Yanomami blood sample return: Some update information

On March 25 we posted a discussion of research ethics that was brought about by the return of some blood samples we had for many years housed in our lab at Penn State.  We explained why this had been contentious, and why many aspects of the demand for return were based on reasons wholly unrelated to anything done by the investigators with these samples.  Rather, the concern had more to do with experiences of the Yanomami tribal members over many years, due to outside interference with their lives.

There was a flurry of publicity from various news sources, showing the return of the samples (links below), and we would like to correct some of what was said.  In many of the stories, the source of the samples was mis-attributed to the University of Pennsylvania, when in fact it was Penn State.  There also seems to be a misapprehension or allegations in the news stories that the samples were collected without permission and implying that we were the ones who collected them.  Whatever one's views about how the Yanomami were treated and their experience of the outside world, or how they currently feel about the samples, these involve quite irresponsible mistakes.  My lab has housed a set of these samples for many years, after the person (JV Neel) whose group collected them had retired, he divided the samples up for safekeeping and curation into three sets, one for the Anthropology department at Penn State, one for an investigator now at Penn, and one for the National Cancer Institute, where they had various potential research interests in them, in case new methods became available that could enable things to be learned about cancer that the original methods, of the '60s and '70s, were incapable of resolving.  Michigan would have destroyed them otherwise.

There is plenty of room for debate about scientific studies by the industrialized nations, of indigenous or dependent populations.  The nature of informed consent was discussed in our earlier post on this problem.  Feelings expressed now by Yanomami representatives may be entirely sincere and even justified from their point of view.  At the time, the filming of the collections and the trade goods and whatever else was involved offered in exchange as part of the Yanomami's participation, including the provision of the blood (and other biomedically related samples and information) made the collection seem totally voluntary.  The degree to which cultural and/or power differences and the like led to misunderstanding about the samples and what was to be done with them is impossible for us to know, and there are differences of views for many reasons.

Not the least of the problems is the passage of decades of time, and of the lives of both investigators and subjects.  Retrospective judgments about informed consent, coercion, recompense, and relevance of the anthropological studies to the Yanomami experience with the outside world, are important issues, but not ones we ourselves can judge.

It should also be pointed out that the issues about the Amazonian indigenes and the outside world are not new.  Indeed, around 1800, when Alexander von Humboldt visited the Yanomami general area (and one of the main sites of the work now in question), there were already long-established mission stations with a lot of western culture already brought into the area.  So external influence, helping, and/or meddling with the lives of the indigenous populations have a deep ancestry.  Hopefully, newer ethics or protections will prevent further problems of this kind.

A few of the stories (in English, Spanish and Portuguese):
http://g1.globo.com/rr/roraima/noticia/2015/04/sangue-yanomami-repatriado-dos-eua-e-enterrado-em-aldeia-indigena.html

http://www.lavoixdunord.fr/france-monde/bresil-des-yanomami-rendent-a-la-terre-leur-sang-ia0b0n2755248

- BBC: http://www.bbc.com/news/world-latin-america-32178286
- American Indian and Friends (BBC): http://americanindiansandfriends.com/news/indigenous-tribe-s-blood-returned-to-brazil-after-decades
- News 24 (AFP): http://m.news24.com/news24/World/News/Indian-tribe-buries-blood-samples-taken-by-US-researchers-20150405
- 9 News, Austrália (AFP): http://www.9news.com.au/world/2015/04/06/02/11/brazilian-native-tribe-holds-ceremony-for-blood-samples-taken-by-us-researchers

Informed consent -- who's it supposed to protect, anyway?

A piece by Erika Check Hayden in this week's Nature on current confusion with respect to informed consent  begins with a discussion of the patent 23andMe filed in late May to protect their findings from their research on Parkinson's disease.  As Hayden points out, many consumers of 23andMe, the direct-to-consumer genotyping company, were surprised to learn that the company was filing to patent a gene -- gene patenting having been one of the earliest and most controversial aspects of the commercialization of genetic research and one that several of the company's founders were known to oppose. We blogged about this when the patent announcement was made. 

