The Scripps Research InstituteThe Scripps Research InstituteBiosafety CommitteeBiosafety Committee

Donald E. Mosier, PhD, MDDonald E. Mosier, PhD, MD

IBC ChairIBC Chair

TSRI Campus MapTSRI Campus Map

IBC MembershipIBC Membership

Donald E. Mosier, PhD, MDChair

Bruce Beutler, MDInnate immunity

Alana AlthageLab tech

Dennis R. Burton, PhDHumoral immunity

Juan C. de la Torre, PhDVirology

Beth Ford, DVMAnimal welfare

Richard J. GuliziaBSL-3 Director

Eric F. Johnson, PhDMolecular medicine

Joyce JosephCommunity member

Carolyn Keierleber, PhDBiosafety Officer/EH&SDirector

Thomas Northrup, JD, PhDLegal

Marta Perego, PhDBacteriology

Ellen TresterCommunity Member

J. Lindsay Whitton, MD, PhD -Virology/Immunity

Mark J. Yeager, MD, PhDMedicine

Submission & Review ProceduresSubmission & Review Procedures

• All investigators must complete online biosafety training prior to acceptance of Microbiological Hazard Registration

• Agent specific training must also be completed

• Compliance and test results are recorded at website

Microbiological Hazard Training

New!!! Please note, if you have already completed sections 1 and 2, basic and infectious agent training, you may go directly to the infectious agents list to train on individual infectious agents. There is no quiz associated with individual agents. You must enter your user ID to get credit for this section.

Welcome to the Microbiological hazard training site home page. This is TSRI's first Web-Based Training Program. Our goal is to make the program

* convenient - training should be available 24 hours a day, 7 days a week.* informative - our aim is to provide an overview of microbiological safety at TSRI, and to provide sufficient detail to provide a reasonable foundation

These training pages will serve as your introduction to working safely with microorganisms. As we stress in several places, this web-based training complements, but does not replace, the "hands-on" training necessary to competently handle potentially pathogenic materials.

Continue training >After you have completed this training, you may wish to refresh your memory about a particular item. Rather than requiring you to enter at the beginning, and read all the pages until you reach the information you need, you can browse the Microbiological Hazard Reference section. You may reach the browsable section on the Biosafety Home Page.

Forms

Note: All forms are in Adobe Acrobat 4 pdf format. While these forms are printable in Acrobat version 3, to be able to fill them out electronically, you need Adobe Acrobat Reader version 4. If you want to be able to save the edited forms, you need the full Adobe Acrobat 4 package. You can download Acrobat Reader 4 from Adobe, or contact Procurment for information on the full Acrobat package.

It is recommended that you download the forms before filling out and printing. If your browser is set up to open pdf files in the browser, you can download the pdf files by (on a Windows system) holding down the Control key, then clicking on the link, or (on a Macintosh system) holding down the Option key and clicking on the link.Biosafety

Please note: Effective 11/14/01, the TSRI IBC requires that a vector map must be submitted for all "non-standard" vectors. Non-standard vectors include those that are not commercially available as well as vectors that are commercially available but not in wide distribution. A vector map must be provided for any vector that will be introduced into human cell lines or animals. Please contact the Biosafety Office at 4-8240 for further information.

Annual Update For Microbiological Hazard RegistrationMicrobiological Hazard Registration FormRecombinant DNA Registration DocumentAddendum To Biosafety Registration DocumentDeclination Of Immunization

TSRITSRIRecombinantRecombinant

DNA DNA Registration FormRegistration Form

TSRITSRIMicrobiologicalMicrobiological

HazardHazardRegistration FormRegistration Form

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0102030405060708090

100

Number Reviewed

1996 1998 2000 2002

Year

rDNAMBH

Review of recombinant DNA andReview of recombinant DNA andMicrobiological Hazard Registration FormsMicrobiological Hazard Registration Forms

