because they are collaborating andconceive of an invention together. Other times, thefaculty alone or sometimes the student may be deemedthe inventor based on these concepts. Inventorship maybe determined by a patent attorney who asks all partiesto describe their personal contributions to the claimedinvention. If a legal dispute arises, inventorship is deter-mined by careful documentation of notebook pages orother tangible proof of inventorship.

Specifically, a patent gives one the right to ‘‘excludeothers from making, using or selling the claimed inven-tion.’’ Such an exclusion is not enforceable until thepatent has been granted, a process that may take 3 to 5years at a cost of some $30,000. In some countriesoutside the United States, the process is even morearduous. One myth is that a patent is only as valuable asone’s willingness to defend it---legal actions and costspotentially incurred are beyond the scope of mostindividual inventors. The reality is that most patentsare never litigated. Patents are valuable as threats oflitigation. The larger the threat or the larger the entitybeing threatened, the greater the value of the patent.

Generally, there are 2 phases in the patent process:the idea phase and the ‘‘reduction to practice’’ phase.The reduction to practice phase is where the innovation oc-curs that enables a potential device to function. An intel-lectual property estate could be as many as 50 patentsbefore it completely protects a single commercializedproduct.

Most inventors begin to obtain intellectual propertyprotection via a ‘‘provisional patent,’’ which involves a$100 filing with the patent office (www.uspto.gov) thatany inventor can file. Something as simple as a napkindrawing can be submitted or a full patent can be submit-ted. This provisional filing can enable one to documentthe invention date, and to establish a priority date. Aprovisional patent essentially produces a 12-monthplaceholder across the world before a nonprovisional,or utility patent, needs to be filed. If this follow-on utilitypatent is not filed, then the provisional patent goesabandoned and the invention date is lost. Thus, the12-month window is a critical value-building period dur-ing which the $100 affords enough protection to talkwith others who can help to determine the value ofthe idea and the process of innovation. During thistime, involved parties can be legally bound to nondisclo-sure agreements and subject to trade secret laws. For themost part, protection during this phase is another myth.Often an inventor is given a false sense of security by pro-visional patents. The reality is that unless the provisionalpatent has all the elements of the invention, the date of

the actual inventive claims is the filing date of the actualfiled patent. For example, Joe Inventor files a provisionalpatent on day 1, a napkin picture and a title. He goes toBigCo in the hopes BigCo will pay for some research tofurther the idea. BigCo files a detailed patent the nextday on new ideas. Joe Inventor never hears from BigCoagain until he notices that his invention is now a pub-lished patent application and 5 days later BigCo’s identi-cal patent application publishes. Joe Inventor’s claims donot stand relative to BigCo’s claims because Joe Inventorhad not disclosed the breadth of the invention in hisown patent.

The team. There has never been a substitute formultidisciplinary teams, which become even more im-portant as technology has become more advanced.Frequently a series of teams evolve; the commercializa-tion team is not necessarily the same as the brainstorm-ing team. Although teams have been and will continueto be emphasized, the role of a single ‘‘champion’’cannot be denied. Many times this person is the physi-cian-inventor. Beyond the champion, many others areneeded as described in The Ten Faces of Innovation.21 Be-cause of these broad requirements and extended time-line, the process of innovation is frequently moreimportant than the idea/invention itself.

Prototyping. A prototype is a physical demonstra-tion of a device or product; words or even drawings arenot enough to describe the device to others. A device,however simple, that one can hold and play with in onehand is extraordinarily powerful. Most prototypes can bemocked up from remnants; Dr. Thomas Fogarty says thathe never throws out anything in his laboratory. Once apreliminary notion is established, larger and then sub-sequently real-sized devices can be developed.28

The iterative process continues with a frequent play-back to reassess the problem and proposed solutions.Prototyping and animal testing can take 6 to 12 months;if successful, there may be 1 or 2 solutions that are readyfor human testing and commercial strategy.

Commercialization. A simplistic overview of thecommercialization of a medical device innovation isdepicted in Fig 2, which sequentially follows Fig 1. Plan-ning for commercialization begins towards the end ofthe animal studies outlined in Fig 1. The Food andDrug Administration (FDA) process and quality controlare essential to ensure the safe translation of an inven-tion to an improvement in patient care. In the simplestiteration, a class I Surgical Device such as forceps, com-pliance with regulations about sterility and other compo-nents is all that is needed. A 510(K) device (a device thatis substantially equivalent to a predicate device) requiresincrementally more compliance outlined by regulatoryagencies. A Premarket Approved (PMA) device (a devicewithout a predicate or one associated with a significantrisk; eg, a new pacemaker defibrillator) requires an in-crementally greater number of controls. The complexprocess of FDA consideration was recently reviewed byConnor.29 The simplest, but not always the most effec-tive, path is to license the development to an existing

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commercial entity. If that route is chosen, the inventorcedes control of further development to an outside com-pany, which licenses the technology and pays a royalty tothe university. Each university has a specific policy for re-turning royalties to the inventor(s), cognizant depart-ment, and school, and the parent university. Alwaysconsult your OTL to best understand the rules ofengagement.

