Wednesday, July 25, 2012

Genome Sequencing - III: Presidential Commission for the Study of Bioethical Issues Meeting 8, February 2, 2012 (cont.)

Meeting 8 Session 4: Privacy III – Law Enforcement Use and Access to Genomic Information

Melissa Mourges, J.D.
Melissa Mourges, J.D., Assistant District Attorney, Chief, Forensic Sciences/Cold Case Unit, New York County District Attorney's Office works in the Manhattan DA's Office, the setting of the TV show Law and Order.  She gave a rapid survey of the progression of collection of crime evidence, from the old days of using sterile swabs taken from the victim’s body, to the forensic database CODIS, the Combined DNA Index System, that allows identification of a 13-marker DNA “signature” sample taken and amplified from a very small saliva, blood or semen crime-scene stain and matching with DNA obtained from the suspect. A FAQ on how it works is here

She went on to say that in 15 years use of the CODIS database has expanded from  rape and homicide cases to property crimes – now amounting to over half of the 10,000 samples collected in New York City each year.  She described a typical case in which a burglar who left behind a Starbucks cup with a saliva stain was convicted by a DNA match with a probability of error of “one in greater than a trillion.”

From the point of view of privacy, she stated that “Forensic DNA typing looks only at the areas of DNA that do not code for any known trait or characteristic, so-called junk DNA…”  New York and other states also have laws about “de-identifying” the data by using bar codes, and prohibiting release of the data for “anything other than law enforcement purposes.”

However, what she did not say was that in an era of whole-genome sequencing it is becoming more evident that so-called “junk DNA” may actually have a purpose that one day will be discovered – as research is increasingly showing that causes of diseases, conditions or traits are multi-factorial gene combinations rather than a single gene.

Pilar Ossorio, J.D., Ph.D., Associate Professor of Law and Bioethics, University of Wisconsin-Madison set the use of forensic genomics evidence in a wider context by pointing out that government and private sector surveillance capacity is expanding in many different ways. 

Pilar Ossorio, J.D., Ph.D.
She went on to describe “law enforcement efforts to generate phenotype profiles based on genotyping of crime scene samples.”  The goal is to come up with an image of what the suspect might look like, but she pointed out that not only can gender and ancestry be readily determined, but also “…there is nothing actually to prevent law enforcement from explicitly attempting to find medical information in genetic material left at a crime scene.”

She gave the example of genetic analysis revealing that a possible suspect had an illness that required specific medications or a condition like sickle-cell anemia, which could lead police to look in pharmacies or pain clinics for the person.  Also, the biological materials left at the crime scene may not actually have come from a suspect, Ossorio cautioned.

She cited the case of United States v. Jones, where the court ruled that the Fourth Amendment prevents warrantless use of a GPS tracker to map a suspect’s whereabouts.  The police did have a 10-day warrant, but it had expired by the time they installed the tracker, and it was used in a different jurisdiction as well.

Ossorio observed “…neither our privacy jurisprudence nor our bioethics scholarship, I think, adequately addresses the distinction between privacy and anonymity…” and that surveillance technologies “…are getting rid of our opportunities for anonymity in any place outside of our homes.”  

She concluded “So, courts have held that, you know, looking at someone's biological material is like looking at something discarded, that the person has no privacy interest and no Fourth Amendment interest in that biological material once it is outside of your body and outside of your private property, like your home or your deck on the back of your house.”

Amy Gutmann, Ph.D. Commission Chair

Meeting 8 Session 5: Roundtable

After presenting papers on ethical issues with whole genome sequencing, the meeting participants were given the opportunity to respond to one another.  Here are some highlights:

