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Lab Mistakes Hobble Cancer Studies But Scientists Slow to Take Remedies

Susan Notes:

If you want to read research with a point of view--connected to this shocking article below--I recommend The Immortal Life of Henrietta Lacks by Rebecca Skloot. You can read quite a bit at Amazon. I agree with Jad Abumrad's review, which stresses that what makes Rebecca Skloot's book mesmerizing--and important--is that she asks

  • Who was Henrietta Lacks?

  • How did she live?

  • How she did die?

  • Skloot also asks: Did her family know that she'd become, in some sense, immortal, and how did that affect them? And, not-so-incidentally, Skloot used a significant part of the book's profits to set up Henrietta Lacks Foundation, which "provides financial assistance to needy individuals who have made important contributions to scientific research without personally benefiting from those contributions, particularly those used in research without their knowledge or consent."

    You can find a review of the book at the bottom.

    This horrendous situation in cancer cell research revealed in this Wall Street Journal article is important to teachers for reasons besides those which would concern John Q. Citizen. After all, the corporate-politicos often tell us that education should be more scientific, that we should take a few hundred pages from medical training and practice and make it our own.

    Read the article and you'll see that the US Department of Education, partnering with the Bill and Melinda Gates Foundation, has already led us down this questionable path.

    How the U. S. Department of Education Emulates the Medical Field in Promoting and Using Contaminated, Misidentified, Carelessly Handled, Misused Data

  • basing mandates for teacher work with students on wrong data

  • funding the study and implementation of the wrong problem [using phonemic awareness, Algebra, et al as a cure for poverty]

  • making sure policy makers and the media ignore a problem that is in plain sight
    [over half the children attending urban public schools live in poverty]

  • doing--and applying--research without the knowledge or consent of those involved

  • ignoring researchers who yell the loudest about the real problem

  • utterly wasting public money, charity money, time, and human resources

  • encouraging the field of researchers who don't want to admit they made a mistake to carry on

  • If you think it's an exaggeration to compare mislabeled cancer lines with implementing Race to the Top and the Common Core State [sic] Standards, consider the Prince Georges County homeless 12-year-old sitting in school with abscessed teeth. I don't know how he did on his daily lessons or on his high stakes tests, but I do know that he died in a D. C. hospital after an infection from a molar spread to his brain. When his 10-year-old brother finally saw a dentist, he had six abscessed teeth.

    Shouldn't basic health care be the top priority for the nation's children? Shouldn't health care come before phonics and fractions?

    Richard Rothstein has documented the number of poor children sitting in our classrooms with toothaches--and how relatively cheap it would be to provide them with dental care. But our corporate-politicos would rather spend the money on Race to the Top and Common Core State [sic] Standards, on test prep workbooks and reading tutors.

    To quote John Masters, a professor of experimental pathology at University College London, UCL. "The whole ethos of science is to strive for the truth and produce a balanced argument about the evidence. Yet, all this crap is being produced."

    At the moment, the whole ethos of our U. S. Department of Education seems to be striving to blame teachers for the economy. There is no truth, no balanced argument about the evidence. What we have in common with the cancer researchers is that what is being produced is crap, crap that can kill people.

    Our first priority in schools must be:

  • Who are these children?

  • How do they live?

  • How can we prevent their death--physically and spiritually and intellectually?

  • By Amy Dockser Marchus

    Last year, cancer researcher Robert Mandic got news no scientist wants to hear.

    After publishing a paper on a rare head-and-neck cancer, he learned the cells he had been studying were instead cervical cancer. He notified the journal Oral Oncology, which retracted the article.

    "To base something on wrong data is bad, so it needs to be reported and I did," said Dr. Mandic, a researcher at the University Hospital Giessen and Marburg in Germany. "But it wasn't pleasant to call."

    Dr. Mandic entered a largely secret fellowship of scientists whose work has been undermined by the contamination and misidentification of cancer cell lines used in research labs around the world.