Financing. The process of moving an invention toan innovation at the patient’s bedside requires consid-erable investment. The harsh reality is that, if a goodinvention is not a good business, such investments areunlikely. Without a source of capital investments of allsorts, including intellectual, risk, and financial,27 nodiscovery or invention will ever be translated into aninnovation to improve patient care. Over the years,grants have been considered the only viable supportfor discoveries, and corporations the only path for in-novation. More options exist. Government-sponsoredresearch has had profound impact [Defense AdvancedResearch Projects (DARPA) funded the DARPA-Net,which later became the Internet]. Other governmentgrants such as Small Business Innovative Researchand Small Business Technology Transfer grants fundproof-of-concept projects that seed proof of conceptbeyond the discovery, but may involve more researchand risk than can be tolerated by even the earliest-stageinvestor.

If an inventor/innovator eschews licensing to anexisting company, the startup route is available. Ifchosen, this path requires the arduous task of raisingcapital. In early stages, so-called angel investors are anoption. Such investors are typically affluent and experi-enced entrepreneurs who provide capital for a businessstartup, usually in exchange either for convertible debtor for ownership equity. They may function as individ-uals or band into groups. Angels typically invest theirown funds as opposed to venture capitalists, who managethe pooled money of others in a professionally managedfund. Such angel investors may bridge the gap in startupfinancing between friends and family who provide seedfunding and subsequent venture funding. Thus, al-though it may be difficult to raise more than a few

Fig 2. A simplistic overview of the commercializationprocess for a medical device.

hundred thousand dollars from friends and family andmost traditional venture funds do not consider invest-ments of less than $2 million, angel investment is acommon intermediate or second round of financing.

Another source of funding is the venture world,ranging from small boutique funds to large funds thatonly pursue billion-dollar projects involving long timelines and large clinical trials. Venture investment re-quires some ownership to change hands and therefore abusiness entity. The right venture firm, however, can bean incredibly potent partner to facilitate the develop-ment and commercialization of discoveries.

Training the next generation of surgeon-innova-tors. Given both the imperative for innovation and itscomplexity, it seems reasonable to consider training inthe process and the path finding of successful discovery,invention, innovation, and entrepreneurship. Beginning7 years ago, Stanford began a systematic training pro-gram in medical device innovation (http://innovation.stanford.edu). The Stanford Biodesign Innovation Pro-gram for the first time addressed medical device innova-tion as a discipline, specifically teaching the process in away not previously achieved in existing graduate andpostgraduate programs. This type of translational educa-tion provides an early career opportunity for an amal-gam of surgeons, engineers, and entrepreneurs todevelop the talents that translate basic discoveries intoimportant new treatments. As currently constructed,the Biodesign Innovation Program applies a specificand proven methodology for teaching the knowledgeand skills for biomedical technology innovation, andtranslation. It includes the following:

d A 2-month boot camp to teach surgical science to

engineers and engineering science to surgeons, and

to inculcate both in the process and language of

innovation;d An introduction to the techniques of clinical needs

finding and characterization;d Surgical specialty immersion;d Needs analysis, validation, and specification;

d A systematic approach to inventive solutions

(brainstorming);

d Early prototyping;d Methodic process for planning regulatory and reim-

bursement pathways;d Preclinical testing; andd Clinical testing.

After the first year of core knowledge acquisition,surgical trainees move forward in their second year tocharacterize and test their most promising inventions,beginning the process of technology translation andinitiating a set of studies that carries them into the nextphase of their career. This project-based methodology ismodeled on other project-based educational programsand mimics the project-based educational programs inour doctoral and postdoctoral research laboratories. Themost important output is not a product or a technology,

SurgeryFebruary 2008

190 Krummel et al

but in the education of the next generation of surgeon-innovators.

