March 31, 2014

Virginia Establishes Standards for Genetic Counselor Licensing, Allows Conscience Clause Exemption

Genetic counseling services have proliferated in the age of molecular medicine, as health care practitioners increasingly make use of genetic information as a basis for determining risk, diagnosis, treatment and prognosis. The professional field of genetic counseling now encounters the trend of state licensure standards for professional practice. To date, about 15 states mandate licensing for genetic counselors. Licensing is endorsed by the National Society of Genetic Counselors, which publishes model licensing standards and practice guidelines. Virginia has now passed a genetic counselor licensing statute, defining genetic counseling: 
"Practice of genetic counseling" means (i) obtaining and evaluating individual and family medical histories to assess the risk of genetic medical conditions and diseases in a patient, his offspring, and other family members; (ii) discussing the features, history, diagnosis, environmental factors, and risk management of genetic medical conditions and diseases; (iii) ordering genetic laboratory tests and other diagnostic studies necessary for genetic assessment; (iv) integrating the results with personal and family medical history to assess and communicate risk factors for genetic medical conditions and diseases; (v) evaluating the patient's and family's responses to the medical condition or risk of recurrence and providing client-centered counseling and anticipatory guidance; (vi) identifying and utilizing community resources that provide medical, educational, financial, and psychosocial support and advocacy; and (vii) providing written documentation of medical, genetic, and counseling information for families and health care professionals.
Virginia is now the first state to incorporate a conscience clause into the licensure of genetic counselors: 
Nothing in this chapter shall be construed to require any genetic counselor to participate in counseling that conflicts with their deeply-held moral or religious beliefs, nor shall licensing of any genetic counselor be contingent upon participation in such counseling. Refusal to participate in counseling that conflicts with the counselor's deeply-held moral or religious beliefs shall not form the basis for any claim of damages or for any disciplinary or recriminatory action against the genetic counselor, provided the genetic counselor informs the patient that he will not participate in such counseling and offers to direct the patient to the online directory of licensed genetic counselors maintained by the Board. 
Conscience clauses have been added into licensing or accreditation laws since the Roe v. Wade decision in 1973. Such clauses were initially written so that health care professionals or institutions with moral or religious objections to the offering of abortion services were not compelled to do so. In the decades since Roe, conscience clauses have proliferated in both federal and state laws, largely aimed at the delivery of reproductive-related services, including abortion, contraception and sterilization (thus affecting not only direct health care professionals, but pharmacists as well).The rationale for the inclusion of the Virginia statutory provision has not been made explicit, but commentary suggests that the intent is to allow genetic counselors to refuse services to same-sex couples or unmarried persons who seek genetic counseling for reproductive purposes, or to clients who may consider abortion if genetic testing reveals serious genetic disease. It’s not clear when in the sequence of service delivery the counselor may decide to withdraw from the provision of services. The clause includes a provision that removes liability for the counselor for any consequences of denying service or withdrawing from services. What is clear, however, is that this clause would authorize the denying of particular services (the more typical conscience clause) but it would also allow denial of all services to particular individuals or groups, effectively discriminating against certain individuals who seek professional care. That possibility potentially raises the specter of an equal protection challenge as services are denied to classes of individuals based on their identity or status (similar to the recent Arizona legislation that would have allowed frank discrimination by business owners against gay people; it was vetoed by Gov. Brewer). Virginia has already opened the door to denial of professional services to classes of individuals, as it enacted a conscience clause limitation for adoption agencies in 2012 (North Dakota has also done so).Thus, claims of the exercise of religious liberty in the delivery of professional services potentially conflict with established anti-discrimination laws and guarantees of reproductive autonomy. Similar overtones of the clash between claims of religious liberty and legal guarantees of equal access have surfaced in the recent Affordable Care Act litigation over mandates for the coverage of contraception, Sebelius v. Hobby Lobby Stores, Inc. (argued last week at the Supreme Court).

