Fostering Communication and Collaboration
The nihCatalyst A Publication for NIH Intramural Scientists
National Institutes of Health Office of the Director Volume 4, Issue 4 July-August 1996
MCL, Moving Forward, Charge! Safety and Science Card Project Goes NIH-Wide Forward in Tandem by Celia Hooper and Rebecca Kolberg by Rebecca Kolberg slim piece of plastic and a little Immunological Genetics Section of NCH-
shopping savvy is all it took to save GR’s Laboratory of Gene Transfer a quar- an NCHGR lab more than $250,000. ter-million dollars with her smart use of the mproving safety and improving ease A that a act to fol- I of scientific research are not neces- Although may be tough charge card. In the pre-card era, the lab of NIH’s charge-card sarily mutually exclusive. Proof of that low, the expansion bought the recombinant interleukin-2 will soon give hundreds more (IL-2) it cells has just arrived on the south edge of program that uses to culture T from scientists their the NIH campus in the form of a newly intramural Life Technologies Inc. in to save time renovated facility for research involving own chance Gaithersburg, Md., at a cost and, possibly, big bucks. of about $250,000 a year. pathogens that demand the highest lev- “I THINK THE REAL the basis of the els of containment. On Now, armed with an NIH results of a 30-card pilot pro- and a prescrip- Although the new Maximum Con- VALUE OF THE CARDS charge-card at and NCI, written an M.D., tainment Laboratory (MCL) is located in gram NCHGR tion by NIH is moving ahead and Pepper went to Giant Dis- the same space as NIH’s old Biosafety IS IN THE TIME offering all institutes, centers, Level-4 (BL-4) facility in Building 41 A, count Pharmacy and bought and divisions (ICDs) the year’s supply of IL-2 for the difference between the old and new SAVED—TIME SAVED a opportunity to allow their re- facilities extends far beyond a simple $2,490—saving a cool searchers to apply for their $247,510. name change. Gone is the old “glove- TO DO SCIENCE.” cards, box” approach, in which walls separat- own charge or pur- What accounts for the chase cards, as administra- mind-boggling price differ- ed researchers from pathogens, forcing —Amy Pepper, them to manipulate pathogen-exposed tors prefer to call them. If ence? Pepper says a Giant animals, samples, and equipment efforts to automate the rec- NCHGR pharmacist told her the through bulky gloves inserted in fixed onciliation and payment answer probably lies in the portholes. Inside process proceed as planned, packaging that typically MCL, researchers scientists who apply for the accounts for two-thirds to clad in plastic cards and undergo the required half-day three-quarters of a drug’s price. The IL-2 astronaut-like training session should have their cards in purchased from Giant came in bulk vials suits, with their hand by August, says Donald Kemp, an ana- of 22 million units at $415 each, while the own spiral breath- lyst in the Office of Procurement Manage- IL-2 from Life Technologies came in 5-mg ing tubes hooked ment (OPM) who is coordinating the charge- vials of 25,000 units at $49 each. But what up to an outside card program along with staff from the about quality? So far, Pepper says her lab air source, will Office of Financial Management (OFM), has seen no difference between the be able to move DCRT, and the Intramural Reinvention expensive and cut-rate IL-2 when it about in relative Working Group. comes to stimulating T-cell growth, freedom and con- “We’ve tried to limit the ‘thou shalt duct scientific and nots’,” says Kemp, noting that since the pilot continued on page 14. animal-care pro- began, restrictions have been removed on cedures more like using the cards to pay for NIH parking stick- they would in a ers and to rent meeting space. As of May 5, CONTENTS normal lab. the 15 cardholders at NCI had made 704 2 11-13 “We built MCL purchases totaling about $251,000 and the From the DDIR Recently Tenured with flexibility in 15 cardholders at NCHGR made 2,214 pur- chases totaling nearly $1.17 million. A com- mind—although it may seem like an 4 13 plete audit by of half of the card oxymoron to mention BL-4 contain- OPM Ethics Forum; What’s in Store for instiaites indicated that all ment in the same breath as flexibility,” records both Ryan Report At Research Festival says Deborah Wilson, chief of the purchases were justified. 5-6 15 Occupational Safety and Health Although some NCI scientists have Alternative Awards reported problems tracking their purchase- Branch in NIH’s Division of Safety. Medicine's card orders and reconciling them with When it is completed later this sum- Intramural Foray 15 mer, the $3.6 million MCL will be one monthly statements, NCHGR’s Amy Pepper Cartoons of only three “suit-system” BL-4 says she’s found the additional bookkeep- 7-10 ing duties to be well worth the effort. And Special Pullout: 16 continued on page 14. Pepper knows what she’s talking about: Interinstitute Interest Catalytic Reactions Group Directory the lab technician has already saved the The NIH Catalyst From the Deputy Director for Intramural Research
Changing Demographics of NIH Scientists
lie commitment of the NIH intramural program American). Lest we congratulate ourselves too hastily
to excellence in science goes hand in hand for this progress, it should be noted that current Twith our commitment to a diverse, talented sci- trends are not in the right direction. Of the 33 latest entific staff. The reports of the External Advisory additions to the tenure track who were identified as a
( Marks-Cassell ) Committee (1994), the Committee on result of a search process carefully crafted to encom- the Status of Intramural Minority Scientists (see TJje pass both excellence and diversity, nine were women NIH Catalyst. July 1994), and the Task Force on the and six were Asian American, but, unfortunately,
Status of NIH Intramural Women Scientists (see The there were no underrepresented minorities. I find this NIH Catalyst, June 1993) each pointed out deficien- statistic quite worrisome, and we are currently redou- cies in representation of women and minority scien- bling efforts to recruit underrepresented minorities tists at various levels of training and leadership at into our tenure-track program. NIH. In this column, I report on some progress and The Central Tenure Committee now has a two-year Michael Gottesman problems on our path toward a multi-talented, multi- track record in making recommendations for appoint- ethnic community of men and women scientists. ment to tenure. Forty-seven scientists have been consid- Although currently lacking a complete picture of ered by the committee, and 35 (74%) were approved at the intramural program, we have a few windows the time of first review. An additional six were through which we can gauge the changing demo- approved after further review, bringing to 87% the over- graphics of our staff. The impression of a diverse all approval rate of the committee. In the past two population of NIH postdoctoral fellows is supported years, only tlvee of the six women proposed for tenure
by the most recent data, which show an almost equal received it. No underrepresented minorities were number of U.S. (IRTA) and foreign postdocs (visiting brought forward for tenure during this two-year period, fellows), a goal established a decade ago when the but both of the Asian Americans brought foiward were
IRTA program was initiated but achieved for the first tenured. It is too soon to know the significance of these time only last month. Our visiting fel- numbers since they represent small lows come from more than 80 differ- cohorts of scientists whose careers were ent countries, providing NIH with a We are currently initiated almost 10 years ago at NIH, but rich tapestry of different scientific we are watching carefully to be sure training, points of view, and cultural REDOUBLING that there is no inherent bias against heritage. The vast majority of these either women or minorities achieving EFFORTS RECRUIT visiting fellows return home after their TO tenure at NIH. Of the eight Senior Bio- training through this scientific medical Research Service scientists UNDERREPRESENTED exchange. Our population of IRTA fel- recmited from the outside over the past lows has a gender distribution close to MINORITIES INTO two years, two were women and one that of recent graduates in biological was Hispanic. science, as evidenced by the self-iden- OUR TENURE-TRACK Parallel to these improvements, tified pool of applicants for the Fel- women at NIH have increasing repre- lows’ Awards for Research Excellence PROGRAM. sentation among our section chiefs (FARE). About 35% of the applicants (18% this year compared with 13% in in this recent competition among NIH 1992) and lab and branch chiefs (10% fellows for travel money were women, as were 32% this year compared with 4% in 1992). Compared with of the award winners. Unfortunately, we do not have 1992, when NIH had only one female scientific direc- any reliable current information about the distribution tor, two of our scientific directors are women today. of underrepresented minorities among our fellows. In addition, two acting scientific directors are women.
It is good to see the increasing visibility of minority One major problem that has made it difficult to and women postdocs and other scientists through the evaluate the demographics, research interests, and efforts of the "Women Scientist Advisors, the Black Sci- productivity of NIH scientists is the lack of a uniform, entist Association, and the Asian/Pacific American Her- central database from which such demographic data itage Committee at NIH. Recrtiitment of minority fel- can be easily extracted. "We are now planning to lows to NIH continues to be a high-priority goal. One assemble such a database. area in which minority recruitment has been extremely The statistics we do have now, however spotty, successful is among our clinical associates. A two-year- suggest that NIH is moving steadily but slowly toward old loan-repayment program for physicians from disad- our goal of a diverse and multi-talented community vantaged backgrounds who are participating in clinical of scientists. Increased efforts to recruit, train, and research has led to the recaiitment of 19 clinical asso- retain our women and minority scientists will ciates, most of whom are underrepresented minorities. improve our ability to provide opportunities for a NIH’s future scientific leadership is reflected now diverse group of highly motivated and capable indi- among our tenure-track scientists. The establishment viduals. This, in turn, will enhance the development of a clearly defined tenure track two years ago has of the novel ideas and strategies for the medical
made it possible to get a clearer picture of the future research to which NIH is dedicated. Our efforts must demographics of NIH tenured scientists. The news is go forward at all levels of our scientific staff, and I generally encouraging. Among the 202 current urge all of you to become part of this process. tenure-track scientists, 30% are women, 21% are minorities and 8.5% are underrepresented minorities Michael Gottesman (4% African American, 4% Hispanic, and 0.5% Native Deputy Directorfor Intramural Research
2 . — .
