Supreme Court

Here’s The Scary Truth About Science & The Death Penalty

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A recent pair of botched executions has renewed the debate over lethal injection and whether it’s actually less inhumane than other methods used to execute condemned prisoners.

In January, when Ohio used a new drug “cocktail” to execute convicted rapist and murderer Dennis McGuire, he reportedly gasped repeatedly and took more than 25 minutes to die. Days earlier, when Oklahoma executed Michael Lee Wilson, the convicted killer uttered these last words: “I feel my whole body burning.”

Leaving aside the issue of whether the death penalty itself is inhumane, one might think that science could be enlisted to help devise a method of execution that spares the condemned from needless suffering.

Certainly there are historical examples of scientists and physicians offering their execution expertise. In the late 19th Century, researchers in the U.S. developed the electric chair as a more humane alternative to public hangings. Despite their efforts, executions using the chair often proved to be quite grotesque. As U.S. Supreme Court Justice William Brennan wrote in a dissent to the Supreme Court in the case of Glass v. Louisiana (1985):

The prisoner’s eyeballs sometimes pop out and rest on [his] cheeks. The prisoner often defecates, urinates, and vomits blood and drool. The body turns bright red as its temperature rises, and the prisoner’s flesh swells and his skin stretches to the point of breaking. Sometimes the prisoner catches on fire … Witnesses hear a loud and sustained sound like bacon frying, and the sickly sweet smell of burning flesh permeates the chamber.

Roughly a century earlier, French physicians Joseph-Ignace Guillotin and Antoine Lois developed the guillotine to be a painless and efficient execution machine.

In any case, many doctors today are guided by the Hippocratic Oath, which forbids them from willfully inflicting harm on others.

“It is unethical for physicians (the only ones with the requisite knowledge) to participate in the unwilling demise of any human being,” Dr. David Lubarsky, anUniversity of Miami anesthesiologist who has conducted research on lethal injection, told The Huffington Post in an email. “We don’t kill people who want to live. We don’t help others kill people who want to live… Once you cross the line as an agent/enabler of the state to cause the death of someone not seeking to die, you are no longer a healer.”

When lethal injection got its start in 1977, the medical community certainly kept its distance.

As Deborah Denno, a Fordham University law professor who has testified in many lethal injection cases, said of the invention of the three-drug protocol typically used in lethal injection, “There was no medical testing of the drug combination. There was no science. I think it was the pretense of science and a medical veneer. It was basically concocted in an afternoon.”

Now, in some states, critical drug shortages have forced corrections departments to find new untested drug alternatives.

“It’s not like you have a scientific expert sitting there and saying ‘these are the drugs you should use and in this amount.’” Denno said. “To the contrary I think one of the reasons we see these constant problems and this jump from drug to drug is these people, either they’re getting no advice whatsoever or the advice they’re getting is very bad and it’s all under the table.”

Even if science could aid in the development of a more humane killing method, Denno said, those with the appropriate expertise are unlikely to get involved.

“In light of a long-standing history from the late 1800s up to the present time, I would be extraordinarily surprised if the scientific community ever got involved in this issue.”

Keep reading for a look at methods of execution in use at various times.

Importance of data sharing.

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Withholding information on the clinical significance of genetic variants from the scientific community impedes the progress of research and medicine.

Imagine you are a physician or researcher and seek to get more confirmation on the clinical impact of particular genetic variants. If your search of public databases comes up empty this does not necessarily mean that nothing is known about the mutations in question. Rather, the information may be locked away as a trade secret in a genetic testing company’s proprietary database.

Physicians and their patients are not able to independently verify the medical significance of a testing company’s finding, instead the results have to be taken on blind faith.  Researchers are limited in their knowledge of the vast mutational landscape in genes associated with diseases such as cancer which in turn may limit their understanding of the molecular underpinning of the disease.

Robert Nussbaum, at the University of California, San Francisco, recently pointed out that in other fields of medicine such an approach would be unthinkable. In a Technology Review he said, “Imagine if radiological images or histopathology slides of cancers were examined by a single monopoly holder without the medical community being able to assess and learn from what these images and tissue specimens teach us.” He launched  the Sharing Clinical Reports Project, an initiative to collect de-identified information on genetic testing data on the BRCA1 and 2 genes (as discussed in our August editorial).

With more genetic testing companies likely to enter the market, after the US Supreme Court invalidated some gene patents, the problems caused by proprietary data may increase. Clinicians may now have more options to obtain a genetic test, but, if they go with the less established testing company, they are then left with a suboptimal interpretation with possibly grave implications for the patient.

