Stem Cells - A New Sheriff in Town ?
BigU lures Jonathan Slack from Bath

The Star-Tribune reports on a new faculty member at BigU:

Last update: April 04, 2007 – 9:32 PM

'Headless frog' scientist to lead U stem cell efforts

By Maura Lerner, Star Tribune

Ten years ago, British scientist Jonathan Slack set off an international furor when he told a reporter that his lab had created a headless tadpole, and that it might be possible to do the same thing with human embryos.

This week, the university announced that Slack, 57, had been named head of its stem cell program after 11 years at the University of Bath in England.

A widely respected biologist and author, Slack is best known for his pioneering work on turning liver cells into pancreas cells (a potential treatment for diabetes). And for his studies on how animals (tadpoles) regenerate limbs.

The university saw him as dynamic enough to replace the institute's internationally known founder, Dr. Catherine Verfaillies, who left as director to return to her native Belgium.

Eventually, the furor died down, but not before facing criticism around the world. At one point, he even removed his nameplate from his parking space, fearing an attack from animal rights activists. Arthur Caplan, a medical ethicist and former University of Minnesota professor, and J. Craig Venter, a prominent genetic scientist, upbraided him in Science magazine for unleashing a "torrent of silliness" about a "ridiculous" idea.

Mr. B. trusts that Dr. Slack has learned his lesson. The MCCL folks in ColdState as well as the state legislature and the animal rights terrorists can be extremely troublesome. Dr. Slack will need to have a good command of administratese in order to stay out of trouble. Let's hope that he does not get out of the bath and into the frying pan.

Ciao,

Bonzo

Speaking of Stem Cells
Cheese State Takes a Potential Hit from the Feds

The Milwaukee Journal Sentinel reports:

Preliminary decision against UW may set up years-long legal battle

By JOHN SCHMID
jschmid@journalsentinel.com
Posted: April 2, 2007

The U.S. Patent and Trademark Office has issued a preliminary rejection of three key stem-cell patents owned by the University of Wisconsin-Madison, setting up a legal battle with potentially big economic and psychological ramifications for the state's biotech economy.

The Wisconsin Alumni Research Foundation, the licensing arm of the university, vowed to appeal the ruling in every venue at its disposal, even if the dispute drags out in federal courts for years.

The agency acted in response to complaints from two public-interest foundations, which alleged in July that the patents are so broadly written that they give WARF potential to reap royalties from a broad range of stem cell-related treatments. In their complaint, the Foundation for Taxpayer and Consumer Rights in Santa Monica, Calif., and the Public Patent Foundation in New York also argued that UW-Madison researcher James Thomson was not the first to isolate human embryonic stem cells, therefore diluting the propriety of his 1998 work.

The groups say WARF's control of the technology discourages potentially lifesaving research by imposing licensing costs and drives stem-cell work abroad to places where WARF's patents are not recognized.

At stake for WARF is a potential loss of royalty revenue if both the agency and courts uphold the preliminary rejection.

A repeal also could dampen the excitement associated with research that has drawn hundreds of millions of dollars of investment and research funding to Madison, elevating the university town to one of the world's pre-eminent biotech hubs.

John Simpson, an official at the Santa Monica consumer rights group, was jubilant over the preliminary outcome.

"This is a great day for scientific research," Simpson said in a statement released late Monday. "The patents should never have been issued in the first place."

The final outcome is far from decided. The agency gave WARF two months to prepare a response.

There's no doubt the case will attract attention until it's resolved.

Goaded by Gov. Jim Doyle, Madison has made biotech the center of its economic growth strategy, putting it in competition with biotech centers from Boston to Singapore. Californians voted in November to fund $3 billion of embryonic stem cell research in their state over the next decade.

And embryonic stem cells by their nature have become lightning rods of controversy. Research in many cases means destruction of human embryos, raising heated arguments over ethical issues.

Mr. Bonzo thanks a colleague for calling this article to his attention. WARF - the Wisconsin Alumni Research Foundation - over the years has been a major contributor to scientific research funding at Wisconsin. The financial implications of invalidating the stem cell patents are very serious. The question of whether patents are good for innovation as well as the effect of the Bayh-Dole amendment on university research will be discussed in the future.

a stunned Mr. Bonzo

Stem cells here, stem cells there, stem cells everywhere...
The Minnesota Daily weighs in

The folks at the Daily have gotten around to the topic. In haste someone appears to have forgotten the spelling checker. AlexBonzo, who used to work for the Arizona Wildcat, will be teasing me about this.