Hayden's piece hits close to home because in her second paragraph she quotes MT's own Holly Dunsworth who left a comment on the 23andMe blog post announcing the patent application.  Holly said that she didn't believe she'd agreed to the possibility that one of her genes could be patented when she signed her consent for their genetic services. (She's aghast that genes can be patented, and is against it -- that makes it unanimous here at MT.)  But Hayden points out that "the language is there" in the consent forms.  Well, that may be so if you're a lawyer and it occurs to you that "If 23andMe develops intellectual property and/or commercializes products or services, directly or indirectly, based on the results of this study, you will not receive any compensation" means that if they find something they want to patent in your genome, they will and it's theirs.

The non-legal crowd isn't as likely to have read it that way, and didn't realize they were signing on to the possibility that the company might patent one of their genes, without sharing any of the profit, and without explicitly broaching this sensitive ethical issue with participants.  It's more than a bit disingenuous of 23andMe to claim to be open and free with knowledge on the one hand, engaging customers because of this open access policy and on the other hand committed to constraining that freedom when there's profit to be made -- by them! 

But beyond what this means about 23andMe, this does point out one of the problematic issues having to do with informed consent, and that is that when what can be done with the materials a subject or donor consented to give a researcher or company access to can change as technologies change or as findings accumulate, "informed consent" is in fact not that.  23andMe's consent asks their customers to agree essentially to blanket use of their genetic data.  It's an open-ended consent, as many researchers and institutions prefer these days, seeking permission to do anything with the sample in perpetuity.  Some consent agreements, though, impose specific time or usage limits instead.  Given how quickly technology changes however, these limiting agreements may well be used less and less as genetic research goes forward.  You can be pretty sure that once researchers get their hands on your samples they aren't going to want to give them up.

Another approach is George Church's no-consent-at-all model for the Personal Genome Project.  When people sign on to the project he requests that participants allow all their biomedical data to be freely accessible online, along with their whole genome sequence.  The idea is that because researchers can't predict what they'll find, or what new technologies will come along, science will best progress if participants allow anything at all be done with their data and their biomedical information now and in the future. 

Of course this kind of consent can't be properly 'informed' in any serious sense, relative to being what is fair to call a blank check for the researchers. They know this, of course, and any benefits that do happen to become possible will likely go to them.  Researchers don't get to set all the limits, though.  Any consent for a study using federal funding must allow research participants to be free to remove their samples and data from a study.  And,  Hayden says that several US states, including California where 23andMe is based, are considering laws to constrain what can be done with a person's DNA.

However, genetic data are different from, say, demographic data because even anonymized, no names attached, it's possible to identify individuals if reference genetic data are available, and identifying ethnicity is often trivial.  Not to mention that no genome is an island, so if you are genotyped, that tells you a lot about your parents as well as your siblings.  So, if you consent to genotyping or whole genome sequencing but your parents don't, that can be a problem.  And of course once a sequence is published or summarized in statistical data, it is no longer removable.

Who is informed consent for, though?  Who is it designed to protect?  It stems from Nuremberg Trial protections that were the result of the Nazi experiments in World War II.  They were indeed for protecting human subjects.  Human subjects protections have evolved over the years however, and now while still nominally for protection of, well, human subjects, there's a whole lot of CYA going on, as universities and companies try to avoid the kinds of legal difficulties that researchers such as those working with the Havasupai in Arizona got into not long ago (a case we blogged about here).

Indeed, Hayden quotes Mishra Angrist, genome policy analyst at Duke University, and participant in the Personal Genome Project saying, “Institutions use informed consent to mitigate their own liability and to tell research participants about all the things they cannot have, and all the ways they can't be involved. It borders on farcical.”

The interests of researchers and subjects don't always coincide, of course.  It is only human to expect those with their hands on the data to be tempted, and at least occasionally to yield to the temptation, to seek private gain from the samples, beyond their salaries and job status.  Also, researchers generally and naturally want to be allowed to do whatever they want with their hard-earned samples, while subjects often want constraints -- if they even understand the study.