A resolution  from the American Medical Association passed in June 2013 supports public access to genetic data. The resolution calls for companies, laboratories, researchers and providers to publicly share data on genetic variants in a manner consistent with privacy and HIPAA protections.

Whether such calls will be heeded is another question. In a New York Times OdEd piece aptly named “Our genes, their secrets” the author wonders if the recent Supreme Court decision will prompt genetic testing companies to rely more on this strategy of treating information on the clinical impact of mutations as trade secrets and thereby try to deter competition and ensure revenue.

How can this be prevented? Cook-Deegan et al.  – in a recent article in the European Journal of Human genetics – call for joint action by national health systems,  insurers, regulators, researchers, providers and patients to ensure broad access to information about the clinical significance of variants. Some of their suggestions, besides the promotion of voluntary sharing, include sharing as a condition of payment or regulatory approval of the testing laboratories.

The battle about who may offer certain genetic tests is certainly heating up. Ambry Genetics and Gene by gene, two of the companies now offering BRCA1 and 2 testing, have been sued by Myriad Genetics for patent infringement.  A few days later, on July 12, US senator Patrick Leahy, a democrat from Vermont, wrote to Francis Collins, the director of the NIH, urging him to force Myriad to license the patent on reasonable terms to other parties to ensure affordable life-saving diagnostic tests.  As the federal  agency that provided the funding for the research behind Myriad’s patent  the NIH has the authority to do so, based on a provision in the Bayh-Dole Act that enabled universities to own inventions based on federal funding. Whether it will exercise this authority is unclear. Collin’s reply is still outstanding.

Ambry Genetics disputes that it infringes any of Myriad’s patents and a company spokesperson told Nature Methods that Ambry plans to share their testing data.

If enough companies follow suit, the desirable equilibrium of compensating a company fairly for the cost of its test and at the same time letting the public benefit from the results of these tests should be within reach.

Source: http://blogs.nature.com

 

Heritable genetic changes in the open.

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To correctly interpret human genetic variation in hereditary disorders, researchers and clinicians should populate databases that distribute aggregated information on the clinical significance of these variants.

Closely linked to the recent Supreme Court decision (docket 12-398) limiting the scope of patenting human genes, discussion has been growing about whether anonymized data collected by genetic testing laboratories should be freely available. The perceived unwillingness by some companies, who often are the sole provider of a particular test, to share such anonymized data on genetic variants has drawn sharp criticism from researchers and clinicians.

Myriad Genetics provides a good illustration for how big the difference between what is known by a company and what is available to the community can be. Until the court decision, the company held the monopoly on testing for hereditary mutations in the DNA repair proteins BRCA1 and BRCA2; some of these mutations confer a high risk for breast and ovarian cancer. With data from an estimated 1 million tested patients, Myriad’s database allows high-accuracy classification of a patient’s variants as one of four classes indicating the degree of pathogenicity. Only 3% of the variants Myriad encounters in the United States fall into a fifth class, that of variants of unknown significance (VUSs).

In contrast, with freely accessible databases, an average of 15% of BRCA1 and BRCA2 variants cannot be classified and remain VUSs, says Alvaro Monteiro, who is part of the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium focused on classifying BRCA mutations.

This puts researchers outside of Myriad, as well as clinicians, at a considerable disadvantage with respect to fully understanding the impact that changes in these genes can have.

Myriad’s and other companies’ hands may be tied when it comes to data sharing. According to a company spokesperson, Myriad is subject to oversight from the Clinical Laboratory Improvement Amendments and the US Food and Drug Administration. “Consistent with these regulations, we are not allowed to distribute our variant databases, as they may only be used to interpret clinical test results for patients tested in our laboratories.” The company does, however, collaborate with researchers, given their appropriate institutional approval, to help classify VUSs in the context of a specific study and allows the results to be published.

This is a laudable, if small, step that may narrow the knowledge gap, but scientists want to bring information on all variants into the public domain on a much larger scale and are organizing efforts to that end. These efforts will stand or fall depending on community support.

Robert Nussbaum from the University of California, San Francisco, started a grassroots effort, the Sharing Clinical Reports Project (SCRP), appealing to patients and clinicians to share data on BRCA testing in appropriately anonymized form. The aggregated data are submitted to open databases such as the Breast Cancer Information Core (BIC) or ClinVar. SCRP is ready to submit its first 1,885 variants, including 351 that are new to BIC, according to Lawrence Brody, who founded BIC in 1995. These numbers show that the project resonates with people and is gaining traction.