Doubts raised over U study

A magazine claimed to have discovered discrepencies [sic] in a scientist's studies.

For the second time in the past year, serious questions are surfacing about the work of a prominent University stem cell scientist.

According to Peter Aldhous, the magazine's San Francisco bureau chief, while analyzing a 2001 Verfaillie paper printed in the medical journal Blood and a patent application approved in 2006, the publication discovered three images that seemed to have been duplicated between the two.

"What appears to be the case is that there were three occasions where there is a gel described, in the paper Blood published in 2001, where the same image is in the patent. But in the patent, it is supposed to be describing a different protein, and in most cases a different experiment," Aldhous said.

Timothy Mulcahy, University vice president for research, said the images appear similar, but the University is reserving judgment until an investigation is completed.

"Admittedly, if you look at it quickly, they could be the same, and they may be," he said. "And if they are, it begs the question how the same figure got used representing three different things of three different natures."

"We are being completely objective in this, so at this time we're not presuming one thing or another," Mulcahy said. "We're simply saying let's look at the facts and let the facts speak for themselves."

This latest incident comes on the heels of another University investigation that wrapped up last August, involving problems found in papers published in the journals Nature and Experimental Hematology, which New Scientist also uncovered.

In that instance, a panel reviewed the papers and found no evidence of foul play, but did conclude the studies' methods to be "significantly flawed," calling into question the results.

Despite so many uncertainties raised in such a short time, the vice president said he doesn't believe it will seriously damage the research reputation of the Stem Cell Institute or the University.

"In the long run, how we handle this at the University is actually going to enhance the University's reputation," he said.

Anyone who just wandered into this and is unaware of the stem cell controversy at BigU may wish to consult an earlier post concerning Photoshop manipulation of scientific data. The link to "infographic" shows a figure from the New Scientist that illustrates the problem.

Second Stem Cell Inquiry Slated at BigU

This just in from the NewScientist website:

Inquiry into prominent stem-cell research underway

* 31 March 2007
* From New Scientist Print Edition.

FOLLOWING concerns raised by New Scientist, the University of Minnesota has launched an inquiry into some prominent stem cell research.

Last week, we revealed that three images from a paper on adult stem cells in the journal Blood were apparently used to describe different results in a US patent (New Scientist, 24 March, p 12). One of those images also seemed to be used twice, in mirror-flipped versions, within the Blood paper.

The university has informed Catherine Verfaillie, who led the research team, and a former student, Morayma Reyes, that an inquiry is under way. It will determine whether there is evidence to merit an investigation into possible misconduct. The Catholic University of Leuven (KUL) in Belgium, where Verfaillie now works, has also launched an inquiry into the matter.

From issue 2597 of New Scientist magazine, 31 March 2007, page 7

Bonzo

Photoshop Manipulation of Scientific Illustrations

Stem Cells at BigU, the Continuing Saga

The Scientific American web site has an interesting article concerning rampant Photoshop treatment of scientific illustrations in publications:

March 23, 2007

---

Journals' Spot-Checking of Images for Photoshop Manipulation Comes Too Late To Stop Latest Stem Cell Fraud

As New Scientist reported in a commendable bit of enterprise journalism, images from a paper in Nature (vol 418, p 41) on a supposed new and groundbreaking type of adult stem cell appear to have been duplicated "in a second paper that was published at about the same time, where they were supposed to relate to a different experiment." But it gets worse:

Now New Scientist has examined a US patent (number 7015037) [Inventors: Reyes, Verfaillie, Furcht ] granted in 2006...

Within the patent are three images that appear to be duplicated from another paper from Verfaillie's group [Authors: Reyes, Lund, Lenvik, Aguiar, Koodie, Verfaillie], published in 2001 in the journal Blood (vol 98, pp 2615-2625)...

The problem is that in each case the duplicated image is used in the patent to describe the production of a different protein from that described in the Blood paper.

New Scientist also has a great infographic showing each of the original images that were allegedly duplicated--and you don't have to be a conspiracy theorist to see how they might be construed as a rather sloppy fraud. [The infographic link doesn't always work, so I've put it at the top of this post.]

Awaiting further developments, I remain, your servant,

Bonzo

Stem Cells at BigU, part II


The local papers have picked up on the recent New Scientist article (see previous post).

The Pioneer Press reports:


U stem cell research raises new questions
Journal says one image apparently used in patent for three discoveries
BY JEREMY OLSON
Pioneer Press

The accuracy of pioneering adult stem cell research at the University of Minnesota is under scrutiny again, as a scientific journal is questioning whether U researchers used a single image of a protein to represent three different scientific discoveries.