March 27, 2014

Colorado Referendum on Labeling of Genetically Engineered Foods Survives Ballot Challenge

The movement to place a referendum on the ballot in Colorado this year that would authorize the labeling of foods with genetically engineered (GE) ingredients has survived a legal challenge by opponents. Initiative 48 has been submitted by Right to Know Colorado GMO, which must now collect 86,105 signatures needed for the measure to appear on the 2014 Colorado ballot.  A challenge to the proposed referendum was filed by an association of retail grocers, alleging that the measure was “misleading.” That petition recited various misleading aspects of the ballot measure, including this allegation: 
The titles do not inform voters that the essence of the Proposed Initiative is that the failure to label genetically modified food is treated as "misbranding" of food. 
In an order issued by the Colorado Supreme Court, the court affirmed an earlier decision of the Title Board, which characterized the initiative in its brief to the court: 
The meat of the initiative is not misbranding. It is the creation of new labeling responsibilities to inform consumers.   
If Right to Know Colorado can submit enough signatures for the ballot, it will appear later this year. In general, state-level developments in the labeling of genetically engineered food or ingredients emerge through direct legislative enactments (see here) or by ballot measures (see here). Many state-level legislative attempts to require GE labeling have failed (such as this effort in Colorado last year), so the direct ballot route becomes an alternative. That, however, is no guarantee of electoral success (a mandatory GE food labeling referendum, Proposition 37, appeared on the California 2012 ballot, and was defeated). In fact, defeat of that referendum has swung the pendulum back to a direct legislative effort in California this year (supporters note that “SB 1381 is a simpler, clearer version of Prop. 37).” 

March 21, 2014

En banc 9th Circuit: California's DNA Collection and Profiling of Arrestees is Constitutional

In a long-awaited opinion issued yesterday in Haskell v. Harris, the en banc 9th Circuit has upheld the constitutionality of the California law that authorizes the collection and testing of DNA samples from all persons arrested for or charged with any felony or attempted felony (profiles are entered into the national CODIS database). The practice of collecting DNA from arrestees began in Louisiana in 1997. The recent trend in state DNA collection practices for law enforcement has been to expand DNA profiling from those convicted of crimes to those arrested for various crimes. The Supreme Court upheld the constitutionality of arrestee DNA collection against a 4th Amendment challenge in Maryland v. King (2013) (see earlier post). California’s expansion of its DNA database was initiated with the passage of Proposition 69 in 2004, and expanded to include arrestees in 2009. An earlier 9th Circuit panel upheld the practice in 2012, while a state court disagreed and found the practice unconstitutional. In yesterday's ruling, Judge M. Smith filed a concurrence that accompanied the terse per curiam opinion from the full panel, acknowledged the impact of King
The Supreme Court’s decision in King is fatal to Plaintiffs’ claims. 
The court did note some of the safeguards in California’s policy (and which are found in most state policies):
Only law enforcement officials may access a DNA profile, and they may only use the DNA for identification purposes. Id. §§ 295.1(a), 299.5(f). Unauthorized access or disclosure is punishable under state law by imprisonment and a criminal fine. Id. § 299.5(i). Federal law imposes similar penalties for unauthorized use of, or access to, CODIS. See 4 2 U.S.C. §§ 14133(c), 14135e(c). An arrestee who is not ultimately convicted may ask the trial court to order the sample destroyed and the DNA profile expunged. Cal. Penal Code § 299(b). 
This case took an interesting twist in 2012, when scientists in the ENCODE project published more annotation of the human genome and the development invited an analysis that the genetic markers used in forensic DNA science were more informative (and thus the collection was more invasive) than law enforcement claimed (see submission to the court by the Electronic Frontier Foundation and earlier post). There is no mention of the ENCODE-based arguments in the opinion just released. In its amicus brief, the Obama administration sided with California in arguing for the constitutionality of the law.The 9th Circuit opinion signals that 4th Amendment challenges to arrestee DNA collection are unlikely to succeed in view of King. It's possible that more detailed annotation of the human genome might provide a basis for future arguments that the CODIS markers are more informationally revealing than is currently believed (thus altering the privacy calculus), but the 9th Circuit's ruling ignored the opportunity to opine on the relevance of evolving science, leaving that to future cases.

