Technology & Innovation: Volume 18, Number 4

INVENTION IS NOT AN OPTION Table 1: Design Characteristics and Proposed Design Solutions Used during Development 271 of PolySTAT Table 1. Design Characteristics and Proposed Design Solutions Used During Development of PolySTAT Desired Characteristic Design Solution Specific clot Peptide that binds fibrin but not fibrinogen recognition Multivalent display of fibrin-binding peptide on Crosslinks clots polymer backbone Bioactivity Access internal injury Injectable, water-soluble polymer sites Clears out of the body a few hours after Molecular weight ~40-60 kDa injection Affordable and Synthesis by controlled living polymerization reproducible large- techniques Production scale production Does not require cold Completely synthetic material; avoid protein storage components survived the time course of the study. Furthermore, VIPER: A Non-Viral Nucleic Acid Delivery Vector PolySTAT-treated rats had significantly less blood loss Suzie and her team also work on VIPER, a non- compared to all other control groups (6). These results viral nucleic acid delivery vector. Nucleic acids are suggest that PolySTAT is able recognize injury sites a relatively new class of drugs and include oligonu- after intravenous injection and help to stop bleeding cleotides (such as Vitravene, an anti-viral drug that and increase survival rate in this animal model of is FDA-approved for treatment of cytomegalovirus trauma. retinitis), small-interfering RNA, messenger RNA, In addition to use as an injectable hemostat, and gene therapies (such as Glybera, the first gene PolySTAT could be used in wound dressings to medicine approved for use in Europe and used to improve the activity of hemostatic gauze. Therefore, treat lipoprotein lipase deficiency). A major challenge Suzie’s team also partnered with Dr. Tae Hee Kim’s in clinical translation of gene therapies is efficient group at the Korean Institute of Industrial Technology and safe delivery, a process called “transfection.” The to integrate PolySTAT into chitosan gauze. Com- delivery technologies for nucleic acid drugs can be pared to commercially available chitosan gauze, their categorized into two main technology groups: viral PolySTAT-imbued gauze showed improved efficacy in vectors and non-viral vectors. Viral vectors are engi- the rat femoral artery injury model; animals treated neered viruses altered to minimize pathogenicity with the PolySTAT/chitosan gauze lost less blood and and insert instead therapeutic genes. Viral vectors required less fluid resuscitation compared to animals tend to be highly efficient at gene transfer but have treated with the commercially available gauze (8). challenges related to safety and high cost of large

272 COMEDY ET AL. scale manufacture (9). In contrast, non-viral vectors, membrane to facilitate release of the virus from such as lipids and polymers, offer advantages in safety the endosome. They therefore designed a polymer, and production cost but are typically much lower called VIPER (Virus-Inspired Polymer for Endosomal in delivery efficiency, especially in complex living Release), that similarly masks a membrane-active pep- organisms (10). tide. Upon sensing the endosomal environment, the One of the critical steps in achieving efficient polymer complex rearranges to expose the peptide, non-viral gene transfer is endosomal escape. Both resulting in endosomal membrane destabilization viral and non-viral vectors are taken up into the mam- and cargo release from the vesicle (11). malian cell via lipid-membrane encapsulated vesicles VIPER, also synthesized by RAFT polymerization, called endosomes. These endosomes ferry cargo to the contains two segments (Figure 3A). The first block, lysosomes, often described as the ‘garbage disposal shown in green, is hydrophilic, or water-loving, and and recycling centers’ of cells. Thus, without efficient also positively charged for binding nucleic acid cargo. escape from the endosomes, the nucleic acid drugs The second block, shown in pink, is hydrophobic, or carried by these vectors are neutralized and degraded water-hating, at physiological pH (pH 7.4) but that within the lysosomes. However, endosomal escape becomes hydrophilic at acidic pH (e.g., pH < 6.0). requires selective disruption of the endosome mem- The second block is grafted with a bee venom peptide brane without affecting the cell membrane, which has called melittin (shown as the yellow and black-striped a similar composition; disruption of the cell mem- triangle). Melittin disrupts lipid membranes and has brane would result in toxicity to the cell. been shown to improve gene delivery when con- In order to develop a synthetic delivery vector jugated to polymer carriers, but at the cost of cell with efficient and selective endosomal membrane dis- survival (12-14). ruption ability, Suzie’s team designed a material that The hydrophobic sections of VIPER therefore drive mimics the endosomal escape strategy employed by self-assembly of the polymer at pH 7.4 into nanopar- adenovirus. Adenovirus contains a membrane-active ticles that hide both the hydrophobic polymer blocks protein called protein VI that is hidden by the virus and the membrane-disruptive melittin peptides. After protein shell until the virus is taken into the host cell. entry into the cell, the VIPER nanoparticles contain- There, the virus protein shell rearranges and exposes ing gene therapies are exposed to the acidic endosomal protein VI, which then interacts with the endosomal environment. In response to the environmental Figure 3. (A) Schematic of VIPER and chemical structure of VIPER. (B) Mechanism of VIPER assem- bly, cellular uptake and endosomal escape. See text for detailed explanation. Figure reproduced with permission from Wiley (11. Cheng Y, Yumul RC, Pun SH. Virus‐inspired polymer for efficient in vitro and in vivo gene delivery. Angew Chem. 128(39):12192- 12196; 2016.), copyright 2016.

INVENTION IS NOT AN OPTION 273 change that occurs after cell uptake, VIPER switches ACKNOWLEDGMENTS characteristics, resulting in a conformational Suzie Pun’s work was funded by the National Insti- change that exposes the melittin peptide and dis- tutes of Health (2R01NS064404, 1R01CA177272, rupts endosomes to release VIPER and cargo to the 1R21EB018637), the National Science Foundation cell cytoplasm (Figure 3B). They have shown that (DMR 1206426) and the Washington Research Foun- gene-loaded VIPER complexes are selectively mem- dation. Funding for Dr. Gilbert’s work came from the brane-disruptive in acidic environments and that National Science Foundation, voting system manufac- these VIPER complexes are able to efficiently escape turers, and the U.S. Election Assistance Commission. endosomes after cell entry in contrast to control poly- mers that lack the melittin peptide (11). REFERENCES VIPER is their most potent gene transfer mate- 1. Hirshon B. Voting Machines. Science Updates. rial to date, outperforming commercially available AAAS-Lemelson Invention Ambassadors. 2015 reagents in gene transfer to cultured cells. They have Jul 31, 1:00 minutes. [accessed 2016 Oct 15]. demonstrated that the transfection efficiency in cul- http://www. inventionamb.org/category/sci- tured cells ranges from ~20% for difficult-to-transfect ence-updates/ stem cells to over 90% for certain rapidly-dividing 2. Rivest RL. On the notion of ‘software indepen- cancer cell lines. Importantly, the team demonstrated dence’ in voting systems. Phil Trans R Soc A. successful gene transfer to both tumors and to the 366:3759-3767; 2008. brain in animal models. They are moving forward 3. Murray CJL, Lopez AD. Mortality by cause for now to use VIPER for therapeutic gene transfer in a eight regions of the world: global burden of dis- variety of disease applications, both in their labora- ease study. Lancet. 349(9061):1269-1276; 1997. tory and in collaboration with other academic groups 4. Rogers FB, Osler TM, Shackford SR, Martin F, and industry. Healey M, Pilcher D. Population-based study of hospital trauma Care in a rural state without CONCLUSION a formal trauma system. J Trauma Injury Infect While the inventions of Suzie Pun and Juan Gilbert Crit Care. 50(3):409-413); 2001. are worlds apart, there are some important truths in 5. Myburgh JA, Mythen MG. Resuscitation fluids. the world of inventors. First, inventors can and do N Engl J Med. 369(13):1243-1251; 2013. come from a variety of backgrounds—different fields, 6. Chan LW, Wang X, Wei H, Pozzo LD, White NJ, geographic locations, ages, genders, ethnicities, and Pun SH. A synthetic fibrin cross-linking poly- racial groups. Second, it appears that the first thought mer for modulating clot properties and inducing of would-be inventors is not, “How do I become an hemostasis. Sci Transl Med. 7(277): 277ra29- inventor?” Instead, it is, “How do I solve this prob- 77ra29; 2015. lem?” Third, teamwork is an important part of the 7. Branas CC, MacKenzie EJ, Williams JC, Schwab solution. Teaming with students, fellow researchers, CW, Teter HM, Flanigan MC, Blatt AJ, ReVelle problem-solvers, and people with different types CS. JAMA. 293(21):2626-2633; 2005. of expertise seems to be a prerequisite for success. 8. Chan LW, Kim CH, Wang X, Pun SH, White NJ, Fourth, there is a “can do” attitude that turns failures Kim TH. Polystat-modified chitosan gauzes for into successes and challenges into opportunities and improved hemostasis in external hemorrhage. possibilities. Lastly, there is passion and dedication Acta Biomater. 31:178-185; 2016. to making people’s lives better. 9. Thomas CE, Ehrhardt A, Kay MA. Progress and Seek out inventors in your communities and at problems with the use of viral vectors for gene therapy. Nat Rev Genet. 4(5):346-358; 2003. your institutions—they can show you how they are 10. Pack DW, Hoffman AS, Pun SH, Stayton PS. trying to change the world and how much they believe Design and development of polymers for gene that invention is not an option. delivery. Nat Rev Drug Discov. 4(7):581-593; 2005.

274 COMEDY ET AL. 11. Cheng Y, Yumul RC, Pun SH. Virus‐inspired polymer for efficient in vitro and in vivo gene delivery. Angew Chem. 128(39):12192-12196; 2016. 12. Ogris M, Carlisle RC, Bettinger T, Seymour LW. Melittin enables efficient vesicular escape and enhanced nuclear access of nonviral gene deliv- ery vectors. J Bio Chem. 276(50):47550-47555; 2001. 13. Meyer M, Philipp A, Oskuee R, Schmidt C, Wagner E. Breathing life into polycations: func- tionalization with ph-responsive endosomolytic peptides and polyethylene glycol enables siRNA delivery. J Am Chem Soc. 130(11):3272; 2008. 14. Rozema DB, Ekena K, Lewis DL, Loomis AG, Wolff JA. Endosomolysis by masking of a membrane-active agent (EMMA) for cytoplas- mic release of macromolecules. Bioconj Chem. 14(1):51-57; 2003 [accessed 2016 Oct 15]. http:// dx.doi.org/10.1021/bc0255945.

Technology and Innovation, Vol. 18, pp. 275-279, 2017 ISSN 1949-8241 • E-ISSN 1949-825X Printed in the USA. All rights reserved. http://dx.doi.org/10.21300/18.4.2017.275 Copyright © 2017 National Academy of Inventors. www.technologyandinnovation.org “WHY” VS. “WHAT,” OR “THE BAD PENNY OPERA”: GENDER AND BIAS IN SCIENCE Florence P. Haseltine and Mark Chodos 2 1 1 Alexandria, VA, USA 2 Temple City, CA, USA The research of today has been shaped by how young scientists were viewed and received when starting out decades earlier. The author reflects on her personal experiences as a woman pursuing a science career and looks at contemporary contributions to innovation and science by men and women. Although women have been routinely asked “why” they wanted to enter a scientific field while men have been asked “what” field they wanted to enter, the author asserts that an objective look is revealing. An analysis of the data available on the National Academy of Inventors website demonstrates: 1) equal creativity as shown by categories of patents held by both men and women and 2) the effect of the early, and possibly continuing, bias during the careers of women in that men hold more patents than women. Key words: Gender; Invention; National Academy of Inventors INTRODUCTION Implicit in this question was the assumption that The author notes that she knew by high school there were other options, such as marriage, children, in the 1950s that she wanted a scientific career, but and a life dedicated to both. Why go to graduate when this wish was voiced, she was always asked not school and medical school? The fact that she was as if she was qualified, but why this was her goal. The passionate about science and medicine as any man same line of questioning continued throughout her did not seem to matter much. training and even into the job market. Her brothers were also interested in scientific That question was always “why.” Why did she want careers, but the question that was asked of her broth- to be a physicist? Why did she want to go to graduate ers was never “why”—why were you going to pursue school? After graduate school, the author went to this or that course?—but instead “what” they were medical school, and the same question came up but going to do. What were they going to study? What with a twist. “Why would she go to medical school careers were they going to pursue upon graduation? when she already had a Ph.D.?” These questions con- First impressions are critical; if the initial question tinued at every career juncture. To date, it has never a person has to answer is “why” and not “what,” the stopped being asked in one form or another although total interaction is dismissive. It also makes women many social changes in the last half-century have justify—and possibly even doubt—themselves every modified its deadening effect. single time. Answering the “why” question uses up _____________________ Accepted November 30, 2016. Address correspondence to Florence P. Haseltine, Ph.D., M.D., Emerita Scientist, NIH, Founder, Society for Women’s Health Research, 2181 Jamieson Ave #1606, Alexandria, VA 22314, USA. Tel: 240-476-7837; Fax: 202-318-0224. 275

276 HASELTINE AND CHODOS that valuable introductory time. No wonder successful simply how many men and how many women were women are often considered aggressive and difficult. already involved in STEMM fields (Science, Technol- Overcoming the verbal questioning means being ogy, Engineering, Mathematics, and Medicine). With abrupt with the very people who might be their col- this data, one could learn where the attention needed leagues in the future. to be focused. Progress cannot be made overnight, Social changes in the 1980s and 1990s somewhat and often the dynamics of the challenge for improve- turned the “why” question around for the women who ment would inevitably take decades (2). were able to achieve some prominence. The “why” The induction of the author into the National question was muted by search committees who had Academy of Inventors was an honor she had not to demonstrate that they had considered women for imagined or anticipated. As a founder of the Soci- positions. But it was the concept of quotas, rather than ety for Women’s Health Research, the author and an effort to establish what a woman had to offer, that her coding partner, Mark Chodos, used the tools of brought the change. However, even when the “why” technology to evaluate the success of women and the is unvoiced, if it comes before the “what,” a disservice differential between men and women in the National is done. What follows is an assumption of no or low Academy of Inventors. A project called RAISE was expectations. created at the Society using the information on the Frequently, when a search committee says it will websites of relevant societies and associations. The not discriminate, the discussion will state that women RAISE Project database examines web pages of sci- or minority candidates (often a shorthand for non- entific organizations to identify individuals who win white male) must be “qualified.” Has anyone heard the awards and then identify the sex and gender of the statement that the white males must be “qualified”? winners. The RAISE Project database now has more The only time qualifications are discussed in public is in the context of a white male and a minority candi- than 70,000 cited honors for 375 organizations and date with equal qualifications. Research by Dr. Carnes over 2,200 awards (3). et al. has examined this problem in depth (1). Both It was valuable to look at not only the research women and minorities are required to fulfill all the done on women’s health but also on the scientific existing qualifications in a job description, whereas a workforce involved in this effort. white male will not have to have every requirement. A recent paper from the Information Technology Just being a white male is enough to satisfy the crite- & Innovation Foundation (ITIF) evaluated patents ria. Is there ever a time when “all things being equal” from the most highly innovative companies. The really exists? If you are interviewing a candidate and paper reported that 12% of the innovators were are about to ask someone a “why” question, try a women and 35% of the innovators were immigrants, “what” question instead. The answer may surprise with another 10% being children of immigrants (4). you. By the 2016 meeting of the National Academy of Inventors (NAI), it seemed reasonable to examine RECOGNITION AND AWARENESS OF EQUITY whether these statistics held true for the NAI. How do these observations apply to the careers Knowing that the websites existed, the next step of professional women today? Being a professional was to use a technique called “web scraping” to access woman who constantly had to justify her interest in the extensive information contained on these web- a scientific field raised the author’s concern about sites. how women were treated in the academic world and The United States Patent and Trademark Office how much progress could be expected in the near has a user interface that allows searching for patents future. Reviewing not only personal experiences with by name and also by number for those patents issued a professional career but also using a neutral eye, the after 1976. To do this, scripts were written in python author noted that to make the point that progress was that collected all the patents and exported to a MySQL going to be slow, it was obvious that observations database. depended upon data. The data to be gathered was

“WHY” VS. “WHAT” 277 Table 1. Distribution of Patents by Members of the NAI Number of Patents Men Women 1->10 153 38 11->20 107 17 21->30 74 2 31->40 15 3 41->50 29 2 51->60 23 0 Figure 1. The percentage of patents issued to men and women 61->80 24 0 viewed by the International Patent Classification category defini- tions. Categories: A - Human Necessities; B - Performing Opera- 81->100 14 0 tions, Transporting; C - Chemistry, Metallurgy; D - Textiles, Paper; E- Fixed Constructions; F - Mechanical Engineering, Lighting, 100->129 17 0 Heating, Weapons, Blasting; G - Physics; H - Electricity. 130->150 7 1 151->200 8 0 It is still to be determined how many of these patents should be credited to more than one indi- 201->900 11 1 vidual. Moreover, errors in the data presented can be e data is divided into groups and displays the number of attributed to misspelled names and other common individuals by sex in each group. e number of men is 518 data glitches. and the number of women is 64. e mean number of patents for men is 20 patents and for women is 9 patents. CONCLUSION Table 1 shows the distribution of patents among mem- So, a great deal has been learned, but the question bers of the NAI. Of the 582 members, 518 are men remains: When will more women enter the innovative and 64 (11%) are women. The total number of patents space and their contributions start to change? Aware- identified was 21,247. The range of patents is from 1 ness of the challenges is critical. It is impossible to miss the news stories and articles in scientific journals to 898 with a mean of 19 to 20 patents for the men about the challenges that women and minorities face and 9 for the women. Unlike the paper from ITIF, we (6). However, as the number of women becoming do not know the immigration status of the members. innovators increases, they will no longer be isolated, It is apparent that women do have fewer patents than and their actions will be considered normal. Being men do. The next question was whether they had part of a group is enough justification for why a per- patents in different areas than men. To answer that son is doing something without having to be asked question, each patent was queried, again using the why (1). patent database and the broad international cate- Evaluation of the sex distribution of many awards gories extracted. Figure 1 shows the percentage of given for distinction in a field shows that women are the patents in each category and their distribution starting to be recognized, and evaluation of a large by International Patent Classification (5). Here, we number of awards, as has been done in the RAISE see that both men and women basically patent in the Project (3), shows that there was a change that started same areas. The NAI admits members from research to occur in 1995. It is not surprising that it occurred institutions. The data does not seem to differ from at the same time that women started to become pres- the sex ratio of scientists in the innovative companies idents of organizations. Figure 2, showing Institute that the ITIF examined. of Electrical and Electronics Engineers (IEEE) prizes and awards, is just one example of an organization to which many of our NAI members belong. The

278 HASELTINE AND CHODOS Figure 2. The number of men and women who have received awards from the IEEE. The data is from 63 awards that have been given since 1981. Data retrieved from http://raiseproject.org/BarChart.php?id=1121. RAISE Project database and website have many other ACKNOWLEDGMENTS examples of science organizations, and viewers can Anna Chodos, daughter who faces many academic examine data on how an organization recognizes its obstacles; Alan Chodos; Molly Carnes, professor at women. The graphing of this data makes it easy to the University of Wisconsin; and Adams Nager, eco- see trends and compare different fields, as few pre- nomic policy analyst at ITIF. sentations can make a case better than visualizing information when illustrating inequalities. REFERENCES Today, there are more questions about coding than 1. Carnes M, Devine P, Manwell LB, Byars-Winston why a woman wants to be a scientist. It is hoped that A, Fine E, Ford CE, Forscher P, Isaac C, Kaatz the young girls in middle school and beyond find out A, Magua W, Palta M, Sheridan J. The effect of how much fun math and science is and how much an intervention to break the gender bias habit information they can have going forward if they do for faculty at one institution: a cluster random- choose to pursue these areas. It is to be hoped they ized, controlled trial. Acad Med. (Philadelphia). learn that data is the key, and, when they can compile 90(2):221-30; 2015 it themselves, they will have the upper hand in any 2. Haseltine FP. Woman’s promotions: glass ceiling argument. efforts. J Womens Health (Larchmt). 3(4):251- 253; 1994.