LI - I) J L Y A LI G U S T 1 9 6
Catalytic Reactions
Below are comments that we receivedfor top- tenured staff regardless of the level of ways in which fellows can improve the ics that were raised in the March-April issue. their scientific or supervisory skills. On cjiiality of their training at NIH. They can the outside, people have to compete, work with their labs to enhance commu- On Kovac’s letter about postdocs be productive, and write grants. Not nication and quality of science, they can As Paul Kovac said, many postdocs are here. By the time a postdoc discovers work through the Fellows Committee to weeping and bitter. Their reasons can that NIH has its complications it is far develop institutional solutions to generic be good. Examples known to me can too late to cut and run, and not all have problems, and, if all else fails, they can often be traced to the behavior of a the requisite imagination or drive to move to a different lab or institution.
principle investigator (PI) who exhibits improve their own lots. . . Much of your angst, however, seems to a limited grasp of the concepts of train- Perhaps some postdocs are insecure reflect a malaise that appears to he ing, leadership, and people manage- and unhappy because they are just no spreading among postdocs throughout ment. Also, many postdocs are in a good and it is not the fault of bad old the United States. It might help to remem- panic because they realize that the job NIH at all. Certainly this is possible. I ber that we are all part of an exciting market is getting tougher every year. find myself happier with this place process of discovery and that what we
Many discover that they are not posi- when I am working well, less happy are doing is likely to result in the allevia- tioned to compete successfully. The lat- when I am not working well. But even tion of human disease and suffering. ter is not always their fault and may not if the source of all this postdoc dis- Were are few, if any, other careers that reflect their skills. Recently, one visiting gaintlement is based on their own defi- offer both the intellectual challenges and scientist explained to me how they ciencies, NIH cannot be held free of social benefits of biomedical research. screen applicants for new posts at his blame. After all, how could it be that —Michael Gottesman, DDIR university. First, they throw away all NIH attracts so many bad postdocs? Or applications from NIH. NIH people is it that NIH cannot attract good post- On Dent cartoons have limited teaching experience and docs? Whichever way you cut it, there I felt compelled to throw in my two usually no grant-writing experience, so must be big problems. NIH postdocs do cents when 1 read the criticism of the
they are not worth interviewing. . . not need "nannies and shrinks” [as Dent cartoon. Please keep the cartoon!
Kovac suggests that NIH cannot be a Kovac contends], they need construc- I love it! Although I was never a post- bad place since “everybody wants to tive debate on how to enhance the sci- doc, I am married to a former postdoc come here and stay here.” Not every- entific atmosphere, how to improve the (now a senior staff fellow) at NIH and body wants to come here. In fact, way Pis communicate with their staffs, am quite familiar with the “life as a
American postdocs generally do not and how to prepare for the competitive postdoc” experience. 1 really think the want to come here. Interestingly, many job market outside. Dent cartoon has the exciting/frustrat- postdocs take their position unopposed —Atastair S.H. Goldina?}. NCI ing/funny scenarios at NIH described to by other applicants. It should also be a “t.” I find it really humorous, never remembered that, whether it is a happy Both the evidence and I disagree with offensive, and look forward to each or unhappy place to be, NIH is safe your evaluation of our intramurai post- new cartoon. not because it is a good place, but docs and training program. Where prob- — Cathy Rihaudo, because it nurtures and protects its lems exist, there are many constructive Office ofResearch Services
Microbial Ecology Conference
cientists at an upcoming conference sponsored by Tuomanen, Rockefeller University, New York; John Collier NIDR, NIAID, and CBER will be focusing on the big and John Mekalanos, Harvard Medical School, Boston; S principles governing small creatures. “Microbial Ecology Julian Davies, University of British Columbia, Vancouver, and Infectious Disease,” which will take place July 10-12 at Canada; Ananda Chakrabarty, University of Illinois at Chica- the Pooks Hill Marriott in Bethesda, will highlight the com- go Medical Center; Barbara Iglewski, Rochester University, monalties in how microorganisms interact with their external Rochester, N.Y.; and Jorge Galan, State University of New environment. York at Stony Brook. Among the topics to be addressed are interactions Eugene Rosenberg, a Fogarty scholar sponsored by NIDR, between adhesins and receptors, microbial avoidance of organized the conference. Registration forms are available at host defense mechanisms, signaling within large popula- the Fogarty International Center (FIC), Room 202A, Building tions of bacteria, and bacterial growth in complex environ- l6. For more information, contact FIC’s Jack Schmidt ments. Speakers will include Joshua Lederberg and Elaine (phone: 496-4161; e-mail: [email protected]).
3 — The NIH Catalyst
Urgent Call for Comments on hy Alan N. Schechter, NIDDK, Commission on Research Integrity’s Report and Joan P. Schwartz, NINDS
f adopted as federal policy, the recent misconduct is significant misbehavior that Many concerns have been raised about recommendations of the Commission improperly appropriates the intellectual the imbalance between the rights of the I on Research Integrity would change property or contributions of others, that whistleblower and those of the accused,
significantly the way science is done at intentionally impedes the progress of whether it be a scientist or an institution. NIH and throughout the United States, research, or that risks corrupting the sci- The CRI “bill of rights” would provide sig- especially with regard to resolution of dis- entific record or compromising the integri- nificant protection to the whistleblower,
putes. Therefore, we feel it is imperative ty of scientific practices. Such behaviors but there is no comparable protection—or that as many scientists as possible read are unethical and unacceptable in propos- even acknowledgment—of the rights of the commission's report and comment on ing, conducting, or reporting research, or the accused. Destroying a scientist’s repu-
its recommendations. in reviewing the proposals or research tation through an unsubstantiated allega- Health and Human Services (HHS) Sec- reports of others." tion that has been made public could be retary Donna Shalala established These phrases are followed construed as a form of professional mis- the Commission on Research by examples of misappropria- conduct, and we believe measures that Integrity (CRD in 1993 after Con- tion, interference, and misrep- guard against this should be adopted. For gress directed her to fomr a pan- resentation. In the commis- example, standards for maintenance of el to examine “issues of research sion's judgment, these acts rep- confidentiality by all parties, with sanc- misconduct and integrity.” Con- resent misconduct, but we tions against those who break that confi- gress specifically requested guid- believe the CRTs definition dentiality, are essential components of ance in developing a new defin- overextends the boundaries of any dispute resolution, but they are not ition of research misconduct, an misconduct to matters that fully addressed in CRI’s “bill of rights.” assurance process for institution- would best be left alone or al compliance with HHS regula- resolved by the individuals or Administrative Processes tions, processes by which to institutions involved. For These sections of the CRI report cover
to and monitor related example, it appears that omis- many important issues, starting with how respond Alan N. Schechter administrative processes and sion of relevant references in a NIH intramural scientific misconduct cases investigations, and a regulation to protect scientific paper could be construed as mis- will be reviewed. Other issues include f) whistleblowers. The 12-member CRI, which appropriation, and an editor’s actions in whether the results of all misconduct was chaired by Kenneth Ryan of Harvard declining a paper could be defined as investigations-even those with no finding Medical School in Boston, spent two years interference. Although CRI's approach of of misconduct-should be made public, 2) holding hearings around the country and applying the general principle that “scien- the increased potential for misconduct
issued its final report last November. The tists be truthful and fair in the conduct cases to overlap with civil and criminal report, entitled “Integrity and Misconduct in of research and the dissemination of its procedures, 3) the suggestion that a law Research,” covers three general areas: the results” has attractive features, many scien- enforcement official be involved in all
definition of research misconduct, responsi- tists and professional societies have reacted investigations, and 4) the proposal to ble whistleblowing, and administrative with alarm to the commission’s proposed a.ssign retaliation cases to ORI, rather than reg- processes and investigations. Here is a brief definition because it appears to broaden allowing them to be handled through summary of the recommendations and unnecessarily the scope of misconduct. ular personnel channels. what we see as their implications for bio- Furthermore, CRI specifically notes that medical research. some authorship disputes might fall under Seeking Scientists’ Responses the purview of misconduct. Thus, the new After receiving CRI’s report, HHS Secretary Defining Research Misconduct definition could result in a Shalala appointed William I'he current definition of research miscon- flood of authorship-dispute cas- Raub, who was formerly NIH’s duct, adopted in 1989, was developed in es that are not deemed scientif- deputy director and is now response to a directive from Congress ic misconduct under current Shalala’s science policy advis- after several well-publicized cases of sci- definitions. er, to head a group that will entific misconduct. This definition—“fabri- recommend to her whether cation, falsification, plagiarism, or other Whistleblowing and how the CRI report should practices that seriously deviate from The need to prevent retaliation be implemented. This group is from those that are commonly accepted within against whistleblowers—people currently seeking input the scientific community for proposing, who report fraud, waste, and scientists, and the NIH Com- conducting, or reporting research” mismanagement—has been a mittee on Scientific Conduct like obtain applies to all research funded by the Pub- concern of the federal govern- and Ethics would to as many comments from intra- lic Health Service, but not to that support- ment for the past decade. More r P.n Schwartzc I ^ Joan , , ed by the National Science Foundation or recently, this concept has been mural researchers as possible. submit other federal agencies. Since its adoption, extended to those making allegations of We will collate the comments and com- much concern has been raised about the scientific misconduct—an uncharted area an unofficial response from the NIH vagueness of the “other practices” phrase. in which Congress asked CRI to propose munity to the implementation group. Send One of CRI's main charges was to re- some guidelines. your comments or suggested modifica- (mail: Bldg. 10, examine this hotly debated definition. To In its report, CRI strongly supported tions to Alan Schechter nearly everyone’s surprise, in,stead of fine- draft guidelines issued last November Rm. 9N307: fax: 402-0101; e- tuning the currently accepted definition, by the Office of Research Integrity (ORI). mail: [email protected]). Copies of through the commission proposed a totally new However, the commission added its own the CRI report can be obtained Integrity definition, which it placed in the context touch by drawing up “A Whistleblower’s HHS’s Office of Research Web of a broader category of professional mis- Bill of Rights,” which it suggests be (phone: 301 443-3400; World Wide conduct. The definition states, “Research appended to the ORI’s document. site: http://www.os.dhhs.gov/phs/ori).
