IN THE NEWS

Director’s Message 2

Laser Dentistry 3

Gene Inactivation 4

BECKMAN LASER INSTITUTE Winter 2000-2001

ith fresh funding in the nary environment with access to the Institute W amount of $1.1 million from most sophisticated scientific and the Arnold and Mabel Beckman medical technologies,” explains Insti- Foundation, the Beckman Laser Insti- tute Director Michael Berns. Launches tute is set to launch a five-year Beckman Fellows will conduct re- postdoctoral fellowship program for search on the use of lasers to study New Fellows young scientists in the field of opti- biological and chemical processes in cal biology. molecules, cells, and tissues, as well “This gift allows us to recruit the as applications of this knowledge to Program nation’s brightest young scientists the development of biomedical engi- and place them in an interdiscipli- neering systems for optical diagnos- tics and the treatment of disease. At the end of their appointments, the Beckman Fellows are expected to as- sume tenure-track positions at major universities in the . “Optical medicine holds enor- mous promise in fields like cancer treatment, cellular analysis, and non- invasive physiological imaging, and the Beckman Fellows will be part of our effort to put these exciting tech- nologies in research and medical facili- ties in this country and around the world,” says Berns. The Beckman Foundation will Alexander Karn (left), Senior Writer for Development, accepts the Disneyland Community Service Award for Health Services on fund additional research fellowships behalf of the Institute (see newsbrief below). at four other Beckman Centers across the country. ■

MAGIC KINGDOM AWARD vices. In addition to a $5,000 check, Newsbriefs he Beckman Laser Institute was the Disney Awards Committee pre- T honored at the 43rd Annual sented BLI with a limited edition Disneyland Community Service lithograph depicting Disneyland’s Awards ceremony, held Thursday, Fantasyland castle (see photo above). September 14, 2000, in the Disneyland The cash award will help to sup- Magic Kingdom. port the Children’s Treatment Fund BLI was one of six Orange County (CTF), an indigent care program es- non-profit organizations to earn a dis- tablished in 1989 for the treatment of tinction in the category of Health Ser- (newsbriefs continued on p. 7)

1 D I R E C T O R’ S M E S S A G E

Is Technology Transfer Steaming on the Right Track? by Michael Berns, Ph.D. fer” programs horses of an entirely other principal just doesn’t want to Arnold and Mabel Beckman Professor different color? share inventorship. I have heard sto- President and Director My concern stems from my own ries of scientists supplying their experiences and observations. Over “competitors” with incorrect infor- wo of my mentors, Arnold the years, I have watched repeatedly mation at meetings so as to send ri- T Beckman and David Packard, as inventors squabbled over owner- vals down some “blind alley.” I have were among the pioneers in the trans- ship rights and royalty percentages. seen universities (not UCI) approach fer of ideas from academia to the real I have seen faculty struggle with al- commercialization of intellectual world. Their efforts have left an un- location of their time to potential property so aggressively that science mistakable imprint on society, aca- royalty-yielding research projects at “for the sake of the idea” has all but demia, and the business world. But the expense of innovative basic re- disappeared. I have seen education have these shining examples of in- search. I have seen students, collabo- and the academic process corrupted. dustry and innovation become relics rators, and post-docs excluded from One of my colleagues from a pres- of the 20th century? Is the 21st cen- lab discussions because of proprietary tigious east coast university recently tury academic-turned-entrepreneur a issues surrounding their projects. I have told me about an incident I could reflection of these 20th century pro- seen colleagues who could benefit hardly believe. A scientist from a totypes, or are they and the rapidly from close collaboration keep their biotech firm was giving a widely pub- proliferating academic “tech trans- distance instead because one or the licized lecture at my colleague’s cam- pus. Just before the seminar started, Beckman Laser Institute a university official announced that University of , Irvine (1) individuals not employed by the 1002 Health Sciences Road East, Irvine, CA 92612 (949) 824-4713 (Administration) (949) 824-8413 (Fax) university would have to sign a se- http://www.bli.uci.edu crecy agreement and (2) university employees in attendance were bound Board of Directors by the secrecy agreement which the Linda Cahill, Chairman Arnold O. Beckman, Ph.D., Chairman Emeritus university had already signed with Michael W. Berns, Ph.D., President, CEO, and Vice Chair their guest lecturer’s biotech firm. At- George E. Hewitt, Secretary/Treasurer tendees were basically prohibited George L. Argyros Brian R. Demsey Richard A. Nesbit, Ph.D. from discussing details of the semi- Patricia Beckman Harry Gray, Ph.D. Robert L. Stoy, Ph.D. Thomas C. Cesario, M.D. Gavin S. Herbert David S. Tappan, Jr. nar with people from outside institu- Richard P. Kratz, M.D. tions. I forgot to ask whether students Administration in attendance were asked to leave as Michael W. Berns, Ph.D., President and CEO many probably were not employees J. Stuart Nelson, M.D., Ph.D., Associate Director of the university. Is this really what Bruce J. Tromberg, Ph.D., NIH LAMMP Resource Director academia stands for: secrecy and in- George M. Peavy, D.V.M., Veterinary Director Petra Wilder-Smith, D.D.S., Ph.D., Dental Research Director hibition of the free exchange of infor- Rachel Schreiman, C.P.A., M.B.A., Director of Finance mation and ideas? Joyce Zeiler, R.N., Nurse Director I’m also concerned that this kind Erin Miller, Development Director of atmosphere will help to accelerate Sheryl Cherrison, Administrative Manager academic “brain drain.” How many Beckman Laser Institute News of our best students no longer even Alexander Karn (continued on p. 7)