March 10, 2014

PTO Issues New Myriad-Mayo Patentable Subject Matter Guidelines

The U.S. Patent and Trademark Office (PTO) has issued patent examination guidelines that reflect the impact of two recent Supreme Court patent decisions in the life sciences on the question of what constitutes patent-eligible subject matter. These cases challenged the Court to engage in line-drawing at the boundaries of patentable subject matter ("laws of nature, natural phenomena, and abstract ideas are not patentable"). In Mayo v. Prometheus (2012) , the Court invalidated a patent on methods of optimizing drug dosage, deciding that the patent claims had the effect of preempting a law of nature (a natural correlation). In last year’s AMP v. Myriad opinion, the Court invalidated patent claims to isolated genes on the basis that they fell within the product of nature and law of nature exceptions to patentable subject matter. Now, the PTO has issued guidelines for examiners to determine whether a patent claim differs enough from what exists in nature and thus is eligible, or whether a claim is effectively drawn to something that is naturally occurring. A three-part analysis is provided: 
Question 1: Is the claimed invention directed to one of the four statutory patent-eligible subject matter categories: process, machine, manufacture, or composition of matter? If no, the claim is not eligible for patent protection and should be rejected under 35 U.S.C. 101, for at least this reason. See MPEP § 706.03 for a description of the appropriate form paragraphs to use in rejecting the claim. If yes, proceed to Question 2. 
Question 2: Does the claim recite or involve one or more judicial exceptions? If no, the claim is patent-eligible, and the analysis is complete. If yes, or if it is unclear whether the claim recites or involves a judicial exception, proceed to Question 3. 
Question 3: Does the claim as a whole recite something significantly different than the judicial exception(s)? If the claim recites or involves a judicial exception, such as a law of nature/natural principle or natural phenomenon (e.g., the law of gravity, F=ma, sunlight, barometric pressure, etc.), and/or something that appears to be a natural product (e.g., a citrus fruit, uranium metal, nucleic acid, protein, etc.), then the claim only qualifies as eligible subject matter if the claim as a whole recites something significantly different than the judicial exception itself. 
The Guidelines provide more elaboration of factors that can be applied to the “significantly different” analysis. What’s noteworthy is that neither Supreme Court case, from which the Guidelines follow, used an explicit “significantly different” framework to sort the eligible from the ineligible. Actual touchstones for analysis from the Court include whether a law of nature is “preempted” by a patent claim or whether a natural product is more than merely “isolated” from the surrounding environment. However, the lineage of the new formulation can be traced back to Diamond v. Chakrabarty (1980):
[T]he patentee has produced a new bacterium with markedly different characteristics from any found in nature. 
The new Guidelines call for an examiner to consider whether the claim includes features or steps that demonstrate that the claimed subject matter exhibits a marked difference from what exists in nature (and the focus is on structure, not function). The Guidelines do reveal that the PTO interprets the force of the AMP decision to apply to all manner of natural products and substances, not just nucleic acids (DNA): 
In particular, claimed subject matter that must be analyzed under Question 3 to determine whether it is a natural product includes, but is not limited to: chemicals derived from natural sources (e.g., antibiotics, fats, oils, petroleum derivatives, resins, toxins, etc.); foods (e.g., fruits, grains, meats and vegetables); metals and metallic compounds that exist in nature; minerals; natural materials (e.g., rocks, sands, soils); nucleic acids; organisms (e.g., bacteria, plants and multicellular animals); proteins and peptides; and other substances found in or derived from nature. 
There was little doubt that the rationale for the Court’s rejection of the Myriad gene patent claims could easily be extended to all manner of natural products, and the Guidelines confirm that. Yet this expansive view could be litigated down the line, as proponents of patent claims on isolated products could try again to revive the Parke-Davis v. Mulford (1911) reasoning to argue commercial and therapeutic transformations of a natural product as a basis for patent eligibility (actually a more function-oriented argument). I don’t think this strategy will prevail, ultimately, but the life science-wide implications of the very recent AMP decision are not likely to go unchallenged.

