Is the Havasupai Indian Case a Fairy Tale?

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The Havasupai Indian case is a standard in bioethics circles on how not to handle DNA testing. But it's built on a house of cards.

The Havasupai Indian case, a standard in bioethics circles on how not to handle DNA testing, is built on a house of cards.

Twenty-three years ago, Arizona State University geneticist Teri Markow collected samples of blood from the Havasupai Indians, who live in a remote corner of the Grand Canyon. She was looking for genetic markers of diabetes, but instead, used the DNA in the blood to study schizophrenia — or so the story goes.

In 2003, the Havasupai sued ASU and Dr. Markow.

But it never happened. Dr. Markow never probed the DNA for anything other than standard, generic markers. So how did she wind up the tarnished target of a classic case study in bioethics?

The story — reported in the popular press, the feature sections of science journals, and in the bioethics and legal literature — understandably inflamed Native Americans. Markow was vilified. But consulting primary sources reveals striking holes in the widely-accepted narrative.

When I re-read the reports on the Havasupai for last week’s DNA Science blog post, I suspected something was fishy, for a few reasons.

1. Journalists rarely quoted Markow.
2. She’s had a very successful career since the lawsuit, with impressive academic titles and publications in top journals. She’s a professor at UC San Diego, not exactly where you go to escape genetics.
3. A federal court judge threw out most of the accusations and the lawsuit was settled for $700,000 – a hundredth of what the Havasupai requested.
4. Teri Markow emailed me back instantly.
5. I could not find any published report by Markow about the Havasupai DNA and schizophrenia markers. There never was any such paper.

PubMed and Google Scholar list no references linking Markow to the Havasupai and schizophrenia, but I dug deeper. The mystery seemed solved when I read the papers she did publish about the Havasupai blood.

Gene expression networks in schizophrenia (Mary-Claire  King)

Gene expression in schizophrenia (Mary-Claire King)

WHERE’S THE SCHIZOPHRENIA PAPER?
In 1991, a year after the Havasupai samples were collected, Markow, with the cultural anthropologist who’d asked her to do the study, published a short letter in The Lancet about their “basic research on genetic susceptibility,” and how educating the Havasupai and screening them for diabetes had helped them. No mention of schizophrenia.

The follow-up full article appeared in The American Journal of Human Genetics in 1993. The 10-page paper showed that the Havasupai are not very variable at the HLA A and B gene clusters. (Before the genome era, HLA typing had been a way to estimate genetic variation or, in this case, its absence. Certain sets of HLA gene variants are associated with higher risks of developing certain illnesses.)

I read the AJHG paper very carefully, more than once, looking for the word “schizophrenia.” It wasn’t there. Finally, I stumbled upon the word in the acknowledgements, which cites a grant to Markow from the National Association for Research on Schizophrenia and Depression.

Could that really be the source of the stinging accusations? Had none of the accusers actually read and understood the key AJHG paper?

It’s hardly unusual for disease-associated organizations to help fund basic research, which is what the HLA work was. Basic research is where treatments begin. Such funding happens even more today, with government grants for genetics and genomics shifting from smaller labs to mega-center data-crunchers. Family-run not-for-profits often take over funding, including searches for genetic markers.

Testing Havasupai DNA for schizophrenia was widely reported as fact.

Testing Havasupai DNA for schizophrenia was widely reported as fact.

CURIOUSER AND CURIOUSER

With the sequencing of the human genome came higher resolution maps of genetic variability, overshadowing HLA associations. After Markow had moved to the University of Arizona in 1999, money became available to fund a graduate student back at ASU who wanted to look at microsatellite sequences. These short DNA repeats might reveal diabetes susceptibility genes beneath the radar of HLA typing. Markow wasn’t his mentor, but was on his committee because he’d use the samples she’d collected. Finding markers would counter the hypothesis that diet alone caused diabetes, the pet explanation of the anthropologist who’d started the study.

The student indeed found informative microsatellite markers, and for reasons still unknown to Markow, the anthropologist became alarmed, and alerted the Havasupai. Perhaps it was because the findings countered his hypothesis — I have no idea. He didn’t answer my email.

The anthropologist then brought a Havasupai, who’d donated her DNA, to the student’s thesis defense, in March 2003. All hell broke loose when she stood up and asked if the student had permission to do his work.

Unfortunately for all, the genetic details didn’t seem to matter once the Havasupai woman challenged the student defending his thesis. He had to retract publication of the findings, which might have led to a long-awaited diabetes susceptibility test that could have saved lives. Many in the media painted the withdrawal as an admission of guilt.

But it was too good a story to worry much about accuracy, and the narrative practically wrote itself, so beautifully did the perceived situation fit the history of what the Native Americans have suffered.

A Phoenix NewTimes article trumpeted the terrible tale. Under the headline “Indian Givers” the subhead bellowed, “The Havasupai trusted the white man to help with a diabetes epidemic. Instead, ASU tricked them into bleeding for academia.” Only it was worse. The evil white woman geneticist told the Indians she wanted to help them fight diabetes, and then used their DNA to link them to what they considered a stigmatizing mental illness. So the story went, and grew. Although Markow had published papers on schizophrenia, none had anything to do with the Havasupai.

