These papers were first published in 2001 and were published in journals such as Science Signaling, Cell Reports, Journal of Biological Chemistry, PNAS, Cell Metabolism, Cancer Research, JCI, etc.

Editor: Aeneas Taozi

[ New Zhiyuan Introduction] Gregg L. Semenza, the winner of the 2019 Nobel Prize , who was exposed to academic fraud, has now withdrawn 4 top issues in one day.

The Nobel Prize winners of each session are contemporary scientific giants.

Who would have thought that academic fraud was actually staged in the Nobel Prize winner.

On September 2, 2022, 2019 Nobel Prize winner Gregg L. Semenza withdrew four papers published in the Proceedings of the National Academy of Sciences (PNAS) because there was a problem with the paper's picture. The four articles withdrew from

are as follows:

The above four articles were published in 2014, 2009, 2013 and 2013 respectively.

According to Web of Science data, these papers have been cited more than 750 times in total.

In fact, Gregg L. Semenza was suspected to be a "recurring offender" very early on. Many of his papers published in the past 20 years are suspected of academic misconduct.

Pubpeer has hung at least 40 of his papers. These papers were first published in 2001 and were published in journals such as Science Signaling, Cell Reports, Journal of Biological Chemistry, PNAS, Cell Metabolism, Cancer Research, JCI, etc.

In 2019, Semenza and two other scientists from the United Kingdom and the United States won the Nobel Prize in Physiology or Medicine.

The reason for winning is "discovering how cells perceive and adapt to the availability of oxygen ".

Among them, William G. Kaelin Jr is an American cancer scientist, Peter J. Ratcliffe is a British medical scientist, and Gregg L. Semenza is an American medical scientist.

Why is their research of great significance?

This is because everyone knows the common sense: the food we eat needs to be converted into useful energy through oxygen. However, although we all know that oxygen is very important for human survival, we do not know how cells adapt when oxygen levels change.

And William G. Kaelin, Sir Peter J. Ratcliffe and Gregg L. Semenza's contribution lies in the fact that they discovered the mechanisms in which cells perceive and adapt to changes in oxygen content. During the adaptation process, molecular machines that regulate gene activity are involved. Their research has given us a better understanding of how oxygen content affects cell metabolism and physiological functions, and has also provided us with new ideas for dealing with diseases such as anemia and cancer.

Let's see what Semenza's four papers retracted this time talk about -

Anthracycle chemotherapy inhibits HIF-1 transcriptional activity and tumor-induced mobilization of circularizing angiogenic cells (《Anthracycle chemotherapy inhibits HIF-1 Transcriptional activity and tumor-induced circulating angiogenic cells mobilization, researchers screened the drug library for clinical use based on the cell-reported gene detection, and identified anthracycline chemotherapeutic drugs doxorubicin and daunorubicin as effective inhibitors of hypoxia-inducing factor 1 (HIF-1)-mediated gene transcription.

Hypoxia-inducible factors mediated coordinated RhoA-ROCK1 expression and signaling in breast cancer cells ("Hypoxia-inducible factors mediate coordinated RhoA-ROCK1 expression and signaling in breast cancer cells ("Hypoxia-inducible factors mediate coordinated RhoA-ROCK1 expression and signaling in breast cancer cells"), researchers demonstrated that HIF activates Rho family members RHOA and Rho kinase 1 (ROCK1) Transcription of genes leads to changes in cytoskeleton , which is the basis of the phenotype of invasive cancer cells.

Mutual antagonism between hypoxia-inducible factors 1α and 2α regulates oxygen sensing and cardio-respiratory homeostasism ("Mutual antagonism between hypoxia-inducible factors 1α and 2α") was published in 2013. The researchers found that the balanced activities of hypoxia-inducible factors 1α and 2α are crucial for oxygen sensing in the carotid body and adrenal medulla and their control of cardio-respiratory function.

Hypoxia-inducible factors are required for chemotherapy resistance of breast cancer stem cells

("Hypoxia-inducible factors") published in 2014, researchers discovered the importance of hypoxia-inducible factor (HIF) activity: In the process of treating human breast cancer cells with chemotherapy, the activity of hypoxia-inducible factor (HIF) will affect the degree of enrichment of breast cancer stem cells in surviving cells.

In short, these 4 articles have an important role in improving the treatment of cancer and are of great significance.