“WHY” VS. “WHAT” 279 3. RAISE Project: a project of the Society for Wom- en’s Health Research. Data from the awards in our database. Washington (DC): Society for Women’s Health Research; c2016 [2016 Nov 15]. http://www.raiseproject.org/ results.php. 4. Nager A, Hart D, Ezell S, Atkinson RD. The demographics of innovation in the United States. Washington (DC): ITIF; 2016 Feb 24 [2016 Oct 15]. http://www2.itif.org/2016-demograph- ics-of-innovation.pdf. 5. [WIPO] World Intellectual Property Organiza- tion. International patent classification. [accessed 2016 Oct 15]. http://web2.wipo.int/classifica- tions/ ipc/ipcpub#refresh=page. 6. Kantor R. Men and women of the corporation. New York (NY): Basic Books; 1977. Chapter 8, Numbers: minorities and majorities; p. 206-242



Technology and Innovation, Vol. 18, pp. 281-283, 2017 ISSN 1949-8241 • E-ISSN 1949-825X Printed in the USA. All rights reserved. http://dx.doi.org/10.21300/18.4.2017.281 Copyright © 2017 National Academy of Inventors. www.technologyandinnovation.org FELLOWS KEYNOTE ADDRESS Andrew Hirshfeld United States Patent and Trademark Office, Alexandria, VA, USA Speech delivered before the National Academy to address the NAI Fellows. For me, I was trying to of Inventors Induction Ceremony think how to express in words what it feels like to (Printed from a live transcription, edited for clarity) meet many of you—I met some last night and at prior times—and I couldn’t really find what that feeling United States Patent and Trademark Office was like, but then it hit me: This is like when I was a Alexandria, Virginia child and my father took me to Yankee Stadium, and April 15, 2016 I got to meet the ballplayers I idolized and looked up to. That’s the same kind of feeling that I have when Good afternoon everybody, and thank you Liz I meet all of you. You inspire me, and you awe me. I for that extremely kind introduction. I also want to have been at the USPTO for 21 years, and I have been say thank you to the NAI for having me partake in working in various roles to support people like you. today’s events. It is certainly an honor to be able to It becomes so real to me when I see all the great work do so. I also want to thank the NAI for having me that you’re doing. It’s just absolutely overwhelming. participate in the 2015 Fellows Selection Committee. So I owe you all a huge thank you. That was quite an honor for me. Your work saves lives and enhances the quality of Our new class of NAI Fellows is a phenomenal our lives. It drives our economy. It spurs additional group of academics who lead our way into the future. research and innovation. And you teach our chil- I’m honored to be working with the NAI and to be dren. For me, that’s important to always keep in mind here with all of you today, and it has been extremely because it puts everything we do at the USPTO into gratifying for the USPTO to watch the NAI grow perspective. We are here to support this system, and into one of the foremost organizations that promote at the heart of the system are the wonderful inven- the development of inventions by emphasizing the tors whose works we’re trying to protect; that is all role of patents. The roles of the NAI and the USPTO of you. I know you’ve heard many of the stats about are certainly complementary, and our goals are the the NAI Fellows, but I wanted to go through them same. And that is to support and improve the patent again because they awe and inspire me. system. Our current inductees include six Nobel laureates, Today, I wanted to talk with you all about some seven recipients of the National Medal of Technology USPTO initiatives that we believe will help support & Innovation, and three inductees to the National the patent system. But, before I do, I really wanted Inventors Hall of Fame. Over half of the members _____________________ Accepted November 30, 2016. Address correspondence to Andrew Hirshfeld, U.S. Patent and Trademark Office, 600 Dulany Street, Alexandria, VA 22314, USA. E-mail: andrew.hirshfeld@ uspto.gov 281

282 FELLOWS KEYNOTE ADDRESS belong to the Academy of Arts and Sciences. Addi- officer and director for international affairs, three tionally, the class averages 32 issued patents per of the four directors of our regional offices, and our person. deputy commissioner for patent quality. All women. I’m going to say that again: 32 issued patents per That’s just to name a few. person. That is absolutely staggering. On that note, As you can see, we have women in very prominent I need to thank you also for the job security that you roles at USPTO. Prior to when I became commis- have given me at the USPTO. sioner, the previous commissioner was also a female. There are 582 Fellows that represent 190 uni- And at that time of the agency, I think it was of course versities and governments or nonprofit research the only time, where we had the director who was in institutions across the world. Together, those indi- charge of the agency, and both commissioners—the viduals hold 20,000 U.S. patents. Absolutely amazing. one over patents and the one over trademarks—being Before I dive into the USPTO initiatives, I also females. That’s something to be very proud of. wanted to talk about perspective. It is all your great I’m going to switch now to the Enhanced Patent work that we are trying to help support, and that has Quality initiative, and I spoke a couple minutes ago been the basis of our patent system. At the USPTO, about our goal to constantly improve. I know that we pride ourselves on the quality of work that we do, I’m here with a large number of academics, so you and we pride ourselves on continuing to improve understand what I’m talking about, about constant that quality. As public servants, we should always be improvement. Michelle Lee announced the enhanced striving to do better, to better support inventors like patent quality initiative in late 2014. The goal behind yourselves and of the next generations. this initiative, at least from my perspective, was a way Now I’m going to talk about some of our ini- to challenge all of us at the USPTO to self-improve tiatives, and I want to start with our ALLinSTEM and to ask ourselves, “What can we do to make every- program, which was announced last year by our thing that you do better? How can we better support director, Michelle Lee. The ALLinSTEM program the patent system?” As a career person, I give Michelle was announced to increase the involvement of women an awful lot of credit because she has come to us and and girls in STEM, from early education to corporate said, “Do whatever you need to. I want to know about board rooms. One of the main points of this initiative it. I want to hear about it. I want you to have the is to highlight successful female role models in the freedom to make the choices you need to make. And sciences and change the conversation about STEM I can tell you, as an employee, what better challenge being a male-dominated field. can you have than for your boss to say, “Whatever I will tell you, personally, that I met my wife in you need to do your job better, you can have.” That’s engineering school, and I joked around that I had an absolutely wonderful position to be in. married a third of the women in the engineering class. So this is our way of driving self-improvement. I feel very confident, though, that times are chang- We started with three pillars that we focused on for ing. Tonight’s inductees include 22 women. I’m sure improving patent quality. They were: excellence in that number will grow, but it’s certainly a sign that work products and services, excellence in measuring we’re headed in the right direction. I guarantee those patent quality, and excellence in customer service. As 22 inductees will inspire more young women to you can see, that’s very sweeping, but we wanted to pursue careers in STEM. I’m also the father of three have a significant focus. daughters, and I know they will be inspired by the We’ve also attacked this by working very closely stories that I am about to tell. with the public. It was just over a year ago that we I’d also like to point out that we are very proud of had a public summit, in this room, and we had many the diversity we have and the roles that women play at people over two days come and learn about what we USPTO. You’ve heard me mention our director, who is were proposing and our potential steps forward. We in charge of the entire agency, Michelle Lee. But there had well over 2,000 comments from that summit. are many other prominent roles that women play at We also had numerous federal register notices where the USPTO. For example, our current Commissioner we asked the public to comment on some ideas we for Trademarks, our General Counsel, our chief policy had, and we got feedback from our own employees

FELLOWS KEYNOTE ADDRESS 283 internally. We took all of this feedback and created clearer. So this has been a significant focus of ours. 11 programs. Those programs vary from the way we When I talked about Michelle giving us the free- collect our data to the way we train our examiners dom to really see how we can attack this without to changes in the way we might examine a patent limits, I wanted to talk about a pilot program that we application, for example. They’re wide-ranging, and have where we’re actually giving examiners more time there are certainly too many to get into today, but to do their job, to focus on steps of clarity. Again, that you all can get more information about this if you might sound trivial, but we have over 8,400 exam- are interested from our website, or you can contact iners, and they do an awful lot of cases. As we all me, and I will make sure the right people chat with know, time is money, and so it is a step that, to my you—or I will chat with you—about them. understanding, we have never taken at PTO. We have But I did want to focus on one theme that per- given more time to examiners for various issues, but meates all of these programs and that has to do with we’ve never given them time and said, “We want you clarity. We are taking steps at the USPTO, such as I to be clearer in what you do.” We’re testing that out have never seen in my 21 years, to make sure that now to see how impactful and how helpful it can be. our examiners are very clear in what they do in their So these are some of ways that we’re addressing office actions. And it might sound like a trivial step clarity, and, in the big picture, we’re really addressing forward, but we all know how challenging inventions the question: “How do we self-improve and make are—they’re very complex—and we all know how ourselves the best that we can be?” challenging the laws are. If you put that together, we I’m going to close with where I started: It’s all believe that there’s often a disconnect between the about perspectives. There are people like me; I started USPTO, when looking at a case, and the applicants as an examiner, and I’ve held a variety of jobs, but who file a case. So we’re taking steps to have examiners I’ve always tried to support people like you and the be very clear. We’re doing this in our training, and improvements that we can make together. I think we we’re doing this in every other way that we can think will do an even better job as we progress. of. If we can be clearer, then it will make prosecution With that, I want to say thank you and congratu- easier on all of the wonderful inventors like you. lations to all of you. You are inspiring, and you help We also think issuing patents with clearer bound- everyone move forward in a positive way. Thank you aries will allow competitors to look at the patent and very, very much. know exactly what is covered and make educated business decisions. For example: “Should I seek a ACKNOWLEDGMENTS license, or should I try to design around this patent?” Produced by the United States Patent and Trade- Clarity will be better for applicants because you will mark Office; no copyright is claimed by the United probably reduce litigation if your patent rights are States in this speech or associated materials.



Technology and Innovation, Vol. 18, pp. 285-294, 2017 ISSN 1949-8241 • E-ISSN 1949-825X Printed in the USA. All rights reserved. http://dx.doi.org/10.21300/18.4.2017.285 Copyright © 2017 National Academy of Inventors. www.technologyandinnovation.org THE NAI FELLOW PROFILE: AN INTERVIEW WITH DR. EMERY N. BROWN Emery N. Brown and Kimberly A. Macuare 4 1-3 1 Massachusetts Institute of Technology, Cambridge, MA, USA 2 Massachusetts General Hospital, Boston, MA, USA 3 Harvard Medical School, Boston, MA, USA 4 National Academy of Inventors, Tampa, FL, USA In a recent interview with T&I, distinguished professor, scientist, and anesthesiologist Dr. Emery N. Brown discusses his most recent work and shares his thoughts on the unexpected joys of practicing anesthesiology, his unlikely entrée into the world of neuroscience, and the importance of being the first African-American in all three national academies. INTRODUCTION Technology and Innovation (T&I) is pleased to present Dr. Emery N. Brown—statistician, neuro- scientist, and anesthesiologist—as the subject of this issue’s NAI Fellow Profile. Brown is Edward Hood Taplin Professor of Medical Engineering and Compu- tational Neuroscience at the Massachusetts Institute of Technology (MIT) and Warren M. Zapol Profes- sor of Anaesthesia at Harvard Medical School and Harvard-affiliated Massachusetts General Hospital (MGH). Brown holds a B.A. in applied mathematics (magna cum laude) from Harvard College, an M.D. from Harvard Medical School (magna cum laude), and an M.A. and Ph.D. in statistics from Harvard University. After completing an internship in internal medicine at the Brigham and Women’s Hospital and a residency in anesthesiology at MGH, he joined the faculty first at Harvard Medical School and later at MIT, becoming the only person to hold endowed professorships at (photo courtesy of Emery Brown) _____________________ Accepted November 30, 2016. Profiled Inventor: Emery N. Brown, MD, PhD, 77 Massachusetts Ave., Room 46-6079A, Cambridge, MA 0213, USA. Corresponding Author: Kimberly A. Macuare, PhD, Assistant Editor, Technology and Innovation, Journal of the National Academy of Inventors at the USF ® Research Park, 3702 Spectrum Boulevard, Suite 165, Tampa, FL 33612, USA.Tel: +1 (813) 974-1347; E-mail: [email protected]. 285

286 THE NAI PROFILE both institutions, one of his many unique accomplish- is accumulating evidence to show that these highly ments. The author of over 180 articles and inventor on structured oscillations are keeping the different parts 18 issued or pending U.S. and foreign patents, Brown of the brain from communicating. The structure of is a pioneer in the understanding of how anesthetic the oscillations differs systematically with different agents affect the brain and has opened up import- anesthetic drug classes due to binding to different ant new territory for exploration in neuroscience. receptors and affecting the neural circuits differently. The breadth and innovativeness of his work is evi- The oscillations also change systematically with age. dent in the many awards he has received, including I divide our work into two categories: The first is the National Institutes of Health (NIH) Director’s how can we improve patient care requiring general Pioneer Award, an NIH Director’s Transformative anesthesia given the current levels of technology? Research Award, and the 2011 Jerome Sacks Award How can you optimize it? Assume that we are not for Outstanding Cross Disciplinary Research from the going to produce anything new, there are no inno- National Institute of Statistical Science. He is also one vations, and that we have to make do with what we of the very select group who has been elected to the have. The second category is the obvious one: What U.S. National Academies of Sciences, Engineering, can we create that is new? When I look at the first and Medicine and elected a fellow of the National category, there are four things we can do. We can use Academy of Inventors, the American Association the electroencephalogram (EEG) to monitor patients for the Advancement of Science, and the American better, and, because we monitor them better, we can Academy of Arts and Sciences. more carefully dose the drugs. Second, we can develop Brown, an anesthesiologist-statistician, has suc- control systems to help us control precisely the anes- cessfully brought to bear his talents in medicine and thetic states of the brain. If we have automated systems statistics to investigate the neurophysiology of anes- that can drive cars, why can’t we have computer-con- thesia and develop signal-processing algorithms to trolled systems that help us monitor patients and dose analyze neuroscience data. Using imaging technology anesthetics through feedback control continuously in and statistical methodology, Brown has shown that real time? That is, we can create the autopilot, if you anesthetic drugs cause strong oscillations in the brain would, for the anesthesiologist. The third is coming that interrupt communication among its different up with ways to turn the brain back on given that regions. In addition to offering scientists a better it’s turned off under anesthesia. We term this active understanding of drug and brain dynamics, Brown’s induction of emergence from anesthesia as reanima- research has exciting implications for clinical practice, tion. Under anesthesia, the brain is turned off in a including the ability to give lower and thus safer doses way that is so unnatural. In other words, these oscil- of anesthetic agents to older patients and to awaken lations that I showed in my talk are not things that patients more quickly from the anesthetic state. your brain normally does. Once you realize that, it’s Dr. Brown graciously agreed to an interview with no surprise that your brain doesn’t really work after T&I, discussing his most recent work and sharing general anesthesia. The ideas I was expressing in my his thoughts on the unexpected joys of practicing talk about using Ritalin or finding other agents that anesthesiology, his unlikely entrée into the world of actually activate the brain and help people come back neuroscience, and the importance of being the first and be clear and highly functional as soon as possi- African-American in all three national academies. ble after anesthesia are not only desirable but quite feasible. We are now conducting a phase II clinical INTERVIEW trial testing this idea using Ritalin. The fourth part is working out strategies to deliver anesthesia with T&I: Please tell us about some of the current research less dependence on opioids. I’m sure you’re aware projects you are working on. of the tremendous crisis or epidemic we’re having Brown: Well, I think the main thing that we are work- with the use of opioids in the country now. One of ing on is trying to get a detailed understanding of the things that is contributing to that is that we’ve the neurophysiology of how anesthesia works. So we been very singular in our approach to treating pain. know now, as I mentioned in my presentation, that it We’ve really just used one approach up to now, which is clear that the drugs are creating oscillations. There is administering opioids. The pain system has many

THE NAI PROFILE 287 receptors, many circuits, and the fact that we are hav- more innovations in our hands and in practice right ing this problem now, this overuse, is related directly now. to the fact that we haven’t been very creative about If you look at the things that have made anes- developing alternatives. There are alternatives that are thesia safer in the last few years, one of the major out there that, when put together, could allow us to innovations was 30 years ago when Jeff Cooper and have the same level of care, or arguably even better company at Mass General decided to set monitoring care, with a much reduced risk of long-term depen- standards for patients receiving anesthesia care. The dence, overdose, and addiction. I think it’s totally standards said things that now just seem so obvi- tractable, and some of it can be done by repurposing ous but, in retrospect, were not required at the time. some of the drugs that we already have. What I like Anesthesiologists have to monitor heart rate, blood about these four approaches under category one is pressure, carbon dioxide production, oxygen delivery, that they are sufficiently new. However, they are well anesthetic gas delivery, and temperature. This simply within reach—maybe within two to five years if not means to basically follow the patient’s physiology sooner. They just involve drugs and approaches that on a second-to-second basis. These standards were we have at hand right now and already know about. accepted by the Harvard hospitals in 1985 and a year The second category is: As we learn more about the later by the American Society of Anesthesiologists. brain and how it functions, what we eventually want Substantial improvements in care came about by just is to have targeted ways of producing anesthesia in implementing basic monitoring guidelines. which we inactivate or activate very specific sites. This There hasn’t been that “thing” that has just radi- would give us site-specific control for induction and cally changed practice, if you will. Some people may maintenance of anesthesia as well as for reemergence disagree, but I haven’t seen it. I think that’s the sort from general anesthesia. of thing that could now possibly come about as we T&I: So, in thinking about the trajectory of anes- look more into the neuroscience of anesthesia. thesiology, what would you say has been the greatest T&I: I was thinking when I listened to your talk that innovation heretofore? maybe this could be the next frontier. Brown: To be honest, I think the great innovation Brown: I really think so because look—among all was actually general anesthesia itself. It is 170 years those requirements to monitor, what has not been old now; October 16, 1846, was when it was first required is monitoring the brain. We don’t have to publicly demonstrated here at Mass General, and we monitor the brain. We monitor all the other physi- th celebrated the 170 anniversary this year. That was ological indicators with the exception of the brain, totally transformative. Surgery was basically trans- yet the most profound effects of anesthesia are in the formed from being inhumane butchery into a useful brain and the central nervous system. therapeutic and diagnostic option. Also, now there T&I: It seems counterintuitive. are all of these noninvasive procedures that we can do thanks to anesthesia. Therefore, if we take all of Brown: Completely counterintuitive, but it speaks the innovations that have happened in surgery, they directly to the empirical nature of what we do. This would not exist were it not for general anesthesia. I is also due to the fact that anesthesiology is viewed think anesthesia itself was a major transformative as a subfield of pharmacology and not a subfield of innovation. clinical neuroscience. As soon as you acknowledge There’s a lot of science on anesthesiology. However, that anesthesia acts in the brain and in the central a large part of the progress has been through empir- nervous system, the importance of monitoring the icism. The specialty is viewed as a field of applied brain becomes obvious. pharmacology. The approach in our research and T&I: Moving on from the history of anesthesiology in my clinical practice is to view anesthesiology as a to your own personal history: You’re so driven as a field of clinical neuroscience because the drugs act doctor and scientist, and I was wondering if there in the brain and in the central nervous system. Had was any event or person or persons that motivated this perspective on anesthesiology been adopted by you to pursue science and medicine. That is, what or anesthesiologists, we probably would have had a lot who influenced you to pursue science and medicine?