Surgical residencies teach not only technique andprocedures, but more critically judgment and a way ofthinking. So, too, this 2-year innovation fellowshipteaches a new set of skills to an amalgamated group ofsurgeons, engineers, and entrepreneurs. They learn thelanguage, culture, and values of each other’s disciplinesin a real-world experience with the ultimate goal of alifelong capacity to continually improve the lives ofpatients with unsolved problems.

Ethics of innovation. Although not the specificcharge of this review, any discussion of surgical innova-tion should include serious consideration of the ethicsof innovative surgical care or device testing and utiliza-tion. There is a long conceptual history in the ethicalapplication of new and unproven treatments in patients.A short review by Riskin was recently published in Semi-nars in Pediatric Surgery (Figure 3).17 There are particularnuances and peculiarities to innovative surgical care.The principles outlined by Dr Francis D. Moore,30,31 al-though enunciated some 30 years ago, remain valid tothis day (Figure 4).

Conflict of interest. Even a casual reader will find ahost of investigative journalism reports that clearly dem-onstrate ‘‘how not to do it.’’ The Wall Street Journal, NewYork Times, and others have featured a litany of transgres-sions by physician and surgeon colleagues. Without bela-boring the point, full disclosure both to patients and toone’s institutional colleagues (institutional review board,conflict of interest committee) represents a good start.When in doubt, always disclose and seek the advice of

Fig 3. Milestones in thought about medical ethics in pa-tient care & research.

dispassionate colleagues. Recently, a number of topresearch universities and the Association of AmericanMedical Colleges issued a set of shared guidelines in-tended to protect the public interest when universitiesgrant licenses for the rights to their latest scientific ad-vances to private parties. The report entitled, ‘‘In the Pub-lic Interest: Nine Points to Consider in LicensingUniversity Technology’’ simultaneously aims to encour-age tech transfer agreements to facilitate broad develop-ment and dissemination and, at the same time, tocontinue to work with intellectual property which hasbeen licensed to commercial concerns.32

As with all things, it is certainly possible for thependulum to swing too far. Conflicts of interest areinevitable; the pathologic avoidance of them may take usback to the ethical climate of Hippocrates; namely, firstdo no harm. Doing nothing completely protects butaccomplishes nothing. Stossel’s opinion in a paperentitled ‘‘An Obsession with Financial Conflict of Inter-est is an Impediment to Medical Progress’’ is well worthdiscussion and study.33

CONCLUSION

This short review attempts to make some sense of thelegitimately linked academic activities of discovery, inven-tion, innovation, and entrepreneurship. A framework forunderstanding the process and educating a next genera-tion of surgeon-innovators is outlined; careful attention toboth the ethics of innovative treatment and full disclosureof potential conflicts is essential if this process is tocontinue to bring benefits to our surgical patients.

REFERENCES

1. More universities increasing support for campus start-ups.Wall Street Journal. November 27, 2006. Available from:URL: http://stevens.usc.edu/read_release.php?press_id=12.

2. Stevens Institute, University of Southern California [home-page on the Internet]. 2007. Available from: URL: http://stevens.usc.edu/index.php.

3. Five universities you can do business with. Inc. Magazine.February 2006. Available from: URL: http://www.inc.com/magazine/200060201/views_opinion.html.

Fig 4. Ethics of innovative surgical care.

PATENTS AND RESEARCH: FRIENDSOR FOES?

David H. Sachs, MD, Boston, Mass

From the Department of Surgery, Massachusetts General Hospital,Boston, Mass

HAVING SPENT THE PAST 17 YEARS building and directing aresearch center devoted to transplantation in the De-partment of Surgery at Massachusetts General Hospital(MGH), I am pleased to provide my perspective on theinteraction between industry and academic research.This article represents my personal views, which are builtlargely on my experience trying to manage this interac-tion to the advantage of our research goals without com-promising our independence or our academic freedom.

There is no question that a relationship with industrycan be advantageous to a research endeavor. Once it isclear that collaboration will be of mutual benefit to thelaboratory and to the industrial partner, the availabilityof funding without a lengthy review process providesflexibility in hiring and purchase of equipment andsupplies that can make the difference between the timelyinitiation of a successful project and failure to ever get itstarted. In my case, I had spent 21 years at the National

Accepted for publication November 5, 2007.

Reprint requests: David H. Sachs, MD, Professor of Surgery (Im-munology), Harvard Medical School, Director, TransplantationBiology Research Center, Massachusetts General Hospital, MGHEast, Building 149-9019, 13th Street, Boston, MA 02129.

Surgery 2008;143:191-3.

