Myriads of Indecency: Ruling Against Patenting Cancer Genes Makes Scientific, Legal and Ethical Sense

The decision of a US federal judge to rule against the patenting of the BRCA-1 and BRCA-2 genes this Monday came as a pleasant surprise after a period of several years when the ability to patent human genome segments within the US legal context has been taken for granted. The ruling - a result of the efforts of the American Civil Liberties Union in conjunction with the Association for Molecular Pathology, individual women and others - was, of course, not welcomed by the commercial company Myriad Genetics, which during the period when it thought it had its patent rights secured has been pestering genetic health service providers in the US and around the world with their absurd claims (by implied threats of massive compensation suits) to world monopoly on predictive genetic testing for breast and ovarian cancer, alternatively the cashing in of handsome licensing fees.

Just a quick browsing of the Myriad Genetics website tells you that this company embodies just about everything bioethics researchers have been warning for in connection to the commercialisation of genetic testing since the late 1980's. The University of Utah Research Foundation that held the claimed patent together with Myriad - and that may be assumed to have been cashing in handsomely as a passive partner - should be held equally, if not more, accountable for this attempt to undercut sound business law, decent health care ethical standards, scientific progress and, not least, the health of those people belonging to families burdened by hereditary cancer, whose access to the preventive opportunities offered through genetic testing, and forthcoming advances of medical research, has been undercut. But back to the poverty of Myriad Genetics.

To take just one example of this moral morass, Myriad offers predictive genetic testing for hereditary melanoma - a disease for which the actual risk figure is never given at the Myriad website. Clicking this product, you are immediately told that "Changes in the p16 gene increase cancer risk, making a melanoma diagnosis up to 50 times more likely by age 50", which of course tells you absolutely nothing about what risk of melanoma you actually run before the age of 50 if you have the indicated genetic mutation, but for most people convey the impression that a mutation makes your risk of contracting melanoma before 50 an even game. Clicking further on to the page supposed to give you an in-depth background to hereditary melanoma, you're exposed to the following explanation. Take a minute or so to read it!

Having that horrible mutation must make for a helluva risk, doesn't it? Actually: no! Even considering that the people involved in Myriad are presumably not proper clinical doctors (if they were, AMA would have revoked their licenses by now, right? - I'm being charitable to the US medical profession here), but a bunch of lab rats and business executives, this is as close to actual fraud you can get without actually committing it in the strict legal sense. Remember that nice graph you just saw? Its Y-axis measures not the actual risk of contracting melanoma, but - again! - the change in risk compared to what risk of contracting melanoma you would run were you a random member of the general population. But the impression of the picture is not that - the impression is - once again - that if you carry the mutation you run a 50/50 risk. This message is cleverly conveyed by the sinister manner in which the general population risk figure is illustrated in the graph. That green staple to the right of the tall blue one seems to reach up to the 1 of the Y-axis, right? It's 1% - right? Or something close to 1%? Actually, no! Have a closer look at the graph:



It is <1% - i.e. "less than 1%", i.e. the risk is not given. It could be 0.99%, it could be 0.0000000000000000000001% For all we know based on the information provided, the 50% increased risk may thus equal a 0.0000000000000000000002% risk. Who knows? Obviously not Myriad Genetics - or can they really be consciously hiding highly relevant facts from potential customers??

Just to get some perspective, hereditary melanoma is what geneticists refer to as a multi-factorial disease, i.e. it occurs as a result of the interaction between several genetic mutations and the environment. The p16 test offered by Myriad targets just one among many different genes where a mutation may increase the risk for melanoma. This is actually conveyed by this admirably pedagogic (right!) explanation of what a test result mean. Scroll down and read the message about the "uncertain variant", there you have it! But just above, Myriad boosts about the "comprehensive" (and presumably ridiculously expensive) variant of the test, described thus: "Think of a comprehensive analysis as reading an entire encyclopedia, line by line, to look for a single misspelled word" (italics added by me). Again, as close to fraud as you might dare to wander. The "entire encyclopedia" must be read the entire human genome, including all the other genes that may increase the risk of melanoma - right?? Actually, no! It's the same p16 gene, i.e. it's more or less the same test, just properly done so that all known melanoma predisposing mutations of this particular gene are included. So, suppose you test negative in a "comprehensive" test - this is compatible with you carrying any of the other known genetic mutations of other genes that increase the risk of melanoma - what Myriad so handsomely describe as "no increased cancer risk" when explaining what a test result means. Did anyone mention fraud or deceitful behaviour? - I certainly did not, but it would be interesting indeed to have melanoma or cancer patient organisations trying out that concept in US civil courts (in which case, the University of Utah Research Foundation must, of course, be included in the lawsuit)!