  • “…that we do not find a balance that maintains…whatever the privacy boundaries are that we want to maintain, with the capacity of whole genome sequencing to let us actually start tying traits and gene variation.” (John Wilbanks, on the growing capability of the technology to drill down to specific, individual genetic characteristics)
  • “…what we need to do is make [privacy concerns] more nuanced and allow individuals to have a say about the way in which whole genomes are used or who has access to them.” (Jane Kaye)
  • “…that the clinical utility at this point will not outweigh the privacy risks to individuals, both from their psychological response and also to what third parties might do, based on the information that they could obtain.” (Mark Rothstein)
  • “…the more we look at genes, the less we're going to look at the whole person and the less we're going to take that person's whole life into account, and I think that is a big problem, for privacy, but for just basic control over your life.” (George Annas)
  • “…that we have used anonymity as the way to protect research participants from informational harms for the last 50 or 100 years, at least since the Common Rule went into effect, and we're not taking seriously the fact that we really are having decreasing amounts of anonymity and a decreasing ability to promise that to people, and we're not developing in creative ways alternative governance structures that would protect people and minimize harms, when we can't actually promise them anonymity.“ (Pilar Ossorio)
  • “…I think knowledge is power, and I would hate to give up the knowledge that you can gain through this project, and I think that we figured out how to do it with forensic DNA databasing…” (Melissa Mourges)
  • “…metaphorically, your genome has been called the book of humanity, and if it is, then it's a book that we only understand perhaps one-third of the words.  We can barely speak a single sentence and not even so much as one full paragraph.  And so that is where we stand, with the understanding of the incomplete genome and of biological science and health and disease.  So, my major concern would be that privacy not materially inhibit the rapidity with which we can de-code that book and understand what it means.” (Daniel Masys)
  • “…a lack of the right infrastructure and process to advance genetic literacy and genomic literacy as ubiquitously as we possibly can.” (Richard Gibbs)
  • “…I think that information is a good thing and I think that it's a good thing that can be used in diagnosing a rare disease.  I think that it's something that should be shared in a broader format…” (Retta Beery)

Further issues that came up in the ensuing discussion included:

  • Pediatric genomic data: “…whether parents have the authority to authorize their children to be screened for … late-onset disorders,” e.g. BRCA1 and BRCA2  Now whole-genome sequencing will show such data, where before it required a separate test, and was not done until adulthood. (George Annas).
  • Along with that, the question of consent by the child once he/she becomes an adult, to the use of their childhood biobank data in future research. (Daniel Masys).
  • The fact of greater use of whole-genome sequencing and genetic research being done in majority vs. minority populations – will that further disadvantage healthcare for the minority groups? (Daniel Masys).
  • “I wouldn’t post my 23andMe on the Internet, and I’m reasonably literate in this area, and so, it turns out though that I think my ignorance is much larger than my knowledge, and so, the reason I wouldn’t publicly post that is the unintended consequences of the reuse of that, 10 years from now or 20 years from now, because we just don’t know enough.” (John Wilbanks)

Monday, July 16, 2012

The Ethical Issues Inherited by Evolutionary Genomics

When the draft sequence of the human genome was published in 2001, significant attention was paid to repeat sequences that "...constitute a rich paleontological record, holding crucial clues about evolutionary events and forces..." such as "...the unusual evolutionary history of chromosome Y."   

In 2003, the U.S. National Human Genome Research Institute's vision for the future of genome research included Grand Challenge I-4 that called for "understanding evolutionary variation across species and the mechanisms underlying it.”  As the ability to sequence genomes became easier and cheaper, researchers collaborated on cataloging extensive maps of human variation as part of the 1000 Genomes Project and the International HapMap Project, "…providing the necessary raw material for human evolutionary genomics to operate."

After  reviewing a decade of research in the field of evolutionary genomics, Vitti et alfind that it “..stands at the intersection of two sensitive topics that are widely misunderstood in their own right: evolution and genetics.” In recognition of this need for clarity, their review begins with a glossary of essential terms for discussing the intersection of these two fields such as genetic determinism, genetic reductionism, and genetic drift.

Historically, advances in evolutionary science and genetics "…have been misapplied to provide justification for unethical practices."  When Herbert Spencer devoted a section of his Principles of Biology [1864] to the "survival of the fittest,” the stage was set for evolution to be conceived of as a progressive and teleological force rather than as the "blind process" that it is.  The authors recall the “…now-infamous [1854]  depiction [from Nott and Gliddon’s Types of Mankind] of the heads and skulls of a chimpanzee, an African male and the god Apollo” used over the years to justify racism and social Darwinism.

As an example of the effects of this “dark history” on current research, the authors refer to recent studies of brain size determinants by Mekel-Bobrov et al. and Evans et al. that have provoked both critical and racist responses.

The authors recommend that researchers "…be responsible for devising ‘ethically self-aware research agendas’ to foster ‘interpretative rigor’” and to prevent research findings from “…being warped towards harmful ends.” Such an agenda would consist of three components: methodological rigor, cautious scientific reporting, and educational leadership in the public discourse of science.  