    Cancer experts seeking to solve the problem have found that a fifth to a third or more of cancer cell lines tested were mistakenly identified--with researchers unwittingly studying the wrong cancers, slowing progress toward new treatments and wasting precious time and money.

    In hundreds of documented cases that undermine a broad swath of research, cancer samples that were supposed to be one type of tumor have turned out to be another, through either careless laboratory handling, mislabeling or other mistakes.

    It is a problem hiding in plain sight. Warnings to properly test cancer cell lines have sounded since the 1960s, a decade after scientists started making human cancer cell lines.

    But researchers who yelled loudest were mostly ignored by colleagues fearful such a mistake in their own labs would discredit years of work.

    Leaders in the field say one of the biggest obstacles to finding a cancer cure may not be the many defenses nature affords malignancies, but the reluctance of scientists to address the problem.

    "Screaming and shouting, it doesn't do any good. No one takes any notice for reasons I don't understand," said John Masters, a professor of experimental pathology at University College London, UCL. "The whole ethos of science is to strive for the truth and produce a balanced argument about the evidence. Yet, all this crap is being produced."

    Dr. Masters said cell banks report that 20% of cell lines sent for inclusion in their repositories for use by researchers are improperly identified. He was co-chair of an international committee of scientists that released voluntary guidelines this year to begin solving the problem. They call for, among other measures, routine profiling of cell lines using a DNA technique employed in forensics called "short tandem repeats," or STR.

    Much of cancer research seeks answers to questions of basic biology, so the proper identification of cell lines may be less important, said Dr. Masters. But when seeking cancer treatment for a specific tumor, he said, such mistakes "are an utter waste of public money, charity money and time."

    Worse, he added, "It may be causing drugs to be used which are inappropriate for that particular type of cancer."

    Cancer research relies on cell lines that originate in patient tumors. The cells are usually grown in plastic containers and, with the proper nutrients, can live indefinitely in a laboratory. Scientists store them in freezers for years. The cells mimic particular kinds of tumors, giving researchers a way to understand what drives a disease or to test promising drug treatments.

    It may take a year or more to find the right combination of nutrients to keep cancer cells growing. Once a line is established, scientists often share them with colleagues, who then grow them in their own labs. The problem is that many scientists don't test the cells when shipping or receiving a batch.

    The most famous and ubiquitous human cancer cell line was the first--an aggressive, fast-growing cervical cancer taken from Henrietta Lacks of Maryland before her death in 1951. It has been shared with scientists world-wide in the decades since, playing a broad role in medical research spanning polio to hemophilia.

    The so-called HeLa cells, named for Ms. Lacks, also have taken over other cancer cell lines, many times unknown to researchers.

    These mix-ups are maddeningly difficult to pinpoint: an improperly sterilized pipette, a lab worker momentarily distracted, a misread label or a typo on a record sheet.

    Cell repositories in the U.S., U.K., Germany and Japan have estimated that 18% to 36% of cancer cell lines are incorrectly identified. Researchers at Glasgow University and CellBank Australia found more than 360 such mistaken cell lines, including 100 that turned out to be the late Ms. Lack's cervical cancer cells.

    "All of this sharing of cell lines, it's a bit like having unprotected sex," said David Tarin, a pathologist at the University of California, San Diego.

    Dr. Tarin himself is at the center of a lingering debate over the true identity of a famous breast cancer cell line known as MDA-MB-435.

    Dr. Tarin has spent 25 years working with that cell line--or so he thinks. A body of research suggests that MDA-MB-435 isn't breast cancer; many scientists now believe the cells growing in labs and used in decades of research are melanoma.

    The line originated at the M.D. Anderson Cancer Center in Houston, using cells from a 31-year-old woman who died in 1976, less than a year after she was diagnosed. The cell line was among the most widely used in metastatic breast cancer research.

    In 2000, scientists at Stanford University, working in collaboration with the National Cancer Institute, started testing the 60 cell lines in the institute's permanent collection.

    Michael Eisen, then part of the Stanford team, said they found something surprising about the breast cancer cell line: genes that mimicked melanoma. "It stuck out as problematic," said Dr. Eisen.