Hopefully, the ruling against patenting actual genes or naturally occurring genetic mutations will undercut the sour-tasting business of Myriad Genetics and other similar companies. For one thing, as a legal precedent, it has the potential of putting a stop to attempts of making ethically well-motivated and responsibly handled predictive genetic testing offered by national health services - for instance for colon-, breast- and ovarian cancer - unnecessary expensive and thus accessible for more people at risk. From a moral point of view, it is thus most welcome. From a legal point of view as well, since what judge Robert Sweet argues in the ruling, "...the claimed isolated DNA is not markedly different from native DNA as it exists in nature, it constitutes unpatentable subject matter" has been obvious to anyone from the outset interested in applying actual patent law, rather than laying the foundation for a new branch of business. If Myriad has a unique procedure to detect DNA, they may patent that, of course, but do they? It remains to be seen, but my guess is that they use the same state of the art science and technology as does any molecular genetic research lab, and that they knew very well that their only chance to make a buck was attempting the patenting of DNA trick.

The only defense offered by Myriad's and the UURF's lawyer was that patenting genes promotes "innovation" and therefore promotes health. False. In fact, the patent claims on BRCA-1 and BRCA-2 has made medical research based on these genes that may lead to deeper understanding of the mechanisms of these forms of cancer, and thus to newer and better treatments, slower and/or more expensive. Patents have the potential of furthering innovation only when all of the basic scientific work has been done (until then, the scientific principle of openness, free sharing, access and use of information is far superior), and in the case of human genetics, identifying genes connected to disease-groups is just the first letter of the first name of that long process. When Myriad says "innovation" they mean business and so does - shame on them - the UURF.

[Cross-posted from Christian Munthe's Philosophical Comment blog.  Christian and research fellow Daniela Cutas have agreed to guest blog in the coming months]

Lessons Learned from PrEP Trial Cancellations

Between August 2004 and February 2005, the HIV prevention world was rocked by the suspension and cancellation of two pre-exposure prophylaxis (PrEP) trials in Cambodia and Cameroon. To the considerable surprise of researchers, advocates and donors, these HIV prevention trials became embroiled in escalating controversies and sparked protests by activists speaking on behalf of the communities where trial participants were being recruited. The activists not only raised questions about how the research was being conducted, but also challenged the fundamental ethics and underlying motives of the research.

Just this week, my colleagues at the Global Campaign for Microbicides released two in-depth case studies relating the events that led to these trial cancellations and extracting the lessons they provide for current and future research:

• Research Rashomon: Lessons from the Cameroon Pre-exposure Prophylaxis Trial Site by Elizabeth McGrory, Andrea Irvin and Lori Heise
• Preventing Prevention Trial Failures: A Case Study and Lessons for Future Trials from the 2004 Tenofovir Trial in Cambodia by Anna Forbes and Sanushka Muldaliar

Acknowledging that no single version of the events constitutes the “real story”, the case studies are built from extensive interviews with researchers, policymakers and other government officials, donors, NGO staff, and advocates to reconstruct often incompatible accounts of what eventually led to government intervention that halted the research. The case studies capture the political context and backdrop against which the controversies arose and the underlying and unaddressed conflicts that led to the costly collapse of two Phase 3 trials.

These reports are important and exciting reading for anyone interested in sound science, human rights, gender equality and communication across enormous cultural, social, and economic disparities. The HIV prevention field has made substantial progress since 2005 in forging mechanisms to be transparent and build trust between trial communities and researchers. Still, much remains to be done and the potential for conflict remains.

