Tuesday, March 19, 2013

Crooked science at a major university

Crookedness that became known only because of one honest Chinese statistician  -- who got fired over it.  Maybe it's my Sinophilia showing but I think the Chinese in this matter are the only ones who come out of this with any honour.  The Chinese man involved in the fraud at least had the grace to commit suicide  -- while all the whites are stonewalling and covering up -- with no hint of penitence.

The journal should obviously have published  Yuan's critique immediately.  There was no need to refer it back to the crooked authors.  I have had several critiques of my work published without prior reference to me -- JR

The numbers didn’t add up.  Over and over, Daniel Yuan, a medical doctor and statistician, couldn’t understand the results coming out of the lab, a prestigious facility at Johns Hopkins Medical School funded by millions from the National Institutes of Health.

He raised questions with the lab’s director. He reran the calculations on his own. He looked askance at the articles arising from the research, which were published in distinguished journals. He told his colleagues: This doesn’t make sense.

“At first, it was like, ‘Okay — but I don’t really see it,’” Yuan recalled. “Then it started to smell bad.”

His suspicions arose as reports of scientific misconduct have become more frequent and critics have questioned the willingness of universities, academic journals and the federal government, which pays for much of the work, to confront the problem.

Eventually, the Hopkins research, which focused on detecting interactions between genes, would win wide acclaim and, in a coup for the researchers, space in the pages of Nature, arguably the field’s most prestigious journal. The medical school even issued a news release when the article appeared last year: “Studies Linked To Better Understanding of Cancer Drugs.”

What very few readers of the Nature paper could know, however, was that behind the scenes, Yuan’s doubts seemed to be having profound effects.

In August, Yu-yi Lin, the lead author of the paper, was found dead in his new lab in Taiwan, a puncture mark in his left arm and empty vials of sedatives and muscle relaxants around him, according to local news accounts — an apparent suicide.

And within hours of this discovery, a note was sent from Lin’s e-mail account to Yuan. The e-mail, which Yuan saved, essentially blamed him for driving Lin to suicide. Yuan had written to Nature’s editors, saying that the paper’s results were overstated and that he found no evidence that the analyses described had actually been conducted. On the day of his death, Lin, 38, the father of three young daughters, was supposed to have finished writing a response to Yuan’s criticisms.

The subject line of the e-mail to Yuan, sent by an unknown person, said “your happy ending.”

But in the seven months since, he has wondered why no one — not the other investigators on the project, not the esteemed journal, not the federal government — has responded publicly to the problems he raised about the research.

The passions of scientific debate are probably not much different from those that drive achievement in other fields, so a tragic, even deadly dispute might not be surprising.

But science, creeping ahead experiment by experiment, paper by paper, depends also on institutions investigating errors and correcting them if need be, especially if they are made in its most respected journals.....

While Yuan was growing increasingly skeptical of the lab’s methodology, Yu-yi Lin, who was also working at the lab, was trying to extend it. In the past, it had been applied to the yeast genome; Lin would extend it to the human genome — and this would become the basis of the Nature paper.

Lin, who was from Taiwan, was an up-and-comer. As a graduate student at Johns Hopkins just a few years before, he’d won an award for his work in cell metabolism and aging. He was also arranging for a prestigious spot at National Taiwan University.

At one point, when he was still at the Boeke lab at Hopkins, Lin asked Yuan to help analyze the data that would become the basis for the Nature paper, Yuan says. Yuan said he declined to get involved because he thought the methodology still had deep flaws.

Interactions between Lin and Yuan at the lab were few, Yuan said, and at any rate, Yuan had other things to worry about. He was slowly being forced out. He was demoted in 2011 from research associate to an entry-level position. A disagreement over whether Yuan should have asked Boeke if he wanted a byline on a paper erupted into further trouble, e-mail and other records show.

The Johns Hopkins spokeswoman, Hoppe, declined to discuss Yuan’s job termination.

On Dec. 15, 2011, Yuan was forced to leave the lab. He wasn’t allowed to make copies of his cell collection. He spent the next month trying to keep his mind busy. He read books about JavaScript and Photoshop, which he thought would enrich his research abilities. As he looked for other research jobs, he sensed that he had been blackballed.

Then, in February 2012, the Nature paper was published.

The research was a “profound achievement” that would “definitely be a great help to solve and to treat many severe diseases,” according to a news release from National Taiwan University, where Lin was now working.

Upon reading it, Yuan said, he was astonished that Lin had used what he considered a flawed method for finding genetic interactions. It had proved troublesome in the yeast genome, he thought. Could it have possibly been more reliable as it was extended to the human genome?

Lin, Boeke and their co-authors reported discovering 878 genetic interactions, or “hits.”

But Yuan, who was familiar with the data and the statistics, reanalyzed the data in the paper and concluded that there was essentially no evidence for any more than a handful of the 878 genetic interactions.

One of the key problems, Yuan wrote to the Nature editors, was that the numerical threshold the investigators used for determining when a hit had arisen was too low. This meant they would report far more hits than there actually were.