4 July-August 1996
Alternative Medicine byJenuifer M. King Goes Intramural
ost NIH scien- as well as teaching I and tists wouldn’t I giving lectures on their blink an eye research projects M I flesh at the prospect of a out the fellows’ duties. half-dozen new post- The fellows will doc positions being spend their first six created in the intra- months at NIH in the mural program. But classroom, where they what if those postdocs will be introduced to a are studying alterna- variety of research meth- tive medicine? ods and alternative-med- AJthough many NIH icine practices through
find it researchers may I lectures, seminars, and difficult to accept the teaching labs given by notion of even a small research scientists and number of postdocs at practitioners of alter- the nation's leading native medicine. The biomedical research didactic sampling is only institution venturing part of what Jonas terms into the realm of a “liberal arts research acupuncture, homeopa- education” designed not thy, and herbalism, the only to familiarize the head of the program, postdocs with alterna- Wayne Jonas, says the tive-medicine terms but move is no cause for Information Requests also to provide a sound concern. “The goal of By Therapy underpinning for a suc- the program is not to 1993-1994 cessful research career make a practitioner of by training the fellows in Acupuncture alternative medicine. protocol development, Shark Cartilage The goal is to expose Homeopathy statistical analysis, grant them [the postdocs] to Herbal Medicine writing, critical appraisal those areas so that they Massage/Bodywork of scientific literature, lab Chiropractic can begin to do good and clinical measure- Diet/Supplements research,” says Jonas, Naturopathy ment techniques, and who became director Chelation research design. of NIH's Office of Alter- Biofeedback The second half of Touch native Medicine (OAM) the first year will focus Yoga last summer. “We are on developing and Chinese Herbal not here to train natural structuring individual healers. We are here to projects with the help of teach researchers.” senior scientists. Year In fact, Jonas says two will involve getting he has received some approval for and con- positive feedback from Public Inquiries Received by OAM. ducting research pro- scientists on all rungs jects under the supeivi- of the intramural ladder—from fellows salaries and benefits of five to seven sion of senior staff mentors and OAM. to scientific directors. “There have been intramural fellows per year. Project The final year is devoted to managing a lot [of NIH scientists] who have costs will be borne largely by ICDs, clinical investigations, giving lectures on approached me and said, 'We’re excited although OAM will provide approxi- alternative-medicine topics, and writing that you’re doing this. We’d be very mately $ 15,000 per fellow per year. manuscripts. Any institute, center, or alter- interested in it,’” he says. Over the course of three years, division that has a research effort that native postdoctoral fellows . Under the $440,000- to $590,000- medicine could benefit from having a postdoc per-year program to be initiated in July will be required to complete two or interested in alternative medicine is 1997 will make use of its own three research projects: one systematic encouraged to contact OAM (phone: , OAM Individual Research Training Award review or meta-analysis plus clinical or 402-2466; e-mail: [email protected]). (IRTA) or individual National Research basic science projects. Developing or Pat Mail, a public health analyst at Service Award (NRSA) funds to cover coordinating two clinical investigations NIAAA, says she sees potential applica-
5 tions for alternative-medicine research at her institution. “In addition to the 'tradi- OAM at a Glance tional’ therapeutic approaches to preven- tion and treatment of alcohol misuse, there are a number of approaches uti- Contact: Director Wayne Jonas lized by people in different cultures that Phone; 402-2466 might be beneficially explored,” Mail Location: Building 31, Room 5B-37 says. to mind: the "One example comes Resources: Provides support for adaptation of Western-style group selected postdocs interested in process by American Indians in their alternative medicine and matches alcohol-treatment programs. This adapta- them with appropriate investigators tion is often referred to as 'Talking Cir- cles,’ which describes both the structure at NIH and outside institutions. and the process of these therapeutic Awards extramural grants for alter- groups. ... In an increasingly multicultur- native-medicine research projects. al society, our research should reflect Handles public inquiries about reality, and alternative medicine is the alternative therapies. umbrella under which cross-cultural solutions might be explored.” WayneJonas Acknowledging that “good science" often has not been applied to alterna- A Short History of OAM tive treatment strategies in the past, Jonas says he hopes that OAM’s new he office was founded in 1992 at the direction of Congress under leg- focus on rigorous preliminary screen- islation sponsored by Sen. Tom Harkin (D-Iowa). Its congressional ing and selective funding of both intra- mural fellows and extramural research T mandate is to investigate and evaluate alternative treatments, dissemi- grant proposals will lead to a more sol- nate information to the public, and support research training in alternative- id foundation of knowledge about medicine practices. OAM received $2 million in 1992 and 1993, $3-5 million in such therapies. “Good science is the 1994, and $5.4 million in 1995. It has used that money to fund extramural way to separate the pearls from the grants, establish a popular public clearinghouse, and sponsor a technology- mud,” he says. assessment conference. In this era of limited resources for biomedical research, some may ques- OAM’s first director, Joseph Jacobs, vacated the position after two years. tion the expense of sifting through a He was replaced in July 1995 by Wayne Jonas, former director of Medical ton of alternative-medicine mud when Research Fellowships at Walter Reed Army Institute of Research in Washing- traditional mining more veins of ton, D.C.. Upon his arrival, Jonas reorganized the office and began develop- research may yield far greater thera- ing a plan for the intramural training of postdocs. Since Jonas assumed direc- peutic returns. However, Jonas is torship, the office has more than doubled its staff, from four to 10. quick to point out that alternative medicine is an area of great interest to both Congress and the U.S. public, with one in three Americans reporting its inception, OAM also has awarded they have used some sort of alterna- 42 grants totaling $1.26 million to indi- HIV Funds Deadline tive therapy. vidual extramural researchers and, Jonas emphasizes that the intramur- along with NIDR, NICHD, NCI, and the al research program represents just a Office of Research on Women’s Health, NIH’s Intramural AIDS Targeted small fraction of activities. 10 three-year grants OAM’s One has awarded Antiviral Program (lATAP) has set of its biggest efforts is a phone-in totalling $9.7 million to .set up alterna- Aug. 23 as the deadline for fund- clearinghouse to provide the public tive-medicine research centers at extra- with descriptive information about mural institutions. ing proposals for fiscal 1997 and alternative "It is optimal goal of the Office therapies and related the 1998. For more information on research. The toll-free line (1 800 531- of Alternative Medicine to foster both how to apply for the funds, con- 1794) averages 1,200 calls per month, rigor and realism in complementary with the greatest number of inquiries alternative medicine research,” Jonas tact Janet Smith (402-3444; fax: related to alternative therapies for can- says. “It is our vision to bring togeth- 402-3443; e-mail: [email protected]). cer and acquired immune deficiency er the best of healing and the best of syndrome (.see figures, page 5). Since science.”