ClinVar strives to be the most comprehensive of such databases. Founded in 2012 and hosted by the US National Center for Biotechnology Information, it aims to collect information on variation in any gene that affects human health, together with phenotypic information for such variants. It currently hosts around 38,000 variants (in about 3,000 genes) from about 90 different submitters, including genetic-testing laboratories from industry and academia.

ClinVar does not provide recommendations for medical diagnosis to patients or physicians. It is meant to be a resource for scientists, clinicians and genetic counselors who want to investigate a particular variant and its clinical implications in more detail.

Hopefully community support to expand the number of genes that ClinVar covers will increase. To ensure high data quality, ClinVar will need independent confirmatory submissions on each gene variant. More detailed phenotypic description of the conditions associated with each variant and the likely pathogenicity, where appropriate, would further enhance value.

It is hard to forecast whether genetic testing will increase in the wake of the Supreme Court decision. Lawsuits filed by Myriad Genetics and other plaintiffs against Ambry Genetics and Gene by Gene on 9 and 10 July, respectively, indicate looming legal battles. Regardless, efforts such as SCRP and ClinVar need support to ensure that genetic information is shared in appropriate forms to benefit not only individual patients but the research community at large.

Source: http://www.nature.com

Gene Patents and Personalized Cancer Care: Impact of the Myriad Case on Clinical Oncology.

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Genomic discoveries have transformed the practice of oncology and cancer prevention. Diagnostic and therapeutic advances based on cancer genomics developed during a time when it was possible to patent genes. A case before the Supreme Court,Association for Molecular Pathology v Myriad Genetics, Inc seeks to overturn patents on isolated genes. Although the outcomes are uncertain, it is suggested here that the Supreme Court decision will have few immediate effects on oncology practice or research but may have more significant long-term impact. The Federal Circuit court has already rejected Myriad’s broad diagnostic methods claims, and this is not affected by the Supreme Court decision. Isolated DNA patents were already becoming obsolete on scientific grounds, in an era when human DNA sequence is public knowledge and because modern methods of next-generation sequencing need not involve isolated DNA. The Association for Molecular Pathology v Myriad Supreme Court decision will have limited impact on new drug development, as new drug patents usually involve cellular methods. A nuanced Supreme Court decision acknowledging the scientific distinction between synthetic cDNA and genomic DNA will further mitigate any adverse impact. A Supreme Court decision to include or exclude all types of DNA from patent eligibility could impact future incentives for genomic discovery as well as the future delivery of medical care. Whatever the outcome of this important case, it is important that judicial and legislative actions in this area maximize genomic discovery while also ensuring patients’ access to personalized cancer care.

Source: JCO

The FDA’s Graphic Tobacco Warnings and the First Amendment.

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In the past, constitutional principle gave the government broad authority to regulate tobacco or pharmaceutical advertising. The state’s power to safeguard the public health was strong, and companies’ freedom to plug their products was weak.

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But the Supreme Court has changed course. Whereas it once did not view “commercial” speech as the kind of speech the First Amendment protects, it now gives businesses nearly the same rights to market their goods as it does individuals to speak their minds. And as the Court has broadened corporate freedom to advertise, it has narrowed governmental power to preserve the public’s health. Whereas the Court once gave the government more leeway when invoking its interests in public health than when asserting other state interests, it now tends to hold health-related rules to the same constitutional standards as other types of rules.1

As a result, government today is much more susceptible to challenge when it tries to regulate the promotional activities of the tobacco or pharmaceutical industry. In 2011, the Supreme Court rejected Vermont’s effort to restrict the use of prescription data by drug companies’ sales representatives.2 And last year, the U.S. Court of Appeals for the D.C. Circuit vetoed the new graphic warnings for cigarette packages that had been issued by the Food and Drug Administration (FDA).3 The Supreme Court’s increasing sympathy for corporate speech and decreasing deference to public health authorities makes it more difficult for government to protect the public’s health. The fate of the graphic cigarette warnings is illustrative.

Congress authorized the graphic warnings when it passed the Family Smoking Prevention and Tobacco Control Act in 2009. The Act requires the use of nine new textual warnings for cigarette packages and directs the Department of Health and Human Services to select color graphics to accompany the warnings. The images have to depict the “negative health consequences” of smoking, with text and graphic taking up the top halves of each pack’s front and back panels.