288 THE NAI PROFILE Did you have any early formative experiences that T&I: Regarding your reference to your dual training, pushed you in that direction? you have degrees in medicine and statistics. What is Brown: I think probably the most significant influ- the relationship between those two areas? How do ences were my parents. Both of my parents were they inform each other with respect to your work? high school math teachers, so science and math were Is it a natural “marriage” of disciplines? always being discussed around the house. I kind of Brown: I think there is. I think it is very, very natu- grew up with the idea of becoming a doctor not so ral. If you think of statistics as the science of making much because there was somebody in my family who decisions under uncertainty, and what you do as a was a doctor, but it was always something I wanted physician when you’re taking care of patients is to try to do. It dates back probably to when I was a young to make the best guess at what the disease process is kid, around six or seven, and I used to go often to my given the data that you observe. The science of sta- pediatrician. I remember my pediatrician because I tistics is a process we apply all the time as physicians. always felt so good after I left him. It is rather ironic I can honestly say, though, when I did statistics and because my pediatrician’s name was Dr. Butscher when I trained as a physician, and more specifically (pronounced “butcher”). He was this happy, jovial as an anesthesiologist, I did not have a plan to link guy, and I thought, “This is cool.” One thing that really them. I just did what I tell students to do: Do the used to fascinate me, and I remember the first time things that you really like to do, and you’re going to I got to do it in medical school, was when he would have the most fun and that’s where you’re going to percuss my back—you know, tap with his fingers—to be the most productive and the most creative. That’s see if I had congestion in my lungs. It just seemed like essentially what I did, and for many years, I practiced the coolest thing, so I think those sets of experience anesthesiology not really caring about how the drugs got me interested in medicine. worked or what the mechanisms were. I was just Through the first part of college, even though I trying to be as good a clinician as I could be. I would was thinking of going into medicine, I started off then go off to my research laboratory and work on majoring in romance languages. I entered Harvard developing new statistical methods to analyze neu- College with my fortés being French and Spanish. I roscience data. majored initially in romance languages and eventu- There was no marriage; in fact, in some respects, ally switched into applied mathematics in my junior it was almost like night and day. However, the more year after having exposure to economics and then to I worked in neuroscience, the more I realized that statistics. As a consequence of taking an economics the neuroscience ideas could be brought in to study course and then realizing that statistics was so fasci- mechanisms of anesthesia. As I started doing more nating, I just wanted to do statistics. So, I switched of my own experiments and generating my own data, and completed the major in applied mathematics. I the need to collaborate with people to work on their had to take three applied math or statistics courses data drastically diminished. Instead, I worked on the in each of the last four semesters to complete the data that we were collecting in my own experiments, requirements. It was great. I enjoyed every second of which was accumulating exponentially. Out of that, it! Then I went and studied math for a year in Greno- the marriage for what I was doing was created. This is ble at the Fourier Institute for Applied Mathematics because the area of statistics I needed to analyze our to round out my math background because I wanted EEG readings, local field potential, and neural spike to come back and do an M.D. / Ph.D., and I wanted trains was time series analysis, which is the study of to do my Ph.D. in statistics. That was the beginning data generated by dynamic processes. This was now of my interest in statistics. serendipity because this was my area of expertise in I must admit that one of the people who was very statistics. One of the fascinating things that we found, impressive to watch as a statistician and as a scientist as I mentioned at the outset, was that the brain is was Fred Mosteller, who founded the Harvard statis- highly dynamic under anesthesia. tics department. He was this incredibly clear thinker Ultimately, making inferences from data is really who was quite adept at getting groups of people to what medicine is all about. This has become a little do interdisciplinary research. He was a true giant. more apparent now that the buzzword “big data” has

THE NAI PROFILE 289 come into being. It was always the case and always Brown: I was really attracted by another aspect of it will be the case. Arguably, there should be a lot more that we haven’t really talked that much about. Anes- people who are dually trained, perhaps as I am. There thesiology is even more intriguing and exciting to should be a lot more emphasis on training in statis- me now, given all of the stuff that’s going on in the tics for physicians and for society in general because brain, but anesthesiology was still cool just doing it ignorance of statistics is a huge problem. It’s a key even before I gained all these insights into how its intellectual bottleneck—the lack of understanding neuroscience mechanisms work. Anesthesiology is of statistics—and it is one we will have to overcome real-time physiology. We are dealing with controlling if we really want to makes some real advances in physiological systems so that a patient can tolerate medicine and all areas of science, engineering, and what would otherwise be an unbearable traumatic social science. insult. Things happen in real time, and you have to T&I: Although it is one of the most popular spe- fix them in real time. If someone stops breathing or cialties, anesthesiology is not customarily the first starts bleeding or if a lung gets punctured, you have specialty that comes to mind. Why do you think that to be able to handle these problems quickly. You have is? to diagnose them and act upon them quickly. This is very exhilarating. Hence, anesthesiology always had Brown: It’s not viewed as sexy. People don’t go to the challenge of managing real-time physiology and the hospital to get anesthesia. They go for something pharmacology. Now, if you add the third component, else, and then they need anesthesia. Anesthesiologists which is the really cool neuroscience, then, intellec- have become—partially out of our own doing—the tually, anesthesiology becomes an extremely inviting butt of jokes. We often hear, “You knock people out” specialty. The other thing is that in anesthesiology we or “You pass gas.” We have added to that because of have to work with both our heads and our hands when what we in anesthesiology commonly say to patients. Anesthesiologists tell the public that we don’t know how anesthesia works, and now, of course, I think nothing could be further from the truth. But we also say: “Don’t worry; it’s safe.” And then we say other things like, “We will put you to sleep,” Anesthesia is certainly not sleep; rather, it is a drug induced revers- ible coma. If we anesthesiologists do not understand exactly what anesthesia is and we are not excited about our discipline, no one else is going to be excited about it. But as soon as we start saying that anesthe- siology is a cool specialty, things change. I now have high school students writing me because they are interested in anesthesia and want to come and work in the laboratory or go to the operating room with me to observe. I regularly get questions from the lay public about anesthesia. I had not seen this level of public energy before. This interest reflects now how we treat the specialty. We anesthesiologists have only ourselves to blame for the fact that such interest has not existed before. T&I: When you chose anesthesiology, were you attracted at all by the mysterious nature? What were your reasons for choosing anesthesiology as your specialty? (photo courtesy of Emery Brown)

290 THE NAI PROFILE you are giving anesthesia care. One other aspect of our Over time, my frustration with these factoids specialty is that anesthesiologists are one of the last began to build up, and then a couple of things hap- repositories of whole body physiology. By that I mean, pened. A colleague of mine, Lee Kearse, was going to classic physiology has gone the way of the dinosaur do studies to image patients under anesthesia. This as emphasis in medicine has transitioned into ideas was the coolest thing. This was 20-some years ago, of computational, systems, and molecular biology. and, at the time, functional magnetic resonance imag- Attempts are made to reduce many medical problems ing (fMRI) was only maybe three or four years old. I or diseases to small scales and atomistic elements. told him that I wanted to help him with this. Shortly The body, however, functions by systems that work after we began planning the study, Lee came to me and on a physiological scale. Anesthesiologists have to said, “Emery, this is all you. I’m out of here. I’m going worry about all the physiological systems because we to business school.” I was like: I know nothing about take care of the whole patient when someone’s under imaging and very little about neuroscience. Therefore, anesthesia in the operating room or in the intensive I was left holding the bag. I decided to push on with it, care unit. That unique position is never going to dis- and this is where serendipity starts. The people at the appear. If you couple this with brain science, as I just Mass General Imaging Center, particularly Director said, anesthesiology is a far more fascinating specialty Bruce Rosen, thought it was a cool idea and offered to going forward. help. They provided their expertise and free imaging T&I: Your line of inquiry regarding anesthesia and time. I found Patrick Purdon, an extremely talented graduate student—now my colleague—who decided the brain is so innovative and unexpected if you only he wanted to take on imaging patients under anes- consider our traditional definition of anesthesiology. thesia for his Ph.D. dissertation. In addition, when What initially motivated you to begin thinking about I talked to my anesthesiology colleagues about this the workings of the brain under anesthesia? Did you idea, they just volunteered to help, so we put together have an Archimedean eureka moment? If so, what a team. We had no funding for any of this research was it? at the time. We arranged our schedules to have our Brown: I don’t know if it was that, but there was days out of the operating room coincide so that we a series of things that kept happening, and, after a could anesthetize volunteer subjects in the imaging while, I realized that the force of the evidence or the center, which was not in the main part of the hos- momentum of the situations was pushing me in a pital. Our goal was to simultaneously conduct fMR certain direction. I was practicing as an anesthesi- imaging and record EEG in volunteer subjects who ologist even though my research was in statistics. I were gradually anesthetized and allowed to emerge. was getting a lot of clinical experience in the practice The imaging center is actually in Charlestown, a good of anesthesiology. One thing that bothered me to mile and a half away, so we had to create a situation no end was that there were a lot of what I call “legal where it was safe to conduct these studies. It took us fiction” explanations for things in anesthesiology. the better part of four years to get this study approved That is, there were many concepts that I knew made by the Mass General Human Research Committee. no sense but that I didn’t really have time to inves- This got me going, and then I realized something, tigate myself. These were things that I called “board which was probably my small eureka moment. The factoids”—things that you have to learn to pass your small eureka moment was that, as anesthesiologists, anesthesiology board examination but you probably who is better to do clinical studies than us because we will never use when you practice in actuality and that, basically monitor physiology all the time in patients. in point of fact, probably weren’t even right. This was Every patient is basically a clinical study in a sense. really annoying. People would quote these factoids So, if anything, we were already trained to do this, as if they were truths when you knew that they could but we did not regularly use our skills to do this type just not be true. But I was trapped because unless I of research. What took the study to another level was was investigating them, it was hard to argue against that we figured out that the study subjects were going them, or I would just be creating another opinion to be people with tracheostomies. The reason we did not supported necessarily by compelling evidence that is because when a patient becomes unconscious or research. under anesthesia, he/she generally stops breathing.

THE NAI PROFILE 291 If a subject had a tracheostomy, we could put in a him. He moved a little bit. I did it a second time tracheostomy tube and attach the breathing circuit and eventually a third time over the span of about to it before we started the anesthesia so that, once he/ 20 minutes, maybe a little longer, and eventually he she lost consciousness, we could continue ventilation started to move, and he made a posture that’s called manually. This was the most challenging study that decorticate posturing. Classically you see this when the Mass General Human Research Committee had someone is in a profound coma, the brain is herniat- ever approved. We had tremendous redundancy and ing, and the brainstem is significantly compromised. safety, and this is where being young and a little bit The next thing we noticed, literally a minute later, is intrepid is helpful because this was the most stressful that he was wide-awake. What was happening was thing I have ever done. However, when we got the first the opposite of what happens when someone goes subject through the protocol, it was just amazing! We into a coma. For coma, people go to progressively did a total of seven combined fMRI/EEG studies. All deeper degrees of loss of arousal. What I saw with the of the human studies we have done since then have patient was coma played in reverse. Now that’s what seemed quite simple by comparison. They have been waking up from anesthesia is in general. However, studies in which we only measure EEG, or we measure because of these body postures, if I had not told you EEG, local field potentials, and neural spike trains that this guy was under anesthesia, you would’ve from epilepsy patients implanted with electrodes. thought that his brainstem was herniating. So, for a This was going back to 2004 to 2008. brief moment, the anesthesia simulated the herniating That experience, if you would, gave me confidence brain. It’s just wild. I have a whole cadre of anecdotes to continue. This was coupled with one other thing. like that. These experiences start to give us insights Remember there were all those things in anesthe- into how the anesthesia is working in the brain. What siology that I said were not true or that I wanted it is telling you there is that the anesthesia had his to understand better? I kept a list of them. Finally, brainstem profoundly shut down still. I think it’s these I sat down and used them to write a review article types of insights that blow me away, and they are not about anesthesia, “General Anesthesia, Sleep, and uncommon. Anesthesiologists can see something like Coma,” which I published in the New England Journal this almost every day—if we pay attention. of Medicine in 2010. I wanted to compare anesthesia T&I: In your talk at the NAI Annual Conference, you to sleep and coma explicitly because we often say mentioned the difficulty in training anesthesiologists sleep to patients to be diplomatic in how we describe to consider the brain, as they often view themselves as what is going to happen to them when they are given practicing pharmacology rather than neuroscience. anesthesia. Rather than being sleep, though, general Why are they resistant? Where does that resistance anesthesia is a drug-induced reversible coma. originate? How do you overcome that? T&I: There has been so much that you have found that Brown: That’s a very good question, and it’s no exag- has been exciting and exhilarating. Has there been geration to say that I do ponder some aspect of this anything in your research on the brain and anesthesia almost every day. Anesthesia is clearly a brain and that you find surprising or even unsettling? central nervous system phenomenon. If you look at Brown: I don’t know if it’s really unsettling, but as you what has happened historically, anesthesiologists have pay closer and closer attention to patients as they go taught ourselves how to administer anesthesia with- through the different anesthetic states, you get brief out watching the brain. The natural question is: “Why windows into how the brain and central nervous do I need to know anything about the brain? I’ve been system are working. doing all this without it.” If anesthesiologists never Six or seven years ago, I had a patient who was look at the EEG during general anesthesia or look very slow to wake up from anesthesia. Everybody at the neural circuit mechanisms of how anesthetics was getting concerned that perhaps something had work and there are no guidelines to aid/encourage use happened, such as a stroke. The anesthetic agent had of the EEG, then this perspective will never change. been off for a while. I was examining him, and he Until there are requirements to track the brain or wasn’t breathing yet. I took a suction catheter and until the educational programs (www.anesthesiaeeg. passed it down his endotracheal tube and stimulated com) for anesthesiologists have as part of them the

292 THE NAI PROFILE neuroscience that we are teaching, use of neurosci- All these forces, most of which are sociological, ence in anesthesia care is not going to change because are impairing adoption of our monitoring paradigm. anesthesiologists can practice as they have without If you talk to the residents, who generally have no taking account of what we are saying. I think one of biases one way or the other, our neuroscience para- the things that will help drive this change is as we start digm seems very plausible. They think, “I just finished to show that neuroscience is not just an intellectual learning neuroscience in medical school, and this is exercise, but that it changes practice. That is, patients simply an application of what I learned there.” We will get better care, older patients get less drugs, you know also have to make our educational materials broadly where patient’s brains are at all times when you are available to encourage training in our monitoring taking care of them. As anesthesiologists have more paradigm. To this end, in addition to our lectures at and more of these experiences, the tide will hopefully meetings and at anesthesiology departments around swing. the country and across the world, we will continue The other thing is that it may require the imple- to expand our materials at www.anesthesiaeeg.com. mentation of guidelines to oblige anesthesiologists to T&I: What was it like to be tapped for President move in this direction, just as the monitoring guide- Obama’s BRAIN Initiative Working Group? What lines established in 1986 obliged us to monitor vital have been the most exciting results to emerge from signs. We may require something similar for brain that work? state monitoring. The reticence on the part of anesthe- Brown: It was an honor to be one of the neurosci- siologists stems also from an intellectual barrier. The entists selected by the NIH Director to guide this brain is viewed as complex, and the EEG is viewed as something that is complicated to understand and too important effort. I was thrilled about that, and it was hard to read. The perception has been made worse quite an experience. Over the course of 15 months, in anesthesiology by EEG-based indices, which have we heard from a very significant cross-section of neuroscientists regarding what they thought were been created to track brain states under anesthesia, the important issues to work on. We stayed focused but in so doing have oversimplified what is needed to on our mandate, which was to come up with ways to track the brain states of patients. As expected, these foster the development of tools that would enable neu- oversimplifications broke down. Anesthesiologists roscientists to better study the brain. We got to think hear us recommend use of the unprocessed EEG and about what those tools should be and how they should its spectrogram to monitor the anesthetic state. Unlike be targeted. Although most of the work will be done the empirically derived indices, our monitoring par- in animal models, we added a special emphasis on adigm is based on our neuroscience understanding human neuroscience to encourage the development of of anesthetic-specific patterns we have identified research teams to work specifically in this challenging for each agent and how these patterns change with but critical area. It was a great responsibility to have. anesthetic dose and age. If they do not take time to I was talking a few weeks ago with Terry Sejnowski, appreciate how our monitoring paradigm works, then one of my fellow members on the working group. He it may appear superficially as just the next index that commented that of all the things that he has written, is going to break down in a few years as did all of the our report, Brain 2025, is probably the publication others. There’s a skepticism based on perceptions that that has had the most impact. I’m sure that is the case are not correct. The EEG of a patient under anesthe- for me as well. The report is widely cited, and many sia has the highest signal-to-noise ratio of all of the have turned to it for guidance. applications of the EEG in human neuroscience. This is because under general anesthesia the anesthetics T&I: How has the BRAIN initiative impacted uni- induce oscillations that are 5 to 20 times larger in versity research? amplitude than the normal awake EEG. In addition, Brown: NSF, NIH, and DARPA have put aside funds because patients are immobile under anesthesia, there earmarked specifically for the Brain Initiative. This is also no movement artifact. If we cannot use the encourages people to come together and work on EEG to monitor the brain states under anesthesia, these problems, to form groups that may never have then it cannot be used for any other application in worked on these topics before. Hence, this is very, which the signal-to-noise ratio is much larger. very good. The money that was put aside in the first