2 C L I N I C A L U P D A T E

Getting to the Root of Laser Dentistry

or those who want the facts on fessor of Oral Biology at Flaser dentistry, there is an old UCLA, have already dem- adage worth remembering: things are onstrated in newly pub- never quite as bad as you imagine lished studies that cancerous them to be, nor quite as good as you and pre-cancerous lesions hope they are. “Whenever a new tool in the mouth will fluoresce like the laser comes along, we see a (i.e., glow) when they are kind of pendulum-effect within the treated with certain photo- profession,” says Petra Wilder-Smith, sensitive compounds and D.D.S., Ph.D., Associate Adjunct Pro- subsequently exposed to fessor of Surgery and Director of the the harmless red light that Dental Research Program at the is emitted by diode lasers. Beckman Laser Institute. “This technique should “At first, there is a sense of eupho- allow us to make definitive ria built on premature assertions that diagnoses without surgical the perfect tool has finally arrived. biopsy and, in addition, Later, there is a sense of deep disap- should help us to catch Dental diagnostics: oral cancer is nearly invisible (top) pointment and even despair, as clini- potentially deadly malig- under a conventional microscope, but the malignant cians face the limitations of this new nancies in their early stages cells glow when illuminated with a laser (bottom). tool. Finally, the pendulum swings when they still respond back to the middle where we can well to treatment,” says Wilder- Modeling the Mouth make a realistic assessment of what Smith. Another area where lasers might can and cannot be accomplished.” So Lasers could also play a major role make a significant contribution is what promises and potentials does in the early detection and treatment optical imaging and measurement of laser dentistry hold for the future? of gum disease. Wilder-Smith is col- dental and orofacial structures. laborating with Intelligent Optical Wilder-Smith is working in conjunc- Laser Diagnostics Systems (Torrance, CA) to develop fi- tion with researchers at MetroLaser As a therapeutic tool, lasers play a ber-optic probes which can detect (Irvine, CA) to develop a device limited, albeit effective, role in the the biological agents responsible for which could quickly and accurately dentist’s office. On the other hand, gingivitis and gum disease. “If we construct “optical impressions” of a lasers offer excellent potential for a can identify problem areas before patient’s teeth and mouth. range of dental diagnostics. In fact, there is significant damage, then “Laser holography provides us Wilder-Smith has secured more than there is a good chance we can selec- precise measurement and representa- $900,000 in new funding this year tively target and destroy the bacteria tion,” says Wilder-Smith. “With a from the California Cancer Research responsible for gum disease,” ex- three-dimensional image of the Program, the Cancer Research Foun- plains Wilder-Smith. This would be mouth, we could eliminate the need dation of America, and the National a major development since conven- for plaster molds altogether.” These Institutes of Health to develop “opti- tional methods cannot detect the digital images could even be moved cal biopsy” techniques for the early “bugs” which cause gum disease un- over the Internet to labs where appli- detection of oral cancer. til irreversible damage has already ances and prosthetics could be tailor- Wilder-Smith and Diana Messadi, occurred in the periodontic tissues made for the patient. Indeed, the D.D.S., Ph.D., Associate Adjunct Pro- which support our teeth. future is bright for laser dentistry. ■

