Th E Wi S Ta R in S T I T U T E N O N - P R O F I T U.S

T H E W I S TA R I N S T I T U T E ocus F FA L L 2 0 0 2

Next-Generation Vaccines Self vs. Self? The Path to the Clinic Fr om the Direc t o r T H E W I S TA R I N S T I T U T E Focus CONTENTS ◆ FA L L 2 0 0 2 he reputation of The Wistar Institute as a leading Tcenter of biomedical discover y was firmly established in my mind long before I began work at the 4 Institute on June 10. As I’ve come to know the Engineering the Ins t i t u t e ’s extraordi n a r y scientists better, howeve r , it has N ext Generation become clear to me that Wistar is poised to make even of Va c c i n e s mo r e significant contributions to science and medicine New approaches to in years to come. combating cancer, His t o r i c a l l y , one of the areas in which Wistar has AIDS, and more. contributed most to public health is in the area of vaccines. The most commonly used vaccines against rabies and rubella wer e developed at Wis t a r , for example. Tod a y , vac - 6 cines continue to offer such promise against such a range of diseases that I intend in A St rong Sense the next few years to rec r uit to Wistar a number of new investigators to join the of Self al r eady strong group of immunologists at the Ins t i t u t e . Exploring the causes Wistar professor Hildegund C.J. Ertl, M.D., heads the immunology program and of autoimmunity. is an international leader in creating new vaccines, as detailed on pages 4-5. In her la b o r a t o r y, vaccines are in development to combat several forms of cancer and a number of viral diseases, including HIV. 8 Recent immunological studies in the laboratory of Wistar associate professor Jan To d ay’s Science, Erikson, Ph.D., have identified a population of immune system cells that may be a To m o rrow’s Medicine key to understanding and treating lupus and other autoimmune diseases, as explained How a bright idea moves on pages 6-7. from the lab to the clinic. For discoveries made at Wistar to become useful diagnostic tools and therapies, the Institute must partner with biotechnology and pharmaceutical companies able to 10 P ro g re s s de v elop the res e a r ch findings into drugs and other products for doctors and their The latest from Wistar labs. patients. As described on pages 8-9, the Institute is a leader in promoting this pr ocess under the guidance of Mer yle Mel n i c o f f , Ph.D., Wis t a r ’s director of business B r i efi n g s de ve l o p m e n t . 12 Awards, news, and notes. Bef o r e I assumed the direc t o r ’s chair, the affairs of the Institute wer e under the wise and steady guidance of acting director Clayton A. Buck, Ph.D., and I would be remiss if I did not take this opportunity to thank him publicly for his strong stewa r d- 14 Welcome to Philadelphia! ship of Wistar and for his invaluable counsel to me since my arrival. We all owe Dir ector and CEO Russel E. Kaufman, M.D., Clayton an enormous debt of gratitude for his service to the Ins t i t u t e . meets his new neighbors. As we go forwa r d, I want to let Wis t a r ’s many friends and supporters know how ho n o r ed I am to be given the opportunity to lead this rem a r kable organization. Tog e t h e r , we can—and will—accomplish great things! On the Cove r : Hildegund C.J. Ertl, M.D., is developing innovative vaccines that show promise Russel E. Kaufman, M.D. against HIV and certain cancers. Di r ector and CEO Full story on page 4. Photo by Peter Olson.

Foc us is published three times per year for donors, friends, faculty, and MARION WYCE The Wistar Institute is an equal opportunity/affirmative staff of The Wistar Institute by the Office of Public Relations, 3601 Spruce Street, Editor & action employer. It is the policy of The Wistar Institute Philadelphia, PA, 19104-4268. To contact the editor, phone (215) 898-3943, or Public RelationsAssociate to provide equal employment opportunities to all e-mail [email protected]. For general inquiries, contact The Wistar Institute FRANKLINHOKE individuals regardless of race, color, creed, religion, at (215) 898-3700. Director of Public Relations national/ethnic origin, sex, age, veteran status, Send address changes to: Development Office, The Wistar Institute, 3601 KARLYN ROSEN AIRES disability, or sexual preference for all terms and Spruce Street, Philadelphia, PA 19104-4268. Designer conditions of employment.

The Wi s tar Institu te is a National Cancer Institu te - d e s i g n a ted Cancer Center. hen Lance Armstrong rode his told WH Y Y’s listeners, is the recent comple- pr oteins—the products of our genes—are bi c y cle down the Champs- tion of the draft human genome sequence. at work in cancer cells versus healthy ones. Élysées in Paris in July to win “What the genome project did was Both areas offer the promise of new, more the grueling Tour de France for open up the entire genome,” Kaufman accurate diagnostic tests and can help the fourth consecutive yea r , he said. “And we know that the basic prob - identify novel targets for drug therapies. Wonce again lifted the spirits of cancer lem of cancer is genetic.” Both are also areas of active inves t i g a t i o n patients and survi v ors every w h e r e with his Sometimes the genetics predisposing a at Wis t a r . rem a r kable accomplishment. person to cancer are inherited, he Genetics is not the only scientific area Ar m s t r ong is, of course, one of the explained. Mor e often, howeve r , the genet- poised to contribute to battling cancer, most famous cancer survi v ors in the world. ic error that leads to cancer is acquired he added. Studies of the immune system In 1996, he was diagnosed with metastatic during life through damage to DNA from and cancer are leading to the devel o p - testicular cancer. Giv en only a 50 perce n t disease or environmental factors. ment of vaccines able to spark our bodies chance to live, he was successfully trea t e d “H aving an understanding of all of the to attack tumors while sparing healthy with surgery and a combination of cutting- genes and all of the proteins and how they cells and tissues. Laboratory- c r eated anti- edge drugs, the latest results from the res e a r ch laboratories and clinics. Stories like Armstron g ’s, more common Lance Arms t r ong and today than in the past, lead one to ask: Is the 30-year war on cancer, declared by the Pro m i s e of Re s e a rc h President Richard Nixo n in 1971, becoming winnable at last? Th a t Is the War on Cancer question was put to Becoming Winnable? Russel E. Kaufman, M.D., director and CEO By Franklin Hoke of The Wistar Ins t i t u t e , in late July when he ap p e a r ed on WH Y Y’s “Radio Times,” hosted by Mar ty Moss-Coane. “I think it is winnable,” Kaufman replied. “We are going to continue to make pro g r ess on ever y fron t : diagnosis, treatment, pre- vention. Winnable means that, at some point, we will be able to all fit together will give us an idea of how bodies can differentiate between cancer manage cancer. We will always have some we might develop new therapies to inter- cells and normal ones and are being used forms of cancer, and we won’t be able to vene,” Kaufman said. “We have a trem e n - in both diagnostic tests and innovat i v e pre v ent all of it, but we will be able to dous understanding of how cancer works tr eatments. Her e again, Wis t a r make significant advances on it.” no w.” res e a r chers are at the foref r ont of efforts Ka u f m a n ’s fellow guest on the show, The newly acquired genetic knowl e d g e to enlist the immune system in the fight Rob e r t C. Young, M.D., president of Fox is combining with power ful new laborato- against cancer. Chase Cancer Center and president of the ry technologies to allow scientists to Dev eloping new therapies for difficult American Cancer Soc i e t y , echoed that an s w er types of questions they couldn’t diseases takes patience and persistence as s e s s m e n t . be f o r e. For example, which of our rou g h l y over many years. The inspiring story of “C e rt a i n l y , there are already good exam- 35,000 genes are turned on or off in a Lance Armstron g ’s rec o ver y from cancer ples of its curability, and the challenge is to gi v en tumor? How does that compare to se r ves, howeve r , as a promise and a pr oduce more cures,” Young said. “Th e r e healthy tissue? reminder that res e a r ch scientists have ar e now 8 or 9 million people in the The emerging field of genomics can made extraordi n a r y prog r ess in under- United States who have been cured of can- look at thousands of genes at once to standing cancer over the past sever a l ce r , and we expect that figure to increa s e . ” an s w er that question, Kaufman told the decades, much of it now on the verge of One key reason that the promise of WH Y Y audience. Another new field coming to fruition as improved trea t - res e a r ch is so compelling now, Kaufman called proteomics aims to assess which ments. ◆

F O C U S / FA L L 2 0 0 2 3 E N G I N E E R I N G THE NEXT GENERATION OF VA C C I N E S Might Diseases Like AIDS and Cancer Yield to a New Approach?