THE NAI PROFILE 293 year was only $110 million, which is a very small think about African-Americans and other under- amount. It was designed to be catalytic, and then, as a represented minorities and, most importantly, the consequence, encourage other organizations, such as way students in these groups think about themselves. private foundations, to help out. The Kavli Foundation The students say, “Wow, that could be me.” I realize is a good example of a private foundation that has that although I am the first African-American to undertaken efforts to spur research that will aid the achieve this, I know that I’m not the first person who Brain Initiative. This has been very good. We were has had the accomplishments to achieve this. There not intended to be for neuroscience research what the have certainly been others before me who just did not Human Genome Project was for molecular biology. receive this recognition because they went unnoticed. As another example of the catalytic effect of the Brain I am thinking specifically about African-American Initiative, I was invited to speak at a workshop held scientists and physicians whose work was signifi- at the University of Florida when we were right in cant but not recognized with these accolades. The the midst of the Brain Initiative. The purpose of the accomplishment is an honor as I said. However, it symposium was to bring together investigators from does not go to my head because there are so many across Florida because they said, “Hey, we have all talented people out there in a number of areas whose this neuroscience research going on at the University work is tremendous and has had impact who have of Florida, Miami, Tampa, FSU, so why don’t we try not received this level of recognition. On another to coordinate some of it.” Those sorts of efforts have level, I wanted to be a statistician and a physician. taken place in a number of areas across the country, Neuroscience is something that I took on later as they have sparked a lot of interest, and that’s exactly an interest and a career focus. Part of what is really what we were hoping would happen. We are also gratifying about being in all three Academies is that, hopeful that each year Congress will allocate more to some extent, it says that I’ve done a good job in resources for neuroscience research in particular, and all three areas. And now to be acknowledged as an I think that the Brain Initiative has been very helpful innovator by being elected to the National Academy in keeping the focus on the importance of this area of Inventors is so very cool! of science for improving human health. T&I: In addition to the sheer number of accolades CONCLUSION you have accumulated, you are also widely regarded A gifted polymath, Brown has successfully united as a trailblazer. It has been noted that you are the first his talents in medicine and statistics to create a new African American, the first statistician, and the first frontier for brain exploration that has led to advances anesthesiologist to be elected to all three branches of both intellectual and material. Because of his work, the National Academies: the National Academy of we now have a fundamentally different conception Medicine, the National Academy of Sciences and the of the effects of anesthetic agents on the brain and National Academy of Engineering. What does it mean understand that our previous “legal fiction” models to you to be the first to have achieved these honors? of going to “sleep” lacked neuroscience reasoning. Brown: I am honored and humbled to be recognized In addition to his intellectual contributions, Brown by my peers. It is a pleasure to know that my col- has also made concrete progress toward improving leagues think that what I am doing is important and clinical practice, something that will make anesthesia that my accomplishments are worth acknowledging. use safer and more effective for patients and practi- Regarding being the first African-American elected in tioners. On all fronts, from the lab to the classroom all three of the branches of the National Academies, to the operating room, what is clear to anyone who now that this has occurred, it is more important than speaks even briefly with Brown is that his knowledge I would have imagined because people do notice it. and abilities are only matched by his enthusiasm and Students talk about it. It helps change the way we love for his work.

294 THE NAI PROFILE FURTHER READING PG, Sampson AL, Cimenser A, Ching S, Kopell NJ, Tavares-Stoeckel C, Habeeb K, Merhar R, 1. Brown EN, Lydic R, Schiff ND. General anesthe- Brown EN. Electroencephalogram signatures of sia, sleep, and coma. N Engl J Med. 363:2638-50; loss and recovery of consciousness from propo- 2010. fol. PNAS. 110(12):E1142-51; 2013. 2. Ching S, Cimenser A, Purdon PL, Brown EN, 8. Shanechi M, Chemali JJ, Liberman M, Solt K, Kopell NJ. Thalamocortical model for a propo- Brown EN. A brain-machine interface for con- fol-induced alpha-rhythm associated with loss of consciousness. PNAS. 107:22665-70; 2010. trol of medically-induced coma. PLoS Comput 3. Brown EN, Purdon PL, Van Dort CJ. General Biol. 2013. anesthesia and altered states of arousal: a sys- 9. Purdon PL, Sampson A, Pavone KJ, Brown EN tems neuroscience analysis. Annu Rev Neurosci. Clinical electroencephalography for anesthesi- 363:2638-50; 2011. ologists Part I: background and basic signatures. 4. Solt K, Cotten JF, Cimenser A, Wong KF, Anesthesiology. 123:937-60; 2015. Chemali JJ, Brown EN. Methylphenidate actively 10. Purdon PL, Pavone KJ, Akeju O, Smith AC, induces emergence from general anesthesia. Sampson AL, Lee J, Zhou DW, Solt K, Brown Anesthesiology. 115:791-803; 2011. EN. The ageing brain: age-dependent changes in 5. Ching S, Purdon PL, Vijayan S, Kopell NJ, Brown the electroencephalogram during propofol and EN. A neurophysiological-metabolic model for sevoflurane general anesthesia. Br J Anaesth. 115 burst suppression. PNAS. 109:3095-100; 2012. Suppl 1:i46-i57; 2015. 6. Lewis LD, Weiner VS, Mukamel EA, Donoghue 11. Cornelissen L, Kim S, Purdon PL, Brown EN, JA, Eskandar EN, Madsen JR, Anderson WS, Berde CB. Age-dependent electroencephalogram Hochberg LR, Cash SS, Brown EN, Purdon PL. (EEG) patterns during sevoflurane general anes- Rapid fragmentation of neuronal networks at thesia in infants. eLife. 23:1-25; 2015. the onset of propofol-induced unconsciousness. 12. Lewis LD VJ, Flores FJ, Schmitt LI, Wilson PNAS. 109(49):E3377-3386; 2012. MA, Halassa M, Brown EN. Thalamic reticular 7. Purdon PL, Pierce ET, Mukamel EA, Prerau MJ, nucleus induces fast and local modulation of Walsh JL, Wong KFK, Salazar-Gomez AF, Harrell arousal state. eLife. 4:e08760; 2015.

Technology and Innovation, Vol. 18, pp. 295-304, 2017 ISSN 1949-8241 • E-ISSN 1949-825X Printed in the USA. All rights reserved. http://dx.doi.org/10.21300/18.4.2017.295 Copyright © 2017 National Academy of Inventors. www.technologyandinnovation.org TECHNOLOGY TRANSFER FOR ALL THE RIGHT REASONS James K. Woodell and Tobin L. Smith 2 1 1 Economic Development and Community Engagement, Association of Public and Land-grant Universities, Washington, DC, USA 2 Association of American Universities, Washington, DC, USA By granting universities and faculty the rights to retain intellectual property arising from federally sponsored research, the Bayh-Dole Act of 1980 provided critical motivation to universities and their faculty members to take an active role in commercializing technology based on their discoveries. While many universities feel it is imperative that their technology transfer operations work to recover costs, and dwindling state funding for higher education has caused some state legislatures and university governing boards to view technology transfer as a potential revenue source, we maintain that revenue generation, in most instances, is not the primary motivation for university technology commercialization. If done with the right goals in mind, technology transfer aligns with universities’ overarching research, education, and service missions, helping to ensure that public investment in science is impactful, that it advances broader economic development objectives, and that it serves the public interest. In 2015, the Association of Public and Land-grant Universities (APLU) and the Association of American Universities (AAU) issued recommendations to their members encouraging them to reaffirm their commitment to managing intellectual property in the public interest and calling for an unequivocal declaration by university leaders that technology transfer efforts serve first and foremost the best interests of society. This article relays the recommendations put forth by the associations. Key words: Technology transfer; Intellectual property; Public good; Societal impact; University policy INTRODUCTION created perverse incentives that motivated universities By granting universities and faculty the rights to to manage the intellectual property (IP) derived from retain intellectual property arising from federally federally funded and other research solely for the sponsored research, the Bayh-Dole Act of 1980 pro- purpose of generating revenue. vided critical motivation to universities and their While many universities feel it is imperative that faculty members to take an active role in commercial- their technology transfer operations work to recover izing technology based on their discoveries. In recent costs, and dwindling state funding for higher educa- years, policymakers, members of the business com- tion has caused some state legislatures and university munity, and others have suggested that Bayh-Dole governing boards to view technology transfer as a _____________________ Accepted November 30, 2016. Address correspondence to James K. Woodell, 1307 New York Avenue NW, Suite 400, Washington, DC 20005-4722, USA. Tel: +1 (202) 478-6044; E-mail: [email protected] 295

296 WOODELL AND SMITH potential revenue source, we maintain that revenue BACKGROUND generation, in most instances, is not the primary motivation for university technology commercializa- The Successes of Bayh-Dole tion. If done for the right reasons, technology transfer In 1980, the Bayh-Dole Act created a uniform pat- aligns with and advances universities’ overarching ent policy among the many federal agencies that fund missions of research, education, and service. Tech- research, enabling universities, nonprofit research nology transfer is a mechanism by which universities institutions, and small businesses to retain patent ensure that public investment in science is impactful, and licensing rights to inventions developed by their that such investments enhance economic develop- investigators and supported by federal research fund- ment, and that it serves the public interest. University ing. The purpose of Bayh-Dole is to facilitate the rapid technology transfer must advance teaching and learn- transfer of research discoveries into the commercial ing and research and discovery at the same time it sector to advance the public good. contributes to economic and societal outcomes that Before Bayh-Dole was enacted, the federal gov- help advance the national interest and improve qual- ernment retained ownership of federally funded ity of life. These are the reasons universities engage discoveries, but, in most cases, the government failed in technology transfer. Viewing revenue generation to license discoveries to the private sector for further as the primary objective of university technology development. In fact, of the 28,000 patents the govern- transfer operations is a misguided notion that will do ment owned in 1980, less than five percent had been licensed to industry (1). Bayh-Dole sparked technol- little to help address university finances or to achieve universities’ overarching missions. ogy transfer by creating an incentive for universities Given the growing political and public percep- to secure patent protection for inventions resulting tion that universities have become overly focused from federally funded research. This, in turn, allowed on profiting from their technology transfer oper- businesses to gain the necessary rights to develop and commercialize research discoveries. So successful was ations, however, university leaders must publicly Bayh-Dole that in 2002 The Economist dubbed it as reaffirm their commitment to managing intellectual “Innovation’s Golden Goose,” noting that the act had property in the public interest. There must be an “…helped to reverse America’s precipitous slide into unequivocal declaration by university leaders that industrial irrelevance” (1). technology transfer efforts serve first and foremost Before the 1980 passage of Bayh-Dole, univer- the best interests of society. Two university associ- sity discoveries were rarely commercialized for the ations—the Association of Public and Land-grant public’s benefit. Instead, these discoveries were left Universities (APLU) and the Association of American to languish because the federal government did not Universities (AAU)—have been working with their have the time, interest, or resources to see that these member institutions to encourage clarity of purpose inventions moved from the laboratory to the market- around university technology transfer. place to advance the public good. In 1980, fewer than In 2015, both associations, working with other 250 patents were issued to universities; by 1993, this groups, including the Association of University number had jumped to more than 1500 (2). Accord- Technology Managers (AUTM), the Council on Gov- ing to the most recent survey of the Association of ernmental Relations (COGR), and the American University Technology Managers (AUTM), in 2015, Association of Medical Colleges (AAMC), issued U.S. universities garnered 6,124 U.S. patents, which recommendations to their members encouraging led to the formation of 946 new start-up compa- them to take steps to make such declarations. This nies and generated more than 700 new commercial article relays the recommendations put forth by the products (3). A 2015 Biotechnology Innovation Orga- associations and describes follow-on work that the nization (BIO) study conservatively approximates associations are undertaking to advance the conver- that, between 1996 and 2013, patents commercialized sation. from universities contributed $404 billion to the U.S. gross domestic output, $181 billion to the U.S. gross domestic product, and supported a cumulative total of 1.4 million person years of employment (4).

TECHNOLOGY TRANSFER 297 Thus, the Bayh-Dole Act of 1980 effectively estab- resulted in state legislatures and university governing lished the field of university technology transfer. It boards viewing technology transfer as a potential has been a successful public policy instrument for revenue source for research and public higher edu- encouraging innovation and increasing the transla- cation. They ask, “Why can’t our state university be tion of university research into new discoveries and just like Massachusetts Institute of Technology or technology useful to society. The system that was Stanford University and make technology transfer created by Bayh-Dole has been extraordinarily effec- into a profitable operation?” Such views are short- tive in helping to facilitate translation of discoveries sighted and, unfortunately, are likely to do more from university research to the marketplace, creating harm than good for improving university technol- benefit to consumers and society, creating jobs, and ogy transfer operations if the focus of such efforts is contributing to the economic competitiveness and to serve the best interests of the public and state and technology leadership of the U.S. Simply put, Bayh- regional development. Former president of Stanford Dole has provided a rich return on public investment University John Hennessey has often noted that the in research. university’s success in technology transfer resulted from its technology transfer office’s willingness to Criticisms of University Technology Transfer take risks and to move technology quickly from the Despite its successes, critics of Bayh-Dole have lab to the marketplace as opposed to focusing on questioned whether universities manage their intel- drafting licensing arrangements aimed at maximizing lectual property for the public good, suggesting that revenue. Says Hennessey: universities use government-funded intellectual As universities, we need to emphasize flexibility property primarily for financial gain and are more and appreciate the good things that happen when interested in the monetization of IP than commer- technology transfers. And the ultimate reward to cialization and societal benefit. They point to the a broad-minded institution consists of the long- emphasis on revenue in evaluating the success of term goodwill and philanthropy, and must always technology transfer offices, the challenges faced by be the greater reward for a university—above and potential industry collaborators in coming to IP terms beyond the revenue… Jim Gibbons [formerly with universities, and reports of universities know- Dean of Engineering] liked to say, ‘At Stanford, ingly licensing to patent assertion entities (“trolls”). we never got a license from Hewlett or Packard By and large, these criticisms are based on a few for the technology developed here. But, even had anecdotes rather than concrete data. Moreover, they we actually charged them for those licenses, those ignore the fact that most technology transfer offices dollars would have only been one one-thousandth and the universities they represent are not deriv- of the donations that HP eventually gave back to ing significant financial gains from their technology the university.’ (7) transfer operations. According to one study, more Moving forward, universities must address criti- than half of university technology transfer programs cisms by increasing the visibility of the public good bring in less money than the costs of their operations, derived from managing university intellectual prop- while only 16 percent generate enough funds to fully erty. Working with colleagues at AAU, APLU, AUTM, cover their operating costs after distribution of rev- and other professional organizations, institutions can enues to their faculty inventors (5). The National raise awareness among policymakers and the public Academies of Sciences, Engineering, and Medicine about their responsible and effective IP management have concluded that even when university inventions and the significant public value derived from this have a high social value, they often don’t generate a work. Where improvements in institutional policy significant amount of revenue (6). In the few instances and practice are necessary, collaboration among where universities do make money from their tech- institutions can also help by sharing innovative and nology transfer efforts, the Bayh-Dole Act requires effective approaches to IP management that help to that these revenues be reinvested back into additional address criticism and further advance the economic support for university-based research and education. and societal impact of technology transfer. However, dwindling state support for institutions has

298 WOODELL AND SMITH Nine Points to Consider The NRC report further stresses the responsibility Sometimes lost in the face of public criticism is that of university leaders to develop and adhere to pat- university IP management, by and large, adheres to a ent and licensing policies and practices that do not set of “core values” that are consistent with universi- predicate licensing on the goal of raising significant ties’ missions of learning, discovery, and engagement revenue for the university, but, to the greatest extent in societal challenges. In 2007, ten leading research practicable, aim to “...maximize the further devel- universities, along with the Wisconsin Alumni opment, use, and beneficial social impact of their Research Foundation (WARF) and the Association technologies.” of American Medical Colleges (AAMC), distilled The NRC report endorses several of the principles these core values into In the Public Interest: Nine set out in In the Public Interest: Nine Points to Consider Points to Consider in Licensing University Technology in Licensing University Technology, the white paper (8). AUTM endorsed the Nine Points and solicited described above. Many universities have developed endorsement from universities and other organi- and implemented policies and procedures drawn zations. APLU and AAU, along with more than 100 from key recommendations made by the NRC. We other research universities, associations, and other provide some examples later in this article. organizations, endorsed the statement. Universities AAU and APLU Committees and their IP management efforts would benefit from reviewing the Nine Points and checking for continuity In 2014 and 2015, both the APLU and AAU between these principles and university policy and commissioned committees to examine the issues practice. surrounding the management of university IP in the public interest. The APLU Task Force on Man- Managing University Intellectual Property in the aging University Intellectual Property was charged Public Interest with examining purposes of university innova- In 2011, the National Research Council (NRC) of tion, technology transfer, commercialization, and the National Academies examined a “generation of entrepreneurship (9). The AAU Working Group on experience, research, and dialogue” (6) in university Technology Transfer and Intellectual Property was intellectual property management. The findings and tasked with reaffirming that the primary goal of uni- recommendations included in the NRC report collec- versity technology transfer operations is to advance tively create a compelling story about the successes of the public interest (10). the Bayh-Dole era. The findings and recommenda- Both the AAU and APLU groups asserted that universities have a responsibility to be good stewards tions also caution universities to be clear about their of discoveries and IP developed from federally funded commitment to the public good through management research. The groups recognized that in recent years, of intellectual property and to be vigilant in making however, some critics have asserted that universi- sure that university policy and practice align with ties’ technology transfer operations place too much public purposes. emphasis on maximizing revenues and not enough The first recommendation of the NRC committee’s on moving discoveries quickly into the marketplace, 2011 report, Managing University Intellectual Property where they can advance the public good. Both groups in the Public Interest, states: released statements outlining principles and propos- The leadership of each institution—president, ing specific steps that research universities should take provost, and board of trustees—should articu- to strengthen their commitment to IP management late a clear mission for the unit responsible for IP policies and practices aimed at advancing the public management, convey the mission to internal and interest, which aligns with the core university mis- external stakeholders, and evaluate effort accord- sions of education, the creation and dissemination ingly. The mission statement should embrace and of knowledge, and public service. articulate the university’s foundational responsi- The recommendations disseminated by APLU bility to support smooth and efficient processes and AAU are presented below, along with examples to encourage the widest dissemination of uni- of the ways in which member universities’ policies versity-generated technology for the public good. and practices align with the recommendations.