3 R E S E A R C H U P D A T E

Gene Targeting and Inactivation Via Laser Microscope

or researchers at the Beckman F Laser Institute, two photons re- ally are better than one. Not only has multi-photon (two-photon) laser mi- croscopy revolutionized the field of microscopic biological imaging, but it now seems likely that two-photon techniques will open new frontiers for cellular surgery, including gene targeting and gene inactivation. “We’ve come to a point where we can target individual genes and, with- out otherwise damaging the cell, shut down active sites on single chromo- somes,” says Michael W. Berns, Ph.D., Director of the Beckman Laser Insti- tute and senior investigator on the Zifu Wang, Ph.D., (left) and Joon You have equipped the Institute’s two-photon microscope with remote capabilities, making it possible to perform experiments from “gene inactivation” project. “A good off-site locations and transmit “live” data streams (inset) across the Internet. deal of work remains before this can be applied practically, but the initial In the past decade, two-photon Proceedings of the National Academy of results have been extremely encour- techniques, which deliver two light Science, Berns and Beckman Laser In- aging.” parcels of lower energy rather than a stitute collaborators, Zifu Wang, single photon with twice the energy, Ph.D., Andrew Dunn, Ph.D., Vincent Adjusting Our Focal Points have allowed scientists to better pin- Wallace, Ph.D., and Vasan Venugopalan, Lasers have been used to “knock out” point targets inside the cell. By rely- Sc.D., report that two-photon gene in- the genetic components of chromo- ing upon focal point specificity, activation is now possible with nearly somes for close to thirty years. Berns’ two-photon microscopy provides the 100% cell survival. early single photon experiments with capability to image and probe objects “In photomedicine, specificity and low power visible and ultraviolet la- in extremely precise focal planes with survival make all the difference,” sers demonstrated that irradiation of little or no excitation or effect at other says Berns. “I think we’ve made big nuclear material inside living cells points surrounding the target. strides here in two respects: first, be- could inactivate parts of chromo- “Whereas before we had to blast cause we’re able to introduce photo- somes which had been “labeled” with our way down to these structures, sensitive molecules into the cell photosensitive compounds. regardless of what was in our way, which localize where we want them Unfortunately, in these early stud- now we can deliver light beams and, second, because we’re able to ies, thermal and secondary damage which only produce their effects at achieve the desired photochemical produced by the laser was sufficiently fixed depths within the cell,” explains results in selectively targeted sites.” severe to reduce cell survival. “It was Berns. “The upshot of this is that we like throwing the baby out with the can reduce or possibly even eliminate Scoping New Technologies bath water,” says Berns. “We switched collateral damage to the cell’s other The preliminary success of two-pho- off the genes, but the cell couldn’t en- organelles and structures.” ton gene targeting opens new possi- dure the associated stress.” In a recent study published in the (continued on p. 7)