By Franklin Hoke

n irony underlies the devel o p - fr om a set of genetic instructions. Imp o r - ther even than the ambitious goals of her ment of a promising new vac - ta n t l y , too, the genes that would be needed la b o r a t o r y. cine in the laboratory of Wis t a r by the virus to replicate are deleted. “We should start looking into the pr ofessor and immunology pro- The HIV vaccine is only one of sever- fu t u r e,” she says. “The immune system is gram leader Hildegund C.J. al innovative vaccines moving forward in an extraordinarily power ful tool that can Ertl, M.D. The vaccine, which Ertl’s laboratory. She also has a proto- be harnessed by vaccines not only to com- Ahas so far shown potent effectiveness in type vaccine against a strain of human bat infections and cancer, but also possibly mice, is designed to protect people from papilloma virus that causes cervical can- to fight debilitating diseases such as HI V , the virus that causes AIDS. HIV, or cer, the second most common cancer in Al z h e i m e r ’s disease or atheros c l e ro s i s , an ancestor virus, is thought to have women worldwide. She is working on reduce the impact of allergies, help with cr ossed from chimpanzees into humans two different anti-cancer vaccines, one family planning, and even promote tissue sometime around 1930. that targets the p53 gene, mutated in reg e n e r a t i o n . ” The irony is that Ertl ’s vaccine is a re- more than half of human cancers, and Most vaccines to date have been crea t - en g i n e e r ed version of another chimpanzee another aimed at treating glioblastoma, ed by prog re s s i v ely weakening a disease- vi r us, an innocuous adenovi r us. So, if her an aggressive brain tumor. A longstand- causing virus in the laboratory until it can vaccine is able to protect against HIV ing focus in her laboratory has been to no longer cause disease but is still able to infection, one chimpanzee virus will have improve on the most widely used rabies sp a r k a prot e c t i v e response by the been co-opted to serve as a pivotal tool in vaccines for humans and wildlife, origi- immune system. It’s a tedious, painstaking the effort to counter another virus with nally developed at Wistar. Recently, she pr ocess and one that is more dependent ch i m p a n z ee origins. launched a project that she hopes will on luck than most scientists would like. Giv en the history of HIV, Ertl empha- lead to rapid-response vaccines against Also, some viruses like HIV cannot be si z es the lengths to which she and her viruses that might appear without warn- weakened sufficiently to guarantee their colleagues have gone to ensure that the ing in the population. These might safety for use as a vac c i n e . ch i m p a n z ee adenovi r us vaccine is safe. include emerging new viruses or poten- To eliminate the possibility of any conta- tial bioterror agents. Above: Hildegund C. J. Ertl, M.D., and Anthony minant—a virus like HIV, for example— Ult i m a t e l y , Ertl ’s assessment of the Wlazlo, Ph.D. the vaccine is derived in the laboratory untapped promise of vaccines reaches fur- Facing page: Graduate student Julie Fitzgerald.

4 F A L L 2002 / FOCUS Ertl is part of a new wave of vac c i n e human adenovi r uses being used are ubiq- “The work she’s doing is really on the res e a r chers using the tools of genetic engi- uitous in humans. Most humans are cutting edge of technology,” according to neering to bring the power of the immune infected with the viruses early in child- Gar y Nabel, M.D., Ph.D., director of the system to bear on a broad array of dis- hood, and more than 45 percent of the NI H ’ s Vaccine Res e a r ch Center. Nab e l eases. Often, these novel vaccines go adult human population has neutralizing made the comment in a recent rep o r t on be y ond the familiar uses of vaccines to antibodies circulating in the blood able to Ertl ’s vac c i n e - d e v elopment work that pr otect against future infections, aiming in a c t i v ate an adenovi r us-based vaccine or ap p e a r ed in The Philadelphia Inq u i re r . instead at providing immune therapies for gene therapy veh i c l e . Th e r e are reasons to believe the illnesses already contracted. To get around this, Ertl and Wil s o n res e a r chers may succeed where many oth- The vaccines are built by selecting spe- cr eated a series of experimental vac c i n e s ers have failed in their quest for a vac c i n e cific genetic material from a virus, a bac- based on chimpanzee adenovi r uses, which against HIV. In a proof-of-principle study terium, or a cancer cell to incorporate into possess the immunological strengths of published earlier this year in the Jou r nal of a vaccine carrier system, often a rel a t i ve l y human adenovi r uses without their draw- Viro l o g y, Ertl and Wilson created two harmless virus that has been modified for backs. Although both families of aden- experimental vaccines, one a human aden- the purpose. The genes are carefully chosen ovi r us can infect the cells of both humans ovi r us incorporating a rabies gene, and the to elicit the strongest and most approp r i a t e and chimpanzees in laboratory settings, other a chimpanzee adenovi r us with the immune response possible without them- the strains of adenovi r us that infect same gene. In mice unexposed to either se l v es being able to cause illness or disease. humans are distinct from those that infect type of adenovi r us, the vaccines both Many of the scientists engaged in this ch i m p a n z ees in the wild. This means a elicited strong immune responses. In mice type of res e a r ch have been using human vaccine based on a chimpanzee adenovi ru s pr e-exposed to the human adenovi ru s , ad e n ov i r uses as the platform upon which to build their “ W E N O W H AV E vaccines. Ade n ov i r uses are a common cause of res p i r a t o ry - E X P E R I M E N TA L tract infections in people. VACCINES AGAINST They easily enter human cells CANCER, AUTOIMMUNE and stimulate a vigorou s , DISORDERS, EVEN long-lasting immune A L L E R G I E S . ” response. This innovat i v e approa c h to developing vaccines was pi o n e e r ed nearly a decade ago by Ertl and Uni v ersity of Pen n s y l v ania gene therapist James M. would be new to the immune systems of ho weve r , the vaccine based on the human Wilson, M.D., Ph.D. The two scientists almost ever y human who might rec e i v e it ad e n ov i r us was sever ely comprom i s e d , wer e the first to demonstrate that the and, theref o r e, more likely to be effective. while the one based on the chimpanzee en g i n e e r ed adenovi r uses being used at Ertl, with her knowledge of vac c i n e s , ad e n ov i r us maintained its effectiven e s s . that time excl u s i v ely for gene therapy and Wilson, with his expertise in viral Ertl says she came to Wistar from and related gene-transfer proc e d u re s engineering, formed a team with other Har var d Uni v ersity in 1987 because it was could be used to induce a potent in v estigators to develop a vaccine against one of the major vac c i n e - d e ve l o p m e n t immune response. A prototype vac c i n e HI V . The team includes Wistar prof e s s o r centers in the U.S. She was then, and still pr ovided effective protection against the Roger M. Burnett, Ph.D., an expert on is, committed to vaccines as one of the rabies virus for laboratory mice. the struc t u r e of adenovi r uses; Jef f re y most power ful tools available for control - A number of human adenovi r us vac - Bergelson, M.D., with the Children ’s ling disease and enhancing public health. cines have since then been devel o p e d Hospital of Philadelphia, who discovere d “Twenty or thirty years ago, some peo- against HIV and other diseases, and high the receptor used by adenovi r uses to enter ple felt the need for new vaccines was hopes are riding on these vaccines as they cells; and Norman L. Letvin, M.D., at minimal,” Ertl says. “We had the major wend their way through clinical trials to Har var d Medical School, a world- vaccines, and we had antibiotics. Sin c e test their safety and effectiven e s s . ren o wned expert in HIV vaccine res e a rc h . then, the possible uses of vaccines have Ertl and Wilson, howeve r , did not This group of scientists was rec e n t l y expanded dramatically, so that we now attempt to enter their original adenovi r a l aw a r ded a program project grant from the ha v e experimental vaccines against can- vaccines into clinical trials, opting instead National Institutes of Health to allow cers, autoimmune disorders, even allergies. to refine their approach. An inheren t them to conduct the preclinical res e a rc h For those of us who want to do some- pr oblem with the adenoviral vaccines first req u i r ed to move into human clinical tri- thing practical and make a difference, this spotted by gene therapists was that the als with the new vaccine. is a fantastic area to work in.” ◆