TECHNOLOGY TRANSFER 299 RECOMMENDATIONS office’s mission statement and by making the policy 1) Provide a clear statement of purpose for technology highly visible and transparent on the university’s web transfer at your university. site. These policies should also be agreed upon and University leaders should follow the recommenda- endorsed at the highest levels within the university, tion of the National Research Council’s 2011 report, including the university’s governing board. Managing University Intellectual Property in the Pub- 2) Make visible policies that restrict the university from lic Interest, to create a clear university IP policy. As working with entities that acquire intellectual property noted above, the NRC report’s first recommendation rights with no real intention of commercialization. underscores the need for clear university IP policy University leaders should make visible existing that strengthens the connection between this work institutional policies that restrict the university and the public good. This recommendation and other from working with entities (so-called patent asser- aspects of the NRC report make clear the need for tion entities—PAEs—or patent “trolls”) that acquire clarity around the underlying purposes of university IP rights with no real intention of commercializing IP management—public benefit and societal impact. the technologies and instead rely solely on threats Such policies should communicate that universi- of infringement litigation to generate revenue. In ties protect intellectual property first and foremost instances where such policies do not exist, univer- to provide incentive for investment in early-stage sity leaders should move swiftly to establish them. technology, which helps to “encourage the widest For universities, working with such entities does not dissemination.” Universities must, of course, balance support a commitment to public benefit of intellec- the need for wide dissemination with the need to tual property. University leaders should require that recover costs and to emphasize the economic value of technology transfer offices carefully vet the creden- university discoveries. While discoveries and IP own- tials, practices, and reputations of third-party entities ership can lead to additional resources and important that might assist universities in asserting their patent support for university missions, this should not be the rights against infringers. primary goal of such activities. Keeping this necessary Asserting legitimate patent rights is an essential balance in mind, it is essential that university leaders element of the patent system, and other entities may articulate a clear mission and purpose for university provide needed expertise and resources to support IP management, as recommended by the NRC. universities in this area. University policies should The State University of New York’s Stony Brook University, for example, declares the mission of its not prevent the institution from seeking assistance Office of Technology Licensing and Industry Rela- from entities that can legitimately help them protect their intellectual property. Universities should base tions on the home page of that office’s website: their decision about whether to assert any unlicensed Our mission is to bridge Stony Brook innovation patent against a company based on the legitimate with public benefit in partnership with SBU inven- facts of the claimed infringement and only after good tors and the business community. By successfully faith attempts to negotiate a license to such a com- commercializing innovative discoveries into new pany on commercially reasonable terms have failed. products and services, we enhance well-being, In recent years, a growing number of universities return economic benefit to the university com- have developed specific policies and practices that munity, and strengthen the long-term vitality of restrict licensing to entities whose primary business our innovation ecosystem. (11) model is based on using patents to obtain licensing “Public benefit” and “well-being” are primary in this fees from practicing companies. These universities statement of purpose. While Stony Brook does rec- include Louisiana State University, the University of ognize the importance of “economic benefit to the Illinois, Western Michigan University, the University university community,” it is clear from this mission of Delaware, and Washington State University. It is statement that financial return is not the driving also standard practice for universities to include in purpose of the unit. University leaders should work technology license agreements language that requires to emulate Stony Brook’s example by asserting the of the licensee commercialization milestones and primacy of public benefit in their technology transfer benchmarks for the development of the technology.

300 WOODELL AND SMITH If these are not met, the license is withdrawn by the diligent development of the technologies and university. ways to pull the technology back if licensees are At the University of Mississippi, for example, the not actively pursuing the technology by building Division of Technology Management maintains safe- measures to track development. guards against working with PAEs. Patent rights are • Point 3: Strive to minimize the licensing of not sold to third parties, and the university does not “future improvements.” participate in patent auctions. Further, the university WSU strives to minimize licensing of future does not work with entities that lack the expertise and resources to develop a technology, and the univer- improvements by limiting the licenses to currently developed IP. In cases where the licensee’s invest- sity’s standard license agreement requires a written ment and risk taken in developing the invention development plan in which the licensee summarizes warrants, an option to license a narrow scope the proposed product development activities with a of future license is agreed to. In cases where this is timeline. The university is entitled to terminate the warranted, WSU bears in mind the rights of other agreement if the licensee fails to meet pre-established development milestones. This ensures that the tech- WSU researchers and does not issue options to a broad field of use that might tie up other research nology will not be licensed to a patent “troll” and conducted at WSU. guards against technology being licensed to an entity that is only interested in protecting its own IP from • Point 4: Universities should anticipate and the competition. Policies and practices such as these help to manage technology transfer related have become the norm—not the exception—for most conflicts of interest. public and private research universities. WSU has a well-run conflict of interest man- agement committee that handles the conflicts that 3) Reaffirm commitment to In the Public Interest: arise when WSU faculty and students start Nine Points to Consider in Licensing University Tech- companies based on their research. This was nology. implemented as a result of Washington State eth- University leaders should review and support, as ics board giving the state institutions the ability appropriate, the document In the Public Interest: Nine to set up a body to manage these conflicts. This Points to Consider in Licensing University Technology has been in existence for many years now. and align IP management policies and practices with the Nine Points. Universities should publicly docu- • Point 5: Ensure broad access to research ment current policies and procedures and implement tools. new ones as necessary that align with these principles. WSU also makes the research tools developed with Washington State University’s Office of Commer- public funding widely available via material cialization provided the following articulation of the transfer agreements to other academic institu- ways in which university policies align with the Nine tions and the research community in keeping with Points: the policies of the funding agencies and scientific • Point 1: Universities should reserve the right journals. to practice licensed inventions and to allow • Point 6: Enforcement action should be carefully other non-profit and governmental organiza- considered. tions to do so. WSU has not had an occasion to enforce its pat- WSU always reserves the right to practice ents; however, should such occasion arise, WSU licensed inventions and to allow other non- would strive to approach these actions with a profit and governmental organizations to do so. mission-oriented rationale and/or to protect the • Point 2: Exclusive licenses should be structured rights of a licensee as obligated by a contract. in a manner that encourages technology devel- • Point 7: Be mindful of export regulations. opment and use. WSU’s licenses include export control regulation Exclusive licenses are structured to encourage language to ensure federal compliance and to

TECHNOLOGY TRANSFER 301 safeguard the fundamental research exclusion pro- other university leaders are increasingly focused on vided to academic institutions. long-term relationship development and strategic initiatives—beyond simply striking the best licensing • Point 8: Be mindful of the implications of work- deal. University leaders need to examine changes ing with patent aggregators. happening in the field, benchmark for effective prac- WSU strives to enter into licensing arrangements tices, and work toward implementing practices that with only those entities that further develop the technology and diligently attempt to commercial- help the university, along with its public and private ize it. Attempts to engage with entities that partners, to accelerate realization of the benefits of do not further commercialize the technologies university intellectual property. are actively discouraged. WSU pays particular Washington University in St. Louis has worked attention to the patent aggregators to ensure the to implement an innovative approach to addressing primary licensee’s intent is to compile the body of one often-cited type of challenge that universities face IP needed to diligently advance the technology for in undertaking IP management. Critics frequently public benefit as opposed to those aggregators note long timelines and complexity of negotiations whose primary intent is to enforce them against associated with licensing deals. Many universities users for solely monetary benefit. have sought to overcome this challenge by imple- menting new policies that speed up the process and • Point 9: Consider including provisions that ensure that technology is available to develop as address unmet needs, such as those of neglected quickly as possible at reasonable cost to the licensee. patient populations or geographic areas, giv- Washington University has established the Quick ing particular attention to improved therapeu- Start license agreement. Recognizing that the pri- tics, diagnostics, and agricultural technologies mary goal of a technology transfer office is to enable for the developing world. public utilization of university-generated technolo- WSU’s license agreements include measures to gies, Washington University devised the Quick Start reserve rights for continued academic freedom of license agreement to reduce time spent on haggling research as well as the need to meet humanitarian over IP price and royalties. The Quick Start license needs. agreement is a back-end loaded deal structure with Universities should clearly articulate the ways in no upfront payments, no maintenance fees, no past which the university’s intellectual property policies patent costs, one low flat royalty rate, and a success align with the Nine Points, as Washington State Uni- fee at the time of an exit/liquidation event. The agree- versity’s Office of Commercialization has done, and ment allows start-up companies to invest time and clearly articulate how the Nine Points are reflected in money in developing the technology without the appropriate contractual clauses and language when it burden of an immediate payout to the university. licenses university intellectual property. Universities Quick Start offers a robust streamlined approach to should also make sure that this articulation of align- execute start-up license agreements expeditiously and ments is transparent to the public. turns the spotlight on the company’s management team, commercialization strategy, R&D timelines, 4) Implement innovative and effective approaches to and funding status—critical success parameters for a managing university intellectual property. start-up enterprise. University leaders must continue University leaders should identify and implement to study the effectiveness of novel approaches such as innovative and effective approaches to managing Washington University’s Quick Start license agree- university IP and, more broadly, to engaging with ment—as well as practices at Penn State University entrepreneurs and industry. University leaders (12), University of Minnesota (12), and Georgia Tech should work to emulate practices that have been (13), among others—and adopt those that are found effectively adopted by peers. Universities are con- to be most successful at addressing the challenges stantly evolving in how they engage with licensees, of managing university intellectual property in the entrepreneurs, and large corporations. For example, public interest. researchers, technology transfer professionals, and

302 WOODELL AND SMITH 5) Develop appropriate measures of success for intel- or another. New metrics of success in technology lectual property management and technology transfer. transfer include: measures of both what is brought in University leaders should develop procedures to the university and what is sent out; how relevant and criteria for evaluating a university’s technology the institution is to the local innovation ecosystem; transfer unit without relying solely upon measuring how much diversification of research funding IPIRA revenue generation. Rather, evaluation approaches supports; engagement through public-private part- should focus on aligning the work of these units with nerships and product development partnerships; the research university’s core missions of discovery, speed and efficiency of transactions; and stream- learning, and the betterment of our communities and lining of approaches. Gifts to the university are also society at large. There are many indicators of success part of IPIRA’s success metrics. Enhanced reputation of university intellectual property management, and achieved through actions of IPIRA is manifested, in university leaders should develop a framework for part, by gifts even though gifts are not accounted for assessing their technology transfer intellectual prop- in IPIRA. Gifts might also be received a decade after erty practices and effectiveness to include multiple a given company has a good experience with IPIRA. measures that capture and reflect the university’s IP To recognize IPIRA’s contribution, however, a small management mission and do not overly emphasize percentage of gift funding that comes to the campus as revenue generation. a whole is allocated to the office. Universities should APLU’s Commission on Innovation, Compet- consider, as UC Berkeley has, a variety of indica- itiveness, and Economic Prosperity (CICEP) has tors that can be used for measuring the success of examined assessment and measurement of university technology transfer efforts. Doing so will reduce the economic engagement broadly and has identified impression that universities are managing university indicators, including growing faculty and student intellectual property solely for financial gain. interest in IP-related entrepreneurship, expansion of university-industry relationships, and others. FOLLOW-UP EFFORTS Licensing activity is a good measure, as a starting AAU and APLU continue efforts to support insti- point, of the university’s efforts toward commercial- tutions in clarifying the public interest purposes of ization. Revenue, however, is frequently not a good university technology transfer. APLU and AAU indicator since it is often driven by having one major are collecting and disseminating examples, like the blockbuster drug or home run discovery and is not ones included above, of universities implementing representative of the ability of the university to effec- innovative new policies and effective approaches to tively disseminate and transfer knowledge across a technology transfer—examples that demonstrate wide spectrum of disciplines and commercial and alignment with the Nine Points and the NRC recom- non-commercial venues. While universities should mendations or that, in other ways, demonstrate good continue efforts to recover the costs associated with practice that is responsive to economic and societal IP management and to make their technology transfer needs. CICEP is also convening a working group operations revenue neutral and profitable, measures on the evolution of technology transfer, focused on of success should emphasize economic and social highlighting the ways in which technology transfer impacts of university discovery. A set of non-revenue operations are adapting to become more engaged indicators must be part of IP management policies with and responsive to other stakeholders in regional and practice if we are to ensure public benefit of this innovation ecosystems. AAU is leading an effort to work. develop a comprehensive framework and identify The University of California Berkeley Office of examples of alternative ways universities are assessing IP & Industry Research Alliances (IPIRA) provides the effectiveness of university technology transfer an excellent example of shifting away from a sole operations. The two organizations will continue to focus on patents and licensing as measures of success. work together on these efforts and to help raise the IPIRA considers technology transfer to be a long-term visibility of the impacts in the public sphere of uni- relationship with industry, not just one agreement versity technology transfer.

TECHNOLOGY TRANSFER 303 CONCLUSION State University. The AAU Working Group on Tech- The fundamental purpose of university technology nology Transfer and Intellectual Property was chaired transfer offices is to ensure that federally funded and by Bob Brown, President, Boston University and Eric other university research outcomes serve the public Kaler, President, University of Minnesota. Members interest. AAU and APLU support universities pursu- of the AAU working group included: Rebecca Blank, ing technology transfer to enhance the public good Chancellor, University of Wisconsin-Madison; John and to promote economic development. We provide Hennessy, Former President, Stanford University; recommendations to help assure the public and pol- Linda Katehi, Former Chancellor, University of Cal- icymakers that universities continue to be focused ifornia Davis; Richard McCullough, Vice Provost for on the primary missions of research, education, and Research, Harvard University; Jane Muir, Director of service and that technology transfer operations man- the Florida Innovation Hub, University of Florida and agement serves theses missions. Research universities Past President, Association of University Technology and their management of intellectual property and Managers (AUTM); Mark Redfern, Vice Provost for technology transfer are fundamental to ensuring that Research, University of Pittsburgh; Barbara Snyder, outcomes of federally funded and other university President, Case Western Reserve University; John research serve the public interest. Our universities Swartley, Associate Vice Provost for Research and should—and most often do—pursue technology Executive Director, Penn Center for Innovation, Uni- transfer with the primary goal in mind of making versity of Pennsylvania; Satish Tripathi, President, the world a better place, not generating significant University of Buffalo; Michael Waring, Executive additional revenues. We encourage university leaders Director of Federal Relations, University of Michigan; to continue efforts to demonstrate that their institu- and Phyllis Wise, Former Chancellor, University of tions do this work for all the right reasons. Illinois at Urbana-Champaign. Serving as liaisons to both the APLU task force and AAU working group ACKNOWLEDGMENTS were Bob Hardy, Director, Contracts and Intellectual This article is based on work conducted by com- Property Management, Council on Government Rela- mittees established by the Association of Public and tions (COGR) and Steve Heinig, Director, Science Land-grant Universities (APLU) and the Association Policy, American Association of Medical Colleges of American Universities (AAU). Members of these (AAMC). We would also like to give special thanks committees contributed to final reports, from which to Hannah Poulson, Policy Associate at the Asso- this article is drawn. The APLU Task Force on Man- ciation of American Universities for collecting and aging University Intellectual Property was chaired summarizing key data referenced in the article. by Satish Tripathi, President, University at Buffalo and Sethuraman “Panch” Panchanathan, Executive REFERENCES Vice President, Knowledge Enterprise Development, 1. Innovation’s Golden Goose. The Economist. Arizona State University. Members of the APLU task [2002 Dec 12; 2016 Nov 15]. http:// www.econ- force included: Patricia Beeson, Provost and Senior omist.com/node/1476653. Vice Chancellor, University of Pittsburgh; Grant 2. Stevens A, Toneguzzo F, Bostrom D. AUTM U.S. Heston, Vice President for Communications and Mar- licensing survey, FY 2004: a survey summary of keting, University of Central Florida; Duane Nellis, technology licensing (and related) performance President, Texas Tech University; Lita Nelsen, Direc- for U.S. academic and nonprofit institutions, and tor, Technology Licensing, MIT; Bill Tucker, Executive technology investment firms. Northbrook (IL): Director, Innovation Alliances & Services, University AUTM; 2005. of California Office of the President; Doug Wasitis, 3. [AUTM] Association of University Technology Assistant Vice President, Federal Relations, Indi- Managers. AUTM U.S. licensing survey, FY 2015: ana University; Ruth Watkins, Senior Vice President a survey summary of technology licensing (and for Academic Affairs, University of Utah; Caroline related) performance for U.S. academic and non- Whitacre, Vice President for Research, The Ohio State profit institutions, and technology investment University; and David Wilson, President, Morgan firms. Deerfield (IL): AUTM; 2016.