In June 2011, the FDA unveiled the nine images, including some that were quite explicit. One image showed a man smoking through a tracheostomy (see image). Another showed the corpse of a man with staples in his chest on an autopsy table. Several tobacco companies promptly sued, alleging that the graphic-warning requirements violated their First Amendment rights. The companies prevailed in both the district court and the D.C. Circuit.

In one sense, the result was not surprising, given the Supreme Court’s increased sympathy toward corporations and their First Amendment rights. Regulations of commercial speech often succumb to judicial scrutiny.

However, there was good reason to think that the D.C. Circuit would uphold the graphic warnings. Even as the Supreme Court has narrowed the power of government to regulate corporate speech, it has preserved an important authority to regulate. The graphic warnings seemed to fall within that authority.

The preserved authority reflects the distinction the Supreme Court makes between the regulation of corporate speech that informs and the regulation of corporate speech that misinforms. On the one hand, the Court usually objects when the government tries to block truthful speech by businesses. In the prescription-data case, the Vermont law would have restricted the free flow of information about physicians’ prescribing practices. On the other hand, the Court typically approves when the government tries to prevent false or deceptive speech by businesses. For example, the government may forbid companies from saying things that are not true. It also may require companies to make disclosures that will allow consumers to make informed choices and not be misled by advertising hype. Common disclosure requirements include the corporate prospectus for stock offerings, the total interest payments for a home mortgage, nutritional information for foods, and the textual warnings for cigarettes.

The graphic cigarette warnings appeared to serve purposes similar to those of other required disclosures. The warnings would promote understanding of the risks of smoking and prevent people from being misled by cigarette marketing.

Indeed, the U.S. Court of Appeals for the Sixth Circuit had upheld Congress’s authority to mandate graphic warnings.4 As that court observed, people often do not read textual warnings on cigarette packages. And even when read, the warnings may not be effective in informing consumers about the risks to their health. Adding color images can ensure that textual warnings are noticed, read, and understood. Sometimes a picture really is worth a thousand words.

Even though the Supreme Court let the Sixth Circuit’s decision stand, its effect is limited. The Sixth Circuit considered only whether Congress may require some graphic warnings. The D.C. Circuit considered the constitutionality of the FDA’s actual warnings.

In rejecting the warnings by a two-to-one vote, the D.C. Circuit identified two problems. First, the majority did not think the images were needed to prevent cigarette companies from misleading consumers. Other statutory provisions already prohibited many kinds of deceptive labeling or advertising. The court was not willing to defer to the FDA’s judgment that the new images were necessary. Second, the warnings were not designed simply to ensure that consumers fully understand the risks to their health from cigarettes. Instead, wrote the majority, the warnings would primarily serve to convey the government’s antismoking message. Indeed, each of the new images would include the phone number for the National Cancer Institute‘s tobacco cessation hotline, 1-800-QUIT-NOW. Whereas government may use its own resources to publicize its perspectives, it generally may not force individuals or corporations to spend their dollars to disseminate its viewpoint.

Rather than seek Supreme Court review of the D.C. Circuit’s decision, the FDA opted to return to the drawing board and develop new graphic warnings. In the meantime, we are left with some important questions.

First, when do graphic warnings cross the line between trying to inform and trying to persuade? Does it depend on how “shocking” or how prominent they are? Two of the three D.C. Circuit judges thought that the images were designed to evoke an emotional response rather than to convey factual information. The dissenting judge cited the FDA’s point that warnings more effectively communicate information when they elicit a strong emotional reaction. In addition, the images would provide information about risk when viewed in conjunction with their accompanying text. For example, the image of the man smoking through a tracheostomy accompanied the warning “Cigarettes are addictive” and would have illustrated the tenacity of nicotine addiction. In the dissenter’s view, the images would have been acceptable without the cessation hotline number.

Second, must the warnings correct misleading impressions from the company’s cigarette packaging or current advertisements, or may they also correct misimpressions from past promotional materials?

Third, if courts will not defer to the judgment of public health authorities about the need for disclosure mandates, what kind of empirical evidence must the FDA present in order to justify the use of graphic warnings?