As the first PrEP trials move toward completion this year, these case studies offer a timely look at what we have learned and what pressing challenges remain unaddressed.

The two case studies are available on-line at http://www.global-campaign.org/.


UPDATE: Dr. Free-Ride over at the blog Adventures in Ethics and Science is going to be hosting a virtual journal club on these two case-studies. Join in the fun here.

Ethics on the chopping block

[Cross posted from the Research Ethics blog] Two related stories came to my attention this week. Reading the first one, I was worried. But when I came across the second story, I thought, this needs to be talked about! In two places, both affected by the now globally worrisome economy, strict budget cuts are being made. And the first thing on the chopping block? Ethics.

The University of Tenneessee is considering closing down The Department of Human Values and Ethics in the College of Medicine along with a number of other science and medicine programs. Here's the story from the AAPR Bulletin Today: Possible University of Tennessee job cuts will draw protest.

Across the globe in New Zealand, the government will sign off on disbanding the country's Bioethics Council on Monday. The Bioethics Council was created in 2002 in response to public concern that the government was making decisions — in an ad hoc and unadvised manner — on complex and controversial biotech and genetic issues without considering the unique ethical, cultural and spiritual demographics of the country. Here is the story, from the Radio New Zealand newsfeed: Bioethics Council to be Disbanded

So what does this have to do with research ethics and ethics review boards? Well, plenty.

We should be concerned that the first cuts insitutions and governments want to make are on what they apparently consider to be highly expendable programs, like ethics. Seems to me that in perilous times, we just might need ethics a little more.

Ethics review boards, in either academic or medical settings, should be doing more than reviewing protocols, providing approvals and monitoring ongoing research in a silo somewhere, unconcerned that these kinds of cuts, as they don't name "research ethics" explicitly, have nothing to do with them. While reviewing research takes up a tremendous amount of time and energy, as I well know chairing an ethics review board myself, there is a certain amount of advocacy, outreach and education that an ethics review board must be committed to doing, on an ongoing and iterative basis.

So a few words on each of the three things I've identified here that ethics review boards should be committed to doing:

Advocacy for what? For strong ethics programs that are ideologically and financially supported by the administrators of the institution, situated logically within broader programs that have a commitment to research ethics; for fair, transparent and ethical processes in any context; and for fair treatment of not only participants — yes, that is our mandate — but also novice and experienced researchers, ethics review board members and others involved in research processes without whom researchers couldn't do their work. In these two cases, I would hope that those involved in research ethics at the University of Tennessee and from across NZ would speak out against the discontinuation of these broader ethics programs.

Outreach? Yes, outreach. Ethics review board members can do a great deal of outreach in their own departments and schools by articulating and clarifying what it is an ethics review board does, the kinds of principles upon which we base our deliberations and decisions, the challenges as well as the kinds of rewards that this work affords those who are dedicated to it and the kinds of broader values that ethics review boards, at their best, should be committed to upholding — things like autonomy of persons, voluntariness, maintaining dignity and integrity of persons and facilitating ethically sound research.

Outreach also implies making strong connections between ethics review boards, bioethicists and clinical ethicists, educators and other persons and programs within and between institutions.

Finally, education. As ethics review board members and those who are committed to research ethics in perhaps other ways, it's important, perhaps imperative, that we educate people not only about "what it is we do" but also why it's important to have people, who are concerned with ethics, hanging around. Bioethicists, clinical ethicists, research ethicists, those concerned with environmental ethics, business ethics...the list goes on. Usually most institutions don't think a great deal about these kinds of programs — and the associated dedicated people — until something goes wrong and suddenly, the institution turns to the same programs and people for help, advice and guidance. Seems that UT and NZ might not have anywhere to turn soon.

posted by Nancy Walton, Ph.D. at 6:10 PM

Who Knows What Evil Lurks in the Heart of Men?