6 JUI. 'i -AUGUST 1996
Interinstitute Interest Group Directory
Major Interest Groups/Faculties Neurobiology Behavioral and Social Sciences Meeting time: Not available Interest Group Cell Biology Interest Group Meeting place: Building 49, Meeting time: Monthly Meeting time: Varies, meetings Conference Room Meeting place: See Calendar of Events
restricted to NIH scientists Contact: Ron McKay, NINDS Contact 1: Jaylan Turkkan, NIDA Meeting place: Building 18T, Room 101 Phone: 496-6574 Phone: 443 - 1263 Contact: Jennifer Lippincott-Schwartz, E-mail: [email protected] E-mail: [email protected]
NICHD Listserv: [email protected] Contact 2: Ron Abeles, NIA Phone: 402-1010; 402-1009 Phone: 594-5943 E-mail: [email protected] Structural Biology Interest Group E-mail: [email protected] ListServ: subscribe to CELBIO-L Meeting time, place: Announced by e-mail and regular mail BSSR Methodology Clinical Research Contact: Alasdair Steven, NIAMS and Measurement Interest Group Meeting time, place: Varies Phone: 402-3418 Fax: 402-3417 Umbrella Group: Behavioral Contact: Cliff Lane, NIAID E-mail: [email protected] and Social Sciences Phone: 496-7196 To register for e-mail announcements: Meeting time: First or second Tuesday, E-mail: [email protected] E-mail: [email protected] 8:30 a.m. Meeting place: Building 45, Room 3AS10 Genetics Interest Group Contact: Jared Jobe, NIA Meeting time: Last Tuesday, Other Interest Groups Phone: 496-3137 4:00-5:30 p.m. E-mail: [email protected] Meeting place: Building 49, Conference [Groups in brackets are just getting Room A and B started. Umbrella groups are affiliated Bioinstrumentation Interest Group Contact: Robert Nussbaum, NCHGR major faculties, or other coordinating Meeting time: First Tuesday, 2:00 p.m.
Phone: 402-2146 or oversight groups] Meeting place: Building 13, Room 3W54 E-mail: [email protected] Contact: Steve Leighton, NCRR Listserver: subscribe to Alzheimer’s Interest Group Phone: 435-1948 [email protected] Meeting time: First or second Thursday E-mail: [email protected] post to [email protected] Contact: Gerald Ehrenstein, NINDS Phone: 496-3206 Birth Defects and Teratology Group Immunology E-mail: [email protected] Meeting time, place: Varies
Meeting time: Wednesdays, 4:15 p.m. Contact 1: Kenneth Warren, NIAAA (see NIH Calendar of Events) Antisense Interest Group Phone: 443-4375
Meeting place: Building 10, Umbrella Group: Clinical Research Contact 2: James Hanson, NICHD Lipsett Auditorium Meeting time: Last Thursday, 4:00 p.m Phone: 496-5099 Contact: Pierre Henkait, NCI Meeting place: Building 10, Room 4B36
Phone: 496-I554 Contact : Yoon Cho-Chung, NCI Breast Biology Interest Group E-mail: [email protected] Phone: 496-4020 Meeting time: Fourth Monday, 4:00 p.m. Listserver: subscribe to IMMUNI-L E-mail: [email protected] Meeting place: Building 10, at [email protected] Room 13S235B Apoptosis Interest Group (AIG) Contact: JoAnne Zujewski, NCI Molecular Biology/Biochemistry Meeting time: Once a month E-mail: [email protected] Interest Group on Monday, 4:00 p.m. Meeting time, place: Varies Meeting place: Building 30, [Carcinogenesis Interest Group Contact: Reed Wickner, NIDDK Conference Room 117 Contact: Umberto Saffioti] Phone: 496-3452 Contact: Yves Pommier, NCI E-mail: [email protected] Phone: 496-5944 Cell and Molecular Neuroscience E-mail: [email protected] Interest Group Umbrella group: Neurobiology Meeting time, place: Varies Contact: Ron McKay, NINDS Phone: 496-6574 E-mail: [email protected]
7 The NIH Catalyst
Interinstitute Interest Gro UP Directory
Cell Cycle Interest Group DNA Repair Group Extracellular Matrix Umbrella group: Cell Biology Umbrella group: Molecular Biology Interest Group Meeting time: First Wednesday, Meeting time: Third Tuesday, 12:30 p.m. Meeting time, place: Varies
2:30 p.m. Meeting/Videoconference Locations: Contact 1: W. Stetler-Stevenson, NCI Meeting place: Building 37, Room 6B23 Natcher Bldg., Room H; GRC Phone: 496-2687 Contact: Patrick M, O'Connor, NCI (Baltimore), Room 1E03; FCRDC E-mail: [email protected]
Phone: 435-2848 Building 549, Conference Room A Contact 2: Larry Wahl
E-mail: [email protected] Contact 1: Kenneth Kraemer, NCI E-mail: [email protected] Phone: 496-9033 Cellular and Molecular Biotherapy E-mail: [email protected] Fluorescence Interest Group Interest Group Meeting time: Fridays, 4:00 p.m.
Meeting time: Quarterly Drosophila Interest Group Meeting place: Building 10, Room 5D21 I half-day symposia Umbrella group: Developmental Biology Contact: Jay Knutson, NHLBI
Contact 1: John R. Ortaldo, NCI-FCRF Meeting time: Third Tuesday, Phone: 496-2557 Phone: 301 846-1323; Fax: 301 846-1673 1:15-2:30 p.m. E-mail: [email protected] E-mail: [email protected] Meeting place: Building 6B, Room 4B429
Contact 2: Jack Greiner, NCI Contact: Sue Haynes, NICHD Gene Therapy Interest Group Fax: 496-2756 Phone: 496-7879 Meeting time; Second and fourth E-mail: [email protected] E-mail: [email protected] Tuesdays, 12:00-1:00 p.m. Meeting place: Lipsett Auditorium Chaos and Biocomplexity Drug Discovery Contact: R. Michael Blaese, NCHGR Interest Group Meeting time: Once a month Phone: 496-5396 Meeting time: Once a month on Thursday, 3:00-4:30 p.m. E-mail: [email protected] on Thursday, 4:00 p.m. Meeting place: Building 37, Room 6B25 Meeting place: Building 10, Rose Room Contact: John Weinstein, NCI Glia Club Contact: Julio Licinio, NIMH Phone: 496-9571 Meeting time: Bimonthly on second Phone: 496-6885 E-mail: [email protected] Wednesday, 4:00-5:30 p.m. E-mail: [email protected] Meeting place: Building 36, Room IB
Listserv: subscribe to BCMPLXTY Economics Interest Group Contact 1: Vittorio Gallo, NICHD Limbrella Group; Behavioral Phone: 402-4776 Cytokine Interest Group and Social Sciences E-mail: [email protected]
Meeting time, place: Varies Meeting time: Second Tuesday Contact 2: Joan Schwartz, NINDS
Contact 1: Howard Young, NCI or announced Phone: 496-4049 Phone: 301 846-5700 Meeting place: Announced E-mail: [email protected]
Contact 2: Alan Sher, NIAID Contact 1: James A. Schuttinga, OD Phone: 496-3535 Phone: 496-1454 Glycobiology Interest Group E-mail: [email protected] Meeting time: Once a month
Developmental Biology Contact 2: Agnes Rupp, NIMH on Thursday, 3:00-5:00 p.m. Interest Group E-mail: [email protected] Meeting place: Building 30, Room 117 Umbrella group: Cell Biology Contact: Diana Blithe, NICHD Meeting time, place: Varies Epidemiology and Clinical Trials Phone: 496-6437 (see NIH Calendar of Events) Interest Group E-mail: [email protected]
Contact 1: Igor Dawid, NICHD Meeting time: Monthly Listserver: subscribe to
Phone; 496-4448 Meeting place: See Calendar of Events GLYCO-L@LIST. NIH . GOV
E-mail: [email protected] Contact 1: Martina Vogel, OD
Contact 2: Joram Piatigorsky, NEI Phone: 496-6614 Hard Tissue Disorders Phone: 496-9467 E-mail: [email protected] Interest Group
E-mail: [email protected] Contact 2: Dick Havlik, NIA Umbrella group: Clinical Research Phone: 496-1178 Meeting time: First Wednesday, E-mail: [email protected] 12:00 p.m. Listserv:subscribe to Epidem-L Meeting place: Varies
at [email protected] Contact: Pamela Robey, NIDR Phone; 496-4563
E-mail probey@yoda . nidr. nih .gov :
