John Rasko and Carl Power “What pushes scientists to lie? The disturbing but familiar story of Haruko Obokata” http://www.theguardian.com/science/2015/feb/18/haruko-obokata-stap-cells-controversy-scientists-lie
小保方晴子による所謂STAP細胞騒動*1に関する総括的な論攷。著者のJohn Rasko氏は血液学者、Carl Power氏は哲学者。
さて、著者たちは「現代細胞科学は恐ろしい間違えから出現してきた（modern cell science emerged from a terrible debacle）」という。
The man in the middle of it all was Alexis Carrel, a brilliant and rather dapper Frenchman working at the Rockefeller Institute in New York. Carrel discovered that, if you remove some cells from the body, sit them in a nutritious broth and handle them correctly, they can not only survive, but thrive and multiply. Also, if you take some cells from one culture, you can start a new one and, with that, a third, and so on. The importance of this technique – know as cell “passaging” – can’t be overstated. With it, Carrel literally opened a new era in cell research. Unfortunately, he did so with an experiment that, while earning him international superstardom, proved to be a complete and utter train wreck.
On 17 January 1912, Carrel removed a chick embryo from its egg and cut out a small fragment of its still-beating heart with the aim of keeping it alive as long as possible. He had hardly begun this experiment when he announced to the world that his chicken heart culture was immortal, that immortality belonged potentially to all cells, and that death was only the consequence of how cells are organised in the body. In other words, the secret of eternal life is within us all, an attribute of our basic biological building blocks. It captured the public’s imagination and was soon accepted by the scientific community.
Carrel and his assistants kept – or claimed they had kept – that culture alive for 34 years, which is five times longer than the average chicken. For many years, around 17 January, journalists wrote birthday stories on the chicken heart and wondered how large it would have grown had Carrel nurtured every one of its ever-multiplying cells. (According to calculations, it swiftly dwarfed the Earth and filled up the entire solar system.)
The problem was, no one else could keep a cell culture alive indefinitely. Lab after lab tried and failed, decade after decade. Because Carrel was a giant in the field of cell research and a Nobel Prize winner, few dared to doubt him. Scientists blamed themselves when their cells died. They assumed that they lacked the master’s skill, that his lab had higher standards than they could reach, that they had somehow exposed their cells to infection or failed to keep them properly nourished. We now know that the reverse was true. Other researchers probably couldn’t duplicate Carrel’s results because they weren’t incompetent or dishonest enough.
It was only in the mid-60s – half a century after Carrel established his chicken heart culture – that the dogma of cell immortality came crashing down. That’s when Leonard Hayflick, an ambitious young researcher at the Wistar Institute in Philadelphia, discovered that ordinary body cells have a finite life span – or, more precisely, an average number of times they can multiply in vitro. This is their Hayflick number. For chickens, it is 35. In other words, a population of chicken cells can double about 35 times before they die, which usually takes several months.
By the time Hayflick proved this, Carrel was long dead and his “immortal” chicken cells discarded. Which means that we know Carrel’s most famous experiment was a sham, but not why. If it was fraud, it was one of the most outrageous cases in the history of science. However, the cause may have been carelessness rather than dishonesty. Carrel and his staff used “embryonic juice” as a culture medium and, if they prepared it badly, it might have contained live chick cells. In that case, instead of just feeding their culture, they re-seeded it. It’s an easy enough mistake, but to make it consistently enough to keep their chicken heart cells alive for 34 years suggests an astonishing degree of negligence.
実は科学において、「再現性は通例であるより寧ろ例外である（reproducibility is the exception rather than the rule）」。
By contrast, the speed of Obokata’s undoing should make us feel more confident about the ability of science to correct itself. As soon as she announced the creation of Stap cells, other researchers tried to make their own and, when they failed, wanted to know why. Without doubt, the standards of cell science have improved since Carrel’s day. Biomedical research is more strictly regulated, and wet lab procedures better established. The internet has also played its part, making it faster and easier for scientists to compare notes and spot errors*4.
But before we start to congratulate ourselves on the ever-upwards path of science, we should bear in mind that most experiments are never reproduced. There are simply too many of them. Besides which, researchers often don’t have much interest in repeating the work of others. Scientists may be truth-seekers, but they generally prefer new truths. They want to be the first to make a discovery. That’s where all the glory lies; that’s how to get a name for yourself, attract more funding and advance your career. Confirming – or failing to confirm – someone else’s discovery is unlikely to get you very far. It’s unlikely to even get you into print since science journals tend to favour novel research*5.