304 WOODELL AND SMITH 4. Pressman L, Roessner, Bond J, Okubo S, Planting university technology. [2007 Mar 6; 2016 Nov M. The economic contribution of university/non- 15]. http://www.autm.net/AUTMMain/ me- profit inventions in the United States: 1996-2013. dia/ Advocacy/Documents/Points_to_Consider. Washington (DC): The Biotechnology Industry pdf. Organization; 2015 [accessed 2016 Nov 15]. 9. [APLU] Association of Public and Land-grant http://www. bio.org/ articles/Value-of-Academ- Universities. Task force on managing univer- ic-Industry-Patents. sity intellectual property. 2016 [accessed 2016 5. Abrams I, Grace L, Stevens A. How are U.S. tech- Nov 15]. http://www.aplu.org/ projects-and-ini- nology transfer offices tasked and motivated: is tiatives/research-science-and-technology/ it all about the money? Research Management task-force-intellectual-property/. Review. 17(1):1-34; 2009. 10. [AAU] Association of American Universities. 6. [NRC] National Research Council. Managing Working group on technology transfer and intel- University Intellectual Property in the Public lectual property. 2015 [accessed 2016 Nov 15]. Interest. Washington (DC): The National Acad- https://www.aau.edu/ WorkArea/ DownloadAs- emies Press; 2011. set.aspx?id=16025. 7. Aycinena P. Stanford’s John Hennessey. 2004 11. Office of Technology Licensing and Industry [accessed 2016 Nov 15]. http://www. aycine- Relations. [accessed 2016 Nov 15]. http:// re- na. com/index2/index3/archive/hennessy.html. search.stonybrook.edu/otlir. 8. California Institute of Technology, Cornell 12. Atlantic Information Services. UM, Penn State University, Harvard University, Massachusetts finding success with revamped IP policies, Institute of Technology, Stanford University, options. Report Research Compliance. 12(6):1–3; University of California, University of Illinois, 2015. Chicago, University of Illinois, Urbana-Cham- 13. Georgia Tech Research Corporation. Industry paign, University of Washington, Wisconsin engagement: contract continuum. Atlanta (GA): Alumni Research Foundation, Yale University, Georgia Institute of Technology; c 2016 [accessed Association of American Medical Colleges. In the 2016 Nov 15]. http://industry. gatech.edu/ public interest: nine points to consider in licensing contract-continuum-industry.

Technology and Innovation, Vol. 18, pp. 305-314, 2017 ISSN 1949-8241 • E-ISSN 1949-825X Printed in the USA. All rights reserved. http://dx.doi.org/10.21300/18.4.2017.305 Copyright © 2017 National Academy of Inventors. www.technologyandinnovation.org UNIVERSITY SEED CAPITAL PROGRAMS: BENEFITS BEYOND THE LOAN Donna L. Herber , Joelle Mendez-Hinds , Jack Miner , Marc C. Sedam , 1 2 1 3 Kevin Wozniak , Valerie Landrio McDevitt , and Paul R. Sanberg 1 4 1 1 USF Research & Innovation, University of South Florida, Tampa, FL, USA 2 Office of Technology Transfer, University of Michigan, Ann Arbor, MI, USA 3 The Office of Research, University of New Hampshire, Durham, NH, USA 4 Office of Industry Engagement, Georgia Tech Research Corporation, Atlanta, GA, USA While seed funding for start-up companies certainly provides crucial cash necessary to conduct business, the advantages of these initial infusions go well beyond the actual monies received, particularly for university-based technology start-up companies. Additional benefits for the institution and community can be realized when the seed funding comes from the academic institution where the technology was invented. These benefits include expanded funding opportunities, hiring and retention of top entrepreneurial faculty, goal setting, entrepreneur development, economic development, and university engagement. Examples of seed loan programs at both the regional and university level are numerous, and several case studies are presented to highlight the variety of benefits. We end with a consideration of the metrics that can be used to measure the success of these programs, including revenue generation as well as more traditional technology transfer aims, such as development of industry partnerships and realizing public good from the commercialization of academic research. Key words: Seed funding; Start-up; Technology transfer As the U.S. economy starts to show signs of recov- licensing and start-up activity are very strong, includ- ery (1), university technology transfer offices are ing 914 new companies created, an increase of 11.7% shifting their business aims and increasingly focus- over prior year” (5). ing on start-ups and the development of industry AUTM’s definition of a start-up is a company relationships (2). Moreover, university leaders now formed specifically for the purpose of commercializ- regard technology transfer as a critical component in ing a technology developed at an academic institution attracting top tier faculty and students (3), many of (5). The broader, quintessential definition of a start-up whom are seeking entrepreneurial opportunities (4). company is, “a company that is in the first stage of The Association of University Technology Managers its operations” (6). Oftentimes, these companies are (AUTM) corroborates this increased interest in its initially financed by their entrepreneurial founders 2014 fiscal year report, reporting that “institution as they endeavor to capitalize on delivering a product _____________________ Accepted November 30, 2016. Address correspondence to Paul R. Sanberg, USF Research & Innovation, University of South Florida, 3702 Spectrum Boulevard, Suite 165, Tampa, FL 33612-9445, USA. Tel: +1 (813) 971-5570; Fax: +1 (813) 974-4962; E-mail: [email protected] 305

306 HERBER ET AL. or service for which they feel there is a demand. On BENEFITS account of the early stage of development, limited revenue, or high costs, many of these small-scale Expanded Funding Opportunities ventures cannot be maintained long term without The primary goal of any funding mechanism is to an influx of additional funding, usually from venture provide cash for the company to further develop a capitalists (6). product or service. However, getting that first dollar In order to be successful, start-ups clearly need is a huge challenge (9), and seed loans—along with funding. Some traditional mechanisms of funding for founder money and sweat equity—can provide those the development and commercialization of a technol- crucial first dollars for funding a project. Beyond ogy include federal awards, such as those from the this initial benefit, one of the peripheral effects of a Small Business Innovation Research (SBIR) and Small seed loan investment is the attraction of more fund- Business Technology Transfer (STTR) programs, ing towards the project, basically acting as a money donations from friends and family, angel investors, magnet (10). This added financing can be in the form venture capitalist investors (VCs), and various state of additional founder investment as well as friend and local inducement programs. However, without a and family contributions and angel investment. In mature entrepreneurial ecosystem or significant state some cases, the seed loan can be used to leverage or local economic development, initiatives focused regional or state funds through matching programs on providing early-stage capital funding for nascent (11). Where no matching programs exist, the uni- start-up ventures remain elusive when the relative versity program can be used as a catalyst to bring risk is much greater than the possibility of a financial partners to the table with matching money as well as return on investment. University start-ups are at an to encourage these groups to partner with the uni- even greater risk in many cases than other start-up versity seed loan program to increase the amount of ventures, as the technologies are often far more early- the award. At the federal level, reviewers for the SBIR stage, sometimes not much more than sludge in the and STTR programs are more likely to fund projects bottom of a petri dish or drawings on the back of that have demonstrated some funding to date (12), a napkin (7). Communities and states that provide making university seed funding more important. entrepreneurial infrastructure create an environment This last benefit of aiding with SBIR and STTR can be where university technology transfer can flourish and further augmented by creating crucial relationships benefit from the technology start-ups and business with established industry, as many companies are expansion that result (4). poised to partner for SBIR programs (13). A more recent development in start-up financing, one designed to bridge funding gaps, lies within the Focusing the Company university itself. Universities around the globe have Goal setting can be challenging for university expanded their traditional missions and stepped up start-ups, particularly as the projects initially begin as to fill the gap in early-stage funding with programs research ventures rather than as commercial endeav- originating from university foundations, offices of ors. Many seed programs require their beneficiaries research, and technology transfer offices (8). These to outline specific activities, budgets, and person- programs, which come in the form of grants, loans, nel, and this can kick-start commercial activities by and convertible debt, can target both technologies impelling the start-ups to focus on specific aspects (pre-license) and companies (post-license). Programs of their projects. An indirect but tangible benefit of based at the university are uniquely poised to bridge seed loan programs, then, is to focus companies on the gap between academic research and commercial- concrete, short-term goals that incrementally move ization, as they are housed at the very institution that them towards the larger goals of successful commer- spawned the technology in the first place. While the cialization (14). An overall acceleration of projects money is an essential element, there are many benefits can occur through the achievement of short-term beyond the loan itself. The peripheral effects on the goals (12 to 24 months), which can then lead to over- university, company, technology, founders, students, all acceleration of the time to commercial product and local economy are numerous. launch, acquisition, strategic partnership, or other long-term goals.

UNIVERSITY SEED CAPITAL 307 Entrepreneur Development University Engagement University seed cap programs can be instrumental University-based seed funds can act as a growth in developing entrepreneurship among faculty and driver for a variety of university programs. A dedicated students because these programs provide the funds seed fund demonstrates a university’s commitment to that make it possible for them to dedicate their com- the advancement of technology and the creation of plete attention to their business ventures. A primary start-ups, which can attract seasoned entrepreneurs concern for many new faculty entrepreneurs is time (19). Faculty may also find start-ups more attractive management, as they balance commitment towards as they balance their academic responsibilities and the company and commitments as an academic. their companies. One of the measures of success for Similarly, many students find themselves without university technology transfer offices is the number sufficient time for their ventures because they are of new start-ups created in a given fiscal year (5). forced to seek a primary employer upon gradua- Seed programs dedicated to the funding of promising tion while their start-up gets relegated to a hobby. new start-ups can drive the formation of new entities By providing seed funding, the university can enable in order to qualify for the seed loans. Many seed the founder to dedicate more time (sometimes up to loans are related to incubator programs, resulting in 100%) to the commercial success of the company, increased incubator participation and occupation even if it is just for a year, allowing the start-up to (20). Gap activities to move the basic research into reach key development milestones. In addition to the development stage can be funded by the seed dedicated office time, this seed money also makes it loans, often resulting in sponsored research at the possible for them to participate in programs such as university in the inventor’s lab. Many matching pro- the National Science Foundation (NSF) Innovation grams are designed to be used solely for sponsored Corps (I-Corps) and those provided by incubators research at the university (11). This close tie with the and accelerators, which can also be crucial to their university also leads to increased potential student entrepreneurial education. By allowing the founder involvement by moving students from the research to remove his or her academic hat and take on the laboratory into the development of the technology at mantle of a business person, the seed program can the company. Finally, many programs use convertible assist in the transition of the company from a research debt, allowing for an equity position in the company project to a commercial enterprise (15,16). Likewise, for the university, thereby expanding the potential the entrepreneurial and business experience gained financial benefit to the university (Table 2). by the founders when allowed to focus full time on the company can be invaluable. CASE STUDIES Economic Development University of South Florida Research Foundation Universities are continuously asked to describe Seed Capital Accelerator Program their economic impact on the local region (17). One The University of South Florida Research Foun- often-cited area of direct impact is the formation of dation’s Seed Capital Accelerator Program (USFRF companies and new job creation (18). In light of this, SCAP) for companies affiliated with the Tampa Bay many seed programs are restricted to either state or Technology Incubator (TBTI) was designed to sup- interstate regional companies, thereby encouraging port and provide funds to new and existing TBTI physical location in the requisite area (Table 1). While affiliated start-ups that were formed based on the start-ups typically are not large-scale employers, once licensing of USF technologies (21). The program pro- funded, these micro-entities do begin hiring efforts, vides up to $50,000 of loan funding to enable start-ups thereby further encouraging job creation in the local to quickly improve the odds of overcoming immediate region or state. Particularly, when companies are obstacles to commercialization. Activities are focused affiliated with universities, there is a natural flow of on providing a measurable outcome and return on students through internships and direct employment. investment in the near term. The objective of the Some programs have student participation as part of USFRF SCAP is to help companies reach specific goals their funding requirements, especially when graduate in one year or less, allowing start-ups to reach criti- students familiar with the research can be involved (11). cal development milestones and get to market more

308 HERBER ET AL. Table 1. Examples of Regional Seed Loan Programs State Fund Name Details California UC Ventures Proposed $250 million venture fund, seeded with money from the UC endowment, for commercial opportunities arising out of California’s state university system (27). Florida Florida Institute Seed The Institute provides between $50,000 to $300,000 in seed capital fund funding either as debt or equity. Qualified companies must be located in Florida, developing a technology developed by publicly supported research organization in the State of Florida (including state universities), and secure matching funds (www.florida- institute.com). Georgia Georgia Research Designed to help create new ventures out of research labs. Alliance GRA Venture Includes proof of concept grants, 1:1 matching grants for Program company launch, $250,000 loans, and a venture fund (gra.org). Illinois Illinois VENTURES Seed and early-stage technology investment firm focused on research-derived companies in information technologies, physical sciences, life sciences, and clean technology. Based on work conducted at Midwest Universities and federal laboratories (www.illinoisventures.com). Maryland TEDCO Technology Provides up to $100,000 to support projects coming out of commercialization Maryland companies that fall into these catagories: license or fund research agreement with a publicly supported research organiza- tion in the State of Maryland (including Maryland universities); incubator affiliated; or TEDCO entrepreneurial development program (28). Michigan Michigan Initiative for All 15 Michigan public universities are eligible to compete for Innovation and awards of up to $100,000 per project. Repayment of three times Entrepreneurship Gap the award amount is made through a small percentage of start-up Fund revenue (29). quickly. TBTI and USF Patents & Licensing provide Clearspec was awarded a $50,000 convertible note to support and training along the way and supervise fund the national market launch of the speculum. funded tasks. The funding provided to companies is The funding was extremely timely, as it permitted contingent on agreed-upon project objectives being what was initially a small regional product launch met and may be used to build prototypes, obtain to be expanded into a national launch. The publicity materials, pay salaries, contract for services and assis- generated from the launch has attracted potential tance outside the university, or cover other expenses acquisition partners and accelerated sales volumes. as approved. This case demonstrates that even mature start-ups can ClearSpec benefit from the acceleration of the project afforded ClearSpec, LLC was founded in 2011 in Boca by a seed loan. Two additional programs offered by Raton, Florida, by serial entrepreneur Navroze Mehta the State of Florida contributed to the early progres- to develop a novel sheathed vaginal speculum (www. sion of ClearSpec through manufacturing design clearspecmedical.com). The sheath was invented by and clinical testing, primarily the State University USF physician Dr. Rony Francois and is used during Research Commercialization Assistance Grant and gynecological exams for better visualization. As a the Florida Institute for the Commercialization of participant in the second round of the USFRF SCAP, Public Research Seed Capital Loan.

UNIVERSITY SEED CAPITAL 309 Table 2. Examples of University Seed Programs Institution Fund Name Details Indiana University Innovate Indiana Fund A $10 million fund provides equity seed capital for company formation and to support new ventures at early stages. This fund is available to individuals with an IU connection to start, nurture, and grow technology start- ups and support faculty and entrepreneurs (iufund.iu.edu). Moscow Institute of Phystech Ventures Venture capital fund focused on incubating and growing Physics and Moscow Institute of Physics and Technology related tech Technology companies that solve a measurable problem on a large existing or rapidly growing and sizable market in IT, energy, clean-tech, new materials, and high-tech devices. As an individual investor, it aims to invest around $500,000 in projects, but it is willing to offer more in syndicate deals with other VC firms and business angels (phystechven- tures.com). New York NYU Innovation A seed-stage venture capital fund created in 2010 to invest University Venture Fund exclusively in start-ups founded by and/or commercializing technologies and intellectual property developed by current NYU students, faculty, and researchers. The Fund makes approximately five to six investments per year, from $100,000 to $150,000 each (equity and convertible debt), in partnership with other angel investors and/or VC firms (30). The Ohio State Technology Concept Joint fund from OSU and Ohio Third Frontier for University Fund university start-ups. Concept investments range from $25,000 to $100,000 (convertible note), supplemented by funds from the entrepreneur and co-investment partner(s) (31). Penn State Fund for Innovation Multi-stage funding, including technology proof of concept, company formation, and commercialization activities. Commercialization awards range from $50,000 to $100,000 (32). Purdue University Elevate Purdue Foundry Two tiers of funding for Purdue affiliated start-ups: the Fund “Black Award,” a $20,000 convertible nonrecourse note, and the “Gold Award,” for up to an additional $80,000 debt or equity (22). University of e@UBC Seed Fund Provides seed funds (generated from donations to UBC) for British Columbia companies where at least one of the founders, or key managers, is a current UBC student, faculty, staff member, or recent alumni; new businesses based around research undertaken at UBX (33). University of Innovation Fund A $20 million investment fund focusing on commercializ- Chicago ing early-stage research and supporting emerging compa- nies at the University of Chicago. Grants and investments range from $25,000 to $100,000. For awardees that are not and will not imminently transition to a legal commer- cialization entity, Innovation Fund awards are granted. For awardees that are legally incorporated, Innovation Fund awards will be given in return for convertible debt (https://cie.uchicago/edu/innovation-fund).

310 HERBER ET AL. University of Growth Investment Provides growth equity to the University’s leading spin-out Edinburgh Fund and start-up companies, investing between £100,000 to £400,000 for spin-outs with very high growth potential as part of a larger funding round involving professional investors. Any investments will be made as part of a larger funding round with professional investors (www.oldcollege- capital.com). University of XLR8UH Multi-stage funding, including technology proof of concept Hawaii ($25,000); commercialization ($50,000); and follow-on funding during a qualified round of financing of up to $100,000 (www.xlr8uh.com). University of Michigan Investment in A $25 million investment venture fund. Investments of up to Michigan New Technology $500,000 of university funds in start-ups based on U-M Start-ups Program technology, after they have secured initial funding from a qualified venture capital firm (34). University of Discovery Capital Providing early-stage funding to start-up companies based on Minnesota Investment Program university-discovered technology and innovation; invests up to $350,000 in equity financing once the company has secured a matching investment of an equal or greater amount from an outside investor (35). University of Seed Capital Provides up to $50,000 of loan funding to enable university- South Florida Acceleration Program discovered start-ups to quickly improve the odds of overcom- ing immediate obstacles to commercialization and provide measurable outcomes and return on investment in the near term (www.research.usf.edu/rf/seed-accelerator.asp). University of Texas Horizon Fund Help UT start-up companies make the leap from the university lab and boost its small early investments, thereby helping a start-up attract funding from other investors. This is a $22.5 million fund allocating $100,000 to $2 million per award to UT start-ups (36). University of Utah Commercialization Technology and Venture Commercialization Engine funds are Engine Funding allocated under one of two partnership models: 1) for Program technologies not yet licensed to a company, the funding is non-dilutive and total amounts will be considered during licensing negotiations and 2) for licensed technologies, funding is structured as a non-interest bearing convertible note (www.tvc.utah.edu/tco/engine-funding.php). University of Ideadvance Seed Fund The Ideadvance Seed fund is designed to create new Wisconsin companies from ideas and technologies discovered at University of Wisconsin System campuses and at UW- Extension. Ideadvance grants are also designed to provide start-up “gap” funding. Funds are available, from $25,000 to $50,000 for evaluating customer need and developing a business model. Follow-on funding requires a 1:1 funding match (uwideadvance.org). Washington State Commercialization CGF awards are intended to be the final funding step for University Gap Fund near market-ready technologies in the areas of clean tech, engineering, human and animal health, agricultural, and/or information technologies. Awards of up to $50,000 are made, with a maximum of $5,000 of the proposed budget allocated to business development activities. Funds are distributed using a milestone-driven process with stipulated goals reached before the next funding increment is approved (commercialzation.wsu.edu/Researchers/CGF).