Because of this, Johns Hopkins University where Semenza is located proudly calls him "one of the outstanding researchers today who study the molecular mechanisms of oxygen regulation."

However, all of Semenza's 4 papers have been overturned recently...

PS is good?

Before Semenza won the Nobel Prize, someone pointed out on the academic anti-counterfeiting website PubPeer that his research work had problems such as image copying.

anti-counter pseudonym Claire Francis pointed out online that

Before Gregg Semenza won the Nobel Prize , I found that there was something wrong with the paper he posted. When he won the Nobel Prize, I recognized the man and looked back at his paper. Did I misunderstand him? No, he actually has more papers with questions.

Currently, Semenza has 54 papers questioned on PubPeer.

In the latest 4 articles that have been withdrawn, Semenza is the corresponding author of .

Hypoxia-inducible factors are required for chemotherapy resistance of breast cancer stem cells article published in 2014 has the problem of data reuse and multiple use of one picture.

On PubPeer, some people pointed out that there may be duplicate data in Figures 6C and 8A.

Repeated images also appear in Figure S5A, and the following are the enhanced images:

In addition, the Pac + IL8 nAb in Figure 3E and Vehicle in Figure 5F are complete replicas. Can

still have this operation? It's really eye-opening...

fight against counterfeiting and sturdy, the evidence is conclusive, and Semenza can't sit still. He withdrew the four papers on September 2 and issued a statement saying -

We are withdrawing this article because there are problems with some published data, and we believe that this is the result of selecting the wrong image during the data construction process.

recognizes the correct image and does not require new experiments to correct the above problems. These updated data can be found in a preprint article published on bioRxiv, "Enrichment of breast cancer stem cells following cytotoxic chemotherapy is mediated by hypoxia-inducible factor" (https://doi.org/10.1101/2022.06.27.497729). We believe the overall conclusions of this paper are still valid, but we are withdrawing this work due to potential concerns about these images. We apologize for the inconvenience.

Semenza explained the following in the statement about the doubts on PubPeer:

"There may be duplicate data between the Pac + IL8 nAb panel in Figure 3E and the vehicle panel in Figure 5F.There may be splicing between the first and second channels of the HIF-1α panel of FIG. 4 . Duplicate data may exist between the complete SUM-159 actin panel of Figure 6C and the channels 2-5 of the MDA-231 actin panel of Figure 8A. Duplicate data may exist between the Digoxin and Gemcitabine+Digoxin panels in Figure S5A. Repeated data may exist between the actin panels of Figure S6C and S6E. ”

so... I just repeated the questioner's question in such an understatement, and don't plan to explain it?

Indeed, it is also a picture that is multi-purpose. It is caught in the current situation at once, and there is nothing to refute. ┑(￣Д ￣)┍

Look at this article in 2009 Anthracycle chemotherapy inhibits HIF-1 transcriptional activity and tumor-induced mobilization of circular angiogenic cells.

1 Adjust the contrast of the paper Figure 2 and you will find that the band similarity is very high, as shown in the arrow in the figure below.

In addition, more than one picture was found to have signs of brush smearing.

Semenza's approach to these four papers is exactly the same. She issues a withdrawal statement, admits the problematic pictures, remedy the research that can be remedied, and conducts a verification experiment to attach it to the later.

This car is overturned a bit...

It is worth mentioning that Chinese scholars are present in the latest withdrawn papers. For example, University of Chicago Guoxiang Yuan, Hong Wei, Lisha Xiang, etc.

Another anti-counterfeiting fighter

. In 2020, Leonid Schneider, a scientific journalist and former molecular cell biologist, also made a very detailed disclosure of Semenza's fraud.

Schneider's blog portrait

Schneider wrote in an anti-counterfeiting article: "Just like other areas in cancer research, the hypoxia field is full of fakes, just in PubPeer Just search for "HIF" (the hypoxia inducer factor discovered by Semenza). We hope that the Nobel Prize may provide pleasant exceptions, but, alas..."