To determine “what counts as evidence” in a rigorous way, the authors refer to J. M. Akey’s review of research methods for examining alternate hypotheses and conducting follow-up studies, and cite a PLoS Biology’s editors’ proposal that researchers augment any claim for positive selection by combining the sequence data analysis with other experimental evidence.

Being cautious when reporting study results includes emphasizing the study’s limitations and explaining the conclusions “…in language that is precise and accessible to a lay audience.”  To avoid the common problem of correlation being mistaken for causation, the authors suggest depicting the genome as a recipe rather than as a blueprint for an organism.

To enhance public understanding of biological concepts, the authors propose that researchers be proactive and organize forums to discuss their research findings so that they can “…address misconceptions head-on.”

The authors conclude by suggesting that the pitfalls of evolutionary genomics can be avoided by researchers holding their “…projects at arm’s length and [examining] the genuine ethical dilemmas they inspire.” 

Akey, Joshua M. Constructing Genomic Maps of Positive Selection in Humans: Where Do We Go from Here?  Genome Research 19(5):711-22, May 2009. doi: 10.1101/gr.086652.108

Collins, Francis S.; Green, Eric D.; Guttmacher, Alan E.; and Guyer, Mark S. A Vision for the Future of Genomics Research: A Blueprint for the Genomic Era. Nature 422(6934): 835-847, April 24, 2003.
Evans, Patrick D.; Gilbert, Sandra L.; Mekel-Bobrov, Nitzan;  Vallender, 
Eric J.;  Anderson, Jeffrey R.; Vaez-Azizi, Leila M.; Tishkoff, Sarah A.; 
Hudson, Richard R.; and  Lahn, Bruce T. Microcephalin, a Gene 
Regulating Brain Size, Continues to Evolve Adaptively in Humans.
Science 309(5741):1717-20, September 9, 2005. doi: 10.1126/science.1113722.

International Human Genome Sequencing Consortium. Initial Sequencing and Analysis of the Human Genome. Nature 409(6822): 860-921, February 15, 2001. doi:10.1038/35057062.

MacCallum, Catriona, and Hill, Emma. Being Positive about Selection. PLoS Biology 4(3): e87, March 14, 2006.  doi: 10.1371/journal.pbio.0040087.

Mekel-Bobrov, Nitzan; Gilbert, Sandra L; Evans, Patrick D.; Vallender, Eric J.;  Anderson, Jeffrey R.; Hudson, Richard R.; Tishkoff, Sarah A.; and Lahn, Bruce T. Ongoing Adaptive Evolution of ASPM, a Brain Size Determinant in Homo sapiens Science 309(5741): 1720-2, September 9, 2005. doi: 10.1126/science.1116815.

Nott, Josiah Clark, and Gliddon, George R. Types of Mankind. 
Philadelphia: Lippincott, 1854.
Spencer, Herbert.  The Principles of Biology. London: Williams and  Norgate, 1864. 
[The discussion of “survival of the fittest” begins on page 444 of this digital version at Bayerische StaatsBibliothek (The Bavarian State Library). Click on the three red bars in the upper left-hand corner to advance a page. To download a .pdf file of the book, go here, click on "Ja" and "Weiter" and then click on the highlighted PDF file]

Vitti, Joseph J.; Cho, Mildred K.; Tishkoff, Sarah A.; and Sabeti, Pardis C.  Human Evolutionary Genomics: Ethical and Interpretive Issues. Trends in Genetics: TIG 28(3):137-45, March 2012.  doi: 10.1016/j.tig.2011.12.001

Wednesday, May 2, 2012

Genome Sequencing - II: Presidential Commission for the Study of Bioethical Issues Meeting 8, February 2, 2012

Meeting 8 Session 2  Privacy I: Privacy and the public good

George J. Annas, J.D., M.P.H.
George Annas, J.D., M.P.H., Chair, Health Law, Bioethics & Human Rights, William Fairfield Warren Distinguished Professor, Boston University School of Public Health likened the present state of genomic medicine to two movies: "One is Bill Murray's "Groundhog Day", [that] took an insight, a values insight, for him to get out of that day, and the other is his movie "Lost in Translation", which I think it's fair to say, without getting carried away, a lot of genetics is."