444px-Blood_testWhen the university hired an outside attorney to investigate, evidence, in the form of interviews, emerged. One was with a graduate student who, in 1996, had asked Markow if he could look for genetic markers for schizophrenia in the Havasupai DNA. His mother had the disease, and perhaps he had inherited susceptibility. But the HLA data indicated too little genetic variation among the Havasupai to reveal markers, so on scientific grounds, Markow said no.

Even if schizophrenia had been surreptitiously studied in the Havasupai, it couldn’t have been done without their knowledge. “We’d have to train a psychologist or psychiatrist to give 2 hour oral interviews to each person, and it would have to be blinded, have a separate consent, and probably be videotaped,” Markow told me. The student was disappointed and angry. Then he and Markow argued after he’d forgotten to store some blood samples that had to be discarded. She tried, unsuccessfully, to oust him from her lab. Bad blood, so to speak.

The outside investigator interviewed the grad student, years later, at his day job, in a lab. At night he was incarcerated, punishment for a little sideline during grad school – shipping cocaine from the university to his brother in another state. That fact apparently never made it into the report.

The investigator also interviewed a physician who had drawn the Havasupai blood. While smoking dope with the Indians, he had told them that Markow was really studying schizophrenia and had instructed her co-workers to lie that it was only for diabetes, Markow and others told me. That student became a psychiatrist who is “retired or no longer practicing,” according to rate-your-doctor websites. So much for credible witnesses.

310px-Bullshit.svgTHE TRAIL OF CRITICISM
Like the weapons of mass destruction in Iraq, the narrative that the geneticist sought schizophrenia genes in Havasupai DNA became established fact with the repeating. Soon the accounts of the case began quoting and citing each other, as if the original documents that held the truth didn’t even exist. The IRB-approved informed consent document didn’t mention either diabetes or schizophrenia. The AJHG paper on HLA typing had only the damning grant acknowledgment. Yet google spits out “Therese Markow’s schizophrenia study” because it, too, repeats without thought.

Bioethicists latched onto the compelling story and have yet to let go. “Genomic Justice for Native Americans” in Science, Technology, & Human Values, for example, lays out the bait-and-switch schizophrenia-for-diabetes tale, and it was published in March 2013! Other bioethics articles chanted the schizophrenia mantra, citing each other, or quoting academics who also seemed as if they hadn’t read the science parts of the primary documents. It was such a great case, I was fooled too. I taught it in my “Genethics” course at Albany Medical College and included it in my human genetics textbook. Last week I yanked it from the upcoming 11th edition.

The most damaging account may have been the front page article in The New York Times.

The Pulitzer prizewinning journalist, who had befriended Markow, juxtaposed bits of truth to create an untrue implication that, being in The New York Times, was quoted everywhere, without challenge: “The two professors received money from the university to study diabetes in the tribe. Dr. Markow was interested in schizophrenia research as well, and in the summer of 1990, with a grant from the National Alliance for Research on Schizophrenia and Depression, she and her graduate students began collecting blood samples in Supai.”

The Times editors shaved Markow’s response into meaninglessness. What I find most maddening is that a “Perspective” piece in the prestigious  New England Journal of Medicine cites the New York Times article as reference #1, after the very first sentence, continuing the fable. Were the fact-checkers on vacation?

With all the paper and pixels devoted to the emotional tale of the Havasupai versus the geneticist, I am reminded of fictional accounts of societies that punish criminals before they commit their crimes. And the idea to look for schizophrenia wasn’t even hers, it was the anthropologist’s.

The outrage at what was purportedly done to the Havasupai metastasized, even after the 2010 settlement that gave the Indians 1% of their request. My outrage is instead directed at what was done to Teri Markow. She was in or near tears on the phone with me, and I felt terrible dredging up a past that she’s tried so hard to bury. “I met people at cocktail parties and they said, ‘are you the lady who stole the blood, and sold it to the pharmaceutical industry to make money?’”

(Dept. of Energy)

(Dept. of Energy)

REPERCUSSIONS
Why do I care about an old study that never had much of an impact outside bioethics circles because it didn’t leave a legal precedent? I care not only because the story is still circulating, but because I found a kindred spirit in Teri Markow.

I know what it feels like to be falsely accused.

I was sued over a photo of a young woman with a genetic disease that appeared in one of my textbooks. The photographer was at fault, yet interrogating attorneys reduced me to tears, for hours,  turning the good things I’d done – like winning a large grant to bring science experiments to underserved elementary schools – into conflicts of interest. They turned my email of apology into an admission of guilt, spinning a narrative that was pure fiction. And no one ever apologized for the year of stress.

The case of the geneticist and the Havasupai is so much worse. Why did so many reports fail to mention the good that Teri Markow brought to the community, like winning a grant to prepare Havasupai college students  for grad school? Why did articles twist events to seem as if she had intended all along to study schizophrenia?  And why oh why did no one realize that telling a good story, whether it was true or not, could hurt scientific research meant to help?

Amplifying incidents such as these, based on misunderstanding genetics, will only fuel the fear that Native Americans and other indigenous peoples have towards outside researchers in general, and geneticists in particular — at a time when we finally have the genomic tools to help.