Check out Semanza's magical operations:

Clone a gel band—

"HIF-1-dependent expression Angiopoietin-like 4 and L1CAM mediate the vascular metastasis of hypoxic breast cancer cells to the lungs" gene (2012) doi: 10.1038/onc.2011.365

You can see that there are two gel strips in Figure 1A that are likely to be copied and pasted. Figure 6 uses the same sample in a completely unrelated experiment. From the perspective of band shape and spacing, β-actin blot does not match the gels shown in Figures B and G.

left hand copy and paste, and fuzzy optimization with right hand -

"Hydroxia inducing factor 1 (HIF-1) Promotes extracellular matrix remodeling under hypoxia conditions by inducing the expression of P4HA1, P4HA2 and PLOD2 in fibroblasts" Biologics Chemistry (2013) doi: 10.1074/jbc.m112.442939

Some clever splicings -

"Hydroxia-inducing factor mediates coordinated RhoA-ROCK1 expression and signaling in breast cancer cells" PNAS (2014) doi: 10.1073/pnas.1321510111

H1F2a gel was reused. After some splicing, the sample label remains unchanged except the one marked with the red box.So the question is: Why did the author reuse the gel instead of loading control actin, or H1F1a or pMLC? Maybe it is because the results of these two numbers show slightly different?

The following example looks like a misunderstanding or error at first glance, but the intention behind it is actually worse:

"Expression of hypoxia-inducing factor 1-dependent adenosine receptor 2B promotes breast cancer stem cell enrichment" PNAS (2018) doi: 10.1073/pnas.1809695115

0 should have two types of gels, one for detecting PKCdelta (sum phosphorylation), and the other for detecting STAT3 (sum phosphorylation). But PKCdelta and pY-STAT3 bands are very similar, they must have come from the same gel. So is the pY-STAT3 signal mentioned in the article really a pS-PKCdelta signal? In this case, what changes have happened to the correct pY-STAT3 gel and what exactly do other gels show? This cannot be a mistake made by "accidentally".

is like a tiger. Is the judges blind? (Not mentioning, he really let him get over it)

Schnerder gives a sarcasm that hits the soul: So Semenza teaches students in the laboratory, right?

Finally, Schnerder said helplessly: "All these copied and pasted gel tapes are frustrating. But what is even more frustrating is that it is unlikely that these three journals will withdraw them, or do something else. Because Semenza won the Nobel Prize."

also withdrawn the manuscript

In addition to Semenza, several other Nobel Prize winners have withdrawn their manuscripts.

But unlike him, most Nobel Prize winners take the initiative to withdraw the article after discovering the problem, rather than taking action only after being questioned by netizens.

For example, after the 2018 Nobel Prize in Chemistry winner Frances Arnold announced that he would withdraw his paper published in Science in May 2019 in May 2019 Site-selective energy C‒H amidation for synthesis of diverse lactams.

Frances Arnold has become one of the three winners of the 018 Nobel Prize for his research on the evolution of enzymes, and is the fifth female winner of the award.

In January 2020, she once posted a post saying that

"The first tweet I posted in 2020 about work, I regret to announce that we have withdrawn last year's paper on enzymatic synthesis of β-lactams. Because this result is not repeatable."

In addition, there is also the 2011 Nobel Prize winner in Physiology or Medicine published in Science entitled MAVS, cGAS, and endogenous retroviruses in T-independent B cell responses article, due to problems with subsequent data, its manuscript was also withdrawn.

Most of the time, the award-winning scientists withdraw the papers published after winning the award. However, the following two people withdraw the papers before winning the award.

Linda Buck, one of the 2004 Nobel Prize in Physiology or Medicine, withdrew three papers between 2008 and 2010, one of which was published before winning the Nobel Prize.

And Michael Rosbash, who won the Nobel Prize in Physiology or Medicine in 2017, also had a paper retraction record in 2016.

Even if the paper withdrawal is usually regarded as a taint, the Nobel Prize winner also actively admits that mistakes are an attitude of scientists. The withdrawal of the paper

reflects their willingness to publicly admit their mistakes and convey credible information to their research colleagues.

This move also sets an example for others - even if they don’t have any awards, withdrawing the article is not necessarily shameful.

So, will Semenza's Nobel Prize be withdrawn? At present, there seems to be no precedent for the awarded Nobel Prize to be withdrawn.

However, this big overturn incident undoubtedly cast a big shadow on the authority of the Nobel Prize selection results...

Reference materials:

1https://www.pnas.org/doi/full/10.1073/pnas.2213289119

https://www.pnas.org/doi/full/10.1073/pnas.2213285119

https://www.pnas.org/doi/full/10.1073/pnas.2213288119

https://www.pnas.org/doi/full/10.1073/pnas.2213287119

https://retractionwatch.com/2022/09/03/nobel-prize-winner-gregg-semenza-retracts-four-papers/#more-125592