    At the time, the scientists didn't suspect contamination. They thought the breast cancer patient also might have had undiagnosed melanoma.

    Other scientists, following up on the observations at Stanford, demonstrated that MDA-MB-435 behaved like melanoma because it likely was melanoma--in particular, a skin-cancer cell line called M14.

    As word spread, Michael D. Johnson of Georgetown University Medical Center and a team of colleagues tested stocks of MDA-MB-435 from their lab and others around world. He said the group assumed their laboratory cell lines were the "real ones," and that other scientists' lines had been corrupted. Instead, the group found every one of the cell lines tested was melanoma, not breast cancer.

    Decades of research had been built on insights from research using that cell line. Now, said Dr. Johnson, "I'm not going to use them to study breast cancer. I don't believe they are breast cancer."

    Dr. Tarin disagrees, citing his own study that showed breast cancer tumors can have melanoma-like genes.

    Increasingly, medical journals won't accept research on breast cancer involving the MDA-MB-435 cell line, throwing into question decades of experiments and innumerable published papers based on the line.

    Seeking to solve the problem, a committee led by ATCC, a nonprofit group based in Manassas, Va., released guidelines this year to establish standards to authenticate cancer cell lines.

    ATCC is working with the National Center for Biotechnology Information, a branch of the National Institutes of Health, to establish a central repository and database of cell lines that have undergone genetic testing and whose origins can be verified.

    The National Institutes of Health have, so far, not required cell line authentication as a condition of receiving federal grants. The NIH in 2007 called for more stringent peer-review when cell lines are used in papers submitted for publication. Journals of the American Association For Cancer Research now require authors to disclose how and when their cell lines were tested.

    One challenge is getting scientists to acknowledge their cell line is contaminated. The prevailing attitude, according to researchers, is that the other lab's cell line may be contaminated but not mine.

    Osamu Tetsu, a head-and-neck cancer researcher at the University of California, San Francisco, did a study in 2009 that concluded all six known cell lines used by researchers studying adenoid cystic carcinoma were contaminated.

    All of the work done on the rare cancer--published papers, research, drug studies--had been conducted with mislabeled cell lines, Dr. Tetsu concluded. He called the findings "catastrophic."

    Jeffrey Kaufman, executive director of the Adenoid Cystic Carcinoma Research Foundation, said the group lost about $150,000 on a project that had to be scrapped. He alerted Dr. Mandic, who had a lab perform STR profiling on his cell line, which came from a colleague, who got it from another scientist a decade earlier. Tests revealed it was Ms. Lack's cervical-cancer cell line.

    The scientist cited in Dr. Tetsu's paper as the source of one of the corrupted cell lines said his lab wasn't responsible. Ruy Jaeger of the University of São Paulo in Brazil wrote in an email to The Wall Street Journal that his cell line was, in fact, adenoid cystic carcinoma. He also pointed out he had not directly provided the line used in the published paper.

    Dr. Tetsu said he tested a cell line created from Dr. Jaegar's line by a scientist in the U.S. The only way to resolve the dispute, said Dr. Tetsu, would be to perform STR profiling of Dr. Jaegar's cells and compare them to the DNA of the original cancer patient.

    The problem is particularly damaging for research into such rare cancers as adenoid cystic carcinoma, which strikes 1,200 people in the U.S. each year. The lack of a good cell line slows research and few in the field have the time or resources to create new lines.

    More broadly, the sharing of cell lines is such an intrinsic part of scientific culture, Dr. Tetsu said, that "it is almost impossible to stop."

    University of Washington scientist Stanley Gartler warned about the practice in 1966. He had developed a pioneering technique using genetic markers that would distinguish one person's cell from another. Using the process, he tested 20 of the most widely used cancer cells lines of the era. He found 18 of the lines weren't unique: They were Ms. Lacks' cervical cancer.

    "People were upset," said Dr. Gartler, who published his findings a year later in the journal Nature. "No one wants to admit they made a mistake."