UNIVERSITY SEED CAPITAL 311 Moterum Purdue Foundry Fund: SPEAK MODalities Moterum, Inc. was founded in 2014 by serial entre- SPEAK MODalities, LLC, founded in 2013, was preneurs David Huizenga and Mark Chandler to born out of research conducted at Purdue Univer- develop the Gait Enhancing Mobility Shoe (GEMS). sity by Dr. Oliver Wendt (www.speakmod.com). Dr. GEMS was invented by Dr. Kyle Reed, an assistant Wendt created software applications derived from professor of mechanical engineering, and then grad- clinical research into the efficacy of augmentative uate student Dr. Ismet Handzic for the rehabilitation and alternative communication in autism. SPEAK of stroke patients who have problems walking. As a all!™ is a sensory-friendly communication app that participant in the second round of the USFRF SCAP, allows children to construct and verbalize simple Moterum was awarded a $15,000 convertible note to sentences via graphic symbols. SPEAK more!™ tar- fund the production of a clinical-grade prototype. gets vocabulary learning and enhances complexity of Incorporated in South Carolina, Moterum quickly utterances in autistic learners who communicate via moved to establish a location in Tampa, Florida. The tablets or other speech-generating devices. SPEAK availability of the loan from USFRF SCAP acceler- MODalities benefitted from several funding programs ated the formation of Moterum and encouraged it to offered through Purdue. Initially, the technology was choose a Tampa location in the USF incubator, TBTI. created for the iPad. A $20,000 Black Award from the The loan was then matched by the Florida High Tech Purdue Foundry Fund funded the development of Corridor grant program, which triggered additional an Android-based version (22). SPEAK MODalities founder funding, ultimately leading to hundreds of also received grants from Purdue for the translation thousands of dollars in sponsored research at USF. of the prototype into a commercial version of the Moreover, Dr. Huizenga has deeply engaged with software and the development of follow-up applica- Dr. Reed’s lab and participated in the NSF I-Corps tions. One of the biggest advantages of the awards was program to evaluate yet another rehabilitation tech- the facilitation of a continued collaboration with the nology developed in Reed’s lab. university, which funded and enabled research-driven products, essentially acting as the R&D department Scientific League for the company. Seed funding from Purdue demon- Scientific League, LLC was founded in 2011 in strated the university’s commitment to the project, Tampa, Florida, by USF College of Engineering Ph.D. making it even more attractive to investors, thus gen- graduates Samuel DuPont and Audrey Buttice (www. erating follow-on funding. scientificleague.com). Dr. DuPont and Dr. Buttice created STEM education materials for K-12 based University of Texas Horizon Fund: Cardiovate on the Superhero Training Network. As a partici- Cardiovate, Inc. was founded in 2012 by Jordan pant in the first round of the USFRF SCAP, Scientific Kaufmann, Mauli Agrawal, and Steven Bailey and League was awarded a $50,000 convertible note to focused on Dr. Kaufmann’s stent-graft-tissue engi- fund the production of volumes three and four of neering scaffold for aneurysm repair (TESAR), a their video-based materials. The SCAP funds accel- technology designed to prevent aneurysm leakage erated acceptance of the program by the educational following cardiovascular surgeries (www.cardiovate. community, and the loan was allocated in two $25,000 com). The TESAR technology was invented at the tranches, each contingent upon the results from a val- University of Texas at San Antonio in conjunction idation study. Upon graduation, the funding allowed with the University of Texas Health Science Center at Dr. DuPont and Dr. Buttice to work full time on the San Antonio. Cardiovate received a $50,000 Horizon project without needing to seek outside employment. Fund award to continue the technology development Together, the validation results and commercial mate- after a successful pilot study in animals at the uni- rials led to a contract with a large school district. versity (23). The funds allowed Kaufmann, Agrawal, and Bailey to further refine the manufacturing of the TESAR, secure lab space to further test the device, and support additional market research. The market

312 HERBER ET AL. research led Cardiovate to shift initial development Washington State University Commercialization to a vascular graft to regenerate peripheral vascular Gap Fund (CGF): Reducing Implant Infection tissue before further development of an aneurysm Dr. Amit Bandyopadhyay is one of seven research- treatment. The hope is to ultimately license the ers at Washington State University who received gap technology to a larger corporate partner.  These key funding in 2014 to advance his work in developing actions led to the hiring of Mike Standeford, a sea- novel materials that can improve the design and safety soned CEO who could propel the technology and of joint implants. These materials can be used to create company forward. products that are resistant to infection and reduce the release of metal ions that might build up in the soft University of Chicago Innovation Fund: Genomic tissue of the body, thereby increasing a patient’s risk Prescribing System of cancer. Such technologies are ultimately geared The Genomic Prescribing System (GPS) evolved towards enhancing patient well-being and reducing out of the University of Chicago’s 1200 Patients health care costs overall. By providing critical finan- Project, a study to determine the use of genotype cial assistance to advance inventions that are near information by physicians in a typical health care set- the end stage of research but still require additional ting. The GPS system is a database of patient genetic development before entering the marketplace, the profiles and their responses to specific drugs. GPS CGF helps researchers to get across the low-funded sends that information to doctors who can use it for period of time between academic grants and private comparative analysis. GPS is the brainchild of Dr. investments, the so-called “valley of death” (26). Mark Ratain, professor of medicine, and Dr. Peter O’Donnell, assistant professor of medicine, both of FUTURE the University of Chicago, which provided $100,000 Given the recitation of benefits, one obvious ques- in financial support for the project through its Inno- tion is: How do we measure the success of university vation Fund. The funds are designated for external funding programs? First, we need to recognize that validation of the database (24). The project has also there are direct and indirect measures of success. attracted Ken Bradley, who is the business lead, and Direct measures can include financial criteria, such the investment firm ARCH Venture Partners. as loan repayment or equity payout. Indeed, some funds are managed similarly to traditional angel or Georgia Institute of Technology: Suniva venture funds, with a direct goal of a positive return Suniva, a start-up out of the Georgia Institute of on investment. Other programs seek to be a source of Technology, is America’s leading solar manufacturer funding and support for the companies, and simply (www.suniva.com). Founded in 2007 by inventor Dr. keeping the fund in the black may be a sufficient Ajeet Rohatgi, Suniva is focused on high-efficiency measure of success even if a profit is not realized. Still photovoltaic technologies. Dr. Rohatgi is the founding other programs use less direct but still quantifiable director of The University Center of Excellence for measures, similar to the AUTM reportable metrics, Photovoltaic Research and Education at Georgia Tech. including numbers of license agreements executed, Georgia Tech provided $100,000 in funding early in companies formed, jobs created, sponsored research the company’s life cycle for portfolio evaluation and generated, follow-on funding procured, products crucial gap studies (25). Suniva is a prime exam- launched, etc. Ultimately, success depends on the ple of a successful private/public partnership with goals of the program, and even these may shift over ongoing collaborations with the university to boost time. cell efficiency, characterize materials, and optimize manufacturing. ACKNOWLEDGMENTS The authors declare no conflicts of interest.

UNIVERSITY SEED CAPITAL 313 REFERENCES 11. Research grants. Heathrow (FL): The Florida High Tech Corridor; c2016 [accessed 2015 Mar 1. At last, a proper recovery. The Economist. 15]. http://www.floridahightech.com/assets- [2015 Feb 14; 2015 Oct 15]. http://www. why-the-corridor/research-grants/. economist. com/news/united-states/21643196- 12. Greenwood G, Greenwood J. SBIR proposal writ- all-sorts-americans-are-feeling-more-prosperous- ing basics: a common, critical omission in phase last-proper-recovery. 2 commercialization plans. Sanibel Island (FL): 2. Huggett B. Reinventing tech transfer: US univer- Greenwood Consulting Group; 2009 [accessed sity technology transfer offices are adopting new 2015 Mar 15]. http://www.g-jgreenwood.com/ models in search of increased return on research sbir-proposal-writing-articles/. investment. Nat Biotechnol. 32:1184-1191; 2014. 13. Lockheed Martin. Small business innova- 3. Malakoff D. The many ways of making academic tion research. [accessed 2015 Mar 15]. http:// research payoff: universities are learning that www.lockheedmartin.com/us/suppliers/govt- commercialization means more than patents, programs/sbir.html. licensing fees and startups. Science. 339:750; 14. Cohan P. 3 simple goals you must set for 2015. your business to succeed. TIME. [2012 4. Innovation Associates, Inc. Accelerating June 21; 2016 Jun 1]. http://business.time. economic development through university com/2012/06/21/3-simple-goals-you-must-set- technology transfer. Reston (VA): Innovation for-your-business-to-succeed/. Associates, Inc.; 2005 [accessed 2016 Jun 1]. 15. Lee JY. Seven hundred days of a startup: a day http://innovationassoc.com/docs/CT_NatRpt. in the life of a medical student in Silicon Valley. ExSumm.pdf. Acad Psychiatry. 38:52-54; 2014. 5. [AUTM] Association of University Technology 16. Christopher PJ. The entrepreneur’s starter kit- Managers. Highlights of AUTM’s U.S. licens- 50 things to know before starting a business. ing activity survey FY 2014. Oakbrook Terrace Chicago (IL): Huron Street Press; 2012. (IL): AUTM; 2014 [accessed 2015 Oct 15]. http:// 17. SRI International. Making connections–eval- autmvisitors.net/sites/default/files/ documents/ uation project to assess best practices in EDA’s FY2014% 20Highlights.pdf. University Center program. [accessed 2016 Jun 6. Investopedia. Start-up. [accessed 2015 Mar 19]. 1]. https://www.eda.gov/tools/files/universi- http://www.investopedia .com/terms/s/startup. ty-centers/Evaluation-of-UC-Best-Practices.pdf. asp. 18. [AAU] Association of American Universi- 7. Tajonar A. How to start a biotech company. Mol ties. Economic impacts of AAU universities. Biol Cell. 25(21):3280–3283; 2014. [accessed 2015 Mar 15]. https://www.aau.edu/ 8. Innovosource. Mind the gap. [accessed 2016 Jun research/article.aspx?ID=9266. 1]. http://www.gap funding.org/. 19. Lovering D. Rebuilding Pittsburgh’s entrepre- 9. Start-up Guide: how to raise seed capital from neurial economy: the talent search. Pittsburgh angel investors. Inc. [1 Feb 2006; 2015 Mar 15]. Today. [2012 Jun 13; 2016 Jun 1]. http://www. http://www.inc.com/guides/start_biz/20797. popcity media.com/features/venturecity2061312. html. aspx 10. Schwartz D. U of New Mexico investment 20. Number of university-hosted start-up incu- fund helps startups attract more capital by bators grows. Homeland Security News Wire. matching with private investors. Tech Trans- [2013 Oct 18; 2016 Jun 1]. http://www. fer Central’s Tech Transfer eNews Blog. [25 Feb homeland security newswire.com/dr20131018- 2015; 15 Mar 2015]. http://techtransfercentral. number-of-universityhosted-startup-incuba- com/ 2015/02/25/u-of-new-mexico-investment- tors-grows. fund-helps-start-ups-attract-more-capital-by- 21. Seed capital accelerator program. Tampa (FL): matching-with-private-investors/. The University of South Florida. [accessed

314 HERBER ET AL. 2015 Mar 15]. https://www.research.usf.edu/rf/ http://www.masu.org/ aboutmasu/partnerships/ seed-accelerator.asp. miie/. 22. Paul J. Purdue startups seek millions in cash this 30. Innovation Venture Fund. New York (NY): semester. [2015 Mar 1; 2016 Jun 1]. http://www. New York University; c2016 [accessed 2015 jconline.com/story/news/college/2015/03/01/ Mar 15]. http://www.nyu.edu/about/universi- funding-startups/24222871/. ty-initiatives/ entrepreneurship-at-nyu/fund/ 23. Office of Technology Commercialization. Austin innovation-venture-fund.html. (TX): The University of Texas System; c2016 31. TechColumbus and The Ohio State Univer- [accessed 2015 Mar 15]. http://www.utsys- sity announce Technology Concept Fund. tem. edu/ offices/ technology-commercialization. Columbus (OH): The Ohio State University. 24. Genomic prescribing system (GPS). Chicago [2013 Dec 19; 2016 Jun 1]. http://tco.osu.edu/ (IL): The University of Chicago. [accessed 2015 techcolumbus-and-the-ohio-state-university-an- Mar 15]. https://cpt.uchicago.edu/page/genom- nounce-technology-concept-fund/. ic-prescribing-system-gps. 32. Fund for Innovation aids research commercial- 25. Georgia Tech startup drives down the cost of ization efforts. University Park (PA): Penn State. clean, green solar power. Atlanta (GA): Georgia [2014 Oct 13; 2016 Jun 1]. http://news.psu.edu/ Institute of Technology. [accessed 2015 Mar 15]. story/330079/2014/ 10/13/ research/fund-inno- http:// industry.gatech.edu/category/success-sto- vation-aids-research-commercialization-efforts. ries/page/2/. 33. e@UBC Seed Fund. Vancouver (CA): The Uni- 26. Clark P. Startup rates are on the rebound. versity of British Columbia. [accessed 2015 Mar Bloomberg Businessweek. [2014 Sep 29; 2015 15]. http://entrepreneurship.ubc.ca/seed-fund/. Mar 15]. http://www.bloomberg.com/bw/ 34. MINTS. Ann Arbor (MI): University of Mich- articles/2014-09-29/entrepreneurship-start- igan; c2016 [accessed 2015 Mar 15]. http:// up-rates-rebound-from-great-recession-slump. ipvideos.engin.umich.edu/resources/mints. 27. University of California proposes creation of new 35. New University of Minnesota funding pro- venture fund to invest in UC innovation. Oakland gram will kick-start companies bringing U (CA): University of California. [2014 Sep 15; 2016 discoveries to market. Minneapolis (MN): Jun 1]. http://www.universityofcalifornia.edu/ University of Minnesota. [2014 Aug 18; press-room/university-california-proposes-cre- 2016 Jun 1]. http://discover.umn.edu/news/ ation-new-venture-fund-invest-uc-innovation. science-technology/new-university-minneso- 28. Technology Commercialization Fund. Columbia ta-funding-program-will-kick-start-compa- (MD): TEDCO; c 2015 [accessed 2015 Mar 15]. nies-bringing. http://tedco.md/program/technology-commer- 36. Tansey B. UT Horizon Fund aims to build, cialization-fund-tcf/. and capture, value from its startups. Xconomy. 29. Michigan Initiative for Innovation & Entrepre- [2013 May 21; 2016 Jun 1] http://www.xconomy. neurship. Lansing (MI): Michigan Association com/ texas/2013/05/21/ut-horizon-fund-aims- of State Universities. [accessed 2015 Mar 15]. to-build-and-capture-value-from-ut-startups/.

314 HERBER ET AL. Technology and Innovation, Vol. 18, pp. 315-318, 2017 ISSN 1949-8241 • E-ISSN 1949-825X Printed in the USA. All rights reserved. http://dx.doi.org/10.21300/18.4.2017.315 Copyright © 2017 National Academy of Inventors. www.technologyandinnovation.org 2015 Mar 15]. https://www.research.usf.edu/rf/ http://www.masu.org/ aboutmasu/partnerships/ seed-accelerator.asp. miie/. 22. Paul J. Purdue startups seek millions in cash this 30. Innovation Venture Fund. New York (NY): semester. [2015 Mar 1; 2016 Jun 1]. http://www. New York University; c2016 [accessed 2015 AMERICA’S SEED FUND: HOW THE SBIR/STTR PROGRAMS HELP jconline.com/story/news/college/2015/03/01/ Mar 15]. http://www.nyu.edu/about/universi- funding-startups/24222871/. ty-initiatives/ entrepreneurship-at-nyu/fund/ ENABLE CATALYTIC GROWTH AND TECHNOLOGICAL ADVANCES 23. Office of Technology Commercialization. Austin innovation-venture-fund.html. (TX): The University of Texas System; c2016 31. TechColumbus and The Ohio State Univer- G. Nagesh Rao , John R. Williams , Mark Walsh , and James Moore 2 1 1 1 [accessed 2015 Mar 15]. http://www.utsys- sity announce Technology Concept Fund. tem. edu/ offices/ technology-commercialization. Columbus (OH): The Ohio State University. 1 Office of Investment and Innovation, U.S. Small Business Administration, Washington, DC, USA 24. Genomic prescribing system (GPS). Chicago [2013 Dec 19; 2016 Jun 1]. http://tco.osu.edu/ 2 Office of Governmental Affairs, United States Patent and Trademark Office, Alexandria, VA, USA (IL): The University of Chicago. [accessed 2015 techcolumbus-and-the-ohio-state-university-an- Mar 15]. https://cpt.uchicago.edu/page/genom- nounce-technology-concept-fund/. In order for America to maintain its innovative and technological competitive advantage, it ic-prescribing-system-gps. 32. Fund for Innovation aids research commercial- is imperative that current policy design favor high growth formation through the catalytic 25. Georgia Tech startup drives down the cost of ization efforts. University Park (PA): Penn State. means of institutional financing. The Small Business Innovation Research (SBIR) and Small clean, green solar power. Atlanta (GA): Georgia [2014 Oct 13; 2016 Jun 1]. http://news.psu.edu/ Business Technology Transfer (STTR) programs have historically served as crucial financing Institute of Technology. [accessed 2015 Mar 15]. story/330079/2014/ 10/13/ research/fund-inno- to help de-risk early-stage technology development and enable validation that encourages follow-on private institution capitalization. With new trends in the Internet of Things, artificial http:// industry.gatech.edu/category/success-sto- vation-aids-research-commercialization-efforts. intelligence, advanced materials, genomics, environmental sustainability, renewable energy, ries/page/2/. 33. e@UBC Seed Fund. Vancouver (CA): The Uni- national security, and many other areas evolving over the years ahead, national governments 26. Clark P. Startup rates are on the rebound. versity of British Columbia. [accessed 2015 Mar bear the responsibility for helping seed the inventive fire that enables economic growth as we Bloomberg Businessweek. [2014 Sep 29; 2015 15]. http://entrepreneurship.ubc.ca/seed-fund/. move forward. Mar 15]. http://www.bloomberg.com/bw/ 34. MINTS. Ann Arbor (MI): University of Mich- Key words: Innovation; Invention; Small business; Research; Development; High-Tech; articles/2014-09-29/entrepreneurship-start- igan; c2016 [accessed 2015 Mar 15]. http:// Economic growth; Public policy; Commercialization up-rates-rebound-from-great-recession-slump. ipvideos.engin.umich.edu/resources/mints. 27. University of California proposes creation of new 35. New University of Minnesota funding pro- venture fund to invest in UC innovation. Oakland gram will kick-start companies bringing U (CA): University of California. [2014 Sep 15; 2016 discoveries to market. Minneapolis (MN): Small businesses—from the high-tech focused to opportunity for wealth creation (3). When reading or Jun 1]. http://www.universityofcalifornia.edu/ University of Minnesota. [2014 Aug 18; mom and pop shops—are the creators of jobs and the watching the news, it would seem that many hip “tech press-room/university-california-proposes-cre- 2016 Jun 1]. http://discover.umn.edu/news/ driving force behind U.S. economic performance. start-ups” are focused on reinventing the internet via ation-new-venture-fund-invest-uc-innovation. science-technology/new-university-minneso- Recognizing this truth, the U.S. government estab- means of engagement that are low risk and focused 28. Technology Commercialization Fund. Columbia ta-funding-program-will-kick-start-compa- lished the Small Business Administration (SBA) in on consumer services. (MD): TEDCO; c 2015 [accessed 2015 Mar 15]. nies-bringing. 1953 in order to help Americans start and develop What do Qualcomm, Symantec, Biogen Idec, http://tedco.md/program/technology-commer- 36. Tansey B. UT Horizon Fund aims to build, their own small businesses. Some might question the LASIK surgery, Roomba®, and 3D printing have in cialization-fund-tcf/. and capture, value from its startups. Xconomy. value that small businesses bring to the table, com- common? All of these companies and/or core tech- 29. Michigan Initiative for Innovation & Entrepre- [2013 May 21; 2016 Jun 1] http://www.xconomy. pared with large established research organizations, nologies were seed-financed by America’s Seed Fund, neurship. Lansing (MI): Michigan Association com/ texas/2013/05/21/ut-horizon-fund-aims- when it comes to innovative science and technol- also known as the Small Business Innovation Research of State Universities. [accessed 2015 Mar 15]. to-build-and-capture-value-from-ut-startups/. ogy development. However, numerous articles (1,2) (SBIR) and Small Business Technology Transfer indicate that small businesses, in particular those in (STTR) programs (henceforth SBIR/STTR programs). the U.S., are the backbone of the global economy. These iconic American technologies and companies Specifically, the endeavors relating to high-growth, were fueled with non-dilutive catalytic seed funding technologically-focused industries bear the greatest from the SBIR/STTR programs. Non-dilutive funding _____________________ Accepted November 30, 2016. Address correspondence to G. Nagesh Rao, Chief Technologist & Geek in Residence, U.S. Small Business Administration-Office of Investment and Innova- tion, c/o SBIR/STTR Programs, 409 3 St SW, Suite 6269, Washington, DC 20416, USA. Tel: +1 (202) 281-8899; E-mail: [email protected] rd 315