Whatever the answers to these questions, companies today are better able to promote their products, and government is less able to promote health than was the case in the past. Ironically, early protection of commercial speech rested in large part on the need to serve consumers’ welfare. In 1976, for example, the Supreme Court struck down a Virginia law that prevented pharmacists from advertising their prices for prescription drugs.5 The law especially hurt persons of limited means, who were not able to shop around and therefore might not be able to afford their medicines. Today, by contrast, courts are using the First Amendment to the detriment of consumers’ welfare, by invalidating laws that would protect the public health.

 

REFERENCES

  1. 1

Orentlicher D. The commercial speech doctrine in health regulation: the clash between the public interest in a robust First Amendment and the public interest in effective protection from harm. Am J Law Med 2011;37:299-314
Web of Science | Medline

  1. 2

Sorrell v. IMS Health, Inc., 131 S. Ct. 2653 (2011).

  1. 3

R.J. Reynolds Tobacco Co. v. FDA, 696 F.3d 1205 (D.C. Cir. 2012).

  1. 4

Disc. Tobacco City & Lottery, Inc. v. United States, 674 F.3d 509 (6th Cir. 2012).

  1. 5

Virginia State Bd. of Pharmacy v. Virginia Citizens Consumer Council, 425 U.S. 748 (1976)

Source: NEJM

 

Gene Patenting — The Supreme Court Finally Speaks.

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Are human genes patentable? On June 13, the Supreme Court gave its long-awaited answer — a unanimous “no.” The case, Association for Molecular Pathology v. Myriad Genetics, 1 has generated enormous interest among medical institutions, industry organizations, patient advocacy groups, and scientists. “ Life’s instructions,” James Watson asserted in one of 49 amicus curiae briefs, “ought not be controlled by legal monopolies created at the whim of Congress or the courts.” For some, the gene patents were symbols of a shrinking public domain and an overreaching patent system that traded too much monopolistic power for too little innovation. For others, the challenge to the patented genes amounted to an attack on the intellectual-property protections that fuel private investment in biomedical discovery.

Although ethical and policy arguments were a major feature of the debate surrounding the case, the decision focused squarely on the definitions of two codes: the genetic code and the patent code. All nine Justices of the Court agreed that the segments of DNA that make up human genes are not patentable subject matter under section 101 of the Patent Act2 because they are products of nature. However, the Court held, molecules that are reverse-transcribed from messenger RNA (mRNA) to eliminate intron sequences — so-called complementary DNA (cDNA) — are eligible for patents. The decisive sentence of Justice Clarence Thomas’s ruling crisply stated that, “a naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated, but that cDNA is patent eligible because it is not naturally occurring.”

The decision joins a suite of recent Supreme Court cases that are reshaping patent law, with important implications for innovation in the life sciences. Here we review the Myriad Genetics case and the reasoning of the Court and discuss the implications for health care and the biotechnology industry. Patient advocates and industry groups alike can find something to celebrate in this Supreme Court decision: although it will open up competition in the genetic testing arena and drive down prices, it leaves undisturbed most of the intellectual-property rights on which the biotechnology industry depends.

THE BATTLE OVER PATENTING BREAST-CANCER GENES

The human genes at issue in the Myriad Genetics case are BRCA1 and BRCA2. In federally funded research dating back to the 1980s, Mary-Claire King and others identified a region of chromosome 17 that must contain a gene mutated in families with many cases of breast cancer. That gene became known as BRCA1, and it turned out to also predispose women to ovarian cancer.

King’s 1990 report of genetic linkage for a “breast-cancer gene”3 set off an intense race to clone and sequence it. A team led by Mark Skolnick of the University of Utah won that race4; Skolnick was also a cofounder of Myriad Genetics. In 1994, Michael Stratton and others mapped another locus in chromosome 13,5 which precipitated another furious race to identify and clone what became known as BRCA2. That race ended in a near tie,6 with the Stratton group publishing in Nature 7 just a day after Myriad filed a patent application,8-10 having gotten wind of the Stratton work.11

Myriad sought patent protection for methods of detecting and comparing DNA sequence variations and for the isolated DNA molecules. The claims on DNA molecules included cDNA and genomic DNA, sometimes both in the same claim. The Supreme Court parsed these elements in its decision .Types of Patents Issued to Myriad Genetics Relating toBRCA.). Applications by Myriad for BRCA1 and BRCA2 were broken into separate patents, covering different aspects of the work. These patents undergirded the commercialization of its BRACAnalysis test for predisposition to breast cancer, which Myriad first made available in 1996. Myriad filed subsequent patents and acquired rights to other BRCA patents by out-of-court settlements and now states that it has 24 patents containing over 500 claims relating to this field.12

