# Failure to Replicate: A Sign of Scientific Misconduct?

^{1}

^{2}

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## Abstract

**:**

## 1. Introduction

## 2. Analysis of Experiments

#### 2.1. Biochemical and Radiobiological Considerations

#### 2.2. Replication Attempts: Is There a Bystander Effect?

#### 2.2.1. B and C 100% Experiments

_{1}found in Table 1 of the 2001 [2] paper (cf. also figures 3 and 7 in the 1999 paper [1] and figure 1 in the 2001 paper [2]). A’s survivals are markedly different from those of B and C.

**Figure 1.**Graphs of unpublished experiments performed by B and C following the protocols for exposure of 100% (

**A**) and 50% (

**B**) of V79 cells to tritiated thymidine.

_{1}, the theoretical cross-section for survival in mBq/labeled cell, listed in Table 1 of the 2001 paper. The various symbols represent the results of seven experiments by B and C. There are more than 100-fold more survivors in the experiments by B and C than in A’s experiments at the level of 5 mBq/labeled cell. The symbols in 1B show the results of eight 50% V79 experiments of B and C. The dashed line approximates the 50% V79 survival curves depicted in the two papers. The horizontal line is at 0.70 survival, the approximate level at which the survival curves plateau. There are about 70-fold more survivors in B’s and C’s results than in those of A at the level of 20 mBq/labeled cell.

#### 2.2.2. B and C 50% Experiments

#### 2.3. Statistical Analysis of the Raw Data

#### 2.3.1. Terminal Digit Distributions of the Coulter Counts

^{−5}(highly significant).

**Figure 2.**Terminal digit distributions for coulter counts. (

**A**) B’s and C’s Coulter digit distributions, chi-square for fit to uniform, p = 0.462; (

**B**) A’s Coulter digit distributions, chi-square for fit to uniform, p = 4.49 × 10

^{−4}.

**Table 1.**Terminal digit analysis of coulter counts of experiments (Exps) represented in the published figures. The numbers of the various digit distributions were compared to the corresponding uniform distributions to calculate the chi-squared statistic and the corresponding probabilities for nine degrees of freedom.

Figure | Type | # of Exps | Terminal Digit | Total | Chi-square | p | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|

0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | |||||||

Controls | --- | 100% | 7 | 17 | 18 | 16 | 18 | 31 | 16 | 22 | 22 | 23 | 20 | 203 | 9.2 | 0.42 |

--- | 50% | 8 | 17 | 22 | 22 | 23 | 20 | 23 | 25 | 33 | 24 | 21 | 230 | 6.8 | 0.66 | |

1999 | 3 and 6 | 50% | 2 | 5 | 4 | 12 | 5 | 2 | 6 | 3 | 7 | 13 | 3 | 60 | 21.0 | 1.3 × 10^{−2} |

3 | 100% | 2 | 6 | 9 | 3 | 4 | 11 | 4 | 7 | 4 | 3 | 6 | 57 | 11.3 | 0.26 | |

7 | 100% | 3 | 10 | 3 | 4 | 1 | 3 | 7 | 4 | 4 | 4 | 2 | 42 | 14.2 | 0.12 | |

2001 | 1 | 100% | 7 | 16 | 22 | 27 | 17 | 8 | 24 | 14 | 12 | 11 | 23 | 174 | 20.7 | 1.4 × 10^{−2} |

2A | 50% | 3 | 4 | 11 | 12 | 4 | 0 | 12 | 1 | 8 | 3 | 17 | 72 | 89.7 | 8.7 × 10^{−6} |

#### 2.3.2. Frequency of the Mean in Triplicate Counts

**Figure 3.**Mid-ratio distributions for colony counts. (

**A**) B’s and C’s colonies, 29 of 88 in the 0.4–0.6 interval, 35.4 ± 5.19 expected (p ~ 0.91); (

**B**) A’s colonies, 83 of 111 in the 0.4–0.6 interval, 34.2 ± 5.1 expected, p ~ 3.73 × 10

^{−18}).

**Table 2.**Analysis of the frequency of the occurrence of the rounded mean in the triplicate samples of colony counts. Column 6 is the number N of triplicate samples that contain the rounded mean of the three counts. Column 7 is the number K that is expected based on our model. The z-scores incorporate the correction for continuity.The numerator in Column 5 is the number of qualifying triplicates (triplicates for which the gap (c-a) is greater than two). The denominator in Column 5 is the total number of triplicates.

Figure | Type | # of Exps | # of Triplicates | N = No. with Mean | K = No. Expected | SD | Z-Score | p (N ≥ K) | |
---|---|---|---|---|---|---|---|---|---|

Controls | --- | 100% | 7 | 65/67 | 14 | 12.1 | 3.2 | 0.44 | 0.32 |

--- | 50% | 8 | 71/71 | 7 | 11.7 | 3.1 | −1.7 | 0.96 | |

1999 | 3&6 | 50% | 2 | 19/19 | 14 | 3.0 | 1.6 | 6.7 | 2.1 × 10^{−8} |

3 | 100% | 2 | 20/20 | 12 | 3.1 | 1.6 | 5.2 | 6.1 × 10^{−6} | |

7 | 100% | 3 | 13/15 | 9 | 3.2 | 1.5 | 3.4 | 9.1 × 10^{−4} | |

2001 | 1 | 100% | 7 | 63/66 | 37 | 11.2 | 3.0 | 8.4 | 2.6 × 10^{−13} |

2A | 50% | 3 | 23/24 | 13 | 3.9 | 1.8 | 4.8 | 1.9 × 10^{−5} |

## 3. Discussion

#### 3.1. Can the Discrepancies Be Related to the Times of the Experiments?

#### 3.2. Can the Discrepancies Be Related to Changes in the Two Protocols?

#### 3.3. 100% Survival Results of B and C Are Compatible with the Experiments of Others

#### 3.4. Statistics Can Be a Powerful Tool to Test Numerical Results

## 4. Conclusions

- (1)
- A review of the literature involving the killing of tissue culture cells that have incorporated tritiated thymidine into their DNA predicts exponential survival as reported in two papers published in the journal Radiation Research [1,2] under conditions that were likely not present in the survival experiments performed by A.
- (2)
- Likewise, the early and recent literature predicts biphasic survival curves that were not seen in the two papers under conditions that were likely to have been present in the experiments performed by A.
- (3)
- The expected biphasic survival was seen in the 15 experiments performed by B and C following the same or similar protocols listed by A. These results of B and C appear to be reliable and indicate that under the experimental conditions that prevailed in all of the studies, there is only a small bystander effect.
- (4)
- Statistical analyses of the numerical data that form the background of survival experiments performed by A and reported in the two papers are not consistent with the expectation of the random distributions of numbers.
- (5)
- Statistical analyses of the numerical data that form the background of survival experiments performed by B and C are consistent with the expectation of random distributions of numbers.
- (6)
- This report emphasizes the importance of familiarity with the published literature in the field in question and of access to the raw data on which scientific reports rely.

## Acknowledgments

## Author Contributions

## Conflicts of Interest

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Hill, H.Z.; Pitt, J.H. Failure to Replicate: A Sign of Scientific Misconduct? *Publications* **2014**, *2*, 71-82.
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**AMA Style**

Hill HZ, Pitt JH. Failure to Replicate: A Sign of Scientific Misconduct? *Publications*. 2014; 2(3):71-82.
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**Chicago/Turabian Style**

Hill, Helene Z., and Joel H. Pitt. 2014. "Failure to Replicate: A Sign of Scientific Misconduct?" *Publications* 2, no. 3: 71-82.
https://doi.org/10.3390/publications2030071