A few years ago, Glenn Begley put this suspicion to the test. As head of cancer research for pharmaceutical giant Amgen, he attempted to repeat 53 landmark experiments in that field, important work published in some of the world’s top science journals*6. To his horror, he and his team managed to confirm only six of them. That’s a meagre 11%. Researchers at Bayer set up a similar trial and were similarly depressed by the results. Out of 67 published studies into the therapeutic potential of various drugs (mostly for the treatment of cancer), they were able to reproduce less than a quarter*7.
Two obvious reasons spring to mind. First, unbelievable carelessness. Obokata drew suspicion upon her Nature papers by the inept way she manipulated images and plagiarised text. It is often easy to spot such transgressions, and the top science journals are supposed to check for them; but it is also easy enough to hide them. Nature’s editors are scratching their heads wondering how they let themselves be fooled by Obokata’s clumsy tricks. However, we are more surprised that she didn’t try harder to cover her tracks, especially since her whole career was at stake.
Second, hubris. If Obokata hadn’t tried to be a world-beater, chances are her sleights of hand would have gone unnoticed and she would still be looking forward to a long and happy career in science. Experiments usually escape the test of reproducibility unless they prove something particularly important, controversial or commercialisable. Stap cells tick all three of these boxes. Because Obokata claimed such a revolutionary discovery, everyone wanted to know exactly how she had done it and how they could do it themselves. By stepping into the limelight, she exposed her work to greater scrutiny than it could bear.
But perhaps hubris is the wrong term. While some stem cell researchers may indeed possess that “vaulting ambition” characteristic of Shakespeare’s tragic heroes, from what we have read and witnessed firsthand, scientific fraud rarely springs from a heroic, all-or-nothing decision. It is more like a bad habit you acquire, a gentle slope you descend without realising how deep you’re getting.
It all starts with a temptation, one that every scientist faces and to which quite a few succumb. (In anonymous surveys, almost 2% of scientists actually admitted to falsifying data at least once in their careers, and about 14% had witnessed others doing so.)*8
Imagine it: you have sunk many long hours into your experiment, growing, manipulating and testing cells in various ways, all with a certain hypothesis – a hunch – in mind. You really want to prove that your hunch is right, that the money invested into your work was well spent, and that you aren’t just frittering your life away in a white coat, in a white room, under fluorescent lights. And of course, you want to get ahead in a competitive field, where the pressure to perform can be intense. But you get your results and they are disappointing. You can see straightaway what the data should look like and how, with just a tweak, you can improve them. All you need to do is count something a little creatively, shift a point on a graph or touch up an image. If you get rid of the original data, no one will ever be the wiser. And maybe your hunch is right anyway. Surely it is. You will find more proof – real proof – sooner or later if you just keep looking.
But once you start fiddling with the facts, it’s hard to stop. In part, that’s because you have done some reality-testing and discovered just how easy it is to fool your colleagues. In part, too, you have enjoyed their admiration and your improved chances of being published, promoted and otherwise funded. Maybe you even enjoyed the risk. But things get progressively more complicated. You are now expected to build on your past success, which means adding fiction upon fiction while making sure that the whole contrivance fits neatly together. And as your project thrives, more people will climb on board, and you will have to micromanage their contributions and their perceptions of what is going on. The upside is that their good reputations will lend your work added credibility. The downside is that you will have more eyes peering over your shoulder.
It seems that Obokata was adept at playing this game. She recruited some highly respected figures in the field of cloning and stem cell research and handled them so well that, when questions were first raised about her work, they immediately jumped to her defence, declaring that they had independently verified her work. That is probably what they believed. However, the subsequent investigation revealed that Obokata had always helped her Riken colleagues in their efforts at verification.