Many researchers say that the obvious solution is a broad consent document that gives researchers free rein with the data. But many non-scientists think participants should be able to control how their data are used, says lawyer Tim Caulfield of the University of Alberta in Calgary, Canada, who has surveyed patients about this idea. “There's an emerging consensus within the research community about the need to adopt things like broad consent, but that hasn't translated out to the legal community or to the public,” he says.

 And then there's 23andMe, which gives their customers access to all their own data.  Until they don't.

Henrietta Lacks privacy

A piece in the Sunday New York Times by Amy Harmon, "'Informed consent' and the ethics of DNA research", discusses the issues brought up by the recent case of the Havasupai vs. the University of Arizona (which we posted about here). Can anything be done with DNA samples once the original purpose for which blood was collected, and for which researchers had consent, has been accomplished?

Legally, we have no property right to our cells or tissues once they've left our bodies. But, researchers with federal funding are required to inform subjects what they are going to do with the samples, as a condition of getting the samples. Nowadays, that means everything they plan to do with them, for however long the samples are archived. And that includes the use of unforeseen technologies to look for as of yet unpredictable kinds of information.

This issue is not new, and in fact a sixty year old story about this is described in a recent book by Rebecca Skloot called The Immortal Life of Henrietta Lacks. Ms Lacks was a young African American woman who had the misfortune to have a particularly fast-growing form of cervical cancer, diagnosed in the late 1940s. She died in 1951, at the age of 31. She had been treated at Johns Hopkins, in Baltimore, where one George Otto Gey was then attempting to immortalize cell lines, so was collecting whatever tissue samples he could in his effort to perfect the technology for doing this.

Only when Gey's technician tried to grow cells from a sample of Ms Lacks' tumor were they successful. The significance of this was quickly apparent, and cell lines were immediately distributed throughout the medical world to be used in such research as the polio vaccine, and much more. The cells from Ms Lacks' tumor, and/or the DNA, are still in use in labs all over the world.

Neither Gey nor Hopkins ever profited from this work, but the sample was taken without Lacks' knowledge or permission. This was state-of-the-art at the times. Indeed the courts have recently ruled that samples can be used without the patient's permission or knowledge, even for profit (in a case decided by the Supreme Court of California, Moore v. Regents of the University of California.)

In her book, Skloot describes how she became fascinated by Henrietta Lacks in a biology class she took as a teenager, but was frustrated to discover that very little was known about her. Or perhaps she was fascinated because there was so little known. In any case, Skloot eventually decided to write a book about Lacks, and she spent much of her 30s looking for whatever information she could find. That turned out to be not much. So, she turned to Ms Lacks' surviving children and other family members to try to piece together the story of their mother's life.

Actually, by Skloot's own description she hounded Ms Lacks' children until they finally agreed to talk with her -- in one case, it took a year of frequent phone calls. And she fills her book with everything she learns about this woman and her family who, it turns out, are living largely in poverty in Baltimore, Maryland. Because Ms Lacks died young, and in poverty, the artifacts of her own life are few, and because she died when her children were so young, they remember little to nothing about her. So Skloot delves (intrudes?) into the lives of the children, and tells about a murder, sexual abuse, their religious practices, their scientific beliefs and many other heretofore private details. The book is being very well reviewed, and is selling like hotcakes.

But why? As with the Havasupai, Ms Lacks' family members learned by accident that Henrietta Lacks cells were in such wide use. According to Ms Skloot, that knowledge made them feel both that their mother must have been special and that she was being exploited. But, their mother's life is being conflated with the circumstances of her death; the particular tumor she had, and being in the right place at the right time with respect to the development of a particular technological advance. Or indeed, the wrong place at the wrong time, with respect to her privacy and the privacy of generations of her family to come.

To us, there's nothing about this story that would suggest that the world needs, or has a right to know any of the details about the lives of Henrietta Lacks or any member of her family. This book just continues what Ms Lacks' children originally saw as exploitation of their mother by a world out to make a buck. While Skloot has set up a foundation for the Lacks family with some of the proceeds of the book, this book is still poverty tourism, and it rights no wrongs.