F O C U S / F A L L 2 0 0 2 5 The greatest identity crisis you may ever face could occur in your spleen. Th e r e your immune system determines friend from foe, foreign pathogen from what immunologists term “se l f .” If that usually reliable screening mechanism fails, you r immune system may attack your “se l f ” in a misguided attempt at self-defense. Th e result is an autoimmune disorde r . In the hopes of better understanding ho w the immune system works—and how it sometimes fails to work— W istar associate professor Jan Erikson, Ph.D., and her colleagues study the interplay among dif- fe r ent parts of the immune system. Erikson is an authority in the basic science behind autoimmune diseases such as A S T R O N G SE N S E O F S E L F Immunological Identity and the Causes of Autoimmunity By Greg Lester

lupus, a chronic condition that affects cells that influence them. The implications mo r e than 1.5 million Americans. could be significant in the search for new, Rec e n t l y , her laboratory has focused on mo r e effective trea t m e n t s . the activities of autorea c t i v e B cells—a set An appreciation of indirect paths is not of antibody-producing cells primed to unusual for Erikson, whose career has attack self under certain circumstances. been guided by curiosity and a need to “Su r p r i s i n g l y , even healthy people pro- experiment. duce autorea c t i v e B cells,” says Eri k s o n . Erikson, in fact, never pictured herself “O ur goal has been to find out how as a laboratory scientist while growing up. au t o re a c t i v e B cells can be activated in one Indeed, soon after she graduated from the set of people, but not in another.” Uni v ersity of Pen n s y l v ania in 1978 with a In this past Apr i l ’s edition of the jour- de g r ee in environmental science, she set nal Imm u n i t y , Erikson and her team out to be a farmer. sh o wed that the fate of autorea c t i v e B cells She and her sister briefly tried run n i n g is determined by two classes of white a farm in Chester Springs, about an hour’s la b o r a t o r y of Carlo M. Croce, M.D., then blood cells—T helper cells, which stimu- dr i v e west of Philadelphia. While it was a Wistar res e a rc h e r , now director of the late the B cells, and T reg u l a t o r y cells, wo n d e r ful working with her sister in the Kimmel Cancer Center at Th o m a s which hold the T helper cells in check. beautiful Pen n s y l v ania countryside, she Jefferson Uni ve r s i t y . It was an ideal place The res e a rc h e r s ’ findings suggest that says, the promise of air-conditioning for her to develop an interest in laboratory the best approach to controlling autorea c - br ought her off the farm and into the lab. science—an interest that led to a doctorate ti v e B cells in autoimmunity may be an Erikson returned to the Penn campus in molecular biology in 1986. While still in d i r ect one, through controlling the T and found a job as a lab technician in the in Croc e ’s laboratory, she published her

6 FA L L 2002 / FOCUS Left:Ghazal Zekavat, left, and Simone Nish. ogy that she wants to learn. The feeling Facing page, top, left to right: Ella Ofori, that there is always more to discover is an Jan Erikson, Ph.D., Kristin Hazard, and im p o r tant driver in her res e a r ch, and she Michele Fields. looks for the same motivation in the young people who come to work for her. ings, it was also a return to an institution “The first req u i r ements for joining my wh e r e the culture seems to suit her. For la b — m o r e than anything else—are inter- he r , Wistar rep r esents a diversity of scien- est and desire,” says Erikson. “I have been tific styles, approaches, and opinions in ver y fortunate to have an outstanding close collaboration. gr oup of self-motivated people in my lab. At Wis t a r , one res e a r cher in parti c u l a r Like me, they view practicing science as a has emerged as a frequent collaborator— pr i v i l e g e . ” and not just because they are married. Michele Fields, a doctoral student in Associate professor Andrew Caton, Ph. D . , immunology who works in the Eri k s o n al r eady held a position at Wistar when la b o r a t o r y, was one of a number of stu- first paper as lead author in the pres t i g i o u s Erikson joined the faculty. Inc re a s i n g l y , dent co-authors whose names appeared on journal Nat u r e. she finds her work on B cells informed by th e Imm u n i t y st u d y . Like Erikson, Fie l d s Peter C. Nowell, M.D., is a prof e s s o r Ca t o n ’s investigations of T cells, and is enthralled by the subject, and sees it as of pathology and laboratory medicine at Caton was a co-author on the Imm u n i t y a frontier field that supports a wide var i - the Uni v ersity of Pen n s y l v ania and winner pa p e r . (Perhaps their greatest collaborative of the 1998 Albert Lasker Awa r d for ef f o r t yet turns six this year—his name is Clinical Medical Res e a r ch for his pioneer- Mat t h e w.) “ LI K E M E, ing work on the Philadelphia Chrom o - The drama of B cell activation begins some, the first genetic alteration linked to in the spleen’s white pulp. Th e r e dendritic T H E Y O U N G P E O P L E ca n c e r . He first got to know Erikson dur- cells, which act as multi-armed data hubs ing her time in Croc e ’s laboratory. that gather antigens—particles of forei g n I N M Y L A B V I E W “We wer e collaborating with Carlo cells and macrom o l e c u l e s — p r esent the Croce to identify genes in human antigens to T helper cells. These T helper P R A C T I C I N G S C I E N C E leukemias and lymphomas, using chro- cells are then able to provide B cells with a mosome abnormalities as clues to the confirming co-stimulatory signal that they A S A P R I V I L E G E. location of the genes,” Nowell recalls. “I req u i r e—along with the primary stimula- ” was impressed with Jan ’s intelligence and tion of the antigens themselves—for acti- in i t i a t i v e, as well as her enthusiasm for the vation. T reg u l a t o r y cells, according to ety of theoretical viewpoints with a lot of wo r k and her ability to interact with a Erikson, disarm the T helper cells, thus room for exploration. She ’s also found a wide variety of colleagues.” blocking B cell activation. A balance mentor in Erikson. This was also a time when she began be t w een the two classes of T cells is at “Ja n ’s a great scientist and a great per- fr uitful interactions with Wistar prof e s s o r s the heart of what immunologists call son,” Fields says. “And the projects that Louise M. Sho we, Ph.D., and Kazuko “to l e r a n c e . ” our lab works on are rel e v ant, exci t i n g , Nishikura, Ph.D., both of whom contin- In one set of experiments rep o r ted in and scientifically stron g . ” ue to be valued collaborators. the recent Imm u n i t y pa p e r , the Eri k s o n Eri k s o n ’s view of Wistar is of a place Eri k s o n ’s first postdoctoral fellows h i p la b o r a t o r y tested the limits of B cell toler- wh e r e closely knit, smaller laboratories sent her out to Sta n f o r d Uni v ersity where ance using mice engineered to over p r o- can work comfortably beside larger, pow- she worked under immunologist and duce autorea c t i v e B cells. Under the erhouse laboratories. In fact, it’s one of the Howa r d Hughes Medical Institute inves t i - mi c r oscope, the potentially dangerous B aspects of the organization she most val - gator Mar k Davis, Ph.D. Her second cells wer e seen to be restricted to the edges ues. Her own laboratory usually includes postdoctoral fellows h i p , with Mart i n of the spleen’s follicles, where they have a no more than a half-dozen students and Wei g e r t, Ph.D., at the Fox Chase Cancer sh o r t life span. When given a supply of T la b o r a t o r y technicians. This allows her to Ce n t e r , brought her back to the helper cells, howeve r , and deprived of T stay more in touch with her students Philadelphia region. Wei g e r t, now at reg u l a t o r y cells, the autorea c t i v e B cells while she pursues the scientific questions Princeton Uni ve r s i t y , is a Nat i o n a l wer e able to enter the follicles and differ- that interest her most. Academy of Sciences member, as is Dav i s . entiate to produce antibodies against self. “I don’t know where I’ll be in years to She was offered a position as an assis- The immune system is, to say the least, come—who can really claim to know tant professor in the Wistar tumor complex. Erikson, despite being a card- that?” Erikson says. “But I get such satis- immunology program in 1991. Mor e ca r r ying immunologist, still feels that faction out of working here that it’s diffi- than just a return to familiar surrou n d - th e r e is a great deal more about immunol- cult to imagine being anywhere else.” ◆

