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塞尔比-拉塞尔关于威廉·拉塞尔博士和莉安·拉塞尔博士在巨型小鼠实验中未报告关键数据的争议:历经数十年的情况、现状及一些影响。

The Selby-Russell Dispute Regarding the Nonreporting of Critical Data in the Mega-Mouse Experiments of Drs William and Liane Russell That Spanned Many Decades: What Happened, Current Status, and Some Ramifications.

作者信息

Selby P B

机构信息

Independent Researcher.

出版信息

Dose Response. 2020 Feb 12;18(1):1559325819900714. doi: 10.1177/1559325819900714. eCollection 2020 Jan-Mar.

DOI:10.1177/1559325819900714
PMID:32110168
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7016328/
Abstract

The Russells began their studies of the hereditary effects of radiation in the late 1940s, and their experiments contributed much to what is known about the induction of gene mutations in mice. I had a close association with them for about 26 years, and they relied on me considerably for database management and statistical support. In 1994, I was shocked to discover that, in experiments on males, they had failed to report numerous spontaneous mutations that arose during the perigametic interval and were detected as clusters of mutations. I realized that their nondisclosure of this information meant that the decades-long application of their data to estimate hereditary risks of radiation to humans using the doubling-dose approach had resulted in a several-fold overestimation of risk. I accordingly reported the situation to funding agencies. The resulting complicated situation is referred to here as the Selby-Russell Dispute. Highlights of the resulting investigation, as well as what occurred afterward, are described, and reasons will be provided to show why, in my opinion, the hereditary risk from radiation in humans was likely overestimated by at least 10-fold because the Russells decided not to report critical information from their massive experiments.

摘要

拉塞尔夫妇在20世纪40年代末开始了他们对辐射遗传效应的研究,他们的实验对我们目前所知的小鼠基因突变诱导方面贡献巨大。我与他们密切合作了大约26年,他们在数据库管理和统计支持方面相当依赖我。1994年,我震惊地发现,在对雄性小鼠的实验中,他们没有报告在配子形成间隔期出现的大量自发突变,这些突变被检测为突变簇。我意识到他们不披露这些信息意味着,几十年来用加倍剂量法利用他们的数据来估计辐射对人类的遗传风险,导致了风险被高估了几倍。于是我向资助机构报告了这一情况。由此产生的复杂情况在此被称为塞尔比-拉塞尔争端。本文描述了后续调查的要点以及之后发生的事情,并将给出理由来说明为什么在我看来,由于拉塞尔夫妇决定不报告他们大规模实验中的关键信息,人类因辐射产生的遗传风险可能被高估了至少10倍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e2/7016328/93a60f6042d1/10.1177_1559325819900714-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e2/7016328/1658fa63c054/10.1177_1559325819900714-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e2/7016328/92ee8c7c44b3/10.1177_1559325819900714-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e2/7016328/b89fd8a6dd83/10.1177_1559325819900714-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e2/7016328/93a60f6042d1/10.1177_1559325819900714-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e2/7016328/1658fa63c054/10.1177_1559325819900714-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e2/7016328/92ee8c7c44b3/10.1177_1559325819900714-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e2/7016328/b89fd8a6dd83/10.1177_1559325819900714-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e2/7016328/93a60f6042d1/10.1177_1559325819900714-fig4.jpg

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引用本文的文献

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本文引用的文献

1
The threshold vs LNT showdown: Dose rate findings exposed flaws in the LNT model part 2. How a mistake led BEIR I to adopt LNT.阈值与线性无阈模型的对决:剂量率研究结果揭示了线性无阈模型的缺陷 第2部分。一个错误是如何导致辐射效应研究委员会第一委员会采用线性无阈模型的。
Environ Res. 2017 Apr;154:452-458. doi: 10.1016/j.envres.2016.11.024. Epub 2016 Dec 11.
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Radiation-induced genetic damage in mice.
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X-ray-induced mutations in mice.X射线诱导的小鼠突变。
Cold Spring Harb Symp Quant Biol. 1951;16:327-36. doi: 10.1101/sqb.1951.016.01.024.
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Description of first germinal mosaic mutation identified in dominant skeletal mutation experiments and considerations about how to deal with this kind of spontaneous mutation in analyses.
Mutat Res. 2004 Jan 12;545(1-2):109-15. doi: 10.1016/j.mrfmmm.2003.09.016.
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Tests of induction in mice by acute and chronic ionizing radiation and ethylnitrosourea of dominant mutations that cause the more common skeletal anomalies.
Mutat Res. 2004 Jan 12;545(1-2):81-107. doi: 10.1016/j.mrfmmm.2003.09.014.
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Bleomycin, unlike other male-mouse mutagens, is most effective in spermatogonia, inducing primarily deletions.与其他雄性小鼠诱变剂不同,博来霉素对精原细胞最有效,主要诱导缺失。
Mutat Res. 2000 Aug 21;469(1):95-105. doi: 10.1016/s1383-5718(00)00060-7.
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Significance of the perigametic interval as a major source of spontaneous mutations that result in mosaics.配子形成间隔作为导致嵌合体的自发突变主要来源的意义。
Environ Mol Mutagen. 1999;34(1):16-23. doi: 10.1002/(sici)1098-2280(1999)34:1<16::aid-em3>3.0.co;2-x.
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Discovery of numerous clusters of spontaneous mutations in the specific-locus test in mice necessitates major increases in estimates of doubling doses.在小鼠的特定位点试验中发现大量自发突变簇,这就需要大幅提高对加倍剂量的估计。
Genetica. 1998;102-103(1-6):463-87.
10
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Genetica. 1998;102-103(1-6):445-62.