G.J. Annas presentation slide
He drew a parallel between genetic privacy and privacy on social networks -- the latter as described in Lori Andrews' book, "I Know Who You Are and I Saw What You Did."  He noted that many people are not concerned about signing releases for the collection and use of their genomic data by others -- as long as it is described as their "medical record,"  and yet object if what they are asked to release is "their genome."  And of course, very little is known about how that data might be used in the future. 

Mark A. Rothstein, J.D.

Mark A. Rothstein, J.D., Herbert F. Boehl Chair of Law and Medicine, University of Louisville School of Medicine was the second speaker of the session. Areas of concern he delineated were as follows:
  • Genomic information in electronic health records may be accessed by healthcare providers without a need to know
  • What to do in the research uses of the information
    • De-identify it (public surveys have shown great unhappiness with this practice)
    • Provision for opting out (many don't exercise that option -- but if you ask, often people are happy to consent)
    • Opt-in provision (which researchers find burdensome to implement)
  • Non-medical uses of genomic information, without consent or authorization (as required for public health for example - victims of abuse, neglect or domestic violence)
  • Compelled authorizations by third parties (as a condition of employment for example)
In follow-up questions, the Personal Genomes Project in Boston was mentioned as an example of present work. The PGP is recruiting several hundred-thousand individuals, whose biobanked genome sequence one day will be made publicly available -- with all of them having consented to that. The question was raised as to whether there ought to be simply consent by individuals or also "social consent" to, or state control of such projects.

By way of exploring social consent in genome research, the National Human Genome Research Institute is sponsoring a clinical trial entitled Informed Consent for Whole Genome Sequencing: Ideals and Norms Referenced by Early Participants

In the detailed description, it is stated: "This proposed study approaches both informed consent and genomic medicine as iterative constructs shaped by civic values and social norms."

Understanding the civic and social contexts where informed consent takes place is crucial in order to adapt it to new realities in genomic research."

Meeting 8 Session 3 Privacy II – Control, Access and Human Genome Sequence Data

Jane Kaye, D.Phil., L.L.B.
Jane Kaye, D.Phil., L.L.B., Director of the Centre for Law, Health and Emerging Technologies (HeLEX), Oxford University spoke on biobanking and privacy.

While traditionally consent is seen as a one-time, individual transaction between the subject and the researcher, Dr. Kaye countered "...what has been suggested and what is used within bio-banking is a broad consent..." 

She went on to say "The second plank of medical research ethics, which is actually challenged by global data sharing is that participants should be able to withdraw from research at any time, and withdrawal cannot be promised when data and samples are shared widely."

J.Kaye presentation slide
She summed up the problem: " my colleague Eric Meslin said, it's a bit like Hotel California, you can check out you any time you like, but you can never leave."

Dr. Kaye concluded by suggesting a change in thinking to see it as a process of forming partnerships with tissue donors. In her view attempting to anonymize donor data is not as important as paying attention to the public preference to be asked about any uses of their data.

John Wilbanks
John Wilbanks, Founder of Consent to Research and Senior Fellow, Kauffman Foundation, among other positions, spoke on the question of privacy from a Web perspective.  He frames it as “…more a debate about agency, which is the right to decide what is done with my data and the right to see a copy of what people know about me.”  He pointed out that communities on the Web like, with over 100,000 people, are generating studies with no connection to IRBs, such as one being done by ALS patients looking at the use of lithium.

He mentioned more ‘do-it-yourself’ Web projects, such as OpenSNP  -- pronounced Open Snip... a website, that would let anyone upload their 23andMe file and let people start attaching papers and annotations to the Snips.  It has zero connection to bioethics in the professional sense.”

J.Wilbanks presentation slide
He also spoke of a project he is involved in, Sage Bionetworks,  which is an attempt to create a “commons” for genome sequences that would help to build “predictive computational disease models” which do not involve patenting.  
The question of consent for the use of individuals’ data has arisen here and through his work with Consent to Research and Sage Bionetworks he is now seeking to develop a web model of consent that would be acceptable to IRBs and thus would encourage researchers to take advantage of a large number of personal DNA genome profiles. He calls it the Portable Legal Consent for Genomics Research, the about-to-be-launched project is described by Erica Check Hayden in Nature News.