316 RAO ET AL. is funding with no loss of ownership, which protects STTR programs showcased 4:1, 14:1, and staggering from loss of profits and control, thus helping to reduce 19:1 dollar returns, respectively, plus extensive job the risks that naturally arise from technology proto- creation valuation (10). typing development. As a result, the developers of The firms that SBIR/STTR seek to invest in are these technologies, which partially or fully originated tackling issues in environmental security, artificial in research laboratories (university and/or federal intelligence, national security, public health, cyber- labs), were empowered to use the notion of a small security, advanced robotics, space exploration, clean business to fully realize the technology’s commercial energy, and agro-tech, among many others. Many of promise. The SBIR program is focused on applied these firms have been founded by technical inventors science and technology development coupled with yearning to capitalize on their creations and unleash a means of requiring the researching entity (in this the true potential of their inventiveness for the benefit case a small business) to actually commercialize the of the global community. technology in today’s growing economy. One unique feature we have within the SBIR pro- The SBIR/STTR programs awarded $2.5 billion gram is its sister STTR program that has a formal of seed funding directly to small businesses last year requirement for small businesses to collaborate with alone and over $43 billion during the last 30+ years a research institution during Phase I and Phase II since the inception of the program in 1982 (annually research and development (R&D) prototype develop- around $2 to $2.5 billion currently) (4). The market ment. The small business company is the prime and caps of just Qualcomm and Biogen Idec alone have must sub-contract 30% of its award to a research insti- a collective valuation of $130+ billion, essentially tution to assist in doing the research. This partnership tripling the return on investment (ROI) of the pro- is essential to bridging the gap between basic science grams over their lifetimes. Looking at the thousands and commercialization. In other words, the SBIR/ of jobs created by both companies in the San Diego STTR programs help to facilitate effective cooperation and Boston/Cambridge regions, respectively, for and diffuse risk by requiring that small high-tech example, one will note that both companies have firms apportion some of their STTR funding to a helped stoke the innovation fires in their respective research institution to aid in the necessary R&D. regions (5-7). That’s a pretty good ROI, but even that A question that is raised a lot is whether this crit- return pales when we consider the numerous positive ical research would have come about on its own of benefits derived from this program for the American free market volition. Figure 1, from a study conducted economy, such as job creation, advances in applied by Professors Albert Link and John Scott, shows the science and technology, economic growth, knowledge critical nature of incentivization that results from the development, and the enabling of futuristic disrup- high-risk, high-reward nature of SBIR/STTR funding tive technology. Simply put, the SBIR/STTR stats are (11). The same study showed the gradual employment astoundingly impressive. One statistic that should be gains that result due to technological validation and of particular interest to the innovation and invention the emphasis on commercialization of technology as community is the number of patents generated by required by SBIR/STTR funding on the small busi- the SBIR/STTR programs: Drum roll please...over nesses. 50,000 patents created (8). That’s an average of seven The SBA and its eleven participating federal patents per day issued since the program’s incep- agency partners also continue to look for ways to tion—patents that have resulted in over 15,000 small improve their outreach and engagement efforts to business firms and/or start-ups created (9). Patents ensure that they are reaching underserved commu- and other forms of intellectual property are tangi- nities. These agency partners include: Department of ble assets that help raise a valuation prospective for Defense, Health & Human Services, Department of high-tech start-ups and small business companies. Energy, National Aeronautics & Space Administra- Recent economic studies conducted around the ROI tion, National Science Foundation, U.S. Department of federal dollars invested into high-tech small busi- of Agriculture, Department of Homeland Security, ness companies by the National Aeronautics & Space Department of Commerce (National Institute of Administration, U.S. Air Force, and U.S. Navy SBIR/ Standards and Technology and National Oceanic

AMERICA’S SEED FUND 317 50 Dentely yes Probably yes 40 Uncertain Probably not Denitely not 30 Percent 20 10 0 DoD NIH NASA DOE NSF Figure 1. Survey of whether or not the research would be performed without incentivization of SBIR funding support. Reprinted by permission from Issues in Science and Technology (Link AN, Scott JT. Real numbers: the small business innovation research program. Issues Sci Technol. 28(4). http://issues.org/28-4/realnumbers-31/), copyright 2012. and Atmospheric Administration), Department greater interest from foreign countries in creating and of Transportation, Department of Education, and implementing similar programs. For instance, the Environmental Protection Administration. The SBA, United Kingdom has their own similar Small Busi- being the programmatic and policy lead for the SBIR/ ness Research Initiative program, and the European STTR programs, has hosted and continues to host a Union initiated the Horizon 2020 program, which series of SBIR Road Tour stops across the country to is similar to SBIR but open to a variety of entities convey the message of the program. Entrepreneurs beyond SMEs. Horizon 2020 will be operating for can meet with program managers at these events to seven years (2014 to 2020) and has been charged with discuss the program, ask questions, and learn about deploying capital to initiate next generation science funding opportunities. Interested entrepreneurs can and technology development (12). A recent op-ed visit www.sbirroadtour.com for more details and to hinted that Canada too needed to initiate a program locate cities the SBA will be visiting this year. As well of this caliber in order to build out their future science as providing the initial gateway business intelligence and technology innovation scene (13). platform, www.sbir.gov also helps inventors, technol- With the advent of globalization and advances ogists, entrepreneurs, and small business firms gain in science and technology permeating industries in access to initial resources and assistance in order to record time and at record rates, we must consider how effectively compete for SBIR/STTR-related funding. to harness and cultivate new innovation ecosystems Furthermore, we highlight upcoming and already moving forward. The academic and independent successful SBIR/STTR-funded firms on SBIR.gov, invention communities are ideal innovation talent helping provide open and transparent evidence of pipelines that should be actively participating in the the success of the inventors and dreamers that the SBIR/STTR programs. The SBIR/STTR programs U.S. government is encouraging to tackle high-risk, serve as catalysts by providing funding opportunities high-reward technological endeavors. that can help enable small businesses to explore their As the program continues to grow in prominence technological potential and provide the tools needed and interest in the high-tech small and medium to profit from commercialization. Including qualified enterprise (SME) scene increases, there has been a small businesses in the nation’s R&D arena stimulates

318 RAO ET AL. high-tech innovation, fosters entrepreneurial spirit, Diego Regional Economic Development Cor- and helps maintain America’s technological leader- poration; 2013 [accessed 2016 Oct 15]. http:// ship in a more globalized economy. www.sandiegobusiness.org/ sites/default/ files/011113-TelecomReport.pdf. REFERENCES 8. Testimony of Jere Glover Before the Comm. on 1. Hecht J. Are small businesses really the backbone Small Business and Entrepreneurship, United of the economy? Inc. [2014 Dec 14; 2016 Oct States Senate (January 28, 2016). http://sbtc.org/ 15]. http://www.inc.com/jared-hecht/are-small- wp-content/uploads/2016/01/ Jere-Glover-Sen- businesses-really-the-backbone-of-the-economy. ate-SBC-SBIR-Reauthorization-Hearing-Testi- html. mony-1-28C.pdf. 2. Washington RA. What’s so great about small 9. [SBIR/STTR] Small Business Innovation business? The Economist. [2011 Jun 30; 2016 Research/Small Business Technology Transfer. Oct 15]. http://www.economist.com/blogs/free- Company listing. [accessed 2016 Oct 15]. https:// exchange/2011/06/ entrepreneur ship -0. www.sbir.gov/sbirsearch/firm/all. 3. Horn J, Pleasance D. Restarting the U.S. small 10. [SBIR/STTR] Small Business Innovation business growth engine. McKinsey & Company. Research/Small Business Technology Transfer. [Nov 2012; 2016 Oct 15]. http://www.mckinsey. SBIR impact. [accessed 2016 Oct 15]. https:// com/global-themes/employment-and-growth/ www.sbir.gov/node/832335. restarting-the-us-small-business-growth-engine. 11. Link AN, Scott JT. Real numbers: the Small Busi- 4. [SBIR/STTR] Small Business Innovation ness Innovation Research program. Issues Sci Research/Small Business Technology Transfer. Technol. 2012 [ accessed 2016 Oct 15] 28(4). Awards. [accessed 2016 Oct 15]. https://www. http://issues.org/28-4/realnumbers-31/. sbir.gov/awards/annual-reports. 5. Park C. Kendall Biogen back. The Tech. [2012 12. Horizon 2020: the EU framework programme Mar 20; 2016 Oct 15]. http://tech.mit.edu/ V132/ for research and innovation. European Union; N13/biogen.html. c1995-2016 [accessed 2016 Oct 15]. https://ec. 6. Blanding M. The man who helped launch bio- europa.eu/programmes/ horizon2020/. tech. MIT Technology Review [2015 Aug 18; 13. Robinson N, Byers C. How Ottawa can pro- 2016 Oct 15]. https://www.technologyreview. vide a powerful spark for innovation. The com/s/540466/the-man-who-helped-launch- Globe and Mail [2016 Dec 9; 2016 Dec 12]. biotech/. http://www.theglobeandmail.com/report- 7. The economic impact of Qualcomm: driving on-business/rob-commentary/how-ottawa- San Diego’s technology growth. San Diego can-provide-a-powerful-spark-for-innovation/ (CA): San Diego Workforce Partnership, San article33271628/.

Technology and Innovation, Vol. 18, pp. 319-330, 2017 ISSN 1949-8241 • E-ISSN 1949-825X Printed in the USA. All rights reserved. http://dx.doi.org/10.21300/18.4.2017.319 Copyright © 2017 National Academy of Inventors. www.technologyandinnovation.org THOUGHTS ON IMPROVING INNOVATION: WHAT ARE THE CHARACTERISTICS OF INNOVATION AND HOW DO WE CULTIVATE THEM? 1 Victor Poirier , Lyle H. Schwartz , David Eddy , Richard Berman , Selim Chacour , 1 1,2 1 1 1,3 James J. Wynne , William Cavanaugh , Dean F. Martin , Robert Byrne , and Paul R. Sanberg 1,6 1,4 1,5 1 1 Institute for Advanced Discovery & Innovation, USF Research & Innovation, Tampa, FL, USA 2 College of Global Sustainability, University of South Florida, Tampa, FL, USA 3 IBM Research Headquarters, Yorktown Heights, NY, USA 4 Department of Chemistry, University of South Florida, Tampa, FL, USA 5 College of Marine Science, University of South Florida, St. Petersburg, FL, USA 6 Morsani College of Medicine, University of South Florida, Tampa, FL, USA This paper will review current thinking about innovation and identify key innovative traits as initial steps in exploring the feasibility of teaching innovative thinking. While education may not be able to create innovative traits in individuals, education may improve the ability of individuals to utilize the traits they already possess. Therefore, we begin by defining innovation and identifying the characteristics, traits, and thought processes of innovative individuals or groups of individuals and the environments that they exist in using the existing literature and personal experience. This information will help formulate a process to educate individuals to better utilize their innovative traits. If we can envision a curve depicting the utilization of traits, where on the left of the curve we would place individuals with a low utilization, on the right of the curve would be individuals with a very high utilization rate, and in the middle a distribution between the two extremes, our goal would be to develop an educational process whereby we could show individuals how to fully utilize the traits they have, awaken traits that are dormant, and, in so doing, shift the distribution toward fuller utilization. With greater utilization of innovative traits, we could then expect to increase the number of innovations that individuals or groups of individuals contribute to our society. Key words: Innovation; Creativity; Entrepreneurship; Abstract thinking; Motivation INTRODUCTION and identifying the characteristics associated with While the innovative process is critical, relatively innovative individuals. Although it is unlikely that little is known about how we can cultivate innova- education can create an innovative trait in an individ- tive thinking. Given the centrality of innovation to ual, education may very well be able to improve the current educational and business efforts, this is a ability of individuals to utilize the innovative traits crucial gap to fill. This paper starts with what we do they possess. Therefore, we place particular emphasis know about innovation, exploring the current views on the characteristics, traits, and thought processes of on innovation, articulating the innovation process, innovative individuals or groups of individuals and _____________________ Accepted November 30, 2016. Address correspondence to Victor Poirier, USF Research & Innovation, University of South Florida, 3702 Spectrum Blvd., Suite 165, Tampa, FL 33612-9445 319

320 POIRIER ET AL. the environments in which they exist. These charac- or all of these things. Positive innovation is viewed teristics, gathered from the existing literature as well as an ongoing improvement of an existing product as from personal experience, can then be used as the or an extension of an existing understanding. It is foundation for an educational process to educate not limited to the development of a new and novel individuals to better utilize the innovative traits that single product. It can be a process of adding bits and they possess and to awaken those that are dormant. pieces to an existing product or process, an addition With improved utilization, individuals could improve that improves what was there in the first place (7). their innovative thinking and increase the quality and Innovation is the extension of understanding to number of innovations they create. reach new technical options and arenas. Innovation includes the strategies and technical supporting What Is Innovation? structures as well as standards and norms that allow Innovation has many different definitions, but, applications, certitude of impact, and entrepreneur- in its most simplistic form, “it is the introduction ship. Positive innovation must provide societal value of something new and different that is brought into and have impact in the present or near future; it must our society” (1), specifically “something different that be better than what exists, and an innovation cannot has impact” (2). Innovation, which is created from be trivial (3). The process of innovation, which we inspiration and creativity, is not limited to the areas of will discuss next, requires seeing what others don’t science or engineering but can be viewed as a univer- see or can’t see. sal concept. For instance, an individual studying the arts should be exposed to the concepts of innovation. THE PROCESS OF INNOVATION We should instill in this nascent artist the desire and The elements of the process to move an inspiration drive to innovate, to create something beyond what to public acceptance can be described as follows: exists, and to develop new art, thus providing the Inspiration—Creativity—Motivation—Entrepreneur- roadmap to excel in his or her domain. Innovative ship—Innovation. We have arrived at this process by thinking is critical to everyday lives, regardless of analyzing the definition of innovation as stated in the individual interests and passions, because it provides prior paragraph and breaking it down into logical societal value (3). In addition to occurring in a variety components. The beginning of the process is usually of domains, innovation may and often does occur associated with a fragmented inspiration that, in time, at the interface of different disciplines and requires is further developed by joining with other fragmented collaboration among individuals from different back- thoughts to finally arrive at a complete creative inspi- grounds and experiences. ration. At this point, the motivated entrepreneur While innovation is critical to improvements in must bring the developed creative thought forward how we live, how we benefit from the changes that to determine if it has societal acceptance, is better occur, and how we can enjoy life more fully, innova- than what exists, and has value and impacts society tion is not all positive. The literature is replete with in the near term as well as in the long term. However, what we might call negative innovation (4,5). The this process is not always orderly, as the motivation technological unemployment that is created from a to accomplish something great can take precedence technological advancement or innovation, as exten- over inspiration in initiating the innovation process. sively covered by MIT’s David Autor (6), is one clear In the innovation process, an inspiration or a cre- example. Oftentimes, it is more complex still, encom- ative thought cannot stand on its own. Inspiration is passing both sides of the dichotomy. subordinated to innovation, as innovation requires Innovation can come into being as a new idea, cre- significant societal value and can stand the test of ative process, or, as is in most cases, the evolutionary time. The innovation must prove that it is novel and improvements on existing products, processes, or genuinely new and is valued sufficiently to allow concepts (2). It improves an object, device, or con- the process of entrepreneurship to begin to add it cept, or creates a novel process that could be used to to the culture of our society. Innovation is rarely solve a problem. A particular innovation can be one created by one individual who has an inspiration;