F O C U S / FA L L 2 0 0 2 7 TODAY ’S SC I E N C E, TOM OR ROW ’S ME DIC I N E

ou open up your medicine cabinet Yand count out your daily pills. You take your child to the pediatrician for vac c i n e s to prev ent a host of once-threatening diseases. Your doctor orders up a round of blood tests at your annual physical to monitor your health. Ever y day, medi- ci n e ’s most power ful tools, the products of biomedical res e a r ch, keep us in good health and help us fight off disease. But how does a scientist’s insight become a drug at the local pharmacy or a sc r eening test available at the hospital? The road from the lab to the marke t p l a c e is often a long and winding one, req u i r i n g substantial investments of time, effort, and money, and not a little seren d i p i t y . As a nonprofit res e a r ch institute, it is pa r t of Wis t a r ’s mission to ensure that its sc i e n t i s t s ’ innovations move from the lab- the economic potential of biomedical How a bright idea or a t o r y to the clinic as expeditiously as res e a r ch when he announced the crea t i o n possible. For Wis t a r , as for most nonprof i t of three life sciences “gre e n h o u s e s ” in moves from the lab res e a r ch centers and universities, that Pen n s y l v ania to support biomedical means licensing its discoveries to compa- res e a r ch. “How often do you get to to the clinic nies with the res o u r ces to transform them im p r ove the health of a state and the into commercially viable products. health of its economy at the same time?” By Marion Wyce Inc re a s i n g l y , the transfer of innovat i o n s he said during a April 2001 press confer- fr om academia to industry— s o - c a l l e d ence at Wistar announcing the initiative. opment of rubella and rabies vaccines and technology transfer—is also big business. At the press conference, Wis t a r ’s then- the monoclonal antibody technology that Academic technology transfer added more acting director Clayton Buck, Ph. D . , led to the formation of Centocor, one of than $40 billion to the U.S. economy and noted that the Institute has been a leader the most successful biotechnology ven t u re s su p p o r ted 270,000 jobs in fiscal yea r in transferring its inventions to the com- in the Philadelphia region. 1999, according to the Association of me r cial sector for more than 25 years and If the benefit of technology transfer for Uni v ersity Technology Managers. For m e r has more than 100 active licenses. Among the public is new treatments and diagnos- Pen n s y l v ania Governor Tom Ridge cited its notable successes, he said, are the devel - tics and, for the economy, new jobs, the

8 FA L L 2002 / FOCUS Facing page: Meryle Melnicoff, Ph.D., and Palatin is conducting phase II clinical tri- D. V .M., are one such res e a r ch tool. Meenhard Herlyn, D.V.M. als of LeuTec h ® for other indications, Herlyn has one of the largest banks of including post-surgical abscess, fever of melanoma cell lines in the world, and un k n o wn origin, inflammatory bowel dis- dr ug companies are using them for scree n - benefit for academic res e a r ch centers is an ease, and pulmonary imaging, and in col- ing purposes, Melnicoff says. Herlyn has a additional source of valuable funding. In laboration with the U.S. Army, is inves t i - st r ong track rec o r d of making discover i e s 2001, technology transfer added gating LeuTec h ®’s potential as a diagnos- with important clinical implications; he $1,896,000 (7 percent of rev enues) to tic for inhalation anthrax. was among the inventors on the original Wis t a r ’s bottom line—money that helps “He r e you have a discover y made at patents involving monoclonal antibodies offset the high cost of doing cutting-edge Wistar in 1977, and a product res u l t i n g that led to Centocor’s founding. Tod a y , he res e a r ch. A portion of licensing fees is fr om it will first reach market more than is developing three-dimensional models of sh a r ed with the inven t o r . 25 years later,” Melnicoff says. “It takes human organs including the skin, colon, “Typically at Wis t a r , our scientists will years of res e a r ch from the time of an ini- blood vessels, esophagus, and breast. “Th e make a discover y that increases the under- tial discover y to show its relationship to cells in these artificial tissues behave ver y standing of a fundamental process, such as disease and develop a product. Then, for a similarly to normal tissues in the human cell division or cell activation, which therapeutic, you need to go through three bo d y ,” Herlyn says, “and we can manipu- could be invol v ed in a disease such as can- phases of clinical trials, to show safety, late the cells in these artificial tissues and ce r ,” explains Mer yle Mel n i c o f f , Ph. D . , ef f i c a c y , and determine the dosing. Fewer rep r oduce disease for res e a r ch purposes.” who oversees Wis t a r ’s technology transfer than one in 20 of the drugs that start out Wistar has applied for several patents on ef f o r ts as director of business devel o p - on that process comes out of it as a candi- this technology. ment. “From a tech transfer perspective, date for FDA approval . ” Cl e a r l y , it can take decades before the we ask if there is a way this information is Melnicoff works closely with Wis t a r full value of a res e a r ch discover y is rea l - going to be useful for creating a therapy, scientists to learn as much as possible iz ed. But the implications for human diagnostic, or res e a r ch tool.” It’s a bit of a guessing game, Mel n i c o f f TH E P ROD U CTSOF B IOM E DIC A L says, to predict which innovations will pr ove to be commercially useful. Oft e n , R E S E A RC H K E E P U S I N G O OD H E A LT H the value of a basic science discover y do e s n ’t become apparent for years, even A N D H E L P U S F IG H T OF F DI S E AS E. decades. And sometimes an inven t i o n pr oves to be useful in unexpected ways. Take, for example, the story of SSEA1, about their work and to identify the dis- health sometimes prove to be far-rea c h i n g . a monoclonal antibody that was devel - co veries that are likely to have commer- The Wistar vaccines for rubella, devel o p e d oped at Wistar in 1977. First discovere d cial value and should be protected by a by Dr. Stanley Plotkin in the 1960s, and in the mid-1970s, monoclonal antibodies patent. To file a patent application, a dis- for rabies, developed by Dr. Tad e u s z ar e laboratory- p r oduced substances that co ver y must be shown to be both novel Wiktor in the 1970s, are still the primary can locate and bind to particular cell and useful. Sometimes a discover y is vaccines used to prev ent these serious dis- types wherev er they are in the body, often in t e r esting scientifically but it isn’t imme- eases. Rec e n t l y , Melnicoff licensed the used in cancer detection or therapy. diately possible to show its utility, seed stock for these vaccines to organiza- Wistar scientists developed SSEA1 as a Melnicoff says, in which case it isn’t possi- tions in Asia who want to make the vac - tool for identifying certain cancer cells ble to file for a patent application. Onc e cines for their local use. In Jan u a r y, Th e that mimic embryonic tissue. Ten yea r s Wistar applies for a patent, if needed, Philadelphia Inq u i re r rep o r ted that the passed before a biopharmaceutical com- Melnicoff and her staff market the tech- U.S. was on the verge of eradicating pany licensed SSEA1 to develop a deriva- nology to find companies that may want rubella, thanks to Plo t k i n ’s vaccine, the ti v e of it for diagnostic purposes. Th e to license the technology. only one in use in the U.S. and Euro p e company went through various reo r g a n i - The licenses that Mel n i c o f f ’s office since 1979. za t i o n s and in 1997, its successor, Pal a t i n negotiates fall into two categories: thera- “The vaccine has exceeded my expecta- Technologies Inc., relicensed the anti- peutics and diagnostic licenses, which tions,” Plotkin told the Inq u i re r . “It is bo d y . Their product, LeuTec h ®, has com- include all licenses by companies intend- gratifying to think that the laboratory and pleted clinical trials as an imaging tool to ing to develop products for patient care, clinical work I did at The Wistar Ins t i t u t e assist physicians in diagnosing appendici- and res e a r ch licenses, which make a 30 to 40 years ago has resulted in the near tis. The clinical trials wer e successful, and res e a r ch tool or reagent broadly avai l a b l e disappearance of congenital rubella from the company is now awaiting final FDA- to other scientists. the United States. And I would like to see ap p r oval and expects to begin marke t i n g Melanoma cell lines developed by the same thing happen in the rest of the Le u Te c h ® in mid-2003. In addition, Wistar professor Mee n h a r d Her l y n , world.” ◆

