Inside Opinion: Fears Over European Stem Cell Decision Overstated – a View from the Trenches

Posted By Dr. Torsten Holm Nielsen – Dec. 11, 2011

Dr. Torsten Holm Nielsen is a Danish physician who has practised in Denmark and Sweden. Dr. Nielsen is also an oncology researcher investigating innovative drug treatments for difficult to treat B cell lymphomas.

The recent ruling from the European Court of Justice (EJC) banning patents on materials derived from human embryos, hereunder-embryonic stem cells, has drawn much attention of late. European stem cell researchers in both academia and industry as well as legal professionals have warned that the decision may weaken the ability of European stem cell research to attract funding which will lead to an exodus of stem cell research from the European Union (EU) to areas of the world where better legal protection for novel technologies/applications is available. In my opinion, this is likely an exaggeration and I think the impact of this ruling on European stem cell research may be less severe than feared for two reasons. First, any new technologies involving embryonic stem cells will almost certainly also involve other highly complex methods and technologies not directly related to embryonic stem cells and therefore patentable under EU law, thereby offering a degree of protection of the combined technology. Second, stem cells can be “induced” from non-stem cells derived from adult tissues, thereby obviating the need for embryonic stem cells. Technologies derived from these induced pluripotent stem cells would not be subject to the decision concerning embryonic stem cells, making them an attractive alternative. The EJC’s ruling probably represents a desire on the part of the Court to very clearly convey the message that human embryos are not to be commercialized. It is to be hoped that this message does not also spell the end of European stem cell research.

House of Representatives Passes Protect Life Act

Posted By Rosel Kim – Nov. 28, 2011

On October 13, 2011, the U.S. House of Representatives passed the controversial H.R. 358, better known as Protect Life Act, amending federal coverage to abortions and protecting the rights of institutions and persons refusing to perform abortions. The Act has been met with condemnation from the Democrats, as well as women’s rights groups. Nancy Pelosi strongly opposed the Act by stating: “women can die on the floor and health care providers do not have to intervene.” This strong criticism comes from the Act’s measures that will protect health care facilities or an individual practitioner’s refusal to perform abortions.

The Act gives immunity to institutions or individual health care services, or physicians that refuse to provide coverage or services for abortions. Neither the federal government nor the State government can interfere with or force health care services to provide abortions. Governing bodies cannot punish services – including institutional or individual health care entity – and individuals who refuse to perform abortions. The modifications to coverage could circumvent services like Planned Parenthood from providing abortions by blocking its federal stipends from being used for, not only direct abortion procedures, but also services like counselling (since it could fall under “referral.”)  The section on “Limitation on Abortion Funding” reads as following:

OPTION TO OFFER COVERAGE OR PLAN

“Nothing in this subsection or section 1311(d)(2)(b)(i) shall restrict any non-Federal health insurance issue offering a qualified health plan from offering separate coverage for abortions for which funding is prohibited under this subsection, or a qualified health plan that includes such abortions, so long as –

(A)  premiums for such separate coverage or plan are paid for entirely with funds not authorized or appropriated by this Act;

(B)  administrative costs and all services offered through such coverage or plan are paid for using only premiums collected for such coverage or plan; and

(C) any such non-Federal health insurance issuer that offers a qualified health plan through an Exchange that includes coverage for abortions for which funding is prohibited under this subsection also offers a qualified health plan through the Exchange that is identical in every respect except that it does not cover abortions for which funding is prohibited under this subsection.1

By protecting the refusal to perform abortions under the language of “nondiscrimination,” the Act essentially characterizes the denial of abortion as a “right” as opposed to the eradication of a right. Health practitioners who oppose abortion on moral grounds become a protected group of citizens, as opposed to professionals who have duties and obligations towards others. Health care is no longer seen as a service that meets the needs and protects the interests of those receiving the services, but instead as an expression of the practitioner’s beliefs (whether it is for or against abortion):

“Federal agency or program, and any State or local government that receives Federal financial assistance under this Act (or an amendment made by this Act), may not subject any institutional or individual health care entity to discrimination, or require any health plan created or regulated under this Act (or an amendment made by this Act) to subject any institutional or individual health care entity to discrimination on the basis that the health care entity refuses to –

(A)  undergo training in the performance of induced abortions;

(B)  require or provide such training;

(C) perform, participate in, provide coverage of, or pay for induced abortions; or

(D) provide referrals for such training or such abortions.” 2

Prior to the Act, the Hyde Amendment had already eliminated abortion from eligible medical services available through the Medicaid program, a federal health care service for low-income population.3 The Act now frames abortion as an “extra” matter that does not belong in the core of health care services. No health care coverage or abortion services receiving federal funds can provide a plan or subsidies for abortions. This places the cost of abortions solely upon those seeking the procedure. The blocking of abortion from all federal agencies or funding marginalizes a procedure that should be considered a basic health procedure for women.

