Abandon the mouse research ship? Not just yet!

Marcin F. Osuchowski, Daniel G. Remick, James A. Lederer, Charles H. Lang, Ansgar O. Aasen, Mayuki Aibiki, Luciano C. Azevedo, Soheyl Bahrami, Mihaly Boros, Robert Cooney, Salvatore Cuzzocrea, Yong Jiang, Wolfgang G. Junger, Hiroyuki Hirasawa, Richard S. Hotchkiss, Xiang An Li, Peter Radermacher, Heinz Redl, Reinaldo Salomao, Amin SoebandrioChristoph Thiemermann, Jean Louis Vincent, Peter Ward, Yong Ming Yao, Huang Ping Yu, Basilia Zingarelli, Irshad H. Chaudry

Research output: Contribution to journalReview article

91 Citations (Scopus)

Abstract

Many preclinical studies in critical care medicine and related disciplines rely on hypothesis-driven research in mice. The underlying premise posits that mice sufficiently emulate numerous pathophysiologic alterations produced by trauma/sepsis and can serve as an experimental platform for answering clinically relevant questions. Recently, the lay press severely criticized the translational relevance of mouse models in critical care medicine. A series of provocative editorials were elicited by a highly publicized research report in the Proceedings of the National Academy of Sciences (PNAS; February 2013), which identified an unrecognized gene expression profile mismatch between human and murine leukocytes following burn/trauma/endotoxemia. Based on their data, the authors concluded that mouse models of trauma/inflammation are unsuitable for studying corresponding human conditions. We believe this conclusion was not justified. In conjunction with resulting negative commentary in the popular press, it can seriously jeopardize future basic research in critical care medicine. We will address some limitations of that PNAS report to provide a framework for discussing its conclusions and attempt to present a balanced summary of strengths/weaknesses of use of mouse models. While many investigators agree that animal research is a central component for improved patient outcomes, it is important to acknowledge known limitations in clinical translation from mouse to man. The scientific community is responsible to discuss valid limitations without overinterpretation. Hopefully, a balanced view of the strengths/weaknesses of using animals for trauma/endotoxemia/critical care research will not result in hasty discount of the clear need for using animals to advance treatment of critically ill patients.

Original languageEnglish (US)
Pages (from-to)463-475
Number of pages13
JournalShock
Volume41
Issue number6
DOIs
StatePublished - Jun 2014

Fingerprint

Ships
Critical Care
Research
Endotoxemia
Wounds and Injuries
Medicine
Burns
Transcriptome
Critical Illness
Sepsis
Leukocytes
Research Personnel
Inflammation