F O C U S / FA L L 2 0 0 2 9 ■ P R O G R E S S

associate professor at The Wistar Ins t i t u t e Ne u ro l o g i c a l and senior author on the study. “In neu- rons, it pulls its cargo down microt u b u l e s , Diseases Linked which can be thought of like the rails for the locomotive. Kinesin-1 is vital for effi- he genes responsible for neurof i b r o- cient protein trafficking within neuron s Tmatosis, a common neurol o g i c a l and other cells, and it’s of great interest to di s o rd e r , are linked to a protein thought to us to find it linked to the genes that cause play a role in Alzheimer’s disease, accord- ne u ro f i b ro m a t o s i s . ” ing to a new study by Wistar scientists. Unr elated recent studies have also In establishing a connection betwee n sh o wn that kinesin-1 interacts with a the two diseases, the res e a r ch opens new pr otein called amyloid precursor prot e i n , lines of thinking for investigators studying or APP, which has been implicated in both diseases, while also providing basic Al z h e i m e r ’s disease, a major cause of biological insights into vital cellular dementia in older people. pr ocesses. The study was published in “I f kinesin-1 is the locomotive, then August in the Jou r nal of Bio l o g i c a l AP P ’ s role appears to be to hook the cargo Ch e m i s t r y. to the locomotive,” Shiekhattar explains. The protein shared by neurof i b r o- “F inding kinesin-1 in protein complexes matosis and Alzheimer’s disease is called that also contain the genes associated with Frank J. Rauscher III, Ph.D. kinesin-1. This protein is known to be ne u ro f i b r omatosis clearly ties neurof i b r o- in vo l v ed in the movement of var i o u s matosis and Alzheimer’s disease to a com- needed proteins from one part of a nerve mon cellular pathway.” Gene Silencer cell, or neuron, to another along a system The two genes linked to the disease are of microtubules—small tubes. Prob l e m s among the most commonly mutated Di s c o v e re d with the internal transport of proteins can genes in the entire human genome. Sin c e lead to neuronal malfunction and death. the discover y of these genes, howeve r , lthough the human genome is esti- “This protein, kinesin-1, is like a loco- most aspects of their activity in the body A mated to contain about 35,000 mo t i v e that pulls cargo throughout the and in neurof i b r omatosis have remained a genes, only a fraction of these genes are cell,” says Ramin Shi e k h a t t a r , Ph.D., an my s t e r y. Neu ro f i b r omatosis is a common turned on in a given cell under normal di s o rd e r , more prev alent than cystic fibro- ci r cumstances. Precise control of gene sis, muscular dystrop h y , Hun t i n g t o n ’s dis- ex p r ession is essential; many cancers have ease, and Tay - S achs disease combined. It been linked to the improper activation of can cause tumors along nerves throu g h o u t genes that should remain rep r essed, or the body and can affect the devel o p m e n t si l e n c e d . of non-nervous tissues such as bones and Now, res e a r chers at The Wis t a r skin. The disease can also cause learning Institute rep o r t the identification of a new disabilities of differing sever i t y . Wh i l e enzyme that is req u i r ed for the silencing most cases of neurof i b r omatosis are mild of certain genes. The enzyme functions by to moderate, it can lead to disfigurem e n t , placing a molecular marker on a gene that blindness, deafness, skeletal abnormalities, causes the gene to be silenced. When this ret a r dation, and tumors of the skin, spine, molecular marker is lost, certain genes and brain. may be improperly rea c t i v ated, which can Science Daily and other news organiza- result in cancer. Dis c o ver y of the enzyme tions rep o r ted on the res e a rc h . could lead to new cancer therapies. Th e The lead author on the Jou r nal of res e a r ch was published in the April 15 Biological Chemistry study is Moh a m e d - A l i issue of Genes and Deve l o p m e n t . Hakimi, Ph.D., at The Wistar Ins t i t u t e . “I n this study we showed that when Wistar professor David W. Spe i c h e r , this enzyme is active at a particular gene, Ph.D., collaborated on the study. Th e it places a molecular marker on the gene,” res e a r ch was supported by grants from the says Frank J. Rauscher III, Ph.D., a pro- Ramin Shiekhattar, Ph.D. National Institutes of Hea l t h . fessor at The Wistar Institute and deputy