8 - I U I, Y A II G U S T 19 9 6
Image Processing [Molecular Modeling Nucleic Acid Biochemistry Meeting time, place: Varies Interest Group Interest Group Contact: Bonnie Douglas, DCRT Meeting time: To be decided Umbrella group: Molecular Biology
Phone: 496-2847 Meeting place: Building 12, Room B51 Meeting time: Third Friday
E-mail : [email protected] . nih .gov Contact: Robert Pearlstein, DCRT Meeting place: Building 5, Room 127 Phone: 402-3043 Contact: Janet Yancey-Wrona, NIDDK Integrative Neuroscience E-mail: [email protected]] Phone: 496-2038 Interest Group E-mail: [email protected]
Umbrella group: Neurobiology ! Motility Interest Group Meeting time: Alternate Thursdays, Meeting time: First Monday Pigment Cell Research 4:00 p.m. (except July and August) Interest Group Meeting Place: Building 49, Meeting place: Building 10, Meeting time: Third Monday, Conference Room Bunim Room 3:00 p.m.-4:30 p.m. Contact: James Olds, NINDS Contact: Leepo Yu, NIAMS Meeting place: Building 37, Room 6B23 Phone: 402-6079 Phone: 496-5415 Contact: Vincent Hearing, NCI E-mail: [email protected] E-mail: [email protected] Phone: 496-1564 Listserv: subscribe to E-mail: [email protected] [email protected] Mouse Club Umbrella group: Developmental Biology Postdoctoral Structural Biology Lambda Lunch Meeting time: Once a month Interest Group (Bacterial and Phage Genetics) on Tuesday, 4:00-5:30 p.m. Meeting time: Once a month Meeting time: Thursdays, Meeting place: Building 31, on Tuesday, 3:00-5:00 p.m. 11:00 a.m.-12:30 p.m. Room 2A-52 Meeting place: Building 31, Meeting place: Building 36, Room 1B13 Contact: Heiner Westphal, NICHD no room given Contact: Susan Gottesman, NCI Phone: 402-0545 Contact: Teresa Strzelecka, NIDDK Phone: 496-3524 E-mail: [email protected] Phone: 496-2815 E-mail: [email protected] E-mail: [email protected]
Anonymous FTP site: ETP.CU.NIH.GOV Nerve Growth Factor (NGF) Cluh directory “LAMBDA_LUNCH” Meeting time: Eirst Tuesday [Prostate Cancer Interest Group (see NIH Calendar of Events) Contact: W. Marston Linehan, NCI
- Lymphoma and Leukemia Meeting place: Building 49 Phone: 496 6353 ] Interest Group Contact: Gordon Guroff, NICHD Meeting time: Second Monday, Phone: 496-4751 Protein Folding 2:00 p.m. E-mail: [email protected] Meeting time: Thursdays, 4:00 p.m. Meeting place: Building 10, Meeting place: Building 12A, Room 9S-235 Nerve-Muscle Interest Group Room 3026 Contact: Ivan Horak, NCI Meeting time: Every other Wednesday, Contact: Joe Bryngelson, NCI/DCRT Phone: 594-1127 8:30 a.m.-9:30 a.m. Phone: 496-II 35 E-mail: [email protected] Meeting place: Building 36, Room 1B07 E-mail: )[email protected] Contact: Matt Daniels, NHLBI Mass Spectrometry Phone: 496-2898 Protein Trafficking Interest Group Umbrella group: Structural Biology E-mail: [email protected] Umbrella group: Cell Biology Meeting time: First and third Thursdays, Meeting time: Second Tuesday, 10:30 a.m. Neuroimmune Interactions 3:30-5:00 p.m. Meeting place: Building 10, Interest Group Meeting place: Building 10,
Room 7C101 Meeting time: Once a month Room 9S-235 ( Bunim Room) Contact: Lewis Pannell, NIDDK on Tuesday, 4:00 p.m. Contact: Harris Bernstein, NIDDK Phone: 402-2196 Meeting place: Building 10, Phone: 402-4770 E-mail: [email protected] Room llS-235 E-mail: [email protected] Contact: Esther Sternberg, NIMH Phone: 402-2773 E-mail: [email protected]
9 The N I H Catalyst
Intekinstitute Interest Gro UP Directory
Human Retrovirus Interest Group Transcription Factors X-ray Crystallography Meeting time: Third Wednesday, Meeting time: First Thursday Umbrella group: Structural Biology noon-1 :00 p.m. (except July-Sept.), 2:15 p.m. Meeting time: Sporadically announced Meeting place: Natcher Conference Meeting place: Building 49, to members via e-mail
Center, Room B First Floor Conference Room Meeting place: Building 5, Room 231
Contact: Fatah Kashanchi, NCI Contact 1: Stoney Simons, NIDDK Contact 1: James Hurley, NIDDK Phone: 496-0987 Phone: 496-6796 Phone: 402-4703 E-mail: kanshancf@dce4l, nci.nih.gov E-mail: [email protected] E-mail: [email protected]
Contact 2: U. Siebenlist, NIAID RNA Club Phone 496-7662 Youth and Family Interest Group Umbrella group: Molecular Biology E-mail: [email protected] Umbrella group: Behavioral Meeting time: First Tuesday, Listserv: subscribe to TEACTORS and Social Sciences 4:00-6:00 p.m. Meeting time: Third Tuesday; Meeting place: Building 41, Room C509 Virology Interest Group time to be set
Contact 1: Carl Baker, NCI Meeting time: Third or fourth Thursday, Meeting place: Building 31, 6A23 Phone: 496-2078 3:30 p.m. Contact: Carmen Moten, NEI
E-mail: [email protected] Meeting place: Building 4, Room 433 Phone: 496-4308 Contact 2: Susan Haynes, NICHD Contact: Edward Berger, NIAID E-mail: [email protected] Phone: 496-7879 Phone: 402-2481 E-mail: [email protected] Listserv: contact [email protected] To make additions or changes, contact - Signal Transduction Interest Group Washington Area Yeast Club The NUT Catalyst (fax: 402 4303; Meeting time, place: Not available Umbrella group: Molecular Biology e-mail: [email protected]).
Contact 1: John Northup, NIMH Meeting time: Second Wednesday, Phone: 496-9167 5:15-7:15 p.m. E-mail: JKNGTP@helix Meeting place: Building 6B, Room 4A-05 Contact 2: Jim Battey, NIDCD Contact 1: Reed Wickner, NIDDK Wanted: Phone: 402-2829 Phone: 496-3452 Grad-School Director E-mail: [email protected] E-mail: [email protected]
Contact 2: Alan Hinnebusch, NICHD If shaping a curriculum interests you Social Structure & Demographic Phone: 496-4480 as much as designing an experiment, Issues in Health Interest Group E-mail: [email protected] the Foundation for Advanced Educa-
Umbrella group: Behavioral tion in the Sciences ( FAES) may have and Social Sciences WorldWideWeb Interest Group the perfect job for you. EAES is seek- Meeting time, place: To be announced. Meeting time: Second Tuesday, 2:30 p.m. ing a scientist to serve as the new director for its Graduate School at Contact 1: Laura E. Montgomery, Meeting place: Bldg. 10, NIH, a 37-year-old education pro- NCHS/CDC Lipsett Auditorium gram that has an enrollment of more Phone: 436-3650 x 177 Contact : Dale Graham, DCRT than 2,500 students and offers nearly E-mail: [email protected] Phone: 402-1805 100 courses. The part-time position is [email protected] Contact 2: Julie Reid, NHLBI E-mail: being vacated by NIDDK’s Louis Phone: 435-0410 Cohen, who is stepping down after E-mail: [email protected] Xenopus/Zebrafish Interest Group leading the school for the past 35 Umbrella group: Developmental Biology years. FAES says the new director Meeting time: Last Eriday must be a scientist who is familiar
(except summer), 4:00 p.m. with NIH and its science-education Meeting place: Building 6B, Room 429 needs, but he or she does not need Contact: Tom Sargent, NICHD to be employed by NIH. Among the responsibilities will be Phone: 496-O 369 director’s curriculum for the E-mail: [email protected] developing a new school, including courses that use a modern molecular biology teaching lab. Eor more information on the directorship, contact Lois Kochanski at FAES (phone: 496-7975; e-mail: [email protected]).