The American Civil Liberties Union (ACLU) and the Public Patent Foundation, representing more than 20 plaintiffs, filed suit against Myriad in May 2009 in federal court for the southern district of New York. The litigation arose in large part because, in the intervening decade, a steady drumbeat of criticism had grown against the business practices of Myriad and against patents on genes in general. Objections raised by public health advocates included the restriction set by Myriad on certain uses of its genes in the context of research, its refusal to allow independent confirmatory testing of ambiguous initial results,13 and the high price of its genetic test (up to $4,000).14Advances in sequencing technology had made it possible for patients to have dozens of genes sequenced for less than what Myriad charged for BRCA1 and BRCA2 testing.15 Fueling advocates’ arguments were surveys showing that gene patents reduced access to testing16,17 and research showing that legal restrictions on gene sequences reduced product development by up to 20 to 30%, as compared with diagnostic products arising from freely available sequences.18

Inventors must satisfy several statutory criteria in the Patent Act to obtain patent protection, but theMyriad case focused on just one: whether the claimed inventions met the basic definition of patentable subject matter. That is, did they constitute inventions at all? The Patent Act defines the scope of patentable subject matter as “any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof.”2 The Supreme Court has previously established that “Anything under the sun that is made by man” is eligible for a patent19but has read into the patent statute an important implicit caveat that laws of nature, natural phenomena, and abstract ideas belong in the public domain.

In March 2010, Judge Robert Sweet of the southern district of New York issued a summary judgment order in the Myriad case, invoking long-standing Supreme Court doctrines to conclude that this caveat excluded DNA from patentability.20 He invalidated all 15 claims challenged in seven of the Myriad patents. The next year, a divided panel of the Court of Appeals for the Federal Circuit tempered the district court holding. The three-judge panel unanimously affirmed Judge Sweet’s determination that Myriad could not patent its method of testing for cancer risk by comparing a patient’s isolated BRCA1 and BRCA2 sequences to the reference sequences. By contrast, the panel upheld the method claim for the use of BRCA1 and BRCA2 in screening potential therapeutic agents against cancer and held that cDNA could be patented.

Most controversially, the Federal Circuit split 2 to 1 on whether DNA molecules corresponding to sequences found in cells were patentable because they were described in the patent claim as “isolated.”21 The two judges in the majority reached their conclusion that isolated DNA is eligible for patents in different ways. Judge Alan Lourie reasoned that the act of severing covalent bonds in the process of isolating the DNA created a new molecule, and Judge Kimberly Moore argued that not only fragmentation but also the demonstrable utility of isolated DNA sequences, as compared with native DNA, was the basis for patent eligibility.22 Judge William Bryson wrote a vigorous dissent arguing that isolated molecules were not eligible for patents because they were not different enough from their natural counterparts.

The Supreme Court reviewed the decision of the Federal Circuit court in 2011 but sent the case back for reconsideration in light of a newly issued Supreme Court decision invalidating a patent on a method of diagnostic testing.23 The Federal Circuit court judges did not substantively change their opinions in 2012, reiterating the same logic and coming to the same 2-to-1 split.24 On November 30, 2012, the Supreme Court agreed to hear arguments on one question only: Are human genes patentable?

SUPREME COURT DECISION

To answer this question, the Supreme Court returned to the opaque and oft-contested boundary line between human inventions and discoveries of naturally occurring phenomena. Writing for a unanimous Court, Justice Thomas cited the long history of the Court of drawing a distinction between compositions of matter that are made by humans and those that are naturally occurring.Major Supreme Court Decisions Defining the Boundary between Inventions and Products of Nature.). The relevant doctrine, however, has been “vague and malleable,” in the words of Justice Felix Frankfurter in a seminal 1948 case.25 Cases have lacked clarity and consistency during the past hundred years, with the criterion that inventions must involve the application of human ingenuity seemingly established in different ways.

In considering patents on DNA sequences, Justice Thomas struck a balance between the long-standing principle that discoveries of natural phenomena are not patentable and the competing notion that “all inventions at some level . . . apply laws of nature, natural phenomena, or abstract ideas” by drawing a line between genomic DNA and cDNA. The isolated DNA sequences were not the proper subject of patents, he wrote, because they were not markedly different from the sequences found in nature. Indeed, they derived their diagnostic usefulness from having the identical sequence. Justice Thomas distinguished between the claims of Myriad and those at issue in the landmark 1980 case of Diamond v. Chakrabarty, which ushered in the modern explosion in biotechnology patents. In that case, a bacterium was genetically engineered to contain four naturally occurring plasmids, each of which was useful in breaking down oil. The inventor inserted the plasmids into the DNA of the microbe, giving rise to an organism not found in nature. No similar transformation of a product of nature was present in the claims of Myriad covering the isolated DNA sequences.