A lengthy discussion ensued, with Commission members and members of the public exploring the contrast between the socially-cooperative nature of Web-based genomics projects and the fear of losing control of one’s own personal data – which it was pointed out, is not intellectual property in a legal sense, but rather, as John Wilbanks suggested, a kind of individual "trade secret."

Related article            Flash videos of all sessions with slides

Friday, April 27, 2012

Issues in Familial Searching in Forensic Investigations

Source: Wellcome Sanger Trust article on the NDNAD
Erica Haimes, Professor of Sociology at Newcastle University, Newcastle-upon-Tyne, United Kingdom,  discusses familial searching in forensic DNA databases. Professor Haimes was the Founding Executive Director of the Policy, Ethics and Life Sciences (PEALS) Research Centre at the University.  Familial searching of DNA databases is the process of searching to see if there is a close match to a crime scene profile when there is not an exact match.  In the United Kingdom the UK National DNA Database (NDNAD) is used in this fashion to determine whether crime scene DNA belongs to a close relative of someone profiled in the NDNAD.  The purpose of this paper is to discuss the social and ethical problems of this process with an eye to family studies.
Potential problems with forensic screening are:
  • Violating the privacy of the person in the NDNAD;
  • Violating the privacy of the pool of relatives who are not the subject of forensic investigation;
  • Reinforcing the view that the prevalence of criminality is higher in certain families;
  • Revealing to relatives the presence of a family member in the NDNAD;
  • Revealing a previously unknown genetic link or a lack of genetic connection between persons.
Haimes raises the following questions on the impact of familial DNA searching on the family members.

The Person in the Forensic Database

  • What obligation does this person have to provide information about his/her relatives? This person is the entry point into the family network – a genetic informant.
  • How does a previously unknown genetic link or lack of a genetic connection affect this person? 
  • Is there a right ‘not to know?’
The Immediate Family

  • What is the impact of exoneration or genetic scrutiny on family members?
  • How does a previously unknown genetic link or lack of a genetic connection affect the family?

The Wider Family Network

  • What effect does being related to someone in the genetic database have on family relations?
  • How does a previously unknown genetic link or lack of a genetic connection affect the group?
  • What is the effect of being a part of a family under criminal investigation?
The following suggestions are made to mitigate the effect of forensic screening on all parties involved:
  • A detailed study of the practices currently involved should be done;
  • Current guidelines in the UK for forensic screening should have input from family specialists and genetics personnel;
  • Careful consideration of the method of contacting all involved should be taken;
  • Careful training of genetic, forensic  and social service personnel would be beneficial;  the end of inquiry for the forensic investigation may be just the start of inquiry within the family involved;
  • Error rates in the database should be considered;
  • Ethics awareness training may be beneficial to for all personnel.
Haimes, Erica. Social and Ethical Issues in the Use of Familial Searching in Forensic Investigations: Insights from Family and Kinship Studies. Journal of Law, Medicine and Ethics. 2006 Summer; 34(2): 263-276.  doi: 10.1111/j.1748-720X.2006.00032.x

Friday, March 23, 2012

Genome Sequencing - I : Presidential Commission for the Study of Bioethical Issues Meeting 8, February 2, 2012

Commission Chair, Amy Gutmann (l) and Vice-Chair, James Wagner (r)
In her opening remarks, (Transcript) Chair Amy Gutmann, Ph.D observed that the Commission has completed three reports in the last year and a half. “Turning now to the future…” she said, “…We're going to focus on issues related to genome sequencing and privacy and access to the data available, as the result of whole genome sequencing and its use in research and clinical care.”

Session 1 Ethics and the practice of whole genome sequencing in the clinic: Transcript

Retta Beery described her family’s personal success story, the result of whole genome sequencing done of her twin children, Noah and Alexis. They suffered for several years after birth from the many ill effects of a genetic metabolic disorder similar to, but misdiagnosed as Cerebral Palsy.  Finally, when the sequencing was done while they were in their early teens, a problem with serotonin uptake was discovered.  Administration of 5-HTP amino acid cleared up the symptoms and today the children are healthy.
The story is detailed in Bloomberg News Online: Genome Proving Cure for Ailing Twins Paves Breakthrough to Doctor’s Office By John Lauerman - Jan 30, 2012 5:40 PM ET.