1 0 FA L L 2002 / FOCUS di r ector of The Wistar Institute Cancer Ce n t e r . “This molecular marker is cruc i a l New Grant Awa rd s in silencing sets of genes.” The Wistar Institute and its scientists continue to compete successfully for grants to Rauscher notes that it has rec e n t l y su p p o r t res e a r ch and programs. Below is a list of recent awards . been shown that when you lose this molecular marker on a particular set of genes, a P R I VAT E G R A N T S normally nonaggres s i v e breast cancer can AMERICAN ASSOCIATION OF ANAT O M I S T S F. M. KIRBY FOUNDATION, INC. become ver y aggres s i v e and metastatic. The Wistar Museum Collections, towards the cata- Ellen Heber-Katz, Ph.D., “New Model for Central logue for the exhibition “Mammoth Scale: The Nervous System Regeneration,” one-year grant of “N ow that we have found a new Anatomical Sculptures of William Rush,” $2,000. $250,000. enzyme that is req u i r ed for the silencing THE COCA-COLA FOUNDAT I O N LUPUS FOUNDATION OF AMERICA, INC. of certain genes,” Rauscher says, “we The Wistar Institute, Biomedical Technician Michele Fields, laboratory of Jan Erikson, Ph.D., be l i e v e it will be possible to create specific Training Program, $30,000. “The Effect of T Regulatory Cells on Activation of CONCERN FOUNDATION FOR CANCER RESEARCH Anti-dsDNA B Cells,” Gina Finzi Memorial Student dr ugs that can either rep r ess or activat e Jumin Zhou, Ph.D., “Regulating Enhancer- Summer Fellowship, $2,000. gene expression through the targeting of Promoter Interactions by a Novel cis Element, LUPUS FOUNDATION OF SOUTHEASTERN PTS,” one-year grant of $50,000. this enzyme. This could lead to therapies P E N N S Y LVANIA, INC. MICHAEL DUNITZ CRISIS FOUNDATION, INC. Heath Guay, laboratory of Andrew J. Caton, Ph.D., for cancer, specifically for controlling the The Wistar Institute, cancer research programs, “Formation of Autoantibodies in the Absence of metastatic spread of cancer.” $2,500. Overt Stimuli,” summer student preceptorship award, $2,500. Rauscher says that his laboratory is now EMERALD FOUNDAT I O N Frank J. Rauscher III, Ph.D. , “Transcriptional Andrew Rankin, laboratory of Andrew J. Caton, wo r king to discover which genes in the Events in Fibroblast that Lead to Kidney Fibrosis,” Ph.D., “B Cell Development and Autoreactive CD4 human genome are silenced by this newl y one-year grant of $100,000. & T Cell Help,” summer student preceptorship award, $2,500. di s c o ver ed enzyme. His res e a r ch team is EUGENE GARFIELD FOUNDAT I O N David Kritchevsky, Ph.D., “Dietary Effect of MARCH OF DIMES BIRTH DEFECTS also interested in finding chemical Conjugated Linoleic Acid,” $25,000. F O U N D AT I O N inhibitors of this enzyme. Fin a l l y , they are ELISABETH GLASER PEDIATRIC AIDS FOUNDAT I O N Kazuko Nishikura, Ph.D., “RNA Editing and Luis J. Montaner, D.V.M., D. Phil., “Correlates of Congenital Dyserythropoietic Anemias,” three-year studying breast, colon, and lung cancers to Antiviral Immunity and Immune Reconstitution,” grant of $204,948. determine whether the gene that codes for two-year grant of $192,000. THE MARY L. SMITH CHARITABLE this enzyme is mutated in these diseases. I RVING A. HANSEN MEMORIAL FOUNDAT I O N L EA D T RU S T Frank J. Rauscher III, Ph.D. , “Using an Engineered David W. Speicher, Ph.D., “Systemic Detection of Genomics and Genetics Wee k l y an d Repressor for Rhabdomyosarcoma Therapy,” one- Breast Cancer Serum Markers,” one-year grant of other media organizations carried news of year grant of $15,000. $60,000. the res e a r ch. In addition to senior author Rauscher, GOVERNMENT GRANTS the lead author is David C. Schultz, C O M M O N W E A LTH OF PENNSYLVA N I A N ATIONAL INSTITUTE OF ALLERGY Ph.D., formerly of The Wistar Ins t i t u t e Louise C. Showe, Ph.D., Bioinformatics Consortium AND INFECTIOUS DISEASES for Cancer Research, three-year grant of $640,000. Hildegund C.J. Ertl, M.D., “HIV-1 Vaccine-Induced and now with Case Western Res e r ve CD8+ Memory Cells,” two-year grant of $472,741. D E PA RTMENT OF HEALTH AND HUMAN SERV I C E S Uni ve r s i t y , and co-authors are Kasirajan Hildegund C.J. Ertl, M.D., “HIV-1 Vaccine Based Luis J. Montaner, D.V.M., D.Phil., scientific equip- Ayyanathan, Ph.D., Dmitri Neg o re v , on Chimp Serotypes of Adenovirus,” five-year grant ment, one-year grant of $196,897. of $9.3 million. Ph.D., and professor Ger d G. Mau l , N ATIONAL CANCER INSTITUTE Ge r d G. Maul, Ph.D., “HIV DNA Vaccine Improv e m e n t Ph.D., all of The Wistar Institute. Th e Paul M. Lieberman, Ph.D., “Regulation of Epstein- by Nuclear Tar geting,” two-year grant of $502,239. res e a r ch was supported by grants from the Barr Virus Latency,” five-year grant of $1.5 million. Luis J. Montaner, D.V.M., D. Phil., “APCs and Steven B. McMahon, Ph.D., “Role of Innate Immunity in HIV Disease,” four-year grant of National Institutes of Health, the Irvi n g Acetyltransferases in Transformation by c-MYC,” $1.6 million. A. Hansen Memorial Foundation, and five-year grant of $1.5 million. N ATIONAL INSTITUTE OF GENERAL MEDICAL The Susan G. Komen Breast Cancer David W. Speicher, Ph.D., “Technologies for S C I E N C E S Identifying Proteins Secreted by Tumors,” four-year Gerd G. Maul, Ph.D., “Characterization of a Foundation. Early parts of this work wer e grant of $1.4 million. Potential Nuclear Protein Depot,” four-year grant of $1.3 million. su p p o r ted by the Pew Scholars Prog r a m David W. Speicher, Ph.D., “Development of N ATIONAL INSTITUTES OF HEALT H in the Biomedical Sciences. ◆ Methods for Cancer Biomarker Detection,” three- year grant of $1.3 million. Luis J. Montaner, D.V.M., D.Phil., to support the 5th In t e r national Workshop on HIV Cells on Macrop h a g e N ATIONAL CENTER FOR and Dendritic Lineage and Other Reservoirs, $22,400. RESEARCH RESOURCES N ATIONAL SCIENCE FOUNDAT I O N Donald L. Ewert, Ph.D., “Human Subjects Roger M. Burnett, Ph.D., “Molecular Organization Research Enhancements Program,” one-year grant Inf o r mation on Wistar technologies of Mammalian Viruses,” one-year renewal grant of of $99,535. $100,000. av ailable for licensing can be found on the N ATIONAL HEART, LUNG, AND U.S. ARMY MEDICAL RESEARCH Ins t i t u t e ’s Web site, www.w i s t a r. u p e n n . e d u , BLOOD INSTITUTE ACQUISITION ACTIVITY under “Tec h n o l o g y Tran s f e r .” Kazuko Nishikura, Ph.D., “Functions of ADAR1 Ramin Shiekhattar, Ph.D., “Deciphering the RNA Editase in Erythropoesis,” four-year grant of Molecular Mechanism of Breast Cancer,” three-year $1.5 million. grant of $447,642.