February 26, 2014

FDA Hearings Consider Merits of 3-Parent IVF to Prevent Mitochondrial Disease in Offspring

The FDA is considering the merits of an assisted reproductive technology (ART) that has a goal of eliminating the transmission of genetically based mitochondrial diseases. Mitochondria, small DNA packages in the cytoplasm of the cell, are inherited in the maternally-provided egg during reproduction. For women who could transmit mitochondrial disease to offspring, this ART protocol involves the production of an altered egg, which has the nuclear DNA of the mother swapped into the egg of a woman without the genetic disease. Thus the egg is a genetic hybrid. Conventional in vitro fertilization (IVF) follows the manipulation of the egg. This technique has been dubbed "3-parent babies" because the child would inherit DNA from 2 females and one male. Is it safe? In the U.S., the FDA halted the use of a fertility treatment involving cytoplasmic transfer in eggs that was used in 2001, asserting its authority to regulate this technique as part of its ongoing supervision of the production and use of biologic products (e.g. cells, tissues, etc). Although technically genetic material is swapped around in order to “delete” the disease-causing genes, this is not quite the genetic engineering often imagined in which the nuclear genetic material would be deleted, supplemented or rearranged (”designer genes).” In fact, cellular structure makes this technique quite conceptually simple as the mitochondria are cellular organelles that exist outside the nucleus, facilitating a replacement scheme such as the one here. An Oregon scientist, Dr. Shoukhrat Mitalipov, has published experiments documenting success with the use of the technique in monkeys and would like to begin the use of the technique in humans. He would need FDA approval to begin any clinical trials in humans. In two days of open public hearings this week, the Cellular, Tissue, and Gene Therapies Advisory Committee of the FDA invited testimony from scientists and other commenters regarding the scientific, technical and clinical concerns for the use of mitochondrial manipulation technologies. They described their task: 
The committee will discuss oocyte modification in assisted reproduction for the prevention of transmission of mitochondrial disease or treatment of infertility. 
The FDA asserts its authority over the use of this technique as deriving from its role in regulating the production and use of biologic materials, from its ongoing review of protocols that involve genetic manipulation, as well as its goal of insuring the safety of human study subjects. In a briefing document prepared for the hearings, the committee cited a long list of potential safety concerns for both mother and child from the use of the mitochondrial replacement technique: 
Potential risks to the women could include: 1) failure to become pregnant; 2) failure to deliver a child; 3) risks associated with the specific mitochondrial manipulation technology procedure; and 4) toxicities of the reagents used in mitochondrial manipulation technologies. Potential risks to their children could include: 1) mitochondrial disease (particularly in women with mitochondrial disease), as a result of carryover of abnormal mitochondria and heteroplasmy; 2) disorders due to nuclear mitochondrial incompatibility; 3) disorders related to aberrant epigenetic modifications ; 4) birth defects and other disorders associated with the specific mitochondrial manipulation technology procedure; and 5) toxicities of reagents used in mitochondrial manipulation technologies. There may be additional risks that are difficult to predict because of limitations in current knowledge. 
The FDA will receive public comment on a draft guidance it has issued to those designing protocols for early-phase clinical trials with such techniques. The public comment period closes May 9, 2014. Although fertility clinics in the U.S. are not subject to extensive oversight from the FDA or any other agency, this proposed ART technique comes under FDA purview by its use, manipulation and transfer of biologic products into humans. Effectively, and critically, this technique is a germ-line modification of an embryo, meaning that the genetic manipulation will be carried into future offspring which inherit the replaced mitochondria. That fact heightens the concerns over the safety and ethical dimensions of potential use. Germline modification of embryos is prohibited in at least 40 countries, and there has been a kind of international consensus against use of these techniques. However, in a sign that a more nuanced regulation of certain ARTs may be developing, the UK is also considering whether to approve this use of this ART.