A Special Halloween post:

No, not the Shadow - try Selmer Bringsjord, cognitive scientist at Rensselaer Polytechnic Institute. Although he admits it is 'creepy,' he is working on what is evil and how to formally define it. According to the article in Scientific American, Bringsjord says that to be truly evil, someone must have sought to do harm by planning to commit some morally wrong action with no prompting from others:

"Bringsjord's research builds on earlier definitions put forth by San Diego State University philosophy professor J. Angelo Corlett as well as the late sociopolitical philosophers and psychologists, Joel Feinberg and Erich Fromm, but most significantly by psychiatrist and author M. Scott Peck in his 1983 book, People of the Lie, The Hope for Healing Human Evil. After reading Peck's tome about clinically evil people, 'I thought it would be interesting to come up with formal structures that define evil,' Bringsjord says, 'and, ultimately, to create a purely evil character the way a creative writer would.' " His team has developed a computer representation of evil, a character called "E."

Peck described evil as "anti-love"and suggested that one of the dangers of studying evil that one may become tainted by it.

"Bringsjord acknowledges that the endeavor to create pure evil, even in a software program, does raise ethical questions, such as, how researchers could control an artificially intelligent character like E if "he" was placed in a virtual world such as Second Life, a Web-based program that allows people to create digital representations of themselves and have those avatars interact in a number of different ways.

'I wouldn't release E or anything like it, even in purely virtual environments, without engineered safeguards,' Bringsjord says. These safeguards would be a set of ethics written into the software, something akin to author Isaac Asimov's 'Three Laws of Robotics' that prevent a robot from harming humans, requires a robot to obey humans, and instructs a robot to protect itself—as long as that does not violate either or both of the first two laws.

'Because I have a lot of faith in this approach,' he says, 'E will be controlled.' "

If only the same could be said for everyday encounters with evil -- Sounds a like a great topic for a podcast.

The whole article in Scientific American can be accessed here.

A quip only a bioethicist might appreciate...

Overheard at a recent gathering of bioethics colleagues:

Question: Can you explain the difference between morality and ethics?

Response: Lipstick.

Bioethics: Finding Our Shared Moral Core

Under the direction and management of psychologist, author and founding member Valerie Tarico, Phd, the Wisdom Commons is one of the newest ethics initiatives of the Women’s Bioethics Project.

The purpose of the Wisdom Commons is to affirm, inspire, and shed light on humanity's shared moral core, meaning the convergence of our religious and secular wisdom traditions and emerging wisdom culture. Many times we define ourselves in terms of our differences. But the truth is that some of our deepest concerns and highest values transcend the boundaries of culture and tradition. Early in childhood, before we even can walk and talk, the moral emotions, empathy, shame, and guilt begin to emerge. They guide us as we take our first steps toward living in community with each other.

Around the world people recognize that the joy and pain of others are similar to their own joy and pain, and wisdom traditions express this through different forms of the golden rule. We also generally agree about what kind of qualities we seek in our friends, our leaders, and ourselves. These instincts, emotions, understandings and agreements form our moral core. This moral core in turn serves the well-being of the intricate web of life around us and, foremost, the well-being of humans within that web.

The Wisdom Commons belongs to all who use it and contribute to it. Members have the ability to create personal wisdom pages that include their favorite quotes, stories and so forth from the library. A personal wisdom page can also include content that is authored by that member. Over time, we seek to build a diverse community of stewards reflecting the various traditions of our users. These stewards will also create personal wisdom pages so that their core values are visible to our members and users.

The Wisdom Commons emerged out of two years of conversations among people who share a passion for these issues. It was catalyzed into existence by a five day event in April of 2008, Seeds of Compassion, the realization of a dream by the Venerable Tenzin Dhonden and Dan Kranzler of the Kirlin Foundation. Seeds of Compassion brought over 150,000 people together to discuss how best to nurture compassion in our children and communities. It was televised in 24 languages around the world.

It is impossible to acknowledge everyone who shaped or contributed to the project, but they include Valerie Tarico, Brian Arbogast, Jennifer Hobbs, Katherine Triandafilou, Porter Bayne, Kathryn Hinsch, Darcy Rubel, Yaffa Maritz, Lee Colleton, Clif Swiggett, Bruno Alabiso, Jonathan Mark, Kathy Washienko, Matt Lerner, Mike Mathieu, Laura Peterson, John Rae Grant, Brynn Arborico, Marley Arborico, Zuzana Nemcova, Iris Chamberlain, Jean Harrison, James Peterson, Ruth Lipscomb, and others.