F O C U S / FA L L 2 0 0 2 1 1 ■ B R I E F I N G S

Ar t at Wis t a r Taxin. Former 76ers star Julius Erving was among those teeing off in support of brain ometime about 1808, the ren ow n e d tumor res e a r ch. The Wistar Institute is SPhiladelphia physician Caspar Wis t a r , grateful to all participants, volunteers and namesake of The Wistar Institute, asked sponsors including Charlap & Mil l e r , the sculptor William Rush to make a PNC Bank, Cozen O’Conner, The Dav i d series of large-scale anatomical models. Cutler Grou p , Mellon Pri v ate Asset Rush, known as a maker of civic statuary William Rush, model of the sphenoid bone, Management, Mar cia and Ron Rub i n , and ships’ figureheads, responded with the 1808. The Wistar Museum Collections. R. A . F . Industries, and the Taxin family. strangest works of his career: a massive inner ear, a cumbersome jaw, and some 19 other large-scale models in wood and In the News Em e r ging Issues papier-mâché of human body parts. Th e se v en surviving models will be on view he Associated Press turned to Luis J. in Science with related works for the first time in TMon t a n e r , D.V.M, D.Phil., an asso- “M ammoth Scale: The Anatomical ciate professor in The Wistar Ins t i t u t e ’s he Wistar Institute has launched a Sc u l p t u r es of William Rush.” The exhi- immunology program who inves t i g a t e s Tne w seminar series, called “Eme r g i n g bition opens to the public on Fri d a y , HI V , for expert commentary for a story Issues in Science,” to provide Wistar friends October 18, 2002, and will remain on about chimpanzee s ’ resistance to HIV and and other interested members of the public vi e w for one year in the Ins t i t u t e ’s atrium. its variants. The August AP story discussed with an opportunity to learn about the lat- Hours are Monday to Fri d a y , 9 a.m. to a paper by Dutch res e a r chers that theorizes est in biomedical res e a r ch. Wistar Dire c t o r 5 p.m. Admission is free. that an AIDS-like epidemic wiped out and CEO Russel E. Kaufman, M.D., was The creation of Rus h ’s over s i ze d huge numbers of chimpanzees two million speaker at the first seminar on October 8, anatomical sculptures stems from the pop- years ago, leaving modern chimps with titled “Using Genes to Predict Risk—You r ularity of the medical lectures Caspar resistance. Montaner was consulted for an Health and Your Pri va c y. ” Wistar gave as chair of anatomy at the independent assessment of the paper. The next seminar, “Nutrition Wit h o u t Uni v ersity of Pen n s y l v ania. Teaching class- The AP story quoting Montaner was Tears—The Link Bet w een Diet and es with as many as 500 students, Wis t a r picked up by newspapers and Int e r n e t Disease,” will be Th u r s d a y , November 14, found it impossible to demonstrate minute sites nationwide, including Th e fr om 5 to 7 p.m. at The Wistar Ins t i t u t e . anatomical struc t u r es to his large audi- Philadelphia Inq u i re r , The Boston Glo b e , David Kritchevsky, Ph.D., Caspar Wis t a r ences. He commissioned Rush to crea t e The Dallas Mor ning New s , the San Scholar at the Institute, will explore the the models so that his lectures would be Francisco Chron i c l e , and CNN.com often conflicting rep o r ts about nutrition understandable to ever yone who attended. (World Edition). and disease. “M ammoth Scale” displays for the first For more information about the series time several of Rus h ’s anatomical sculp- or to register for the upcoming seminar, tu r es that wer e previously believed lost. Golf Classic call Laurie Mellon at 215-898-3805. The exhibition is the first to focus excl u - si v ely on Rus h ’s anatomical sculptures and a Win n e r the only one to include all known survi v - ing models, which belong to the Wis t a r he Sev enth Annual Albert R. Tax i n Museum Collections. TGolf Classic was a great success. The exhibition was organized by Th e Some 175 participants, volunteers, and Wistar Institute. Guest curator is guests gathered at Green Valley Country Alexander Nem e r ov, Ph.D., professor of Club on June 17, 2002, for the even t , the history of art at Yale Uni ve r s i t y . which raised more than $80,000 for the Major funding was provided by the Al b e r t R. Taxin Brain Tumor Res e a rc h William Penn Foundation. Add i t i o n a l Ce n t e r . The tournament honors the su p p o r t was provided by the Pen n s y l va n i a me m o r y of Albert Taxin, who died in Historical and Museum Commission, Th e 1993 from an inoperable brain tumor. Wistar Director and CEO Russel E. Kaufman, M.D., second from right, with Taxin Golf Classic Co- Bay Foundation, the American Association Co-chairs for the event wer e Ste p h e n Chairs (from left) Stephen Cozen, Esq., Doris of Anatomists, and the Barra Fou n d a t i o n . Co z en, Esq., Ron Rubin, and Dor i s Taxin, and Ron Rubin.

1 2 FA L L 2002 / FOCUS Students Complete Training Prog r am Update ◆ EDWAR D A. BOTCH W E Y, PH.D . , a postdoctoral fellow at Wis t a r , has been award- Training Prog r a m ed a prestigious United Neg r o College Fun d - Me r ck Postdoctoral Science Res e a rc h Fel l ow s h i p . Botchwey is one of only 10 fellowship recipients nationwide, and the ix students wer e honored on July 23 only recipient in the Del a w a r e Val l e y . The award is given to outstanding African- Sfor completing the Bio m e d i c a l American scholars pursuing postdoctoral studies in the biomedical sciences and car- Technician Training Program. Joi n t l y ries with it a two-year stipend of $70,000. Botchwey works in the laboratory of pro- de v eloped by The Wistar Institute and fessor Elliot M. Levine, Ph.D., and collaborates with investigators in the laboratory Community College of Philadelphia, the of Mee n h a r d Her l y n , pr ogram prep a r es community-college stu- D. V .M. The topic of his dents for res e a r ch-technician careers in res e a r ch project is “New Phi l a d e l p h i a - a r ea biomedical, pharmaceu- Gene Therapeutic Str a t e g i e s tical, and biotechnology institutions and for Tissue Engineering of companies. Launched in 2000, the pro- Bone.” Mer ck provides a gram has completed its pilot phase and senior staff scientist as a co- been added to the Community College’s mentor for each fellows h i p curriculum. The program offers associ- recipient; Botchwey ’s mentor at e ’s- d e g r ee students a struc t u r ed path at Mer ck is Dr. Don tow a r d res e a r ch-technician caree r s Kimmel, who works at th r ough core coursewo r k at Community Merc k ’s facility in Wes t College and supervised, hands-on labora- Point, PA. Botchwey to r y experience. rec e i v ed his Ph.D. from the The Wistar Institute and the Fel s Uni v ersity of Pen n s y l va n i a ’s Elliot M. Levine, Ph.D., and Edward A. Botchwey, Ph.D. Institute for Cancer Res e a r ch and Dep a r tment of Molecular Biology at Temple Uni ve r s i t y , Bio e n g i n e e r i n g . which joined the program in 2001, serve ◆ CAR M E N SAN MART I N , PH.D . , a postdoctoral fellow in the laboratory of Rog e r as training sites for the students. In addi- M. Burnett, Ph.D., has rec e i v ed the 2002 Ching Jer Chern Memorial Awa r d. Th e tion, Cephalon Inc., based in Wes t aw a r d was established in memory of Dr. Chern, a Wistar scientist, and rec o g n i ze s Ch e s t e r , Pa., joined as a training partn e r the best scientific publication by a postdoctoral fellow in the previous yea r . San in 2002. Mart i n ’s winning paper, which deals with the struc t u r e of a bacteriophage (a virus The ceremony honoring the students that infects bacteria), was published in 2001 in the journal Stru c t u r e. She pres e n t e d was featured on WPVI-TV 6 Action News. her res e a r ch following a luncheon in her honor on June 14, attended by Mrs. Jun e Chern, wife of the late Dr. Chern. ◆ HON G Z H UA N G PEN G , PH.D . , a postdoctoral fellow in the laboratory of Frank J. News and Notes Rauscher III, Ph.D., has won the 2002 Christopher Davis Memorial Fel l ow s h i p . The one-year fellowship was established in memory of Christopher Davis, son of ◆ The Wistar Ins t i t u t e ’s new web site, Bo a r d of Managers member Har old Davis and his wife, Eleanor Davis. The fellow- which debuted in Jan u a r y 2002, won an ship supports breast cancer res e a rc h . Awa r d of Excellence in the 2002 Awa rd s ◆ SU-JE A N SEO , PH.D . , a trainee in the laboratory of Jan Erikson, Ph.D., was one for Publications Excellence competition in of two winners in May of the 2002 Saul Winegrad Awa r d for outstanding disserta - the Most Imp r oved Web Site category. tion in the immunology graduate group at the Uni v ersity of Pen n s y l v ania. Seo ’s The Wistar staff invol v ed in the red e s i g n di s s e r tation title is “Anti-double-stranded DNA B cells in health and disease.” wer e Franklin Hoke, Marion Wyce , Soheila Nik p o u r , Don Ewer t, Ray Prei s , and Nina Long. including Joseph Leidy: The Last Man Wh o who won for her essay titled “New ◆ A new book by Institute Prof e s s o r Knew Every t h i n g . Vie ws of the Brain in the Res e a r ch of Le o n a r d War r en, M.D., Ph.D., Ade l e ◆ The winners of the 2002 Hig h Mental Dis o r ders.” The Hon o r a b l e Marion Fielde: Feminist, Social Act i v i s t , School Essay contest wer e honored at an James R. Roebuck, Pen n s y l va n i a Sc i e n t i s t , was published in Mar ch by aw a r ds ceremony on June 6. The grand Rep re s e n t a t i v e for the 188th Dis t r i c t , Routledge. War r en has published sever a l pr i z e winner was Evelyn Walters, a stu- pr esented the awards to Walters and the books on medical and science history, dent at Julia R. Masterman High School, other winning students. ◆