The Act coincides with a new case in New Jersey involving 12 nurses asserting their right to refuse to assist women getting abortions.4 The debate leads the question of scope in “assisting,” and whether it includes indirect procedures such as taking down a patient’s name.

With the upcoming presidential election, the Act undeniably seems to serve a political purpose for the Republican Party. The Act is currently undergoing Senate debates.

1 Protest Life Act, s. 2(c) (9) available online: .

2 Ibid. s.2 (g)

3 Exception to the Hyde Amendment included abortion involving cases of rape, incest, and endangerment of a pregnant woman’s life by disorder or injury.  For more information on the Hyde Amendment, see: <www.a< span=”” style=”box-sizing: border-box;”></www.a<>clu.org/reproductive-freedom/public-funding-abortion>.

4 See “New Jersey nurses claim right to refuse assisting in abortions” Online: <www.glo< span=”” style=”box-sizing: border-box;”></www.glo<>beandmail.com/life/the-hot-button/new-jersey-nurses-claim-right-to-refuse-assisting-in-abortions/article2251859/>.

Embryonic Stem Cell Based Patents Banned in Europe: Brüstle v. Greenpeace

Posted By Kaitlin Soye – Nov. 21, 2011

On October 18th, the European Court of Justice blocked patents for procedures using human embryonic stem cells in a case on appeal from the Federal Patent Court in Germany.

The European Court interpreted relevant provisions of Directive 98/44/EC of the European Parliament and of the Council of 6 July 1998 (the Directive) which dictates that the human body, at any stage of development, cannot be patented (Article 5(1)).

In its decision, the Court adopted a broad definition of “human embryo” to mean a fertilized human ova if that fertilization is such as to commence the process of development of a human being (Directive, Article 6(2)c).

In adjudicating whether the human ES cells that serve as the base material in the patented process held by Brüstle should be included within the concept of “human embryos”, the Court found in the affirmative. The block on these patents on human embryos apply to both scientific research as well as commercial and industrial purposes.

Embryonic stem (ES) cells have almost unlimited self-renewal and differentiation capacity. Groundbreaking ES cell research offers a wide variety of biomedical applications including addressing issues of donor tissue shortages.

The ruling cannot be appealed and applies to all member states of the European Union. It specifically bans procedures that create ES cell lines by destruction of the embryo and use previously developed cell lines. The decision is based on concerns of ethics and public policy. Clara Sattler de Sousa e Brito, patent attorney for the plaintiff, suggests that current patents in good standing will not be invalidated, but they remain difficult to enforce.

Similar scientific procedures maintain patent protection elsewhere in the world, including the USA. This ruling has the potential to restrict European scientists and companies from progressing both academic and commercial research. It has been speculated that the lack of patent protection may dissuade companies from investing in European research and negatively impact funding for basic research of ES cells.1

Although this ban has blocked ES cell-based patents in Europe, scientific research continues to advance. This may be an opportunity to revisit the field for research into induced pluripotent stems cell (adult somatic cells forced into pluripotency) based therapies in Europe.

1 Callaway, E, “European court bans patents based on embryonic stem cells” (18 October 2011) available online: Nature.

References:

Oliver Brustle v. Greenpeace e.V, 2011 (C-34/10)

Directive 98/44/EC of the European Parliament and of the Council of 6 July 1998 (L213/13)

Further Reading:

Bishop, AE, LDK Buttery and J M Polal. Embryonic stem cells. The Journal of Pathology. July 2002, 197(4) 424-429.

Briggs, H. European court ruling ‘threatens stem cell work.’ BBC (Online). 18 October 2001.

What’s mine is yours: a commentary on the patenting of human genes

Posted By Rachel Tonelli-Zasarsky – Nov. 5, 2011

In light of the twelfth Annual Conference for Human Genetics, which took place in Montreal on the 14th of October, Le Devoirpublished an article entitled “À qui appartiennent nos gènes?”, or to whom do our genes belong? The article highlights the fact that 20% of the human genome is patented and quotes Professor Gold from McGill University as saying, “Il faut payer la compagnie pour travailler sur ces gènes. Est-ce ainsi que nous voulons considérer le corps humain?” (Translation: a company must be paid to work on our genes. Is it in this way that we want to consider the human body?)