The cDNA claims, the Court held, were another matter. Because cDNA is reverse-engineered by scientists from mRNA to include only the protein-coding exons, it is different from any naturally occurring genetic material. It thus falls on the invention side of the line between discovery and invention. To then earn a patent, a sequence of cDNA would have to meet the remainder of the criteria required in the Patent Act of all inventions, including novelty, utility, and nonobviousness, although these considerations were not at issue in the Myriad case.

The parties challenging the cDNA patent claims argued that cDNA is a product of nature because it represents the naturally determined stretch of nucleotides that codes for the mRNA. Its information is what matters, they asserted, and that is the same as naturally occurring DNA. However, the Court focused on the human ingenuity involved in reverse-transcribing the sequence as a separate nucleotide array. The fact that some DNA sequences mimicking cDNA may occur by chance in nature was deemed insufficient to undercut its patentability.

Myriad represents the third in a series of decisions since 2010 in which the Supreme Court has redefined the boundaries of its three main exclusions from patentability — laws of nature, natural phenomena, and abstract ideas. In each of these categories, the Supreme Court has ultimately shown a more restrictive stance on patent eligibility than the Patent and Trademark Office.

The first case, Bilski v. Kappos, involved an abstract idea. In striking down a patent on an investment strategy, the Court announced that it supported a “high enough bar” on patenting abstract ideas that would not “put a chill on creative endeavor and dynamic change.”26 The patent was invalidated because it “would preempt use of this approach in all fields,” over a vigorous dissent from Justice John Paul Stevens, who agreed with the outcome but wanted to set down an even more formal rule excluding business methods from patent eligibility.

Next in 2012 came Mayo v. Prometheus, in which the Court unanimously invalidated patent claims on a method of adjusting the dose of thiopurine antiinflammatory drugs on the basis of metabolite levels.23 In that decision, the Court expressed concern “that patent law not inhibit further discovery by improperly tying up the future use of laws of nature,” which in that case was the correlation between doses of a drug and its physiological effects.27

Myriad extends this judicial anxiety to the context of DNA molecule claims. In concluding that “[g]roundbreaking, innovative, or even brilliant” discoveries of such natural phenomena are not patentable, the Court stressed the social cost: it “would `tie up’ the use of such tools and thereby `inhibit future innovation premised upon them.’”

IMPLICATIONS FOR HEALTH CARE AND INNOVATION

Advocacy groups have heralded the Myriad decision as a huge win for patients. “VICTORY!,” the ACLU declared, “Our genes belong to us!”28 The invalidation of genomic DNA claims — and the earlier refusal by the appellate court to allow patents on methods of detecting BRCA1 and BRCA 2mutations — permits other companies to market their own genetic tests. Indeed, within days of theMyriad ruling, at least five competitors had announced that they would enter the market.29,30

Myriad has responded to this new competition with further infringement litigation.31 Patent claims by Myriad covering other methods and other “synthetic” DNA sequences such as primers and probes have not been challenged, and the Supreme Court specifically noted that they might indeed cover patentable subject matter. With the prospects for such infringement claims uncertain, however, Myriad may also seek to capitalize on its proprietary library of BRCA mutations, which provides a competitive advantage in interpreting rare mutations. The last deposit of data on BRCA variations by Myriad into the federal Breast Cancer Information Core database occurred in 2004, and a group of coauthors, including some from Myriad, published a manuscript listing 118 additional mutations in 2006.32 Since then, Myriad has not made public other BRCA variations that it received while holding its monopoly on testing. Recently, a physician-led grassroots effort has been organized to obtain data on rare variants directly from patients and their providers and publicly disseminate it, which could undermine this competitive advantage.33,34

Ultimately, the end of the Myriad monopoly should improve access to genetic testing and rapid turnaround of results by driving down the price — DNA Traits, for example, will charge less than $1,000 — and expanding capacity for analyzing samples. When the case was brought, one crucial concern was whether the claims in question blocked analysis by means of whole-genome sequencing. Myriad argued that its patents on isolated DNA involved sequestering BRCA sequences from others in the genome and that whole-genome sequencing would not infringe such patents. The ACLU pointed out, however, that the plain meaning of the claims would indeed cover molecules created during whole-genome sequencing. Given the outcome of the case (and in light of the oral arguments presented by Myriad before the Court), institutions offering whole-genome sequencing should no longer fear lawsuits from parties holding patents on isolated DNA.35