The university is investigating, said Tim Mulcahy, the U's vice president for research.

The latest concerns focus on a 2001 article in the medical journal Blood and a patent application, approved in 2006, related to the stem cell discoveries. Images in both documents are offered as proof that U researchers used the stem cells, derived from adult bone marrow, to create different types of proteins. But close inspection suggests the images are all of the same protein, not different ones, according to an article New Scientist published Wednesday.

While the magazine seems to hint that someone deliberately misrepresented the data, there is no evidence to support that conclusion, Mulcahy said.

"The university is going to conduct an objective, comprehensive review but we have no evidence at this point of any wrongdoing. We have to let the process go forward and await a conclusion from the investigation."

The nature of the errors reported by the New Scientist in this second case seem a little more difficult to dismiss as an honest mistake as is clear from a recent post on the Chronicle of Higher Education website:

March 22, 2007
New Allegation of Misrepresented Results From U. of Minnesota Stem Cell Scientists

Fresh accusations have emerged that stem-cell researchers at the University of Minnesota-Twin Cities misrepresented their results in a published report and a patent application. In a paper published in Blood and in a patent based on findings reported elsewhere, the same image appears to have been used to represent the results of two or three separate experiments, New Scientist reported on Wednesday.

The work, led by Catherine Verfaillie, who has since moved to the University of Leuven, in Belgium, concerns adult stem cells. Dr. Verfaillie’s surprising results showed that some of the cells, found in bone marrow, could make a wide variety of tissues, like bone, blood, and cartilage. Previously they were thought able to make only a limited set of blood-cell types.

The questionable image, a photograph of a gel used to separate out proteins of different sizes, seems to appear twice in the paper. One image shows three blots of protein labeled ß-actin, a protein found in all of the cell types. An apparent mirror image of that gel is shown on the same page, but in the second instance, it is labeled collagen II, a protein found in cartilage. In the patent, the flipped image is said to represent a third protein, one specific to bone, New Scientist reported.

Dr. Verfaillie previously used a single image to represent two different experiments in a papers published in Nature and Experimental Hematology. An ethics review conducted by the University of Minnesota found that instance to be an unintentional mixup. Sanford Shattil, editor of Blood, told New Scientist that the journal would look into the new matter. —Susan Brown

The results of a second investigation at BigU should be interesting.

Ciao,

Bonzo

Stem Cells at BigU
Curiouser and curiouser...

The stem cell brouhaha (or worse) continues at BigU. An earlier post serves as an introduction. The sleuths at New Scientist have done further digging and uncovered:


Fresh questions surround some of the highest-profile research on adult stem cells. For the second time, New Scientist has discovered apparently duplicated data being used to describe results from different experiments in work published by a group of scientists at the University of Minnesota, Minneapolis.

Now New Scientist has examined a US patent (number 7015037) granted in 2006 that covers the isolation and use of MAPCs. The patent is exclusively licensed to a company called Athersys of Cleveland, Ohio, which hopes to launch clinical trials of the cells to treat conditions including heart attacks and stroke.

Within the patent are three images that appear to be duplicated from another paper from Verfaillie's group, published in 2001 in the journal Blood (vol 98, pp 2615-2625). These images relate to experiments in which MAPCs were grown in culture dishes and made to differentiate into other cell types, such as those found in bone, cartilage, fat and the linings of blood vessels. The images document the presence of proteins specific to each type of cell being produced.

The problem is that in each case the duplicated image is used in the patent to describe the production of a different protein from that described in the Blood paper.

In the most striking example, one of the duplicated images also seems to be used twice within the Blood paper itself, to represent the results from two different experiments. In the Blood paper, this image, which shows a series of three bands on a gel, is first used to represent a control for an experiment in which a culture of stem cells is made to differentiate into cells found in bone. What seems to be the same image is used later on the same page, though this time it is flipped over horizontally, producing a mirror image, and contains some small modifications (see top two images, right). Here, it is labelled as showing the production of collagen in a culture of stem cells made to turn into cells found in cartilage.

“One of the duplicated images seems to be used twice in the Blood paper to represent results from different experiments”

In the patent, this flipped and modified image appears again, this time supposedly representing a bone-specific protein found in a culture of stem cells made to differentiate into bone cells (see bottom image, right).