Yuan also calculated that, given the wide variability in the data and the relative precision required to find a true hit, it would have been impossible to arrive at any conclusions at all. By analogy, it would be like a pollster declaring a winner in an election when the margin of error was larger than the difference in the polling results.

“The overwhelming noise in the ..... data and the overstated strength of the genetic interactions together make it difficult to reconstruct any scientific process by which the authors could have inferred valid results from these data,” Yuan wrote to the editors of Nature in July.

His analysis attacks only the first portion of the paper; even if he is correct, the second part of the paper could be true.

Nevertheless, Yuan wanted Nature to publish his criticism, and following instructions from the journal, he forwarded his letter to Boeke and Lin, giving them two weeks to respond.

Just as the two weeks were to elapse, Boeke wrote to Nature asking for an extension of time — “a couple weeks or more” — to address Yuan’s criticism. Boeke explained that end-of-summer schedules and the multiple co-authors made it difficult to respond on time.

A day later, Lin was discovered dead in his office at National Taiwan University.

If there was a suicide note, it has not been made public, and it is difficult to know what went through Lin’s mind at the end of his life. The apparent suicide and the e-mail to Yuan suggest only that Lin may have been distraught over the dispute; they do not prove that he acted improperly.

Shortly after the Nature paper appeared, Yuan hired lawyer Lynne Bernabei to challenge the way he was terminated at Hopkins.

In late August, Yuan asked the Nature editors again whether they would publish his criticism. Lin was dead, but Boeke and the others had had a month to respond, and Yuan hadn’t heard a thing.

On Sept. 28, a Nature editor informed Yuan by e-mail that the journal was still waiting on a fuller response from Boeke and that “experiments are being done and probably a Correction written.”

Such a correction has not appeared.

So as a last attempt, he figured he’d try the federal government, which paid for much of the research. But the government suggested that the threat to the federal research, if there was any, ended with Lin’s death.

“It is our understanding that these allegations are being investigated by Johns Hopkins University,” said the letter from the Office of Research Integrity.


What if New York's Nanny Is Actually a Thug?

And what will they let the government do to us next?

 What if a dictator in America used the force of law to tell you what to eat? What if the same dictator told you what to drink? What if the dictator told you the sizes of the containers in which you could purchase a lawful beverage? What if the dictator just made up the rules according to his own personal taste? What if the product he regulated was lawful, sold nearly everywhere and consumed by nearly everyone? What if that product came in flavors and degrees of sweetness the dictator didn't like? What if that product was part of a huge national market that provides choices to consumers and jobs for those who want them? What if that product was simple soda pop?

What if the dictator declared that you could consume all the soda pop you wish to consume, but you need to purchase it in small containers? What if the enforcement of this container-size rule raised the price of soda pop? What if the container size was just something the dictator dreamed up? What if the dictator believed his judgment was superior to yours with respect to deciding what you should drink and how you should drink it?

What if the dictator pretended his container-size restrictions were based on sound science? What if he hired and appointed medical personnel who feared for their jobs if they did not agree with him? What if he ordered those people to support his container-size regulations whether or not they agreed that this is the proper role of government? What if he constituted these medical lackeys into a Board of Health? What if the Board of Health pretended it seriously studied the detrimental effect of sugar-based soda pop on human beings but never did?

What if the rules for container size were written in secret? What if those rules were so complicated that a judge concluded they would be impossible to enforce? What if the rules only applied to certain sugar-based drinks, such as soda pop and coffee, but not to others, such as chocolate milk and alcohol? What if the rules only applied to some stores and shops but not to all? What if the rules were so ridiculous that in order to buy a cup of coffee larger than 16 ounces, they required you to put milk and flavoring and sugar in yourself, and the seller of the coffee could not lawfully help you or do so for you, even at your request?

What if under the fundamental law of the land the dictator was not authorized by law to write laws but only to enforce them? What if the dictator knew that the governing body elected by the people to write laws would never write the laws he wanted because its members like power and fear losing it, which could happen if they try to tell the voters who elected them how to live? What if the dictator never presented his proposals on sugar-based drinks to the elected governing body because he knew they'd be rejected?

What if the dictator was more interested in his own legacy as a reformer than in personal liberty in a free society? What if he believed he could write any law and regulate any event because his knowledge of human behavior and unintended consequences was superior to that of the people he swore to serve?

What if the same dictator once made campaign contributions to members of the governing board so that they would change the fundamental law of the land -- which only the people directly can lawfully change -- so as to let the dictator stay in office longer than the fundamental law permitted? What if that law could only be changed by the voters themselves, but the dictator persuaded the lawmakers to take his campaign cash and change the fundamental law for him? What if the dictator was very unpopular but continued to impose his will on the people because he desperately wanted a legacy?

What if some people who sell soda pop challenged the dictator in a court he did not control? What if a judge of that court told the people they could buy soda and coffee in whatever sizes it was sold because the dictator did not have the power to regulate their intake of liquids? What if the judge even recognized that there are areas of human behavior immune to regulation by the government?

What if all of this really happened? What if this is not a fable but a fair recounting of life today in America's biggest city? What is the state of human freedom in New York City when the mayor can tell people what soft drinks to consume and how to consume them and the voters let him do it? What will they let the government do to us next?


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