All Science Journal Classification (ASJC) codes

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Osuchowski, M. F., Remick, D. G., Lederer, J. A., Lang, C. H., Aasen, A. O., Aibiki, M., ... Chaudry, I. H. (2014). Abandon the mouse research ship? Not just yet! Shock, 41(6), 463-475. https://doi.org/10.1097/SHK.0000000000000153
Osuchowski, Marcin F. ; Remick, Daniel G. ; Lederer, James A. ; Lang, Charles H. ; Aasen, Ansgar O. ; Aibiki, Mayuki ; Azevedo, Luciano C. ; Bahrami, Soheyl ; Boros, Mihaly ; Cooney, Robert ; Cuzzocrea, Salvatore ; Jiang, Yong ; Junger, Wolfgang G. ; Hirasawa, Hiroyuki ; Hotchkiss, Richard S. ; Li, Xiang An ; Radermacher, Peter ; Redl, Heinz ; Salomao, Reinaldo ; Soebandrio, Amin ; Thiemermann, Christoph ; Vincent, Jean Louis ; Ward, Peter ; Yao, Yong Ming ; Yu, Huang Ping ; Zingarelli, Basilia ; Chaudry, Irshad H. / Abandon the mouse research ship? Not just yet!. In: Shock. 2014 ; Vol. 41, No. 6. pp. 463-475.
@article{d40578b8f9f14ca6ab7003251b4e0748,
title = "Abandon the mouse research ship? Not just yet!",
abstract = "Many preclinical studies in critical care medicine and related disciplines rely on hypothesis-driven research in mice. The underlying premise posits that mice sufficiently emulate numerous pathophysiologic alterations produced by trauma/sepsis and can serve as an experimental platform for answering clinically relevant questions. Recently, the lay press severely criticized the translational relevance of mouse models in critical care medicine. A series of provocative editorials were elicited by a highly publicized research report in the Proceedings of the National Academy of Sciences (PNAS; February 2013), which identified an unrecognized gene expression profile mismatch between human and murine leukocytes following burn/trauma/endotoxemia. Based on their data, the authors concluded that mouse models of trauma/inflammation are unsuitable for studying corresponding human conditions. We believe this conclusion was not justified. In conjunction with resulting negative commentary in the popular press, it can seriously jeopardize future basic research in critical care medicine. We will address some limitations of that PNAS report to provide a framework for discussing its conclusions and attempt to present a balanced summary of strengths/weaknesses of use of mouse models. While many investigators agree that animal research is a central component for improved patient outcomes, it is important to acknowledge known limitations in clinical translation from mouse to man. The scientific community is responsible to discuss valid limitations without overinterpretation. Hopefully, a balanced view of the strengths/weaknesses of using animals for trauma/endotoxemia/critical care research will not result in hasty discount of the clear need for using animals to advance treatment of critically ill patients.",
author = "Osuchowski, {Marcin F.} and Remick, {Daniel G.} and Lederer, {James A.} and Lang, {Charles H.} and Aasen, {Ansgar O.} and Mayuki Aibiki and Azevedo, {Luciano C.} and Soheyl Bahrami and Mihaly Boros and Robert Cooney and Salvatore Cuzzocrea and Yong Jiang and Junger, {Wolfgang G.} and Hiroyuki Hirasawa and Hotchkiss, {Richard S.} and Li, {Xiang An} and Peter Radermacher and Heinz Redl and Reinaldo Salomao and Amin Soebandrio and Christoph Thiemermann and Vincent, {Jean Louis} and Peter Ward and Yao, {Yong Ming} and Yu, {Huang Ping} and Basilia Zingarelli and Chaudry, {Irshad H.}",
year = "2014",
month = "6",
doi = "10.1097/SHK.0000000000000153",
language = "English (US)",
volume = "41",
pages = "463--475",
journal = "Shock",
issn = "1073-2322",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

Osuchowski, MF, Remick, DG, Lederer, JA, Lang, CH, Aasen, AO, Aibiki, M, Azevedo, LC, Bahrami, S, Boros, M, Cooney, R, Cuzzocrea, S, Jiang, Y, Junger, WG, Hirasawa, H, Hotchkiss, RS, Li, XA, Radermacher, P, Redl, H, Salomao, R, Soebandrio, A, Thiemermann, C, Vincent, JL, Ward, P, Yao, YM, Yu, HP, Zingarelli, B & Chaudry, IH 2014, 'Abandon the mouse research ship? Not just yet!', Shock, vol. 41, no. 6, pp. 463-475. https://doi.org/10.1097/SHK.0000000000000153

Abandon the mouse research ship? Not just yet! / Osuchowski, Marcin F.; Remick, Daniel G.; Lederer, James A.; Lang, Charles H.; Aasen, Ansgar O.; Aibiki, Mayuki; Azevedo, Luciano C.; Bahrami, Soheyl; Boros, Mihaly; Cooney, Robert; Cuzzocrea, Salvatore; Jiang, Yong; Junger, Wolfgang G.; Hirasawa, Hiroyuki; Hotchkiss, Richard S.; Li, Xiang An; Radermacher, Peter; Redl, Heinz; Salomao, Reinaldo; Soebandrio, Amin; Thiemermann, Christoph; Vincent, Jean Louis; Ward, Peter; Yao, Yong Ming; Yu, Huang Ping; Zingarelli, Basilia; Chaudry, Irshad H.

In: Shock, Vol. 41, No. 6, 06.2014, p. 463-475.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Abandon the mouse research ship? Not just yet!

AU - Osuchowski, Marcin F.

AU - Remick, Daniel G.

AU - Lederer, James A.

AU - Lang, Charles H.

AU - Aasen, Ansgar O.

AU - Aibiki, Mayuki

AU - Azevedo, Luciano C.