*1:See also http://d.hatena.ne.jp/sumita-m/20140315/1394904519 http://d.hatena.ne.jp/sumita-m/20140318/1395108929 http://d.hatena.ne.jp/sumita-m/20140613/1402655450 http://d.hatena.ne.jp/sumita-m/20140629/1404056302 http://d.hatena.ne.jp/sumita-m/20140630/1404104626 http://d.hatena.ne.jp/sumita-m/20140701/1404181587 http://d.hatena.ne.jp/sumita-m/20140706/1404668892 http://d.hatena.ne.jp/sumita-m/20140714/1405306381 http://d.hatena.ne.jp/sumita-m/20140718/1405614505 http://d.hatena.ne.jp/sumita-m/20140719/1405733823 http://d.hatena.ne.jp/sumita-m/20140724/1406217056 http://d.hatena.ne.jp/sumita-m/20140801/1406824871 http://d.hatena.ne.jp/sumita-m/20140802/1406943404 http://d.hatena.ne.jp/sumita-m/20140805/1407234173 http://d.hatena.ne.jp/sumita-m/20140808/1407425853 http://d.hatena.ne.jp/sumita-m/20140809/1407591494 http://d.hatena.ne.jp/sumita-m/20140810/1407636145 http://d.hatena.ne.jp/sumita-m/20140811/1407771956 http://d.hatena.ne.jp/sumita-m/20140813/1407860802 http://d.hatena.ne.jp/sumita-m/20140819/1408461044 http://d.hatena.ne.jp/sumita-m/20140822/1408678417 http://d.hatena.ne.jp/sumita-m/20140827/1409149926 http://d.hatena.ne.jp/sumita-m/20140828/140919914 http://d.hatena.ne.jp/sumita-m/20140903/1409682036 http://d.hatena.ne.jp/sumita-m/20140907/1410063860 http://d.hatena.ne.jp/sumita-m/20140913/1410625851 http://d.hatena.ne.jp/sumita-m/20140914/1410659469 http://d.hatena.ne.jp/sumita-m/20140915/1410749257 http://d.hatena.ne.jp/sumita-m/20141008/1412732195 http://d.hatena.ne.jp/sumita-m/20141017/1413517431 http://d.hatena.ne.jp/sumita-m/20141114/1415970524 http://d.hatena.ne.jp/sumita-m/20141128/1417173694 http://d.hatena.ne.jp/sumita-m/20141218/1418877881 http://d.hatena.ne.jp/sumita-m/20141220/1419089121 http://d.hatena.ne.jp/sumita-m/20141222/1419219968 http://d.hatena.ne.jp/sumita-m/20141225/1419519878 http://d.hatena.ne.jp/sumita-m/20141226/1419604265 http://d.hatena.ne.jp/sumita-m/20141229/1419825471 http://d.hatena.ne.jp/sumita-m/20141230/1419908212 http://d.hatena.ne.jp/sumita-m/20141231/1420039908 http://d.hatena.ne.jp/sumita-m/20150107/1420559284 http://d.hatena.ne.jp/sumita-m/20150109/1420823036 http://d.hatena.ne.jp/sumita-m/20150126/1422276587 http://d.hatena.ne.jp/sumita-m/20150211/1423582792
*2:See eg. “Alexis Carrel – Biographica” http://www.nobelprize.org/nobel_prizes/medicine/laureates/1912/carrel-bio.html http://en.wikipedia.org/wiki/Alexis_Carrel http://ja.wikipedia.org/wiki/%E3%82%A2%E3%83%AC%E3%82%AF%E3%82%B7%E3%82%B9%E3%83%BB%E3%82%AB%E3%83%AC%E3%83%AB このアレクシス・カレルという人は、生物学者として以外に、優生学論者、ファシスト、特異なカトリック思想家といった側面もとても興味深い。
*3:See eg. Zane Bartlett “Leonard Hayflick (1928- )” http://embryo.asu.edu/pages/leonard-hayflick-1928 http://en.wikipedia.org/wiki/Leonard_Hayflick http://ja.wikipedia.org/wiki/%E3%83%98%E3%82%A4%E3%83%95%E3%83%AA%E3%83%83%E3%82%AF%E9%99%90%E7%95%8C
*4:Alicia Shiu “The STAP scandal: a post-pub review success story” http://blog.publons.com/post/90031790568/the-stap-scandal-a-post-pub-review-success-story
*6:C. Glenn Begley & Lee M. Ellis “Drug development: Raise standards for preclinical cancer research” Nature483 (29 March 2012),531–533 http://www.nature.com/nature/journal/v483/n7391/full/483531a.html
*7:Florian Prinz, Thomas Schlange & Khusru Asadullah “Believe it or not: how much can we rely on published data on potential drug targets?” Nature Reviews Drug Discovery 10, 712 (September 2011) http://www.nature.com/nrd/journal/v10/n9/full/nrd3439-c1.html