10 —
J U L Y - A D G Ll S T 19 9 6
yy—LiiJi
Recently Tenured
Building upon these results, I have rat cerebral cortex as a model system, we Sanford Ttsmsey joined NCI's Division of recently begun a series erf studies to eval- are trying to understand the regulation and Cancer Preventio}! and Control in 1987 uate and possibly improve some tech- physiological role of neurotransmitter is currently investigator in the and an niques that may be useful in a practical receptors in glia during development. division's Cancer Prevention Studies early-detection program for squamous In the embryonic mammalian brain, Branch. Dawsey received his M.D. from esophageal cancer. One study is aimed at oligodendroglial cells divide, migrate, and Stanford Medical School in Palo Alto. evaluating the sensitivity and specificity of differentiate later than neurons. This in Calif, 1976. the currently available esophageal cyto- observation has given rise to the hypothe- major research interest is the pre- My logic samplers and at developing sis that neurotransmitters released by neu- control of cancer vention and esophageal improved models of these samplers. rons may play an important role in the a cancer that kills 10,000 Americans annual- Another study focuses on whether mucos- development of the oligodendroglial lin- ly and is the fourth most common cause of al staining can improve endoscopic local- eage—a hypothesis that we are testing by cancer death among African ization of squamous dyspla- focusing on the main excitatory neuro- Less than American men. 10% sia and cancer, thereby opti- transmitter of the mammalian brain, gluta- of patients with esophageal mizing the visualization of mate, and its receptors. survive five years cancer for such lesions for focal thera- Our previous work, which demonstrat- after diagnosis, largely py. A third study is designed ed that 0-2A cells express glutamate- because most of these tumors to evaluate how accurately receptor (GluR) genes and genes that do not produce symptoms endoscopic ultrasonography encode functional glutamate-gated chan- until it is too late for surgeiy can stage early squamous nels, led to two important findings. First, nonsurgical treatments and cancers so that focal therapy we characterized two subtypes of GluRs curative. are usually not In will not be attempted on with distinct molecular composition and this setting, will probably we tumors that are already too function in cells of the oligodendrocyte lin- need to develop successful Sanford Dawsey advanced. A fourth study is eage. Second, we identified a set of genes primary-prevention and/or aimed at assessing the safety, that are induced by GluR-activation in a early-detection strategies significantly to acceptability, and preliminaiy efficacy of calcium-dependent fashion in 0-2A prog- reduce esophageal cancer mortality. several methods of focal endoscopic ther- enitors. In more recent experiments, we At NCI, I have participated in two apy, including endoscopic mucosal resec- demonstrated that activation of GluRs in nutritional-intervention clinical large trials tion and thermal coagulation. 0-2A cells reversibly inhibits their prolifer- in Linxian, China, a region with extraordi- I am also currently involved in etiolog- ation and prevents lineage progression narily high rates gastric of esophageal and ic studies of the roles of through the indirect blockage cardia cancer. During these trials, my col- human papillomavirus and of delayed-rectifier potassium laborators and I performed several studies certain fungal toxins in the channels. Our future work that were relevant to an early-detection development of squamous will focus on the molecular approach to squamous esophageal can- esophageal cancer, and other analysis of intracellular cer. We carried out two prospective fol- studies of the role of events crucial to glial-cell low-up studies that documented the pre- Helicobacter pylori in the development that are trig- dictive value of esophageal cytology, development of gastric car- gered by GluR activation. another follow-up study that showed that dia cancer. In addition, I am My lab is also using glial high-grade squamous dysplasia is the participating in a group of cells to study how GluR only important near-term histologic pre- new genetic studies of genes are regulated in the cursor of squamous esophageal cancer, esophageal and gastric can- Vittorio Gallo mammalian brain. Our spe- and studies that two endoscopic demon- cers in high-risk Chinese cific goal is to determine strated that lesion this histologic precursor populations. We are hopeful that our etio- whether the DNA regulatory elements and is usually associated with visible mucosal logic and genetic studies will contribute transcription factors that regulate GluR abnormalities that can be biopsed. to the development of additional promis- gene transcription in glia and in neurons Our discoveiy that squamous dysplasia ing strategies for the prevention and con- are the same. We have cloned the entire can usually be identified through an trol of esophageal cancer. rat gene encoding the GluR subunit KA2. endoscope implications for has important This gene, named GR1K5, is abundantly research and clinical practice. In research, expressed in both glia and neurons. endoscopic biopsies should be an accu- Vittorio Gallo received bis Ph.D. from the GR1K5 spans approximately 70 kilobases rate gold standard for validating less-inva- University of Rome i>i 1979. He joined of genomic DNA and comprises 20 exons. sive diagnostic techniques such as NlCHD's Laboratoiy of Cellular and Mole- We identified multiple transcription-start esophageal cytology, and endoscopic pro- cular Neurophysiology in 1992 as head of sites in its 5' flanking region, and also tocols should able to evaluate future be the Unit on Neurohiology, and he is cur- found that GRIK5 displays features of a intervention studies that use squamous rently chief of the lab's Section on the Mol- housekeeping gene. Our analysis in rat dysplasia as an intermediate endpoint. In ecular Neurobiology of Glia. neural cells and in nonneural rat and the clinic, endoscopic biopsies should be My lab’s recent research has centered human cells, as well as in transgenic able to confirm and localize screening- on glial cells of the mammalian brain. Glial mice, demonstrated that a region of detected abnormalities, primary endo- cells do not directly participate in synaptic GRlKS's 5'-flanking sequence restricts tis- scopic screening may be feasible in cer- transmission, and their precise role in the sue-specific expression of this GluR gene tain high-risk groups, focal and endoscop- developing and adult brain is yet to be in vitro and in vivo. Now, we are working ic therapy may be possible for controlling defined. Using oligodendroglial progenitor on characterizing the mechanisms of tran- precursor disease. and early invasive (0-2A) cells purified from the embryonic scriptional regulation of GRIK5 during
11 — The NIH Catalyst
development and identifying the DNA- based STS-content mapping, that we pro- tional neuroscience since the 1950s. I was binding sites involved. posed in 1991 for building a physical map particularly attracted by the group’s repu- Finally, I am also collaborating with of the human genome. tation for fostering collaboration between Mark Mayer and Chris McBain of As a result of our mapping efforts, theoreticians and experimental biologists.
NICHD’s Laboratory of Cellular and Mol- chromosome 7 is among the first targets I was assigned to model the electrical ecular Neurophysiology on projects to for large-scale DNA sequencing within the activity of pancreatic beta-cells in the determine whether GluRs can be regulat- Human Genome Project. In collaboration islet of Langerhans using elaborated ed at the transcriptional level by growth with the genome centers at Washington Hodgkin-Huxley equations that describe factors that are known to modulate glial University in St. Louis and the University neural action potentials. Beta-cells exhib-
development and to define the precise of Washington in Seattle, we have begun it rhythmic electrical activity, similar to role of other membrane ion channels in genomic sequencing of chromosome 7. that observed in many neurons, that glial development. While the notion of sequencing an entire plays an important role in insulin secre- human chromosome may seem daunting, tion. An as-yet-unidentified defect in remember that only five years ago the beta-cell response to blood plasma glu- Eric Green received his M.D.-Ph.D. from idea of making a complete physical map cose is thought to be central to the