Investigators and pathogensInvestigators and pathogens

• 91/300 investigators are registered to use 91/300 investigators are registered to use pathogens in their researchpathogens in their research

• 292 BSL-2 protocols292 BSL-2 protocols

• 21 BSL-2/3 protocols21 BSL-2/3 protocols

• 21 BSL-3 protocols21 BSL-3 protocols

• 94 pathogenic agents/variants94 pathogenic agents/variants

• 5 toxins5 toxins

• 13 select agents13 select agents

AdenoMLVRetro/AmphoLentiAAVOther

Distribution of Viral Vectors Distribution of Viral Vectors Reviewed Reviewed

Select AgentsSelect Agents

• Ebola strains (inactivated)Ebola strains (inactivated)

• Ebola glycoproteinEbola glycoprotein

• HantavirusHantavirus

• Botulinum toxinBotulinum toxin

• Yersinia pestisYersinia pestis

BSL-3 ProtocolsBSL-3 Protocols

• Known human pathogens used in novel Known human pathogens used in novel context; e.g., HIV-1, hepatitis B, hepatitis context; e.g., HIV-1, hepatitis B, hepatitis C, prionsC, prions

• Viruses or viral vectors introduced into Viruses or viral vectors introduced into animals (mice) that generate possibility animals (mice) that generate possibility of recombination and rescueof recombination and rescue

• One interesting example follows:One interesting example follows:

Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice.van der Laan LJ, Lockey C, Griffeth BC, Frasier FS, Wilson CA, Onions DE, Hering BJ, Long Z, Otto E, Torbett BE, Salomon DR. Nature 2000 Sep 7;407(6800):90-4 The Scripps Research Institute, Department of Molecular and Experimental Medicine, La Jolla, California 92037, USA.

Animal donors such as pigs could provide an alternative source of organs for transplantation. However, the promise of xenotransplantation is offset by the possible public health risk of a cross-species infection. All pigs contain several copies of porcine endogenous retroviruses (PERV), and at least three variants of PERV can infect human cell lines in vitro in co-culture, infectivity and pseudotyping experiments. Thus, if xenotransplantation of pig tissues results in PERV viral replication, there is a risk of spreading and adaptation of this retrovirus to the human host. C-type retroviruses related to PERV are associated with malignancies of haematopoietic lineage cells in their natural hosts. Here we show that pig pancreatic islets produce PERV and can infect human cells in culture. After transplantation into NOD/SCID (non-obese diabetic, severe combined immunodeficiency) mice, we detect ongoing viral expression and several tissue compartments become infected. This is the first evidence that PERV is transcriptionally active and infectious cross-species in vivo after transplantation of pig tissues. These results show that a concern for PERV infection risk associated with pig islet xenotransplantation in immunosuppressed human patients may be justified.

Interaction between IBC and IACUCInteraction between IBC and IACUC

• Any animal protocol involving human or Any animal protocol involving human or animal pathogens is reviewed first by the animal pathogens is reviewed first by the IBC and then the IACUC.IBC and then the IACUC.

• Since IACUC approval is necessary for Since IACUC approval is necessary for NIH grant submission but IBC approval NIH grant submission but IBC approval is not, this leads to some expedited is not, this leads to some expedited reviews near grant deadlines.reviews near grant deadlines.

IBC ChallengesIBC Challenges

• Depth of local expertise in infectious Depth of local expertise in infectious diseases sometimes leads to interesting diseases sometimes leads to interesting discussion of CDC guidelinesdiscussion of CDC guidelines

• Required versus highly recommended Required versus highly recommended vaccination policies confront difficult vaccination policies confront difficult medical and legal issuesmedical and legal issues

• "Spontaneous" research collaborations"Spontaneous" research collaborations

Contact InformationContact Information

• For more information, contact:For more information, contact:dmosier@scripps.edudmosier@scripps.edu

or ckeier@scripps.eduor ckeier@scripps.eduor www.scripps.eduor www.scripps.edu