F O C U S / FA L L 2 0 0 2 1 3 W E L C O M E T O P H I L A D E L P H I A ! Director Russel E. Kaufman, M.D., Meets His New Neighbors

By Franklin Hoke

n June 20, local leaders fr om academia, business, and government gathered to welcome Russel E. Kaufman, M.D., Th e Wistar Ins t i t u t e ’s new di r ector and CEO, to the OPhiladelphia community. They joined other friends of the Institute under a large tent in front of Logan Hall, across the 36th Str eet walkway from Wistar on the Uni v ersity of Pen n s y l v ania campus. “I t’s an honor and a wonderful oppor- Russel E. Kaufman, M.D., with John H. Glick, M.D., director of the Abramson Cancer Center at the tunity to have been selected to lead Th e University of Pennsylvania. Wistar Institute,” Kaufman told the grou p after his introduction by Vincent G. “Bu c k ” Bell Jr., rep r esenting Wis t a r ’s tists, and Philadelphia is in many ways the ronment of Philadelphia and with the Bo a r d of Managers. “Many of my scientif- bi r thplace of American science and medi- recent prog r ess of the Human Gen o m e ic heroes in my youth wer e Wistar scien- cine. Tod a y , in the rich intellectual envi- Project and many other areas of molecular bi o l o g y , I think Wistar has all the pieces in place—now we need to put them together to cure disease.” Kaufman promised his listeners that, under his leadership, Wistar would be a good neighbor, a good citizen, and a good pa r tner to the academic and business communities and to the city and reg i o n . “You can’t be successful doing the kind of work we do alone,” Kaufman said. “We can and will help each other.” He then noted a number of Wis t a r ’s longtime friends in attendance under the tent, beginning with Mar g a r et “Mig g y ” Le o n a r d Brown, a member of the Wis t a r family and an emeritus member of the Bo a r d of Managers. From the academic community, Kaufman greeted many colleagues from the Uni v ersity of Pen n s y l v ania, the Ch i l d re n ’s Hospital of Philadelphia, and Clayton A. Buck, Ph.D., Jill Felix, P. Sherrill Neff, RoseAnn Rosenthal, Meryle Melnicoff, Ph.D., Sam Katz, other area medical res e a r ch institutions, and Brenda Gavin. including former Wistar res e a r cher Carlo

1 4 F A L L 2002 / FOCUS M. Croce, M.D., now director of the Kimmel Cancer Center at Th o m a s Jefferson Uni ve r s i t y , and John H. Gli c k , M.D., director of the Abramson Cancer Center at the Uni v ersity of Pen n s y l v ania. Among those rep r esenting the business community wer e Jill Felix, president and CEO of the Uni v ersity City Science Ce n t e r , Brenda Gavin and P. Sherrill Nef f , managing partners with Qua k e r Bio Ve n t u r es, Ros e A n n Rosenthal, pres i - dent and CEO of Ben Fra n k l i n Technology Par tners of Sou t h e a s t e r n Ma rg a r et “Miggy” Leonard Brown, Russel E. Mr . and Mrs. C. Cresson Wis t a r . Pen n s y l v ania, and Sam Katz, CEO of Kaufman, M.D., and Robert A. Fox. Greater Philadelphia First. Pen n s y l va n i a Rep re s e n t a t i v e James R. Roebuck, a long- pl a y ed in the establishment of The Wis t a r ne p h e w Isaac Wistar that led to the time supporter of Wis t a r ’s High School Institute. founding of The Wistar Institute in 1892, Program, was also on hand. The Wistar and Horner Mus e u m securing the future care of the Wis t a r For those unfamiliar with Wis t a r ’s his- medical teaching collection of anatomi- museum collections and beginning a long to r y, Kaufman recounted the role that cal specimens, begun by Dr. Caspar and close association between the Ins t i t u t e Logan Hall, just behind him as he spoke, Wistar in the early 1800s, was housed and the Uni ve r s i t y . for many years on the third floor of Since that time, Kaufman said, a Logan Hall. In 1888, a fire on the fourth unique, independent culture had devel - floor was in full flame before the horse- oped at The Wistar Institute of what he “ Y O U C A N ’ T B E S U C C E S S F U L drawn pumping equipment arrived. Fir e termed a “restless ambition” for discover y. and water combined to cause a parti a l “As we move forwa r d, I can assure you D O I N G T H E K I N D O F W O R K collapse of the building, and many of the that Wistar scientists will be among those museum specimens wer e damaged or making significant contributions to W E D O A L O N E . W E C A N A N D de s t r oyed . pro g r ess in medical res e a r ch,” Kaufman W I L L H E L P E A C H O T H E R . ” The fire and resulting damage sparke d concluded. “And I’m sure we will be col- discussions between the Uni v ersity of laborating with many of you here today Pen n s y l v ania and Dr. Wis t a r ’s grea t in this work that matters so much.” ◆

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F O C US / FA L L 2 0 0 2 1 5 Jan Erikson’s studies of how the immune system wo r k s — a n d sometimes fails to work—are shedding light on the causes of autoimmune diseases like lu p u s .

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