4 S T A F F P R O F I L E

Loretta Sparks: Basking in the BLI ‘Spotlight’

oretta Sparks provided the show- Human Resources. “I love to be Lstopper at last year’s BLI Holi- around people, so the change was a day Party. With microphone in hand good one for me.” Loretta admits that and a twinkle in her eyes, Sparks, “there are days” when juggling the BLI’s Personnel and Payroll Manager, demands of the job can be a chal- treated faculty and staff to an earful lenge, but she is convinced that the of melodious talent. rewards outweigh the stress. “I’m “Karaoke has been a big part of lucky to work in a diverse environ- our lives for about four years now,” ment,” she says. “I truly believe that Loretta says a bit sheepishly. “My we can learn something from every- husband, Ted, is the real star, though. one who crosses our path.” We just have fun with it.” Outside the workplace, Loretta Born in Indiana, but raised in has plenty to keep her busy. She is Loretta Sparks, BLI’s melodious Personnel Payroll Manager. Southern California, Loretta joined actively involved with Beta Sigma the BLI family in February 1998. Af- Phi, a national women’s service or- scholarship programs and charities. ter a temporary assignment as Office ganization. Last year, Loretta and her Loretta also became a grandmother Manager for UCI’s Palo Verde hous- fellow BSP members in California this year. “Daniel is my joy. After a ing unit, Loretta made the switch to helped to raise over $100,000 for million kisses, he knows me.” ■

Institute Contributors and Partners GOV’T AGENCIES AND FOUNDATIONS Mr. and Mrs. Brian Demsey Shoreline Dog Fanciers Association Arnold and Mabel Beckman Fndn. Dr. and Mrs. Norman Frankel S. California Veterinary Medical Assoc., The David and Lucile Packard Fndn. Mrs. Frederick Garry Orange County Chapter Department of Commerce Mr. and Mrs. Walter Gerken S. California Veterinary Medical Assoc., Department of Defense (ONR) Marilyn Hester Gianulias Saddleback-Capistrano Valley Chapter Department of Energy Dr. and Mrs. Frederick Grazer The George E. Hewitt Fndn. for Mr. and Mrs. Gavin Herbert INCUBATOR CORPORATE PARTNERS Medical Research Nora Hester Candela Corporation Hester Family Foundation Mr. George Hewitt Newport Corporation Hoag Foundation Robert L. Jones, M.D. PhotoSense L.L.C. National Institutes of Health Dr. and Mrs. Richard Kasper Whitaker Foundation Mr. and Mrs. Robert Kleist CORPORATE AFFILIATES Dr. and Mrs. Richard Kratz Allergan, Inc. SUPPORTERS Wallace Landholm, M.D. Beckman Coulter, Inc. Dr. and Mrs. Jay Applebaum Richard McCleary and Ileen Frankel Coherent, Inc. The Argyros Foundation Frank and Linda Meyskens ESC Sharplan Lasers, Inc. Dr. Arnold O. Beckman Mrs. Warren S. Myers & Family SmithKline Beecham Patricia Beckman Tricia and Al Nichols Dr. and Mrs. Michael W. Berns Richard and Hinda Rosenthal Foundation INDUSTRIAL ASSOCIATES Dr. and Mrs. Matthew Brenner Mrs. Audrey M. Schneiderman Bio-Safe America Mr. and Mrs. Nathaniel Brenner Mr. and Mrs. Robert W. Scholler Candela Corporation Marilyn Burton Mr. and Mrs. John Stahr Carl Zeiss, Inc. Cheng-Jen Chang, M.D. Mr. and Mrs. Robert Sterman DUSA Pharmaceuticals, Inc. The John Chao Family Thomas T. and Elizabeth C. Tierney Hewlett Packard Dr. and Mrs. W. Andrew Cies D.E.L.T.A. Rescue Medical Optics, Inc. Dr. Howard and Rita Conn Orange Coast Rhodesian Ridgeback Club Olympus Mr. and Mrs. Duke Cooper Premier Laser Systems, Inc. Physical Optics Corporation