0039-6060/$ - see front matter

� 2008 Mosby, Inc. All rights reserved.

doi:10.1016/j.surg.2007.11.001

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Sachs 191

4. University of California Technology Transfer [homepage onthe Internet]. 2007, August. Available from: URL: www.ucop.edu.

5. Bush V. Science—The endless frontier. A report to thepresident. Washington, DC: Office of Scientific Researchand Development; 1945.

6. Bremer HW. The first two decades of the Bayh–Dole act as pub-lic policy. Speech given at: the National Association of StateUniversities and Land Grant Colleges; November 11, 2001;New York, NY.

7. Henderson JA, Smith JJ. Academic, industry, and the Bayh–Dole act: An implied duty to commercialize. Boston: Centerfor Integration of Medicine and Innovative Technology;2002.

8. Bayh-Dole act [monograph on the Internet]. 2007, August.Available from: URL: www.wikipedia.org/wiki/Bayh-Dole_Act.

9. Bremmer HW. Innovation’s golden goose. The Economist.December 12, 2002.

10. The Bayh–Dole act: A guide to the law and implementingregulations. Washington, DC: Council on Governmental Re-lations; 1999.

11. Schacht W. The Bayh–Dole act: Selected issues in patentpolicy and the commercialization of technology. StormingMedia, Pentagon Reports: Past, Definitive Complete. 2005.Available from: http://www.stormingmedia.us/41/4165/A416534.html.

12. Thursdy J, Thursby M. University licensing under Bayh–Dole: What are the issues and evidence? Science 2003;301:1052.

13. Stanford Technology brainstorm [newsletter]. 2006;12(2).14. Malone MS. Bill & Dave: How Hewlett and Packard built the

world’s greatest company. Portfolio 2007.15. Stanford University Office of Technology Licensing [home-

page on the Internet]. 2007, August. Available from: URL:http://otl.stanford.edu.

16. Evans H, Buckland G, Lefer D. They made America: Fromthe steam engine to the search engine: Two centuries ofinnovators. Boston: Back Bay Books; 2006.

17. Krummel TM, guest editor; Grosfeld JL, editor. Advancedand emerging technologies in pediatric surgery and theprocess of innovation. Semin Pediatr Surg 2006;15(4).

18. Entrepreneur [monograph on the Internet]. 2007, August.Available from: URL: http://en.wikipedia.org/wiki/Entrepreneur.

19. Drucker P. Innovation and entrepreneurship. New York:Collins; 1993.

20. Kelley T. The art of innovation. New York: Doubleday; 2001.21. Kelley T. The ten faces of innovation. New York: Doubleday;

2005.22. Berkum S. The myths of innovation. Sebastopol, CA:

O’Reilly Media; 2007.23. Gillmor CS. Fred Terman at Stanford, building a discipline,

a university, and Silicon Valley. Stanford, CA: StanfordUniversity Press; 2004.

24. Davis K. Public libraries open their doors. BIO-IT World[serial online]. 2007, February. Available from: URL: www.bio-itworld.com/archive/111403/plos/.

25. Kawasaki G. The art of the start: The time-tested, battle-hard-ened guide for anyone starting anything. Portfolio 2004.

26. Wall J, Longaker M, Gurtner G. From idea to bedside: Theprocess of surgical invention and innovation. In: Darzl A,Debas H, Athanasiou T, editors. Key topics in surgicalresearch. In press.

27. Osborn A. Applied imagination. Boston: Charles Scribner’sSons; 1957.

28. Stanford University Product Realization Lab [homepage onthe Internet]. 2007, August/ Available from: URL: www.stanford.edu/group/prl/aboutus.

29. Connor J: Making sense of the FDA as found in Krummel,TM, guest ed: Advanced and emerging technologies in pe-diatric surgery and the process of innovation, Sem PediatrSurg, JL Grosfeld, editor, W.B. Saunders Co., Philadelphia,PA, Vol 15(4), November 2006, pp 293-301.

30. Moore FD. Three ethical revolutions: Ancient assumptionsremodeled under pressure of transplantation. TransplantProc 1988;20:S1061-2.

31. Moore FD. The desperate case: CARE (costs, applicability,research, ethics). JAMA 1989;261:1483-4.

32. Guidelines offered for responsible technology licensing. Inthe public interest: Nine points to consider in licensinguniversity technology. Report from a meeting of researchofficers, licensing directors, and a representative from theAssociation of American Medical Colleges; Seattle, WA;Summer 2006.

33. Stossel TP. Regulation of financial conflict of interest inmedical practice and medical research: a damaging solutionin search of a problem. Perspect Biol Med 2007;50:54-71.