The research described in the Blood paper formed part of the PhD work of its first author, Morayma Reyes, and the duplicated images in the paper, including the flipped and modified version, also appear in her thesis. Now at the University of Washington in Seattle, Reyes is named on the patent as one of the inventors, along with Verfaillie, who was her supervisor, and Leo Furcht, who heads the department of laboratory medicine and pathology at the University of Minnesota. Currently president of the Federation of American Societies for Experimental Biology, Furcht founded a company called MCL that was assigned the patent jointly with the University of Minnesota.

Stem cell biologists contacted by New Scientist are sure that the three images referred to above are duplicates. "They're quite clearly the same," says Jeanne Loring of the Burnham Institute for Medical Research in La Jolla, California. "It appears that a piece of data has been used multiple times to represent different things," agrees Arnold Kriegstein, who heads the programme in developmental and stem cell biology at the University of California, San Francisco.

Although the Blood paper is less well known than the publication that followed in Nature, it is significant in terms of the planned clinical trials because it describes cells isolated from the bone marrow of human volunteers rather than experimental mice.

“The Blood paper is significant because it describes cells isolated from the bone marrow of human volunteers”

Verfaillie, who is now at the Catholic University of Leuven (KUL) in Belgium, and Reyes were unavailable to respond to questions from New Scientist asking for an explanation of the apparent duplications. Athersys said it would review the points we raised, while the University of Minnesota said it had no comment.

After being contacted by New Scientist, Blood is now conducting its own inquiry. "We're going to do a serious investigation into this," says the journal's editor-in-chief, Sanford Shattil, a haematologist at the University of California, San Diego.

No doubt we will be hearing more about this situation in the future.

Ciao,

Bonzo

It has hit the NYT

An article about the stem cell business at BigU has appeared in the New York Times.

An inquiry panel has found what it called “significantly flawed” data in a major stem cell paper published in Nature in 2002.


Bonzo

Stem Cells at BigU: It's starting to get ugly...

From the Pioneer-Press (Gem Cities other good newspaper)

Minnesota Legislature / Legislator challenges U stem cell scientist
1973 law on human research in question

by Jeremy Olson

A lawmaker used a House committee hearing on embryonic stem cell research funding Thursday to challenge a University of Minnesota scientist on whether her work violates state law.

Rep. Dan Severson, R-Sauk Rapids, said a 1973 state statute on human research appears to make embryonic research by the U's Meri Firpo illegal.

"I think in this particular case the experiments Mrs. Firpo is doing are a gross misdemeanor," he said.

Firpo responded that she has been assured by U leaders that embryonic stem cell research is permitted under that statute, and a research analyst for the higher education and work force development committee said the statute applies to a relatively narrow definition of human life.

Mr. Bonzo is very concerned about the way this is going...

This just in - Stem Cell Problems at BigU

As mentioned earlier in the PT, stem cell research is a hot topic and is done at The Stem Cell Institute at BigU - see label "stem cells" at left for earlier post.

An article appeared in the New Scientist recently (February 15) that indicated trouble in River City. This was pointed out to me by a colleague but I have not gotten a chance to report on it in detail. The newshounds at the Strib have beaten me to the punch and their article has just appeared:

Stem Cell Study Was Flawed, U Panel Finds

The research, on stem cells from adult mice, was hailed as a breakthrough in 2002, but some data came under scrutiny.

By Maura Lerner and Josephine Marcotty, Star Tribune

Last update: February 22, 2007 – 9:33 PM

Five years ago, a groundbreaking University of Minnesota study found that a type of adult stem cell in mice could have as much potential to treat disease as those taken from embryos. The research made headlines around the world.

But now both the university and the lead scientist, Dr. Catherine Verfaillie, acknowledge that part of the study was flawed.

The university took the unusual step of conducting an inquiry into the 2002 study last summer after questions were raised by a British magazine, New Scientist, about some of the published data. The magazine disclosed the incident in an article published last week.

An expert panel convened by the university concluded that a process used to identify the cells was "significantly flawed, and that the interpretations based on these data, expressed in the manuscript, are potentially incorrect."

Political ramifications

Verfaillie's research was heralded by social conservatives who have pinned their hopes on adult stem cells as an alternative to using embryonic cells, which they oppose on moral grounds.

At the same time, Verfaillie's work had cemented the reputation of the University of Minnesota as a major force in the world of stem cell research.

Verfaillie, 49, ran the university's stem cell institute from 1999-2006 and now heads stem cell research at Catholic University in Leuven, Belgium, while remaining on the University of Minnesota faculty.

"We believe we did everything appropriately," said Tim Mulcahy, vice president of research at the university, who oversaw the inquiry. "From our perspective, this is now an issue for the scientific community."