Although the Myriad decision places in jeopardy thousands of patent claims, its effects on biotechnology companies and innovation will probably be modest. A recent analysis estimated that as many as 3535 unexpired patents on naturally occurring, human gene sequences may be affected,36 although the applicability of the decision will depend on the specifics of each individual patent claim. Furthermore, because nothing about the reasoning of the Supreme Court would prevent its holding from being applied to nonhuman genes, several thousand patent claims relating to other organisms may also be affected, with implications for a range of applications outside human medicine. However, the same study showed that patent claims on merely isolated DNA were already on the decline. Since 2005, companies have sought to patent naturally occurring gene sequences much less frequently than they did in the past, perhaps because the Patent and Trademark Office raised the bar for meeting another requirement for patenting an invention — showing that it has practical utility. Some companies also found it more difficult than expected to profit from these DNA sequences and abandoned their patents.35,37,38 As a result, after Myriad, we expect that companies developing DNA-based therapeutic agents will need to more clearly distinguish their inventions from the genome itself and specify the claimed uses so as to avoid questions about covering the naturally occurring sequences.

Claims on DNA that has been engineered, in contrast, have been on the rise — in both frequency and scientific importance36 — and will continue to enjoy protection after Myriad.35 Patents on synthetic DNA include those on vectors and engineered molecules that could be useful as therapeutic agents themselves (e.g., in gene transfer) or in the process of making therapeutic proteins for so-called biologic drugs. Since these technologies remain squarely within the bounds of patentability outlined by the Supreme Court, the effects on innovation emerging from these areas should be minimal.

The impact of the Myriad decision on innovation will also be muted by the fact that the holding itself was clearly limited by Justice Thomas to isolated DNA corresponding to sequences found in nature. However, it may affect patent applications on DNA-based therapeutic agents, such as (still experimental) DNA vaccines, which will now have to clarify how the active sequence is not merely isolated but has been transformed and has a specific utility. It could also spill over into other areas of medical research, such as the development of diagnostic testing for microbes, which have genomes lacking introns altogether.

Finally, Myriad is important as an expression of strident judicial opposition to patents on methods of making medical diagnoses. The method claims for detecting genetic sequence alterations were struck down unanimously by the Federal Circuit court, and the Supreme Court declined to take up the question on appeal. It will therefore be impossible for companies to mimic a business model of identifying a gene sequence and attempting to control the production of diagnostic tests from it. The combination of the Myriad and Mayo decisions greatly diminishes the prospects of Myriad or any other company claiming monopolies on genetic diagnostic tests alone, without a direct linkage to therapeutic agents or other molecular transformations. For example, companies seeking to develop multigene diagnostic or prognostic tests will have to try to claim some combination of methods of diagnosis and modification of the DNA molecules, rather than relying simply on patents covering the underlying isolated DNA. Whether this will reduce private investment in genetic diagnostic testing and necessitate supplemental public research funding remains to be seen.

CONCLUSIONS

The Myriad decision will be an important symbol for those who seek to foster scientific discovery by protecting and expanding the public domain. It also has symbolic resonance with the ideal that our common humanity cannot be owned. The Universal Declaration on the Human Genome and Human Rights declares the human genome to be “the heritage of humanity” and that “the human genome in its natural state shall not give rise to financial gains.”39 The Supreme Court quietly came to a similar conclusion, though with attention to preserving the incentives important for biomedical innovation.

It is interesting that although the Supreme Court decision concerns human genes, humanness had no bearing on the decision. Nor does the law allow courts to consider whether patenting human genes — or anything else — should be disallowed on grounds of morality. There is a disconnect, then, between the reasons the Supreme Court articulated for its decision and the rich set of ethical and policy concerns that have animated much of the public interest in the case.

Those powerful ideas may or may not have swayed the Court as it considered a vague and open-ended legal doctrine. If the questions raised during oral argument are any indication, however, the justices were primarily interested in innovation — both in preserving patent incentives for investing in research and in the blocking effects that patent rights can have on upstream discovery. Viewed in this light, the decision represents a careful balancing act.

Source: NEJM