I will let Teri Markow have the final word, and thank her for the honor of sharing her story. “The most painful part was that the tribe is not going to let people on the territory to help them. The story spread all over Native American communities nationally. It took on a life of its own, and set back the health of tribes by decades by making them suspicious.”

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49 Responses to Is the Havasupai Indian Case a Fairy Tale?

  1. Brooke says:

    I worked in Dr. Markow’s lab at the University of Arizona when I was an undergraduate. Teri is a wonderful scientist and a great mentor. I remember hearing snippets of this, but never the full story. I can’t believe what a giant mess this whole thing was. Thank you for digging into this and setting the record straight!

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    • Thank you, Brooke. I’m bracing for an avalanche of criticism, but I checked the facts very carefully and left out names intentionally. It is difficult to tell a story based on omissions, but I think a great injustice has been done here. And I’m mortified that I fell for it too.

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      • Brooke says:

        As you point out, once something has been repeated enough times, the facts no longer matter. Hopefully this will remind scientists that we deal in data, not gossip.

        (by the way, sorry about the double post! That was an accident)

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  2. Brooke says:

    I worked in Dr. Markow’s lab at the University of Arizona when I was an undergraduate. Teri is a wonderful scientist and a great mentor. I remember hearing snippets of this, but never the full story. I can’t believe what a giant mess this whole thing was. Thank you for digging into it and setting the record straight!

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  3. Laura Reed says:

    Dr. Markow was my PhD advisor in the early 2000′s. She has trained a number of skilled geneticists who, like myself, have gone on to lead their own research groups. She is one of the most culturally sensatively and progressive people I have had the chance to know. She is an excellent scientist and a highly ethical person. Thank you so much for helping to set the record straight!

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  4. R says:

    Thank you for researching and publishing this. It’s important that incidents like this are discussed and clarified. I was part of a discussion group during my postdoc that brought out this case as a textbook example of why clear informed consent is important. Of course it IS important, but we certainly don’t need to defame a scientist to make the point.

    Also, things like this have repurcussions further up the chain. The federal regulators keep an ear to the ground about these things, and they want to avoid the appearance of impropriety at their level, as well. Something widely publicized like this that turns out to be false could snowball into more red tape or, at the very least, wasted investigational time (and thus, wasted taxpayer money) looking into a problem that doesn’t really exist.

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  5. Randi says:

    Teri was on my committee at ASU back in the late 90′s – early 2000′s. She was an amazing mentor, and she made sure I knew my stuff. I will never forget how she called me out on the mat during my exams and made me a better scientist because of it. Thanks for setting the record straight on her behalf.

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  6. Janis says:

    It’s alarming, depressing, and infuriating how often the way that society deals with ongoing historical wrongs (which Native Americans have certainly endured) committed by an overwhelmingly wealthy, white, male power structure is to find some WOMAN someplace who can be drafted as the scapegoat, manufacture a way to pin all those wrongs on her, and thus allow the predominantly male culture which is truly guilty of the crimes to escape further examination.

    When the Enron scandal hit, and legions of filthy rich amoral white males had been revealed as destroyers of thousands of lives … we all bared our fangs nicely over Martha Stewart’s minor financial peccadillos. While legions of right-wing male politicians plunged this nation into a bloody war that sent the entire world off the edge of total financial collapse … we made fun of Sarah Palin’s hairstyle. Jesus fucking Christ.

    And this woman Markow didn’t even have any comparatively minor sins to inflate! But it didn’t matter — because hey, if you want to grab some chick to turn into a scapegoat, you can always just lie, and the world will gobble it up like pigs at a trough.

    This happens with the regularity of the tides. I wonder when women will get wise, if ever?

    Yeah, I wonder when the sun will rise in the west, too.

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    • Ricki Lewis says:

      Janis, thanks for adding what I intentionally left out. In this vast story of omissions, I left out that it was Dr. Markow dealing with XYs. That’s a side story — but maybe not. You said it well! I admit to not knowing all aspects of this story, blogging is just a sideline. Thanks for reading!

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      • Janis says:

        I figured you had sort of intentionally left it out, but since I’m not in your position, I could sort of throw myself on that grenade. :-)

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        • Thanks. I’m interested to see how my students react. I hope they don’t read the blog first!

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          • Janis says:

            They may not react in ways you expect. The most depressing thing about this social tendency in humans and other primates is the way that women themselves crowd ahead at the trough of bullshit disgorged into the world about other women. Whether it’s jealousy or just tall-poppy syndrome or some other more basic “protect your own offspring” reaction buried in our primate DNA I don’t know, but chances are the male students will stare mutely at the ceiling and the female students will be quick to condemn her.

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  7. Mary says:

    Oh, wow. I was familiar with the tale. I was not familiar with the actual story. Thanks for taking a look at that. It is very chilling.