    Dr. Gartler, an 88-year-old professor emeritus, said a decade after publication of his findings he attended a conference and introduced himself to a scientist. Dr. Gartler recalled the man told him, "'I heard your talk on contamination. I didn't believe what you said then and I don't believe what you said now.' "

    That became a long-held view. Nearly 40 years later, Dr. Masters, in a study of scientific papers published between 2000 and 2004, found nearly a 1,000 citations of the same contaminated cancer lines revealed in Dr. Gartler's 1966 findings, which have since been replicated many times using more advanced techniques. "They are either crooks or stupid," said Dr. Masters.

    Financial donors to cancer research are unaware of the problem, Dr. Masters said, and "it would be a pity if money stopped going to cancer research" because scientists fail to test their cell lines, a procedure that costs about $200.

    From San Diego, Dr. Tarin wrote to the ATCC to say his studies show that MDA-MB-435 is a breast cancer line, not melanoma. He has not heard back.

    Yvonne Reid, who works for the ATCC and was a member of the committee that wrote the new guidelines, said, "It is hard to come down for one or the other" without testing tissue from the breast-cancer and melanoma patients who originated the cell lines.

    Donald Morton, who was part of the team at the University of California, Los Angeles that in the 1980s grew the original melanoma line now believed to have contaminated MDA-MB-435, said his cell line has genetic markers that match the original patient with melanoma.

    Dr. Morton, currently the melanoma program director at the John Wayne Cancer Institute in Santa Monica, Calif., said he would share frozen tissue samples from the melanoma patient with scientists seeking to test against contaminated cell lines.

    His melanoma cells, Dr. Morton said, are indeed melanoma.

    "What happened after that cell line left my lab," he added, "I cannot say."

    Write to Amy Dockser Marcus at amy.marcus@wsj.com

    The Immortal Life of Henrietta Lacks by Rebecca Skloot, reviewed by Jad Aburmrad. Jad Aburmrad is host and creator of the public radio hit Radiolab.

    by Jad Aburmrad

    Honestly, I can't imagine a better tale.

    A detective story that's at once mythically large and painfully intimate.

    Just the simple facts are hard to believe: that in 1951, a poor black woman named Henrietta Lacks dies of cervical cancer, but pieces of the tumor that killed her--taken without her knowledge or consent--live on, first in one lab, then in hundreds, then thousands, then in giant factories churning out polio vaccines, then aboard rocket ships launched into space. The cells from this one tumor would spawn a multi-billion dollar industry and become a foundation of modern science--leading to breakthroughs in gene mapping, cloning and fertility and helping to discover how viruses work and how cancer develops (among a million other things). All of which is to say: the science end of this story is enough to blow one's mind right out of one's face.

    But what's truly remarkable about Rebecca Skloot's book is that we also get the rest of the story, the part that could have easily remained hidden had she not spent ten years unearthing it: Who was Henrietta Lacks? How did she live? How she did die? Did her family know that she'd become, in some sense, immortal, and how did that affect them? These are crucial questions, because science should never forget the people who gave it life. And so, what unfolds is not only a reporting tour de force but also a very entertaining account of Henrietta, her ancestors, her cells and the scientists who grew them.

    The book ultimately channels its journey of discovery though Henrietta's youngest daughter, Deborah, who never knew her mother, and who dreamt of one day being a scientist.

    As Deborah Lacks and Skloot search for answers, we're bounced effortlessly from the tiny tobacco-farming Virginia hamlet of Henrietta's childhood to modern-day Baltimore, where Henrietta's family remains. Along the way, a series of unforgettable juxtapositions: cell culturing bumps into faith healings, cutting edge medicine collides with the dark truth that Henrietta's family can't afford the health insurance to care for diseases their mother's cells have helped to cure.

    Rebecca Skloot tells the story with great sensitivity, urgency and, in the end, damn fine writing. I highly recommend this book. --Jad Abumrad

    — Amy Dockser Marchus
    Wall Street Journal


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