Verfaillie said she requested the inquiry as soon as problems were brought to her attention.

Answering questions by e-mail, she wrote: "I knew that this was an 'honest mistake,' but that given the profile of the paper, of my work, and the political climate, that it could be construed otherwise."

How it began

About a year ago, Peter Aldhous, the San Francisco bureau chief of New Scientist magazine, decided to take a closer look at Verfaillie's work. At the time, he was writing about problems plaguing stem cell research.

Aldhous said he was intrigued with Verfaillie's 2002 study, which appeared in the journal Nature, because "it was a remarkable and exciting finding."

He said he wondered why no one else had been able to show, as she did, that a stem cell from the bone marrow of adult mice could turn into a wide range of other tissues, such as brain and muscle cells.

Aldhous and a colleague started combing through Verfaillie's published studies. And, he said, they found that she had published some of the same data twice, labeled differently, in two journals, including the Nature article.

"I wrote to Catherine saying that we'd noticed these duplications and asking if she was able to explain them," Aldhous said in a telephone interview.

Surprised, Verfaillie said she promptly notified the university. "I pride myself on careful presentation of data and was disappointed at myself," she wrote in her e-mail to the Star Tribune.

Mulcahy said that Verfaillie's prominence and the political sensitivity of the research made it prudent for the university to take a hard look at the questions raised by the New Scientist reporters.

Normally, the university would use its own academic staff for such a review. But this time two of the three members of the panel were from outside the university, he said. They concluded that the data had been duplicated, but that it was most likely an honest error.

Verfaillie notified both journals of the errors.

Editors at Nature said they are reviewing the studies and declined to comment further.

The second journal, Experimental Hematology, notified her Thursday that it plans to print her correction in June. "I don't see this as a major problem," said journal editor Esmail Zanjani.

Disclaimer:

I have not reprinted the whole article, please see the Strib link above. I have simply tried to give an impression of the situation.

Full Disclosure:

I know Dr. Verfaillie slightly and believe that she is a good person. I understand she bakes a mean quiche. If she says it was an "honest mistake," then I believe her. High stakes research, like high stakes poker, is intensely competitive. Under pressure, people make mistakes. This is partly a fault of our insane system for funding science nowadays. [End of sermon]

Stem Cell Woes and Wars

From Inside Higher Ed

Missouri lawmakers cut $113 million in university building projects from a $335 million higher education bill Wednesday, as The St. Louis Post Dispatch reported. Their reason? As the Post-Dispatch puts it, “The committee chairman, Sen. Gary Nodler, R-Joplin, said the projects that had been cut had been identified as possibly housing stem cell research in the future.”

Ouch - scene set...

..one might expect that administrators would be jumping for joy in Minnesota, where a House committee met Wednesday to debate a bill explicitly affirming the ability of the University of Minnesota to spend state-appropriated funds on stem cell research.

Yet, administrators’ lukewarm, “no official position” response perhaps reflects a larger trend for many public universities to insulate themselves, as much as possible, from the political debate.

“My thought is that they need kind of an affirmative statement from the state that this is an appropriate thing to do,” says State Rep. Phyllis Kahn

[Mr Bonzo bows to Representative Kahn’s scientific chops. She has a PhD in biophysics from Yale and her opinions on such matters should be treated with the utmost respect.]

The university’s conservative policy regarding state funds simply reflects its existence within a mixed political climate regarding stem cell research, Wagner [a professor of pediatrics and director of clinical research for the Stem Cell Institute] says — more mixed than in other states like Illinois, Massachusetts, New Jersey and, of course, California, that have more actively pursued the research. “Here we had the forethought of creating a stem cell institute but in an environment that didn’t support it,” he says.

Mr. Bonzo is not usually very sympathetic to BigU’s administration, but in this case he almost feels sorry for them.... Stem cell research is apparently going to be one of those areas that one has to be doing in order to be TrulyGreat. However will we achieve our ambitious aspirations?

Signing out, Mr. B, who will be leaving next Monday to go to Bluest State to talk in Anaheim about biomaterials and perhaps catch a few mice. Mr. and Mrs. Bonzo will also be visiting AlexBonzo in the City by the Bay. the SF orchestra and Hedda Gabler are on tap, possibly lamb chops at John's Grill, so postings likely will be sparse.

ps. (February 10, 2007) This just in from the StarTribune:

Editorial: State should endorse funding of cell studies

U of M's embryonic research is both important and ethical.

Published: February 10, 2007

[There seems to be a pipeline from Morrill Hall (BigU admin office building) to the Strib editorial offices lately...]