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  8. Daniel Garrigan says:

    I am the graduate student who did the microsat work and had *the worst* dissertation defense. A decade later, it still makes me immensely sad the way this all happened, not just for me personally, but because of the gap it widened between the American and scientific communities. There are a number of reasons why things happened the way they did, some of which appear in this article. However, I’m glad that Teri’s voice is finally being heard on the matter, she is a top-notch scientist and a wonderful person. It is perhaps no surprise that both Teri and I work on Drosophila now, but there once was a time when I was highly motivated to understand the genetics of American populations. Yet now that seems like a very long time ago.
    PS- don’t confuse me with the guy who was shipping coke out of the lab.

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  9. Ricki Lewis says:

    Hi, Dan, thanks for commenting. I left out names on purpose, I didn’t want anyone objecting and I’m rushed to fit blogs in between revising textbook chapters. I’m an ex-fly person, Thom Kaufman’s very first grad student. Maybe I’ll see you at the fly meetings next year!

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  10. Jon Marks says:

    The Hart Report, which was the product of the formal investigation into the Havasupai case, says on p. 3: “Doctoral candidate Chris Armstrong’s research was focused on genetic variations in the dopamine receptor genes and a possible association of those gene variants with schizophrenia. Dr. Armstrong was unable to complete his original project because he and ASU were unable to obtain information reflecting who among the Havasupai exhibited schizophrenia. There have been allegations that the Tribe was purposely deceived about the genetic study of schizophrenia underway at ASU. Chris Armstrong stated that he was told by Dr. Markow to deceive and withhold information from the Havasupai about the true focus of his studies, schizophrenia, because it might jeopardize the use of the Havasupai samples for other genetic research. This allegation gas been strenuously denied [by] Dr. Therese Markow. “

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    • Jon Marks says:

      … *has* been strenuously denied…

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      • Thank you Jon for adding the comments from the Hart report. Do you know of a citation in a peer-reviewed scientific journal — not law, not bioethics — that has Dr. Markow’s name on it and the word “schizophrenia” anywhere in the body of the article? If not, then I think we have a he said/she said situation, other than my deduction that the AJHG paper was the source of the confusion. I’ve got more background than went into the blog, and based on it, I wouldn’t trust the Hart report. That’s one reason I stuck to the science media and journals.

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        • Teri Markow says:

          Yes, and in this case, the “HE” is a convicted felon. It ‘s unfortunate that so much rested on the words of someone untrustworthy. Perhaps this was ignored in order to make a sensational story and claims?

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  11. Jon Marks says:

    Apologies for belaboring the point, but I’m now very confused. A 2008 story in Phoenix Magazine by Jana Bommersbach (not a peer- reviewed, scientific publication, obviously) said:

    “[I]n September 1989, Markow applied for a grant from the National Alliance for Research on Schizophrenia and Depression to study schizophrenia in the Havasupai people. They awarded her $92,880, according to the Hart Report.”

    “Markow maintains to this day that she had permission to test for things other than diabetes and that her “proof” is the consent forms signed by some of the Havasupai who donated blood. She insists the project had two focuses: diabetes and schizophrenia.”

    Are you now saying that these statements are false, and that schizophrenia was never studied at all?

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    • I hope Dr. Markow will respond in detail. My point was that just because you are funded from a certain source with a disease name in its title does not mean that you are or are intending to do research on that particular disease. Basic research is the foundation of any eventual treatments. Dr. Markow and her students could not begin to study schizophrenia, even if they’d intended to, without an idea of how genetically variable the population was, so they’d know if a marker for the disease could even show up, that is, generate enough of a signal to be detectable against the genetic sameness that comes from all those years of isolation and a restricted gene pool. So yes, the article in the genetics journal — far more reliable than a newspaper or magazine if the articles aren’t written by geneticists — does not mention schizophrenia AT ALL except for the citation of the funding sources AFTER the body of the paper. And it seemed to me that all those folks who said and wrote horrible things about Dr. Markow had not read that key paper in the scientific literature. That’s why the weapons of mass destruction came to mind. Everybody repeating something that isn’t true as if it is, until people stop looking for primary sources, and just believe it. Science has nothing to do with belief, it is about data and evidence. OK, sorry, off my soapbox now!

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    • Teri Markow says:

      First of all, the consent forms speak for themselves with respect to the breadth of studies. However, without sufficient and appropriate genetic variants, association studies of any disease are not possible. The first step therefore, with our funding, was to seek genetic variability that could be useful in studies of disease. While we did not find sufficient variability with the techniques available at that time to perform association studies, we at least were able to provide people with feedback about their health status with respect to diabetes, because the test for this is simple. Had there been sufficient variability for stringent association studies for any disorder, we could have proceeded. However, even if there had been the requisite variability, stringent diagnostic testing for schizophrenia would require a major effort, including lengthy interviews, that never could have gone undetected by the participants. This fact, plus the fact that I have never published a paper on schizophrenia in the Havasupai, answer your question quite definitively.

      It’s unfortunate that articles like that of Bommbersbach are not rigorously reviewed and therefore can mislead readers. Had there been substance to the allegations, the outcome would have been much more than $700,000 for a$ 70,000,000 suit. This also answers your question quite definitively. Again, I reiterate that the real losers in all of this are not only the Havasupai, but also other tribes who’s mistrust of white researchers and physicians, has been amplified by what I consider to be irresponsible media coverage of this case. Under the guise of exposing a wrongdoing, incredible harm has been done to derail the understanding of health issues and to help resolve them in Native American populations.

