Work from noted gene therapy researcher Savio Woo under scrutiny with slew of retractions

Research from the lab of Savio Woo, a leading U.S. gene therapy scientist, has come into question with the retraction by major journals of at least four of his articles.

The papers, which appeared in the Proceedings of the National Academy of Sciences, the Journal of the National Cancer Institute and Human Gene Therapy, involve findings published between 2005 and 2009, address various aspect of gene therapy. Two of the articles boasted of potential breakthroughs, and even a possible cure, for diseases with extremely high rates of mortality.

The study in JNCI, for example, reported the finding of a genetically modified bacterium that showed promise for the treatment of pancreatic cancer, a particularly lethal malignancy, and other tumor types. Another, published in 2005 in PNAS, claimed to have discovered a possible cure for phenylketonuria, or PKU, in mice—a finding that was cited more than 30 times and trumpeted in the media.

However, in a retraction notice issued this month, Woo wrote that:

It was discovered that some of the micrographs in two papers we published [figure 4 in J Natl Cancer Inst 2008;100:1389-1400 (1), and figure 3 in Hum Gene Ther 2009;20:751-758 (2)] are apparently duplicated. This has been reported to the institutional research integrity committee by the authors and while the outcome of an investigation is pending, the undersigned co-authors respectfully request a retraction of both papers and sincerely apologize to our colleagues.

Human Gene Therapy also is retracting a 2008 article by Woo and colleagues, titled “Site-specific transgene integration in the human genome catalyzed by phiBT1 phage integrase.”

Woo is founding chairman of the department of gene and cell medicine at the Mount Sinai, a position he has held since 1996. According to one biographical sketch, Woo’s

pioneering work on human molecular genetics and gene therapy for inherited disorders is internationally recognized. He is also an authority in the field of cancer gene therapy and his preclinical investigation on active genetic immunization against breast and colon cancer and oncolytic virotherapy for liver cancer has led to the development of novel therapeutic agents and federally-funded clinical translational trials in the respective disease areas.

Reading between the lines, the issues involving Woo’s data appear to go beyond merely duplicated tables—or, to put it another way, the duplication of the tables may be symptomatic of a more widespread problem.

Consider the retraction notice from PNAS, for the paper titled “Complete and persistent phenotypic correction of phenylketonuria in mice by site-specific genome integration of murine phenylalanine hydroxylase cDNA.”

In it, Woo writes:

The undersigned author wishes to note the following: ‘After re-examining the laboratory records, I have concluded that there are data irregularities underlying this paper that warrant its retraction. I regret not recognizing these irregularities before the manuscript was published and apologize for any inconvenience this might have caused.”

Randy Schekman, editor of PNAS, told Retraction Watch that his journal had received no heads-up that the Woo paper was problematic.

Dr. Woo requested this on behalf of his institution, but we were not provided any details from him or the institution.

We called Woo and emailed him for comment but have not heard back. We also contacted Mount Sinai to speak with the research officials and will update this post when they respond. Same for the editors of the other journals.

Update, 1:40 p.m. Eastern, 9/15/10: Y. W. Kan, chair of hematology at UCSF School of Medicine, was one of three experts who reviewed Woo’s PNAS paper. Kan said Woo contacted him recently to let him know about the impending retraction. “As I understand it, the data are not reproducible,” Kan told us.

Kan said Woo’s site-specific method for splicing genes into the mammalian genome is one of two related techniques, but added that it has not gained as much acceptance as the other approach.

See an update to this post, about two of Woo’s post-doctoral fellows who were dismissed, and another about two more papers now being retracted.

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