Washington University in St. Louis in of a human chromosome was equally development of Type II diabetes. In he joined where intimidating. basis 1987. 1994 , NCHGR, On the of Together with fellow the- o> ^ he is head the Physical Mapping preliminary data previ- oreticians now of and I John Rinzel and Section and acting chief of the Genome ous experience, we expect “ Joel Keizer, I tested the Tech)iologv Branch. that our collective efforts will I hypothesis of two NIDDK The major focus of my research pro- yield a first-pass sequence of experimentalists, Illani Atwa- gram over the past five years has been to chromosome 7 within three ter and Eduardo Rojas, that establish the genetic architecture of one to four years. the bursting electrical human chromosome by constructing a The availability of an rhythm of beta-cells is an complete physical map of its DNA and evolving genetic blueprint emergent property of the then determining the DNA sequence. for 5% of the human gap-junction-coupled net- My lab’s efforts have centered on chro- genome is already providing work of cells in the islet of mosome 7, which spans an estimated 170 spectacular opportunities to Arthur Sherman Langerhans, Atwater and million base pairs (bp) and accounts for explore human biology. Our Rojas developed their “chan- roughly 5% of the human genome. Our geographic map of chromosome 7 is now nel-sharing” hypothesis after they found mapping approach uses yeast artificial yielding serendipitous research opportu- that isolated beta-cells rarely displayed chromosomes (YACs) as the cloned DNA nities that cut across biology. We are the bursting rhythm. We demonstrated fragments and sequence-tagged sites actively engaged in several projects to that electrical coupling could not only (STSs) as the landmarks for establishing study the molecular basis of cancer sus- synchronize the activity of inherently the overlapping relationships ceptibility, cardiovascular oscillatory units, but also play a role in among the YACs. STSs are disease, immune response, generating oscillations. short stretches of DNA that and neural development. In More recently, Richard Bertram and I can be specifically detected many of these projects, we have worked with Atwater, Rojas, and using the polymerase chain are in pursuit of genes that others on parasympathetic regulation of reaction (PCR). We have cause human disease. In beta-cell electrical activity. We proposed developed and implemented every case, our detailed that the inositol-1, 4, 5-trisphosphate- and strategies for generating STSs maps, DNA-based reagents, aceytylcholine-mediated release of calci- specific to chromosome 7 and growing body of um from the endoplasmic reticulum leads and for identifying YACs con- sequence data are enhanc- to depolarization via calcium-release acti- taining each of these STSs. ing our ability to study com- vated current (CRAG) channels. Unex- This has involved performing plex biological processes. pectedly, our mathematical model an average of 1,000 to 2,000 These limited examples revealed that the important first phase of PCR assays per day for nearly three years. which reflect only the tip of the future insulin secretion following a glucose We reached a major milestone recently genetic iceberg—illustrate how the fruits challenge might also be governed by when we completed construction of one of the genome project are creating a new CRAG, a prediction supported by follow- of the most detailed maps of a human era for biomedical research. up experiments. chromosome to date—a physical map of Beitram and I have also been collabo- chromosome 7 that provides YAC cover- rating with Elis Stanley of NINDS on age across the chromosome as well as a Arthur Sherman received his Ph.D. from mechanisms of synaptic release. We have mapped STS every 80,000 bp. This New York University in 1986. Since then, developed a mathematical model of Stan- achievement reflects the development of he has worked in NIDDK's Mathetuatical ley's hypothesis that facilitation by high-
more than 2,000 STSs unique to chromo- Research Branch . frequency stimulation is due to accumula- some 7, the mapping of each of these Trained as an applied mathematician tion of calcium bound to release sites. We STSs to individual YACs, the rigorous specializing in the analysis and develop- hope this work will help resolve long- integration of our physical map with the ment of methods for numerical solution standing controversies about synaptic genetic and cytogenetic maps, and the of ordinary and partial differential equa- facilitation and also shed light on
mapping of hundreds of gene sequences. tions, I came to NIDDK to work in the endocrine secretion. These results also provide suppoit for an Mathematical Research Branch—a leading My long-term goals are to continue experimental paradigm, termed YAC- force in theoretical biology and computa- studying the mechanisms and dynamics
12 J U I, Y - A U G U S T 19 9 6
of insulin secretion, delving deeper into tumors. It is a provocative result because its regulation by metabolic and hormonal alpha-particle radiation, although known Research Festival Turns 10 signals. The current flood of detailed bio- to cause single base-pair mutations, might chemical information on vesicle exocyto- not be expected to produce such a highly NIH’s intramural Research Festival sis should also open up exciting opportu- specific DNA lesion. marks its 10th anniversary this year. for the mathematical modeling of research genetic susceptibility nities My on In honor of the occasion, festival this final step in secretion in both neural tests the hypothesis that commonly director Henning Birkedal-Hansen and endocrine cells, inherited allelic variants of selected can- wants to do something old and didate genes, in conjunction with envi- something new at the Sept, lfj-20 ronmental exposures, affect a person’s event: revive VIP posters and begin Jack Taylor received bis M.D. from the risk of developing cancer. Working with a job fair for NIH postdocs. University of Wisconsin in Madison in genetically susceptible subgroups may Birkedal-Hansen, who is NIDR’s 1984 a)id his Pb.D. from the University of allow us to identify the environmental scientific director, got the idea for North Caroli>ia in Chapel Hill in 1993- exposures that cause disease and the the VIP posters from a scientist Taylor joined NIEHS's Epidemiology true risks associated with exposure. It who gave a command poster pre- Branch as a senior staff fellow in 1988, could also lead to programs for protect- sentation at the first Research Eesti- and he is now a lead clinical investigator ing susceptible populations and for tar- val, NIDR’s Abner Notkins. “People in that branch. In he also screening of high-risk thought the VIP poster session was 1996 , became geted groups. head of the Molecular and Genetic Epi- We are studying inherited polymor- great,” says Birkedal-Hansen. “It demiology Group in NIEHS's Laboratory phisms in selected genes that have poten- gave the postdocs a chance— to talk ofMolecular Carcinogenesis. tial links to bladder cancer risk: genes to NIH’s top scientists who are My research is directed toward under- involved in carcinogen metabolism, pro- world leaders in their fields.” This standing the interaction between genes to-oncogenes, tumor-suppressor genes, year, the "VIP posters will not be set and environmental exposures in human and genes involved in DNA synthesis and off in their own session, but will be presented alongside posters from carcinogenesis. There are two main ele- repair. Doug Bell at NIEHS and I have NIH postdocs and other scientists. ments to this work: investigating the role looked at a polymorphism in the gene Invited VIP presenters are expected of environmental exposure in critical-tar- GSTMl, which is involved in detoxifica- to include institute directors, scien- get gene mutation and investigating the tion of certain carcinogens. Interestingly, tific directors, and maybe even role of genetic susceptibility and environ- roughly half of the U.S. population has no Deputy Director for Intramural mental exposure in cancer risk. working copy of this gene (homozygous Research Michael Gottesman and The research on critical-target genes null). We have found evidence of a gene- NIH Director Harold Varmus. addresses the hypothesis that different environment interaction on risk: people At the Sept. 18 job fair, NIH’s environmental exposures cause different with the homozygous null GSTMl geno- Office of Education and the Foun- patterns of mutation in genes that are type have twice the risk of developing dation for the Advancement of Edu- important in carcinogenesis. bladder cancer as people cation in the Sciences will arrange initial focus has been on with at least My one working job interviews and meetings mutational of of the gene but only activation copy — between NIH postdocs and repre- if also to a oncogenes and deactivation they are exposed sentatives of biotechnology firms, of carcinogen, such as cigarette tumor-suppressor genes. many of whom will be on hand for Such patterns can be used to smoke. Although the in- the festival’s tent show for biomed- identify novel critical-target creased risk is fairly small, ical .suppliers on Sept. 19-20. genes and to suggest muta- particularly compared with The 1996 Research Eestival will tional mechanisms by which the risk posed by genes open at 8 a.m. Sept. I 6 at the an environmental agent responsible for familial clus- Natcher Conference Center with a causes cancer. If specific car- ters of cancer, such a gene symposium on prion diseases. The cinogens produce character- Jack Taylor polymorphism can still be symposium will be followed by a istic patterns of gene muta- important to public health poster session from 11 a.m. to 1 tion in tumors, detection of such patterns because both the polymorphism and the p.m. About a dozen workshops would be a powerful tool in studies of exposure are common. We calculate that will run simultaneously from 1:30 environmental risk and in prevention and 25% of bladder cancer may be attributable to 4:30 p.m., and a second poster early diagnosis. to the heritable defect in GSTMl. session will follow from 4:30 to Most of my work has been on lung My two research areas also overlap: 6:30 p.m. The program for Sept. 17 and bladder cancer—two tumors that critical-target genes are often polymorphic will follow the same schedule, have strong environmental determinants. and their inherited allelic variants may starting with a symposium on the disorders. In a recent study done with Teddy Dev- affect susceptibility; conversely, the inher- genetics of complex A searchable program of events will ereux at NIEHS and Geno Saccomanno at ited variant alleles of susceptibility genes be posted on the 'World "Wide 'Web St. Mary’s Hospital in Grand Junction, may ultimately affect the pattern of muta- (http://mantis.dcrt.nih. gov/festi- Colo., we showed that roughly one-third tion in critical-target genes found within a val/). For more information, con- of large- and squamous-cell lung tumors tumor. By combining epidemiology and tact Gregory Roa at the NIH Visitor from uranium miners had an identical molecular biology, my long-term goal is Information Center (phone: 496- mutation in the tumor-suppressor gene to develop a more integrated view of 1776 e-mail: [email protected]). p53- This is one of only four known how exposure, genetic susceptibility, and ; examples of an exposure-specific pattern critical-target gene damage interact in —Celia Hooper of critical-target gene mutation in human lung and bladder cancers.