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  12. Jonathan Kahn says:

    Yes, since Dr. Markow has joined the conversation it would be useful to hear a clear statement that she never intended to use the samples for anything other than diabetes research.

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  13. Jon Marks says:

    As I understand it, the issue at the top of the page is whether schizophrenia research was carried out, not how preliminary or unpublishable the results may have been. Apparently some such research was indeed performed under Dr. Markow’s auspices; I had hoped to see a clear denial of it, on the order of “No, we did not study schizophrenia at all.”

    So it seems to me that the real losers are not the Native Americans, but the scientists who have worked with them in trusting and collaborative relationships, and now have to work to rebuild those relationships.

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  14. Ricki Lewis says:

    I cannot restate the science any more clearly than Dr. Markow already has done. You can do HLA typing without any disease in mind. The scientists weren’t losers, they went on to contribute further using model organisms. The Native Americans lost out in the sense that work leading towards finding markers for diabetes, if that would have been possible, was squelched due to the accusations.

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  15. Daniel Garrigan says:

    To do an association study, you need a phenotype that is variable in the population and densely spaced genetic markers that are also variable. I think Teri’s point is that she had neither of these things at the time and work for *any* type of association never proceeded. Thus, by definition, there can’t be any schizophrenia research. And both sides lost in this case: those who wanted to help and those that could’ve benefitted from that help.

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  16. Jon Marks says:

    What I am hearing is that Dr. Markow sought and received funding from an agency that focuses on schizophrenia, without any intention of actually studying schizophrenia, and ultimately performing no science related to that illness. Additionally, anyone who thinks that the solicitation and receipt of funding from a biomedical agency focused on a particular disease more or less implies an intellectual engagement with that disease, either doesn’t understand science, or is anti-science; and the Hart investigation/report was a smear job. I’m willing to accept it, but you have to admit that it sounds about as credible as A-rod.

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    • Janis says:

      Gee, what I’M hearing is that she accepted money from people who are interested in schizophrenia, and who were hoping that some of her NON-schizophrenia-related research might happen to be applicable to them as well. Lots of scientific research funding bodies fund the occasional thing that might (or might not) tangentially be vaguely related to the topic they are interested in on a good day on the off-chance that something might help them as well.

      Do you just not get how scientific research works? That — for example — folks who manufacture cellphones might take an interest in research done on the planet Mars to see if there isn’t something about communication between planetary orbiters that might apply to making a better cellphone? This is how science works. Research doesn’t happen in a nice, tidy A-therefore-B way. Legions of shipping companies in the 1500s funded astronomical observatories because being able to predict eclipses of jovian moons led to being able to calculate the longitude of a ship’s location on the high seas. This despite the fact that the shipping companies couldn’t give a gnat’s ass about pure research on astronomy, Jupiter, the planets, or any of their moons for their own sakes. Nor did the astronomers who studied the moons of Jupiter give a gnat’s ass for shipping companies. They did research on this thing over here that happened to have an application to that thing over there.

      This whole idea is not that complicated, which leads me to believe that you are really just deliberately trying to concoct a controversy where none exists.

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    • Janis says:

      BTW, funny of you to use A-rod as a point of comparison, because he’s apparently as much of a drughead as your supposed star witness for the prosecution, isn’t he?

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  17. Daniel Garrigan says:

    I can’t speak to the content of the grant proposal in question. But the salient point remains that collecting additional data on a phenotype other than diabetes would have required the active participation of the Havasupai, it could not have been collected otherwise. Based on my own experience with the project, a subset of the markers I received funding to design and assay were linked only to candidate loci for diabetes and HLA (the rest were uniformly spaced across the genome), it was never suggested to me to include any other markers.

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  18. Sue Trinidad says:

    If the main argument here is that no pubs = no research, there’s a massive flaw: research involving humans generally has a hard time getting published unless the author(s) can claim IRB review. As I understand it, the lack of such oversight is one of the key problems with this case.

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    • The original Informed Consent document had approval. The question may be whether broad consent forms hold up as the technology changes and questions change.

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    • Teri Markow says:

      No, the issue is that it was not possible to do the intended work. The issue is NOT that work was done but not published due to lack of IRB approval.

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  19. informative article.Thanks for sharing! :D

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  20. Kristof Van Assche says:

    Whoever reads the official report of attorneys Hart and Sobraske, who, if we are not mistaken, were appointed by the Arizona Board of Regents ITSELF, to independently investigate the case, has to concede that schizophrenia research was not only planned but was indeed performed.
    These are the relevant facts mentioned in their report:

