The Theranos Effect: When Cutting-Edge Scientists Are Frauds
On August 5th, 2014, the Japanese biologist Yoshiki Sasai hanged himself in the offices of the Riken Institute’s Center for Developmental Biology in Kobe, a research center for which he served as associate director. While the content of several letters found among his belongings has not been made public, it is known that at least one letter was addressed to Haruko Obokata, a young researcher whose work Sasai supervised. Eight months earlier, Obokata had been the first author of two articles published in the prestigious scientific journal Nature.
The experimental results described in these articles seemed breathtaking. For over 15 years, biologists around the world had been fascinated with stem cells, a type of cell that can both divide indefinitely and differentiate into any kind of cell found in the human body. The ability to culture stem cells would enable a form of regenerative medicine in which tissues damaged by disease would be replaced by these therapeutic cells. Unfortunately, the isolation and culture of stem cells remains complex, and control of their differentiation is still rudimentary. Yet in the January 30th, 2014, issue of Nature, 32-year-old Obokata and her 13 coauthors announced that they had discovered a disarmingly simple method of transforming an adult lymphocyte (a type of white blood cell) into a pluripotent stem cell—in other words, a cell capable of differentiating into countless types of cells.
According to them, one merely needed to immerse the lymphocytes in a slightly acidic solution for half an hour. Once injected into a mouse, the so-called STAP cells (for stimulus-triggered acquisition of pluripotency) thus obtained proved capable of differentiating into any type of cell, including that of a placenta, a result never previously observed with stem cells. Better yet, the Obokata method displayed a yield 30 times greater than that of the best previously known methods for obtaining pluripotent stem cells.
Dozens of laboratories throughout the world immediately attempted to produce these miraculous STAP cells. All failed. Having gotten their fingers burned, researchers grew suspicious. What if Obokata had committed research fraud? What if she had invented or beautified her data? The administration of the Riken Institute took the rumors seriously and launched an internal investigation. Early in April 2014 its findings were announced. They were damning.
In manipulating the image data of two different gels and using data from two different experiments, Dr. Obokata acted in a manner that can by no means be permitted. . . . Given the poor quality of her laboratory notes it has become clearly evident that it will be extremely difficult for anyone else to accurately trace or understand her experiments . . . . Dr. Obokata’s actions and sloppy data management lead us to the conclusion that she sorely lacks, not only a sense of research ethics, but also integrity and humility as a scientific researcher.
We were also forced to conclude that the normal system by which senior researchers should have been carefully checking all raw data did not work in this case. . . . Drs. Wakayama and Sasai allowed the papers to be submitted to Nature without verifying the accuracy of the data, and they bear heavy responsibility for the research misconduct that resulted from this failure on their part.
On July 2nd, 2014, under extreme pressure from the editors of Nature, Obokata and her collaborators decided to request to retract their articles, which amounts to erasing them from the scientific literature.
Barely a month later, Sasai ended his life. The Riken Institute’s investigation committee had emphasized that he was in no way complicit in Obokata’s fraud and had only criticized him for falling severely short in his supervision of her work. But Sasai stated he was overwhelmed with shame. Charles Valensi, the other experienced scientist involved in the brief saga of the STAP cells, notified his colleagues at Harvard that he intended to take a sabbatical. As for the editors of Nature, they were deeply embarrassed by the online publication of peer-review reports by the experts—or “referees”—who had read Obokata’s manuscripts and pointed out their deficiencies. Why did the prestigious British publication choose to ignore these criticisms and publish work that specialists found suspicious?
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According to Karl Marx, history repeats itself: the first time as tragedy, the second as farce. Marx’s observation remains accurate in describing scientific fraud, but the order has been reversed. While Sasai’s suicide put a tragic end to a case that was the talk of the little world of stem cell biology for a semester, it had been preceded a decade earlier by a comparable case whose outcome was practically laughable.
In February 2004 the South Korean biologist and veterinarian Woo-Suk Hwang published two articles in Science announcing spectacular discoveries in the field of human therapeutic cloning. The researcher’s team claimed to be the first to have cloned a human embryo to obtain lineages of stem cells indispensable for regenerative medicine. These results made international headlines, and Hwang became a celebrity in his homeland. It was expected that he would be the first Nobel laureate in Korean history.
The Korean national airline even offered him lifetime free passage. In 2005 Hwang treated himself to another big splash, returning to the pages of Science to publish a description of the first cloning of a dog. Though the birth of the dog Snuppy did not make the international splash that the birth of Dolly the sheep did in 1997, it was nonetheless recognized as a significant advance in the biotechnologies of cloning.
But, as with Obokata and Sasai, the bloom was soon off the rose. In this case, the problem was not that the results were impossible to reproduce. In a field as complex as cloning, particularly one that is under strict legal restrictions in several countries—South Korea, however, is notoriously lax—few researchers attempted to reproduce Hwang’s experiment. His initial problem appeared on a front he had neglected: ethics.
One of his American collaborators accused him of not revealing his research objectives to the young women from whom he had taken the ova required for his cloning work. This could pass as a minor sin. But now the cloud of suspicion formed. As focus turned to Hwang’s publications and scholars began dissecting his graphs and charts, it became increasingly clear that he had committed fraud. In December 2005 Hwang was forced to recognize his misconduct—he had retouched photographs and faked results—and his articles on human cloning were retracted from Science.
In the wake of these revelations, the scientist was fired from Seoul National University and was sentenced to two years in prison for fraud, embezzlement, and violating bioethics laws. The ruling was reduced to a six-month suspended sentence on appeal.
Are offenders always punished? Only if we ignore Hwang’s astonishing comeback and his ability to redirect his fate from tragedy to farce. While his articles on human cloning have been retracted, the article on dog cloning remains in the scientific literature. In 2006 Hwang made the most of this credit by founding the Sooam Biotech Research Foundation. The purpose of this allegedly nonprofit foundation is to clone household pets for the modest sum of $100,000 per animal.
When prospective clients did not beat down its door, the Sooam Biotech Research Foundation had the clever idea to organize a contest in the United Kingdom whose lucky winner would get to have his or her favorite animal cloned. While the selection criteria remain mysterious, in April 2014, Rebecca Smith, a young Londoner who deeply loved her aging female dachshund, Winnie, celebrated the birth of mini-Winnie, a clone produced by Hwang. After a brief eclipse in the late 2000s, Hwang returned to publishing the findings of his research on cloning as if nothing had ever happened, getting back to his solid prescandal rate of one article every two months.
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Excerpted from Fraud in the Lab: The High Stakes of Scientific Research by Nicolas Chevassus‐au‐Louis, published by Harvard University Press. Copyright © 2019 by the President and Fellows of Harvard College. Used by permission. All rights reserved.
