Over the last few days, a new publication about cloning human stem cells has become very controversial, on the one hand, because of the topic itself and the ethical issues that it raises, and on the other hand, because the veracity of the results has been challenged on the web. Once again, this controversy testifies to the ongoing transformation of research, where the perverse effects of the race to publish are counterbalanced by new alternatives for scientific evaluation.
This article is a translation of “Clonage de cellules souches embryonnaires humaines : enfin possible ?” by Timothée Froelich.
Cloning human stem cells: Between reality and fiction
On May 15th, Shoukhrat Mitalipov et al. published in the journal Cell a study on the reprogramming of human somatic cells. The researcher from Oregon Health and Science University described how cells that were already differentiated could be used to create a cloned embryo.
The scientists adapted the method used for Dolly the sheep in 1996. A skin cell nucleus was retrieved and implanted in an enucleated egg cell. Dolly lived for seven years, but this technique had never been successfully applied in humans. The resulting embryo never went past the eight-cell stage.
In 2004 and 2005, this race to clone human stem cells pushed the team of South Korean scientist Hwang Woo-suk to publish faked results in the journal Science. He notably claimed that he had managed to create human embryo clones and to extract stem cells from them. The truth came out in 2006 and his articles were immediately withdrawn.
Eight years later, the recently published article by Dr. Shoukhrat Mitalipov has reopened the debate. The researcher is very qualified on the subject, having already proven himself in 2007 by obtaining stem cells from primates. At that time, the journal Nature had asked him to provide numerous complementary experiments before publishing his results. In Cell, he presents how he adapted the technique used for Dolly to a young child affected by a genetic disease. Embryos containing a hundred cells (blastocyst stage) were obtained. At this stage, the stem cells are sufficient for use in regenerative medicine.
A possible fraud supplants the ethical debate
Even if the approach invovles no reimplantation of the embryo, others could use this technique to generate human clones. Furthermore, destroying embryos for therapeutic purposes and donating oocytes pose significant ethical problems, too.
For the moment, though, doubts have been raised about the veracity of the results. The polemic came from the site PubPeer, a post-publication evaluation platform, which gives anonymous researchers the opportunity to comment on every scientific paper. One user first pointed out a few inconsistencies in the figures: for instance, some identical pictures show different captions. Other evaluators have also commented the article. The fact that the paper was published in great haste was also highlighted. As a matter of fact, the article was accepted in fewer than 4 days, and planned for publication only 15 days after submission. Emilie Marcus, Cell’s publisher, answered on the same website that the referees had accepted to give the paper priority without jeopardizing their rigor and their conclusions. In response to the debate, Dr. Mitalipov agreed to give an interview, released on May 26th in Nature. He admitted that he and his team rushed to write and publish the article. He wanted to talk about the results at a scientific conference in June. He also recognized that mistakes had been made, but said that they do not give reason to doubt the results. A corrected version is, thus, expected.
Photo by AJC1 (Flickr) cc by SA
What does this new case reveal?
Fraud, plagiarism, and article retractions have been making waves in scientific journals and blogs for some time. This new case comes in addition to other cases of cheatings (Stapel) or unintentional mistakes with very serious consequences, like errors in an Excel table in macroeconomics. It also underlines the competition and the constant pressure that researchers and laboratories are under. Researchers live by the rule of “publish or perish”. The quantity of their publications is often the key factor to their success, at the expense of quality. In the world of research, this involves an insane increase in the number of articles and, so, a proportionally greater number of retractions and frauds. This general atmosphere also encourages abusive behavior and increases the number of published mistakes, intentional or not.
Publishers are not neutral in all this. An anonymous researcher pointed out on PubPeer that “publishers acceptance of submitted articles depends greatly on their network, the institutions and location.” In addition, publishers sometimes do not take all necessary evaluation measures. They, too, are in competion. They all want to publish a “sensational” result before the others do. This is what Nathalie Dewitt suggests in a blog post: “It would have been better to submit the cells for independent analysis and include these results with the paper. But, given the short period of time for review, this reveals competition amongst journals for a high-profile paper, pushing them to promise to publish quickly.”
Moving towards greater research transparency?
This new case also shows a more positive aspect of the current evolution of research practices. The Open Science movement and science 2.0 imply greater visibility on these research missteps and, in the end, greater transparency. Open access publications allow a larger public (both researchers and others) to read the articles and comment on them afterwards. These post-review evaluation practices emerge, in particular, on platforms such as PubPeer, F1000 or Peerevaluation. Another major point is access to data and no longer just to results. This makes a new analysis by other scientists possible and provides an additional evaluation step.
The emergence of new evaluation practices for scientific publications provides a counterbalance to the misuses caused by a research system focused on the mass production of articles. This new case in the field of stem cells offers another example of research stuck in a complex economic, social and financial system that is pushing it to change.