    - Whilst approached to study diabetes, Markow indicated interest in the prospect of studying the high incidence of schizophrenia that the Havasupai allegedly also suffered from.
    - During the preparatory meetings, Markow expressed a desire to include schizophrenia, but was told that the Havasupai would be unlikely to be interested, at least at this point.
    - Markow almost immediately submitted an application to the National Alliance for Research on Schizophrenia and Depression for a grant to study schizophrenia among the Havasupai.
    - On the basis of an interview with Markow, the report states in this regard: “According to Dr. Markow, the medical genetics project that eventually was conceived had two principle foci, first diabetes which turned out to be more of a concern and more prevalent in the Havasupai and second schizophrenia which proved difficult to diagnose.”
    - In May 1990, when the Havasupai Tribal Chair confirmed that the diabetes project could proceed, Markow had already obtained funding for the schizophrenia research, without informing the Havasupai.
    - The first series of blood draws, in June 1990, was paid for with money from the schizophrenia grant.
    - The psychiatrist Markow had appointed to coordinate the draws was instructed to scan the medical files in the tribal clinic for records of psychiatric distress. On the basis of an interview with this person, the report states in this regard: “He did not deduct any unusual levels of psychiatric problems, in general, or schizophrenia in particular, among the Havasupai. He recalls reporting this back to Markow, who was more than a little disappointed by the fact that he had not detected a pattern of schizophrenia in the Havasupai.”
    - The ASU Institutional Review Board approved Markow’s schizophrenia study in January 1991.
    - Beginning in September 1991, Markow’s doctoral assistant analyzed the Havasupai blood samples, hoping to find a genetic variation that could be associated with the development of schizophrenia. However, he was unable to find such variation. In the end, sixty-nine tribal blood samples were used in the context of his PhD research on the ‘general’ etiology of schizophrenia.

    The statement by the author of the blog “I’ve got more background than went into the blog, and based on it, I wouldn’t trust the Hart report” is noted with interest, but can hardly convince anyone. Nothing the author mentions raises doubts regarding the Hart report, which was, again, written by independent experts appointed by the Arizona Board of Regents and not by the tribe.

    It seems that the only reason why nothing was published on the prevalence of schizophrenia in the Havasupai was that no high incidence of schizophrenia nor a relevant genetic variation had been found. Indeed, the fact that the results of the schizophrenia research have never been published in a scientific journal does not mean either that the research was not carried out or that the fact of the research being planned or carried out has not been made public. Such a publication, confirming the tribe’s objections, occurred with the Hart report, which is a publicly available document. Since Markow herself is quoted in the Hart report with regard to the schizophrenia research, then unless she denies the accuracy of the way her testimony was reported, the publication (i.e. the making public of the fact of the research) must be deemed to derive from Markow herself.

    Markow’s statement (in the responses to the blog) that one of the people who spoke to the investigators is a “convicted felon” and thus “untrustworthy” is an interesting substitute for substantiating that the facts are wrong — other than in relation to admissions that might confirm their guilt of a criminal offense, there is no prima facie reason to deny the validity of the testimony of someone with a criminal record. Moreover, the statements of the person concerned in no way seem to be contradicted by the statements made by the other persons interviewed by Hart and Sobraske. If anything, they seem to be corroborated, especially by the statement of the psychiatrist who was appointed to coordinate the first blood draws.

    Moreover, Markow’s statement that “the consent forms speak for themselves with respect to the breadth of studies” proves that she has not had even the most basic of introductions to clinical research ethics and, in particular, the basic requirements for a valid consent. Admittedly, the purpose of the research project, as set forth in the written consent form used during the first blood draw series, was defined broadly enough to include behavioral disorders such as schizophrenia. However, contrary to Markow’s opinion, this did not mean that the Havasupai had adequately consented to the study of schizophrenia. After all, informed consent is not simply a signature on a form, but rather a process of information exchange. The scope of consent is defined on the basis of the overall information provided to the potential research participants. Since in both the discussions with the tribal council and the communication with the individual participants only diabetes research was mentioned, the fact that the scope of the project was defined more broadly in the consent form was not decisive. It is an elementary rule that a person’s consent cannot possibly be broader than the information given at the time of requesting consent.

    It is also interesting to note that the author of the blog does not mention either the inbreeding research or the research on the geographical origin of the tribe, which was perhaps the research which was most offensive to the tribe. Although, admittedly, this research was not carried out by Markow herself, the people who did carry it out clearly must have obtained the blood samples from her. Moreover, this kind of research cannot by any stretch of the imagination be considered as falling under the scope of the project described in the written consent document signed by the participants in the first series of blood draws.

    Even more surreal is her statement “Had there been substance to the allegations, the outcome would have been much more than $700,000 for a $ 70,000,000 suit”, which shows she has very little familiarity with the strategies adopted in this kind of lawsuit. If the Arizona Board of Regents was so confident that there was no substance to the allegations, then why did they agree to settle all of a sudden? Please read what the Court of Appeals of the State of Arizona wrote in November 2008 [Havasupai Tribe v Arizona Board of Regents 204 P 3d 1063, 1067 (Ariz Ct App 2008)]. They clearly did not think the case was a fairy tale! (Note: this is a State Court and not a Federal Court)

    For a more in-depth analysis, see a recently published article we co-authored on the case: http://www.ingentaconnect.com/content/hart/lit/2013/00000005/00000001/art00003

    Dr. Kristof Van Assche & Prof. Sigrid Sterckx, ethicists

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    • Ricki Lewis says:

      I posted the two blog entries on the Havasupai because Henrietta Lacks was once again in the news, and it was time to revamp my online course in Genethics. While rereading what had been published about the case, I noticed omission of the accused researcher’s viewpoint, and since this blog is DNA Science, that was relevant.