The Wisdom Commons draws much inspiration and some of its structure and content from The Virtues Project International, which provides curriculum, training and inspirational materials that elevate virtues in every day life. Many thanks to Linda and Dan Popov and John Kavelin for their thoughtful, patient labor of love. The beauty and meditative feel of the Commons are the handiwork of Jody and Cynthia Baxter, who created WorldPrayers.org.

Please join us.

Primum Non Nocere

First, do no harm. I don't know anyone who practices any aspect of medicine who disagrees with this foundational concept of what medicine should be and do - do no harm. And on an intuitive level, harm seems so self-evident, and easy to avoid.

Except, of course, anyone who's spent more than an hour reading about the history of medical ethics knows that this isn't the case. Harm, unfortunately, is one of those words that is flexible, has a definition that changes depending on context, case, even attitude. Ultimately, what does it mean to cause harm?

I had a class last year where a student would argue that anything which caused someone to be "not normal" was harmful, and therefore doing no harm meant doing your best to make sure everyone was normal. Ignoring the more Harrison Bergeron aspects of that thought for a minute, what does it even mean to be normal? Again, it's one of those things that seems self-evident, until you stop and think for a minute. We're accustomed to this argument now (at least, I hope the folks who'll be reading this are) when it comes to think like Deafness or dwarfism - parents who are dwarfs or Deaf who want children sharing these same genetic and physical traits. It is, for them, what is normal - point being that normal itself is not a concrete concept, but flexible. You could argue that normal is normative.

There's been a lot of debate about whether or not, for example, Deaf parents should be "allowed" to have Deaf children - that is, should fertility doctors be trying to create embryos that are deaf, should couples be able to request eggs or sperm from Deaf donors to increase their chances of having a Deaf child. I've argued strongly for this in the past, and won't go into the reasons here, except to say that part of the reason for my arguing for this is based on the notion of preserving culture, and not making a judgment call on what is normal. There are, after all, many people for whom the experience of being Deaf is perfectly normal, and I'm simply not comfortable pointing a finger and saying "you are abnormal".

That's why this particular YouTube video has been so thought-provoking for me. I suppose, when it comes down to it, I do have a concept of normal that includes "being able to communicate with the world" - I don't assume that means everyone; after all, I don't speak the majority of the languages on this earth. But the idea that someone who has what we would consider severe autism is communicating with the world, and it's simply the world that has not yet figured out how to communicate in return, is a novel and I'll admit, somewhat difficult, concept for me to wrap my head around.


Amanda Baggs, the woman in the video, is featured this month in Wired, and has a blog here.

I won't suggest that Ms. Baggs doesn't bring up interesting - and disturbing - questions in her video (obviously there's something here to think about, or I wouldn't have anything to write). But I wonder - given what she describes as being her language, is it even possible that someone who is not autistic, or cognitively different, could learn to communicate in it? Or maybe even more to the point - in my general notion of a language, it is a device that allows me to communicate with you - we both have the ability to learn it and use it to exchange ideas. Is Ms. Baggs' language one that more than a single person knows, uses, inhabits? I'm not necessarily convinced that, if it is an individualistic thing, if she is the only person speaking this language, than it can rightfully be called a language. But I also don't want to swing so far to the other side as to say it's not possible - I simply don't know.

I have some other concerns that are still marinating, so I'll just leave it at this for now.
-Kelly

The Enhanced Ethicist

Professor Julian Savulescu, director of the centre of practical ethics at Oxford University: "To fail to do beneficial research is as harmful as doing harmful research," he says. The whole article is available here.

And oh, yeah -- and James Hughes of the IEET quips: "When I get enhanced I want to look like Julian. Oh, and be tenured at Oxford also."

Over at the Business Ethics Blog: Sexism in Coffee Shops

Thanks to Chris MacDonald over at the Business Ethics Blog for posting this interesting tidbit about Waiting for Good Joe: Do coffee shops discriminate against women? Who would have thunk it? You can read the full post here.