13 —
T H !• N 1 H Catalyst
Charge Card to follow those in place during the pilot. made it difficult to maneuver sharp continuedfrom page 1. Most importantly, all federal procurement instruments during surgery and other rules apply to purchases made with the procedures. Like BL-4, MCL will be limit- Although such dollar figures are what cards. There is a single purchase limit of ed to research on just one pathogen at grabs administrators’ attention, Pepper $2,500 per order unless a scientist under- any given time. However, the increased says she was equally impressed by the goes three weeks of special procurement workspace of the new facility—about amount of time saved by buying the IL-2 training. There are no limits on how many 2,000 square feet compared with the pre- with her charge card rather orders can be placed per vious glovebox space of less than 500 than going through regular month, and it is up to each square feet—should make it easier to procurement channels. It ICD to set the dollar limits simultaneously conduct a variety of stud- took only three days to get for each scientist's monthly ies involving the same pathogen than it a year's worth of IL-2 using purchases. For more infor- has been in the past, Wilson says. the purchase card com- mation on the cards, contact Mycobacterium tuberculosis will be the pared with a wait of two Kemp (phone: 496-6071). focus of the first research project in MCL: a months or longer under the According to Pepper, series of NIAID studies aimed at creating a paper system. “I think the some of the charge-card limi- suitable animal model to use in testing real value of the cards is in tations might even work to a therapeutic and vaccine interventions the time saved—time saved scientist’s advantage. For against multi-drug-resistant tuberculosis to do science,” says Pepper, example, when Pepper told a (MDR TB). Although M. tuberculosis itself noting that if the lab needs computer supplier that she is not a BL-4 pathogen, the MCL Program a reagent immediately, she could not buy a laptop for Review Committee agreed that maximum can use her card to place her lab because its $2,800 containment was indicated for such studies an order with a local sup- price exceeded her card limit, because the strains to be used in the stud- plier and get delivery by the supplier swiftly lowered ies are multi-drug resistant and because afternoon. the price to $2,500. the inoculum will be delivered by NCHGR Scientific Director Jeff Trent is So what does Pepper’s lab plan to do aerosol—the route by which most TB equally enthusiastic about the charge cards, with the quarter-million dollars it saved infections are acquired. calling them “the single most important rein- using the charge card? “We are trying to On the basis of past work describing vention authority [at NIH] to date.” Although figure out a way under reinvention to the pathogenesis of TB in rabbits, NIAID’s the IL-2 case may be the most dramatic convert the money saved into space Mark Simpson, Thomas Kindt, and Richard example, Trent says there are many other that’s one thing we never have enough G. Wyatt plan to explore the possibility of smaller purchase-card success stories at of!” she says. using rabbits as models for MDR TB. NCLfGR. He cites the purchases of a Plexi- Among those assisting the NIAID team glas container for at a local store com- with the study will be the Division of Safe- $4 Maximum Containment Laboratory pared with $40 through a traditional scientif- ty’s Wilson, a microbiologist whose doctor- continuedfrom page 7 . ic supplier and of a computer seivice that al research was on the effect of vaccination was obtained in 24 hours compared with research units in the Lhiited States. The on guinea pigs that were infected with M. the two-week wait it would take if provided others are at the Centers for Disease Con- tuberculosis through the aerosol route. through NCRR's Biomedical Engineering trol and Prevention in Atlanta and at the Because the researchers want to familiarize and Instmmentation Program. LLS. Army Medical Research Institute for themselves with the new facility and Along with the freedom to place orders Infectious Disease in Fort Detrick, Mcl. NIH because the pathogenesis of MDR and by purchase card comes the responsibility expects that both intramural and extramur- non-MDR TB do not apparently differ, the to reconcile billing statements—checking al researchers will use MCL and has set up initial study will be done with non-MDR shipping statements or invoices with the the MCL Program Review Committee to TB. However, MDR strains will play an charges listed on the monthly statement examine proposals for scientific merit and important role in future studies that will prepared for NIH by the cards’ issuer. safety concerns. analyze interventions. Rocky Mountain BankCard System. While NIH’s previous BL-4 facility, estab- “The design of the old facility would not conceding that bill reconciliation is the lished in the mid-1970s for research have permitted the study of rabbits. Tech- hardest part of the process, Pepper says she involving recombinant DNA and cancer- nology has advanced since that facility can double-check her lab’s $10,000 to causing viruses, later housed NIAID sci- opened, and the new facility will take $20,000 in monthly purchases in about entist Malcolm Martin's transgenic mouse advantage of that new technology,” says 2 1/2 hours using a software program that containing the entire genome of the Wyatt. “The Division of Safety did a superb she created for the chore. In the NIH-wide human immunodeficiency virus. But the job in designing the space.” program, researchers won't have to resort old facility’s design limited the types of Although researchers who use MCL will to writing their own software for bill recon- benchwork that could be undertaken with pay for supplies and animals used in their ciliation becau.se OPM, OEM, and DCRT are pathogens requiring maximum levels of experiments, the Office of Research Ser- setting up a centralized automated system containment and could only handle ani- vices will cover the actual cost of nanning for documenting receipt of orders and rec- mal projects involving small rodents. The MCL. A major expense for researchers onciling purchase-card statements. new facility, with three interchangeable using MCL will likely be the labor costs When the project is expanded to modules of lab and animal-care space, involved in training people to work in the include all of NIH, OPM plans to impose can accommodate animals ranging in size state-of-the-art facility. Wilson estimates a $5-per-order service charge. But many from mice to nonhuman primates. that most staff will require at least a couple observers note that this is cheap com- According to Wilson, the emphasis on weeks of special safety training, including pared with NIH's current procurement- freedom of movement should make work performing dry mns of their experiments, services charges of anywhere from $15 to safer for researchers in MCL. The old before receiving the go-ahead to begin $100 per order for purchases under facility’s cramped and inflexible glovebox their research with a BL-4 pathogen. $25,000. The purchase rules are expected design often led to researcher fatigue and
14 J U L Y - A U G U S T 19 9 6
Maryland Young Scientists Awards
Robert A. Craigie, chief of the Molecu- under the age of 40 who live and
lar Virology section in NIDDK’s Labo- work in Maryland, is sponsored annu- ratory of Molecular Biology, is the ally by the Maryland Academy of Sci- 1996 winner of Maryland’s Outstand- ences. Also cited this year was Alan ing Young Scientist Award. Craigie Wolffe, chief of NICHD’s Laboratory of recently received the honor for his Molecular Embryology. Wolffe was outstanding contributions to the named one of Maryland’s Distin- understanding of retroviral DNA inte- guished Young Scientists for his work gration—a critical step in the replica- on the structure of nucleosomes and Robert A. Craigie Alan Wolffe tion cycle of the human immunodefi- on how the architecture of chromatin
ciency virus (HIV) and other retro- regulates transcription-factor access to DNA. He is particu- viruses—and for his contributions to work that determined larly interested in the role these nuclear components play the structure of the catalytic domain of HIV integrase. The in controlling gene expression during the various stages of $ 2,500 award, which recognizes cutting-edge scientists embryonic development.
Guess Who’s OHSR Home Page Coming to FELLOW-L? Thanks to the power of the World Wide Web, it’s now even easier for NIH
It’s not quite “The David Letter- scientists to get timely information on the regulations and ethical guidelines man Show,” but FELLOW-L, an governing research involving human subjects. The Office of Human Subjects electronic forum that provides Research’s (OHSR’s) new home page on the Web offers intramural announcements relevant to the researchers ready access to a variety of resources, including electronic ver- postdoctoral community, recently sions of its “Gray Booklet” that contains guidelines for human-subjects started a lively new feature research and NIH’s Multiple Project Assurance document. Also available at showcasing the views of invited the site are a collection of 12 information sheets prepared by OHSR. To
“guests.” In May, the first guest, reach the OHSR site, go to the NIH home page on the Web and click on NINDS’s Joan P. Schwartz, who “Institutes and Offices” and then click on “Office of the Director.” The page is co-chair of NIH’s Committee can also be accessed directly at the uniform resource locator (URL): on Scientific Conduct and Ethics, http://www.nih. gov:80/od/ohsr/ answered anonymous questions and comments on the subject of mentoring. The starting point for the discussion was Schwartz’s article in the March-April 1996 issue of The NIH Catalyst. Schwartz’s responses were post- ed on FELLOW-L and the ftp archive (ftp://helix.nih.gov/fel- com). Anyone with an interest in postdoc issues is welcome to subscribe to FELLOW-L. Postings on the list regularly include sci- entific questions, offers and requests for equipment, confer- ence and seminar-related an- nouncements, and discussions about jobs. To sign up, send an e-mail message that reads SUB- SCRIBE FELLOW-L YOUR NAME to [email protected]
15 . The NIH Catalyst
Catalytic Reactions
n this issue, we are asking 1) What do you think of NIH’s charge-card initiative? Do you plan to apply for a card? If so, I for your reactions in four in what situations do you think it will come in most handy? areas: charge cards, ethics report, Hot Methods Clinic, and parking. Send your responses on these topics or your comments on other intramural research 2) What are your general reactions to the Commission on Research Integrity’s report (see p. 4)? concerns to us via e-mail: What specific things would you like to see added, deleted, or otherwise modified? [email protected]; fax: 402-4303; or mail: Building 1, Room 334.
3) The Hot Methods Clinic will return in the next issue. What updates can you provide on previous In Future Issues. . Hot Methods? What techniques would you like to see covered in the future?
Building 50, A Peek at the Plans Hot “Cold” Methods: Reducing Radioactivity 4) We are considering an article about on-campus parking. Have you experienced any problems Telemedicine’s Ties lately? How could the parking system be improved to meet scientists’ needs? To Clinical Research NIH’s Chemistry With Chemists
The NIH Catalyst is published PUBUSHER SciENTTEic Editor Editorial Advisory Board bi-monthly for and by the Michael Gottesman Celia Hooper Jorge Carrasquillo, CC intramural scientists at NIH. Deputy Director for David Davies, NIDDK Managing Editor Address correspondence to Intramural Research, OD Michael Fordis, OD, OE Rebecca Kolberg Dale Graham, Building 1, Room 334, DCRT Editor NIH, Bethesda, MD 20892. Hynda Kleinman, NIDR Lance Liotta Copy Editor Ph: (301) 402-1449; e-mail: Elise Kohn, NCI Chief, Laboratory of Pathology, Cynthia Allen [email protected] Susan Leitman, CC NCI Bernard Moss, NIAID Editoriai. Assistant Michael Rogawski, NINDS Deputy Editor Lorna Heartley Joan Schwartz, NINDS John I. Gallin, Intern Gisela Storz, NICHD Director, Warren Grant Magnu- Jennifer M. King son Clinical Center, and Associ- ate Director for Clinical Research Photographer Ralph Isenburg
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