      Also stunningly absent was any information on the exact nature of the schizophrenia work she was accused of having done. I was interested in this aspect because schizophrenia is a very complex disease, one that is not a simple “the gene for” situation. I thought non-geneticists might misinterpret the nature of the research.

      Also, a blog is only about 2000 words. My perceived omissions of the legalities and the other possible uses of the blood samples are due to time and space constraints.

      I’ll try to answer Dr. Van Assche’s points where I can, but my expertise is in genetics, not the law.

      Perhaps most important is that no one I have encountered believes that the original consent form that I quoted in the first blog post was adequate. We all agree here. It was much too broad. Consent forms today are much more detailed – I made that point in the first post, with an example.

      I only know what was not published in the peer-reviewed scientific literature, and no one has yet to correct this. If Dr. Markow indeed had other results, I’d have no way of knowing about this. I emailed her anthropologist colleague, who according to sources originated the study of and idea to look at schizophrenia. He hasn’t answered.

      A scientist can apply for and use a grant from a disease-based organization without ever coming up with data directly relevant to that disease. The schizophrenia organization paid for the blood draws? Yes. So what?

      I’m not trying to convince anyone of anything. I’m trying to introduce a controversial topic about which only one side seems to have been presented in the media, and get people talking. I am also trying to show my students that they need to dig deeper than reports parroting each other. I would have them read the paper that Dr. Van Assche referenced in his comment, but you have to pay a lot to do so. I requested a copy but so far haven’t gotten one.

      Dr. Markow has indeed stated over and over that the facts in the Hart report are wrong. I have not been in touch with the two men who accused her, although I tried to find the psychiatrist. He’s no longer in practice. All of this is in this blog post.

      The DNA was used to look for mitochondrial markers of diabetes susceptibility, because the tiny genome includes genes involved in cellular energetics. Mitochondrial sequences are used to trace matrilineal lineages. Therefore, one might conclude that probing the miniscule mitochondrial genome might have had the intent to provide evidence for an Asian origin of Native Americans – a well known fact that no one disputes would likely upset the Havasupai. I included this in my first draft, but no one reads a very long blog post. I tossed it. I had a few thousand words to discuss an extremely complicated case. Not 50-plus pages in a journal that is not open access. Is consent legally required for ancestry research? HIPAA wouldn’t apply. I don’t know.

      Speaking not as a lawyer but as a scientist and journalist, it seems logical that if a group asked for a certain amount and received 1/100th of it in a settlement, all of their claims might not have been deemed valid. Common sense, not legal expertise. I could be wrong. I did read the recommended court documents before I blogged.

      Considering that the Supreme Court made a genetics gaff just a few weeks ago, the legalities are not what I chose to focus on. So I appreciate Dr. Van Assche’s contribution to the discussion.

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  21. That is a great example how rampant journalistic run for a sensation can ruin not only careers and human lives, but also instil a long term damage on science. This case damaged reputation for entire genetic community and hindered research of genetically isolated populations. Thanks to the press the REBs became a overcautious and the informed consent forms illegible for study participants. One of clinical trials for Type 1 Deiabetes now is being required to get nice separate informed consent forms for each study participant. Do the REBs help research or stalling it??
    Another “great example” of cheap publicity is the autism and vaccination tale that perpetuates for decades despited to be a proven case of fraud..

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    • Yes, the autism/vaccine disaster is the perfect example! But with the Havasupai we have the added complexity of a highly victimized population.

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  22. Julian Cockbain says:

    Dear Ms Lewis

    An interesting blog, but not one which shows you in a squeaky-clean light, or even as one qualified or capable of commenting on the ethics of human genetics research. I trust that my comment will not also be ‘delayed’ or suppressed under the fiction of being ‘moderated’.