AU - Bahrami, Soheyl

AU - Boros, Mihaly

AU - Cooney, Robert

AU - Cuzzocrea, Salvatore

AU - Jiang, Yong

AU - Junger, Wolfgang G.

AU - Hirasawa, Hiroyuki

AU - Hotchkiss, Richard S.

AU - Li, Xiang An

AU - Radermacher, Peter

AU - Redl, Heinz

AU - Salomao, Reinaldo

AU - Soebandrio, Amin

AU - Thiemermann, Christoph

AU - Vincent, Jean Louis

AU - Ward, Peter

AU - Yao, Yong Ming

AU - Yu, Huang Ping

AU - Zingarelli, Basilia

AU - Chaudry, Irshad H.

PY - 2014/6

Y1 - 2014/6

N2 - Many preclinical studies in critical care medicine and related disciplines rely on hypothesis-driven research in mice. The underlying premise posits that mice sufficiently emulate numerous pathophysiologic alterations produced by trauma/sepsis and can serve as an experimental platform for answering clinically relevant questions. Recently, the lay press severely criticized the translational relevance of mouse models in critical care medicine. A series of provocative editorials were elicited by a highly publicized research report in the Proceedings of the National Academy of Sciences (PNAS; February 2013), which identified an unrecognized gene expression profile mismatch between human and murine leukocytes following burn/trauma/endotoxemia. Based on their data, the authors concluded that mouse models of trauma/inflammation are unsuitable for studying corresponding human conditions. We believe this conclusion was not justified. In conjunction with resulting negative commentary in the popular press, it can seriously jeopardize future basic research in critical care medicine. We will address some limitations of that PNAS report to provide a framework for discussing its conclusions and attempt to present a balanced summary of strengths/weaknesses of use of mouse models. While many investigators agree that animal research is a central component for improved patient outcomes, it is important to acknowledge known limitations in clinical translation from mouse to man. The scientific community is responsible to discuss valid limitations without overinterpretation. Hopefully, a balanced view of the strengths/weaknesses of using animals for trauma/endotoxemia/critical care research will not result in hasty discount of the clear need for using animals to advance treatment of critically ill patients.

AB - Many preclinical studies in critical care medicine and related disciplines rely on hypothesis-driven research in mice. The underlying premise posits that mice sufficiently emulate numerous pathophysiologic alterations produced by trauma/sepsis and can serve as an experimental platform for answering clinically relevant questions. Recently, the lay press severely criticized the translational relevance of mouse models in critical care medicine. A series of provocative editorials were elicited by a highly publicized research report in the Proceedings of the National Academy of Sciences (PNAS; February 2013), which identified an unrecognized gene expression profile mismatch between human and murine leukocytes following burn/trauma/endotoxemia. Based on their data, the authors concluded that mouse models of trauma/inflammation are unsuitable for studying corresponding human conditions. We believe this conclusion was not justified. In conjunction with resulting negative commentary in the popular press, it can seriously jeopardize future basic research in critical care medicine. We will address some limitations of that PNAS report to provide a framework for discussing its conclusions and attempt to present a balanced summary of strengths/weaknesses of use of mouse models. While many investigators agree that animal research is a central component for improved patient outcomes, it is important to acknowledge known limitations in clinical translation from mouse to man. The scientific community is responsible to discuss valid limitations without overinterpretation. Hopefully, a balanced view of the strengths/weaknesses of using animals for trauma/endotoxemia/critical care research will not result in hasty discount of the clear need for using animals to advance treatment of critically ill patients.

UR - http://www.scopus.com/inward/record.url?scp=84901626481&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901626481&partnerID=8YFLogxK

U2 - 10.1097/SHK.0000000000000153

DO - 10.1097/SHK.0000000000000153

M3 - Review article

C2 - 24569509

AN - SCOPUS:84901626481

VL - 41

SP - 463

EP - 475

JO - Shock

JF - Shock

SN - 1073-2322

IS - 6

ER -

Osuchowski MF, Remick DG, Lederer JA, Lang CH, Aasen AO, Aibiki M et al. Abandon the mouse research ship? Not just yet! Shock. 2014 Jun;41(6):463-475. https://doi.org/10.1097/SHK.0000000000000153