Richard Gibbs, Ph.D., Wofford Cain Professor, Department of Molecular and Human Genetics, Director, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX spoke on "Genome Data: Research to Clinic to Consumer"

He described recent advances in sequencing. For example, instead of doing whole genome sequencing the "next gen" rapid sequencing of isolated gene portions only, costs 1/5 the amount.

In his "armchair futurist's view of genomic and genetic data," Dr Gibbs stressed the importance of medical record and social/other factors is growing versus the population studies to which they are tied.

Responding to questions posed by commission members at the end of the session Gibbs said, "Tomorrow's challenge is community genetics education."  On 'snake oil' salesmen selling genetic sequencing for individuals he added, "Don't slow the pace of genomics... there's a tension here -- the danger of not knowing is as enormous as the risk of knowing."

On patenting he said, “As more specific genotype and phenotype information becomes available, we need to look at patenting that information -- we need to avoid a "land-grab" as a private company attempted to do in attempting to file for a wide patent during the race to sequence the human genome.”

Daniel Masys, M.D., Affiliate Professor, Biomedical and Health Informatics, University of Washington School of Medicine, Seattle, WA addressed the question of “Electronic Medical Records and Genomics: Possibilities, Realities, Ethical Issues to Consider”
He described an electronic medical records system set up at Vanderbilt to link doctors pharmacists and patients, to detail personal genetic data that suggests the efficacy or not of particular drugs in treating a patient's condition.

By taking genome-wide association studies a step further, and looking at phenotype-wide association studies, scientists are now able to look at associations of diseases within phenotypes -- for example, diabetes type II and asthma, or myocardial infarction and peripheral vascular disease -- as studied by sites in the eMERGE network (electronic Medical Records & Genomics) that link biorepositories to electronic medical records in doing genomic studies.
He underlined the magnitude of the task of finding the molecular data:
  • Structural genomics, “the DNA in residence" studies about 22,000 genes per genome.

  • Functional genomics, looks at the 1-2% of genes switched on

  • Proteomics examines the 400,000 proteins coded for by the 22,000 genes

He suggested the caption of a New Yorker cartoon says it all: "The good news is we have the human genome, the bad news is, it's mostly just a parts list."

He stated the issues to consider:
  • Is it ethical to allow health care providers to continue to practice without a systems infrastructure for decision support?"

  • Is it ethical to discard person-specific DNA data that currently has uncertain or unknown significance?

  • How does 'genomic consent' differ from standard consent for healthcare services?"

Flash videos with slides are available here.

Monday, February 6, 2012

Yes, Genes Should be Patentable

Stephen H. Schilling thinks so. The author proceeds from the point of view that those who object to patenting genes " to adequately consider the role that gene patents and patents on similar biomolecules play in facilitating investment in the costly, lengthy, and risky developmental processes required to transform the underlying biological discoveries and inventions into marketable products. "

Discussing the biology of genes, and the appeal of gene patents, he then deals with litigation on patentability requirements. He refers to the 1980 case that opened the door to gene patents (Diamond v. Chakrabartyand by contrast, Funk Brothers Seed Co. v. Kalo Inoculant Co., (1948), in which "a mixture of root-nodule bacteria that aids plants in fixing nitrogen was held unpatentable, because it was a "handiwork of nature." 

Since the 1980 decision, the author contends courts have agreed on the following status quo:  "An isolated and purified DNA molecule that has the same sequence as a naturally occurring gene is eligible for a patent because
  • (1) an excised gene is eligible for a patent as a composition of matter or as an article of manufacture because that DNA molecule does not occur in that isolated form in nature, or 
  • (2) synthetic DNA preparations are eligible for patents because their purified state is different from the naturally occurring compound... 

Source: Biopolitical Times: Cathy Wilcox Cartoon
It was the status quo, at least, until the arrival of the hot topic case of Associated Molecular Pathology v. USPTO. Popularly called Associated Molecular Pathology v. Myriad Genetics it deals with Myriad's patents of the BRCA1 and BRCA2 genes, of associated methods for screening for breast cancer, and for testing drugs by comparing BRCA gene sequences to patients' gene sequences.

The author states: "This status quo, however, was called into question by the district court's holding... that isolated DNA is an unpatentable product of nature because the unaltered information-encoding function of DNA is also central to the utility of DNA in its isolated form... Although the Federal Circuit reversed this holding on appeal...  the case has not been finally resolved by the courts..." 