5 P H O T O N I C I N C U B A T O R

Implanted Therapy: Targeting Brain Cancer with Lasers

new surgical device developed brain cavity, we can continue to treat Aby visiting researcher Henry the periphery of the tumor site where Hirschberg, M.D., Ph.D., could offer stray cancer cells might otherwise try new hope to patients with migrating to regenerate,” explains Hirschberg. and regenerating brain cancer. Hirschberg is collaborating with Hirschberg, who currently splits Steen Madsen, Ph.D., Assistant Pro- his time between the Beckman Laser fessor of Physics at the University of Institute and the Department of Neu- Las Vegas, and Chung-Ho Sun, Ph.D., rosurgery at University Hospital, on a series of dosimetry studies to de- Rikshospital (Oslo, Norway), has de- termine what combination of drugs veloped a balloon-tipped applicator and laser light will be most effective for combined brachy-photodynamic in arresting tumor regeneration. therapy. The device, which will be The device holds excellent com- Implantable laser applicators allow used in patient trials in Norway, is mercial potential. Hirschberg has ap- physicians to provide post-operative treatment for patients with brain cancer. implanted in the cranial cavity fol- plied for a patent and is conducting lowing routine surgical resection so talks with Proxima Therapeutics, Inc. pounds which will be tested for use that doctors can continue to deliver (Atlanta, GA) to begin producing the with Hirschberg’s novel applicator. ionizing- and light-radiation to the device. Additional talks are under- “Ultimately, we hope the device will tumor site on an ongoing basis. “By way with PhotoCure (Oslo, Norway) be available to hospitals around the keeping the applicator inflated in the to develop new photosensitive com- world,” says Hirschberg. ■ Veterinary Outreach Director Collects Anthony Award

eorge M. Peavy, D.V.M., can learn a lot from your dedication,” G BLI’s Veterinary Director, has Hatch said. “We’ll continue to rely on received the Russell H. Anthony veterinary research and biotechnolo- Award, given by the American Vet- gies as means to unlock the secrets of erinary Medical Association (AVMA), disease and for the development of in recognition of outstanding contri- appropriate [treatments].” butions to the veterinary profession “I’m honored to be recognized,” in the area of governmental affairs. says Peavy. “I think it’s important for Peavy was recognized at the individuals to be involved in the is- AVMA’s 137th Annual Conference sues and political processes of their held in Salt Lake City, Utah. The An- community.” thony Award was presented at a lun- Peavy served on the AVMA’s Po- cheon attended by Utah Senator litical Action Committee from 1982 to George M. Peavy, D.V.M., received the Orrin G. Hatch. The five-term sena- 1989 and the Council on Governmen- Russell B. Anthony Award at this year’s meeting of the AVMA in Salt Lake City. tor thanked conference attendees for tal Affairs between 1992 and 1999. He the contributions of veterinary re- is credited with founding the legisla- Association. Peavy also served on a search to the nation’s biomedical re- tive and political action programs of health advisory committee to U.S. search industry. “Human medicine the California Veterinary Medical Senator Samuel I. Hayakawa. ■