In Canada, the issue of patenting genes has been recently addressed in two cases: Harvard College v. Canada and Monsanto Canada Inc. v. Schmeiser. Both of these cases deal with the patenting of life forms; the former establishes that humans and animals, or “higher life forms”, cannot be patented, whereas the latter establishes that engineered genes and cells are patentable, even when their intended use is insertion into life forms such as plants. Despite the ruling in these cases, the Canadian courts have not yet directly addressed the issue of patenting human genes that have not been genetically modified or engineered.

However the issue has recently arisen in the United States in the case of Association for Molecular Pathology v. United States Patent and Trademark Office, 2010, United States District Court: Southern District of New York.  The plaintiffs pleaded that Myriad’s patents relating to the human Breast Cancer Susceptibility Genes 1 and 2 (BRCA1, and BRCA 2) should be revoked given that they were broad enough to reach BRCA1/2 DNA isolated from any human being. The judgement for the case was delivered by Judge Sweet in favour of the plaintiffs, although the case is currently under appeal.

The patents under question in this case allowed Myriad to protect unmodified portions of DNA corresponding to BRCA1/2 genes (BRCA1/2 DNA sequences). In other words, everyone has BRCA1/2 DNA sequences in their genome and through its patents Myriad claimed ownership over these portions of DNA.

The following question arises: should companies be allowed to own a specific gene sequence? Or in other words, should Myriad be allowed to own my BRCA1/2 DNA sequence even though I have never interacted with them? Of course, my gut reaction to this question is no. Why should I give up the rights to gaining knowledge about the state of my genome, and have to pay some company to be able to have access to this information? But upon further reflection, answering yes is not so outrageous.

When a particular DNA sequence is determined to be indicative of the risk of a disease state, gene testing is used in the patient to look for DNA sequences that deviate from the known normal risk- free DNA sequences, or for DNA sequences that match sequences that are known to be indicative of disease. These techniques “look” directly at the patient’s DNA to ascertain whether information which codes for the disease is present, such that the risk of the occurrence of the disease may be identified before the disease manifests itself. Gene testing techniques are therefore useless without the knowledge of what DNA sequences code for the disease. Patents that protect genes provide protection for DNA sequences that code for the disease, as well as sequences that code for the normal disease-free state. These sequences are not artificially modified.

The main objection to patenting gene sequences that have not been modified is precisely the fact that they have not been modified, and are therefore not new. United States Code Title 35 –Patents, s.101 Inventions Patentable states that:

Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title

Similarly, s.2 of the Canadian Patent Act states that:

Invention means any new and useful art, process, machine, manufacture or composition of matter, or any new and useful improvement in any art, process, machine, manufacture or composition of matter;

Judge Sweet in the Myriad case maintains that gene sequences are not patentable because they do nothing but describe DNA, and given that DNA in itself is descriptive, the gene sequences are not “new”. The function of DNA is to direct the composition of proteins; it is a recipe. The protein produced will then result in the manifestation of disease. Therefore Judge Sweet maintains that that the function of DNA is to describe the manifestation of the disease, and an unmodified DNA sequence which is used to aid in the description of what the DNA under scrutiny describes, is not patentable. While this argument may be compelling, I do not agree with it.

The role of DNA is to dictate protein formation, however it is not the role of DNA to describe the risk of disease manifestation. The calculation of risk is a human construct; the risk is not ascertainable by simply “looking” at the DNA. As such, using DNA to express the risk of disease is a repurposing of DNA.

Looking at the DNA and describing its content is content is not useful, however understanding the meaning of the description is. There is a difference between simply saying that a gene responsible for breast and ovarian cancer exists, and saying that certain deviations from a standard form of the gene lead to ovarian and breast cancer. I believe that the latter is the basis of a diagnostic tool and should be patentable, whereas the former is a statement of fact and should not be patentable. These genes are not being patented to exploit their function as a protein recipe; they are being patented as baseline comparison standards. This purpose is evident in Myriad’s methods claims. The novelty does not lie in a new composition or manufacture, then, but in the repurposing of the DNA from a protein recipe to a means of diagnosis.

What is being rewarded through the patent is not an observation of the existence of a cancer gene, but rather the ability to be able to diagnose the possibility of cancer before it manifests itself. Viewed in this way, I believe that Myriad’s patents, and patents which aim to protect gene sequences, should be read in accordance with their. If the methods claims suggest that the gene sequences are to be used as comparison standards, then I believe that this is the aspect of the gene sequence that should be protected. In other words, I do not think it is appropriate for Myriad to enforce its patents against laboratories who are researching the gene sequence for a purpose other than using it as a comparison standard, but it is ok for them to hold exclusive rights to use a particular gene sequence as a comparison standard.