In the reversal the Federal Circuit upheld the patentability of the genes and Myriad's patent of a method of screening for breast cancer using the genes, while affirming the unpatentability of a process that analyzes BRCA gene sequences and compares them with cancer-predisposing mutations in so-called "normal" or "wild-type" gene sequences.

He goes on to discuss the patent law's concepts of utility, novelty and nonobviousness. He gives the example of the case  Brenner v.Manson, 383 U.S. 519, 534-36 (1966) which notes "...that 'a patent is not a hunting license' but rather is 'compensation for [the] successful conclusion' of a search for something useful;" adding that "[a]n invention is novel if it has not been previously disclosed;" and to be eligible for a patent an invention must not be an obvious conclusion from "prior art," but rather, "nonobvious" as in providing the resolution to a previously insoluble problem.

The author then proceeds to describe "Alleged problems created by gene patents." Noting that "20% of human genes are allegedly patented," he critiques the arguments against patenting genes:
  • Diminishing Patient Access
  • Diminishing Quality of Patient Care
  • Impeding Research and Innovation

The remainder of the article contains a fuller discussion and critiques of the Myriad case and of the "SACGHS Report on Gene Patents and Licensing Practices and [its]Impact on Patient Access to Genetic Diagnostic Tests"

The author proposes a "narrowly tailored solution:"
  • Limited exemptions for diagnostic testing or whole-genome sequencing to address patient-access and standard-of-care concerns
  • Increased transparency in genetic diagnostic testing, gene patents, and licensing

Since the article was published a decision was taken by the both the plaintiffs and Myriad to appeal the Federal Circuit's reversal, and when that was denied, the American Civil Liberties Union asked for the Supreme Court to rule on the case. It has been accepted for the court's 2012 Spring session. 

Further reading on the topic, from GenomeLawReport: 

Genotype-driven Recruitment

Emily E. Namey, past coordinator of qualitative research at the Duke Institute for Genome Sciences and Policy (IGSP), and Laura M. Beskow, Assistant Research Professor at the IGSP present results of twenty-nine interviews of epilepsy patient-participants from the study, “The Genetics and Pharmacogenetics of Epilepsy” conducted at Duke University Medical Center. The interviews were conducted between February and October 2010.

Brain. Source: National Institutes of Health
In the initial study, some participants were found to have large heterozygous deletions. The significance of this deletion for the study of epilepsy is not known and participants with the deletion were recruited for a follow-up study, so-called genotype-driven recruitment. 

Namey and Beskow sought to better understand how research participants with a known condition (in this case, epilepsy) give meaning to their personal genetic results. Because the validity and utility of such results are not known at this time, some researchers are reluctant to give individual results to which patients may over-respond. 

The interview group for the current empiric study consisted of nine (9) persons with the deletion and twenty (20) persons without it. The consent form of the original study stated that individual results would not be given. Thus, the researchers faced an ethical quandary:  avoiding giving confusing information when recruiting while at the same time providing true informed consent.

The following questions were asked:

  • If you had been contacted for the follow-up study, would you want to know your results?
  • - 28/29 responded Yes.
  • If the results were of "uncertain validity" or "limited utility," would you want to know your results?
  • - Results of "uncertain validity"- 50% Yes 50% No
  • - Valid results, but not clinically actionable 75% Yes

The questions participants hoped would be answered by knowledge of their individual test results were:

  • Why do you want to study me more?
  • What have you learned about my condition?
  • Can epilepsy be passed on in a family?
  • Is there anything (more) I can do?

This cohort of persons has a specific broad-based condition, epilepsy, for which they want specific, in this case genetic, answers. This poses a problem for the way that genetic researchers recruit participants.

The authors conclude that clear communication concerning the validity and clinical utility of genetic results are necessary if patients do receive results in the process of recruitment for additional research.

Namey, Emily E. and Beskow, Laura M. Epilepsy Patient-Participants and Genetic Research Results as “Answers.” Journal of Empirical Research on Human Research Ethics. December 2011; 6(4): 21 – 29. DOI: 10.1525/jer.2011.6.4.21

Related article: 
Beskow, Laura M.; Linney, Kristen N.; Radtke, Rodney A.; Heinzen, Erin L.; Goldstein,  David B. Ethical challenges in genotype-driven research recruitment. Genome Research 2010 June; 20:705-709 doi:10.1101/gr.104455.109