6 (cont’d from p. 4) (cont’d from page 1) GENE TARGETING AND INACTIVATION Newsbriefs bilities for both basic and applied re- equip two-photon systems at BLI and children with disfiguring birthmarks. search, and Berns expects BLI to be the University of California, San Di- Since 1989, the CTF has assisted 72 at the forefront of these efforts. “With ego, with remote capabilities. “With children by providing more than the development of photosensitive gene inactivation and other cell ma- $330,000 in partial and full treatment probes that can target specific genes, nipulations we need to follow the subsidies. it should be possible to offer an en- progress of the cell for twenty-four “The need, unfortunately, never tirely new method for regulating hours or more,” says Wang. “Now we seems to diminish or go away,” says genes and proteins,” says Berns. can do that from any Internet termi- Institute Director Michael Berns. “I To this end, the BLI team is con- nal. There’s no reason for us to stay feel strongly about our obligation to structing a new microscope system locked in the lab, and we should even continue offering this program to chil- designed specifically for multi-pho- be able to conduct laser manipulation dren in need, and we’re certainly hon- ton experimentation. Innovations to studies remotely.” ored to have been recognized by the two-photon microscope system Berns and his team envision a time Disneyland, whose own record of phi- include the addition of remote con- when collaborators from around the lanthropy in the community is so ad- trol capabilities. These enhanced ca- world will “tune in” via the Internet mirable.” pabilities, powered by broadband to conduct experiments with a com- The CTF Review Board receives Internet technologies, enable remote puter keyboard or joystick. “We’re requests for assistance from an aver- experimentation which will facilitate refining our software and addressing age of five patients every month and studies that require long-term cell bandwidth limitations to make these considers all referrals on an indi- tracking and assessment. things possible,” says Berns. In rec- vidual basis. Physicians provide pro “For experiments that take a long ognition of the potential impact of bono treatment, and facility and ad- time, remote-control offers clear ben- multi-photon gene inactivation, the ministrative costs for the manage- efits,” says Zifu Wang, Ph.D., who journal Nature Biotechnology selected ment of the CTF are incurred by UCI has taken the lead along with doc- this study for special recognition in rather than by patients, their families, toral student Joon You in the effort to their October 2000 issue. ■ or donors. If you would like more informa- tion about birthmark removal or the (cont’d from p. 2) Children’s Treatment Fund, please DIRECTOR: TECH TRANSFER TALES call (949) 824-7980. consider an academic career because of the missions of the university is to of the attraction of wealth and oppor- provide well-trained and talented OPTICAL BIOPSY FUNDING tunity in the private sector? How people for the private sector. This is Zhongping Chen, Ph.D., Assistant many faculty are “spinning off” their the backbone of our free-enterprise Professor of Surgery, has received own companies and leaving aca- economy after all. new funding from the National Sci- demia when conflicts of interest and But perhaps it is time to assess the ence Foundation (NSF) to develop time commitment become over- impact of the aggressive marketing micro-electric mechanical systems whelming? And how many of those and licensing of university-derived (MEMS) technology for optical biopsy who do stay compromise and corrupt (often with public funds) intellectual devices. the academic process by doing so? property. Of course, the income to The three-year NSF grant, worth I don’t know what the precise fig- universities from royalties as well as $450,00, will support collaborative re- ures are. My observations represent future philanthropic gifts from grate- search involving Cornell University only a small sample, and they shouldn’t ful “company founders” may make and the Integrated Nanosystems Re- lead to hasty conclusions. Clearly, these questions seem rhetorical or search Facility at the University of there are many positive examples of even moot. Still, there is a question California, Irvine (UCI). NSF provides technology transfer to consider as worth posing: how can we get the these funds as part of its initiative on well as faculty who leave academia most from academia without under- biophotonics partnerships. for the private sector. Certainly one mining the academic mission? ■ (newsbriefs continued on p. 8)

7 NEWSBRIEFS

(cont’d from page 7) CONGRESSIONAL ‘FINDINGS’ A stream of congressional repre- sentatives and staffers have made their way to the UC Irvine campus this year to review the unique re- search and “tech-transfer” programs which help to keep the Beckman La- ser Institute on the biomedical fast- track. Institute Director Michael Berns isn’t surprised: “With so many major government-funded programs operating at our facility, it makes sense that our elected officials want Congressman-Elect (South Orange County) visited the Beckman Laser Institute on August 11, 2000. Issa (second from right) reviewed BLI’s unique research to have a look at the breadth and and tech transfer programs. For more on Issa’s “findings,” please see story at left. depth of our research.” Congressman-Elect Darrell Issa bers for (47th dis- standing BLI supporter Ron Packard, (48th district) became the latest mem- trict), (46th district), who is retiring from his seat in Con- ber of the House to learn more about and Jerry Lewis (40th district) toured gress after nine terms. “It’s an honor new technologies in the field of pho- BLI earlier in the year. to have Mr. Issa visit us,” says Berns. tomedicine when he paid a visit to Issa, founder and CEO of Directed “I think he got a very good taste of BLI on August 11, 2000. Staff mem- Electronics (Vista, CA), replaces long- the innovative work we do here.” ■

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