    Your blog works by asking the readers:
    (i) to accept unsubstantiated allegations by you (‘I’ve got more background than went into the blog, and based on it, I wouldn’t trust the Hart report’ 16.08.13 at 20.52 in response to Jon Marks (presumably Jonathan M Marks, Professor of Anthropology at Uof North Carolina);
    (ii) to discount testimony from ‘discredited’ persons (even though they are not discredited in relation to their testimony – (‘She tried, unsuccessfully, to oust him [the grad student] from her lab. Bad blood, so to speak. … At night he [the grad student] was incarcerated … for … shipping cocaine… While smoking dope with the Indians, he [presumably the physician who had drawn the Havasupai blood, a second witness] had told [the Havasupai] … that Markow was really studying schizophrenia … That student [physician?] became a psychiatrist who is “retired or no longer practicing” … So much for reliable witnesses.’ 15.08.13). It is to be noted that, in her contributions to your blog, Ms Markow has NOT denied starting or continuing research on subject matter other than the approved subject matter, diabetes, despite your repeated statements to the contrary. Thus Ms Markow says ‘Yes, and in this case, the “HE” is a convicted felon. It’s unfortunate that so much rested on the words of someone so untrustworthy’ 17.08.13 at 02.46. ‘Had there been sufficient variability … we could have proceeded’ 17.08.13 at 04.03. ‘No, the issue is that it was not possible to do [i.e. complete] the intended work. The issue is NOT that work was done but not published…’ 19.08.13 at 20.33. (Text in italics emphasised). Jon Marks, supra, put it succinctly: ‘I had hoped to see a clear denial of it, on the order of “No, we did not study schizophrenia at all.”’ 17.08.13 at 17.00. There has been no denial on the blog other than in your words, reinterpreting the words oh so carefully chosen by Ms Markow, words which, properly parsed, do not contain that denial. Perhaps we could see an entry on this blog from Ms Markow stating in clear words “we did not begin, continue or finish any research on Havasupai blood concerning schizophrenia”? However, do not hold your breath dear reader, as such a statement would be tantamount to an admission that the grant providers were frauded with their funding being spent for other purposes (is Ms Markow about to offer to refund those funds if they were indeed spent for other purposes?). The issue could be settled satisfactorily, in my mind, by Ms Markow placing a statement on this blog to the effect that ‘I profoundly regret that research which was not consented to by the Havasupai tribe was started, continued and/or completed using blood samples from the tribe that were in my control. I accept that on ethical grounds I was wrong to perform such research and/or to permit such research to be performed. I undertake never in future to carry out or permit or facilitate the carrying out of research on human samples for purposes other than those expressly and informedly consented to by the sources of such samples.’ Your call, Ms M.
    (iii) to sympathise with your ‘innocent’ use of a photo in your teaching materials. That innocence is actually, like Ms Markow’s actions, the combinastion of ignorance and arrogance. If you work with human materials, you are not entitled to be ignorant of the duties you owe to the providers, e.g. true anonymity. The ‘scientific’ position that ‘if it’s a fact’ then I have no responsibility, is one of arrogance. Perhaps you should study ethics a tad more deeply before you teach the ethics of genetic research to students?

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    • Teri Markow says:

      FYI: I had IRB approval and a consent form that specified more than one disease. The population had many health problems that could have been researched given these permissions, which was the intent of making it broad. But the only disease I studied was diabetes. The reason there are no publications on schizophrenia is because I did not conduct studies of this illness in the population. If this doesn’t make it clear, some of you commentators obviously are not interested in the truth but have a different agenda.

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      • Julian Cockbain says:

        Dear Ms Markow
        You accepted the money to do schizophrenia research, or did you not (a YES or No will suffice)? Did you do that research or not (a YES or NO will suffice)? If you did accept the money and you did NOT do the research, did you return the money (a YES or NO will suffice)?
        Julian Cockbain

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        • Julian Cockbain says:

          On a separate point, did you, or did you not allow access to Havasupai blood samples to other researchers for research without limiting that to research on diabetes (again a YES or NO will suffice)?
          Julian

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          • Julian Cockbain says:

            And finally, Ms Markow, the quality of your scientific work is NOT being questioned. However, are you prepared to make the statement mentioned above (that ‘I profoundly regret that research which was not consented to by the Havasupai tribe was started, continued and/or completed using blood samples from the tribe that were in my control. I accept that on ethical grounds I was wrong to perform such research and/or to permit such research to be performed. I undertake never in future to carry out or permit or facilitate the carrying out of research on human samples for purposes other than those expressly and informedly consented to by the sources of such samples.’ ) ? Again a YES or NO answer will suffice.
            Julian

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  23. I am quite done with being insulted by male lawyers for trying to start a conversation about science. I had a very valid personal reason for delaying approval of Dr. Van Assche’s comment, it was neither intentional nor “fictional.”

    Anyone else notice that male researchers are called Professor and we women with PhDs are Ms?

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    • Julian Cockbain says:

      Hi Professor, Dr, Ms Lewis
      Believe me sex/gender doesn’t come into it when people stray into fields they don’t understand. No-one calls me Dr either. What matters is what people say and substantiate. One of the demons in the Havasupai case is male, the other female, a 50/50 split. One, perhaps the foremost one, of the angels is clearly female.
      j

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  24. Jonathan Kahn says:

    I think the contention is arising primarily around the fact that your initial post was not just about science. It was about science and ethics – and a related legal action. If you are speaking to legal and ethical issues then lawyers and ethicists are going to want to have a say. The fact that they generally do not publish in peer reviewed scientific journals does not make their knowledge or opinions any less valid. The adequacy of a consent process is not the type of thing that can be evaluated through a double blind trial or a microarray.

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  25. Victoria Costello says:

    As PLOS BLOGS Network Community Manager, I want to thank everyone who has offered comments on this post. At this point, we’re satisfied that most if not all points of view on the central issues in this debate have been represented. We do not think this blog is an appropriate forum to do any further re-litigation of the the legal case being discussed, so we will close commenting on this post. Please refrain from leaving any further comments specifically dealing with this topic on any subsequent DNA Science posts. PLOS is committed to providing a forum for civil and informed debate on matters of importance to the scientific community and the public at large. We hope you will come back to read and comment again on any of our staff written and independent science and health blogs. Thank you!

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