The field of biotechnology is evolving and makes use of tools that mimic cellular functions in order better understand the role played by each of the cellular components. One of these cellular components is DNA, a recipe for protein encoding. Being able to understand what the recipe means constitutes the basis of diagnostic tools that act as predictors. The value of this understanding lies in the ability to repurpose DNA from a simple recipe to a diagnostic tool. A diagnostic tool attaches meaning to the recipe which was not there otherwise. In this way, I believe that gene sequences that are used as comparison standards are new and useful improvements of the function of DNA, which, as found in nature and unmodified by the human mind, do not on their own act as a predictor of disease.

Unanswered Questions on the Risks and Promises of Pharmacogenetics and Personalized Medicine

Posted By Daniel Mastine – Oct. 26, 2011

On October 5th the McGill Research Group of Health and Law convened an interdisciplinary panel to discuss emerging developments in the fields of Pharmacogenetics and Personalized Medicine (PM). The panel was moderated by Professor Richard Gold and included Professors Jennifer Fishman, Yann Joly, Michael Phillips and Dr. Agnes V. Klein.

One might initially ask how these two seemingly distinct subjects are linked, and what potential impacts they could possibly have on society and medicine? To answer these questions, one must first address what Pharmacogenetics and PM entail. It is important to keep in mind that neither are new areas of medicine, and that they have begun to interact in a concerted manner previously unheard of.

For those who may not be aware, Pharmacogenetics is a specialized subfield situated between clinical and research medicine. It seeks to catalogue the genetic makeup, or biomarkers, of individuals and populations. The results assist researchers to understand why no two patients react/respond to a drug in quite the same manner. This endeavor provides pharmaceutical researchers and medical practitioners with a better understanding of how genetic diversity influences why medications are metabolized differently.In so doing, the safety of pharmacological treatments and their efficacy are enhanced and a truer picture of drugs is achieved.

PM conversely, is a popular medical model which seeks to optimize patient outcomes by tailoring patient treatment plans to individual characteristics. Some examples include: family health histories, the presence of a chronic disease, behaviours or even personal habits of patients to name a few. Practitioners, who ascribe to PM, essentially question the one size fits all norms of standardized medical. They tweak, but do not necessarily alter, customary treatment modalities to suit their patients’ needs. Society is after all based on variation: gender, ethnicity, diet, socioeconomic class, environment, illness, and yes, even genetics. Imagine if medicine could better account for these differences!

So how exactly are Pharmacogenetics and PM linked? As genetic mapping has become more accessible and less costly, some PM practitioners have recently begun to incorporate information from genetic research and personalized testing to guide their treatments decisions. However the slow but steady proliferation of Pharmacogenetics in an era of PM has led some members within the greater medical community to question this budding relationship from legal and bioethical perspectives.

During the panel presentations and subsequent Q and A, four distinct concerns were raised. Three out of the four include: race, informed consent, and privacy/confidentiality. The notion of race within Pharmacogenetics and PM was highlighted as problematic due to conceptual ambiguity and its potential to foster new forms of societal discrimination. Informed consent was noted to be too broadly defined within Pharmacogenetics and PM, leaving research participants and the public with little understanding of the purpose or process. Concerns for privacy and confidentiality were raised regarding the ability to secure the identities of Pharmacogenetic research participants, and in considering the “who, when and how” of data storage and retrieval.

The fourth not yet elaborated element of the discussion focused upon how the emerging intersections between Pharmacogenetics and PM are altering the pharmaceutical industry and medical function. Specifically, what obligations arise or are altered for both as biomarker testing becomes more readily available? The panel discussion suggested that over time, for both researchers and practitioners, the duty of care will increasingly expand to account for genetic factors. This is likely to play out with the expansion of available frontline diagnostic testing to identify individuals at risk. In turn, patient expectations and medical standards will begin to emerge. This will foster a duty for practitioners to prescribe treatments that take into account biomarker testing results. How health care is delivered will be redefined.

Where do we go from here one might ask? The future of medicine may well involve visits to the doctor, where each patient will provide the doctor with their personal genetic information. This scenario would revolutionize PM. Presently however there are just too many uncertainties and unknowns about Pharmacogenetics. This limits its accessibility for practitioners and application to patients as an exercise in PM. The panelists stressed the potential value of a closer relationship between Pharmacogenetics and PM. But they also posed challenging questions which denote the need for both dialogue and transparency in moving forward. This may in turn enable society and the medical community to address the legal and bioethical concerns that Pharmacogenetic research raises.