Category Archives: Genetics

Autism Spectrum Disorders in Children Conceived with Donor Sperm: How Should the Law Respond?

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Laurie Rosenow

In 2017 an Illinois mother of two children diagnosed with Autism Spectrum Disorder  (ASD) filed a complaint against a sperm bank alleging that the sperm donor used to conceive both of the children was not the man he claimed to be.[i]  Not only did Danielle Rizzo learn that donor H898 lied about his education, but he had failed to disclose a history of learning disabilities and other developmental issues.[ii]  Ms. Rizzo later discovered that she was not alone.  To date at least a dozen other children conceived with donor H898’s sperm have been diagnosed with Autism Spectrum Disorder.[iii]

In 2010 Ms. Rizzo purchased donor H898’s sperm from Idant Laboratories, who listed the donor as a 6’1 blonde-haired, blue-eyed college graduate with a master’s degree that had passed all of the lab’s health screenings.[iv]  The only thing that turned out to be true was his appearance.  Based on conversations with other women who had used donor H898 to conceive their children, some of whom had even met him, Rizzo learned that the donor had neither an undergraduate nor graduate degree as advertised and was diagnosed with ADHD, did not speak until age 3, and attended a special school for children with learning and emotional disabilities.[v]

When Rizzo’s children were 3 and 4 years old, she contacted geneticist and autism researcher Stephen Scherer, Director, Centre for Applied Genomics at The Hospital for Sick Children in Toronto and connected him with other families who had affected children from donor H898.  This group, known as an autism “cluster” offer a rare opportunity for scientist to study what causes and how to treat the disease.  Dr. Scherer cautioned that while his research to date is still preliminary, his hypothesis is that something in the donor’s DNA caused the children to develop ASD.[vi]

The word “autism” is derived from the Greek root for “self” and describes a wide range of interpersonal behaviors that include impaired communication and social interaction, repetitive behaviors, and limited interests.  These can be associated with psychiatric, neurological, physical, as well as intellectual disabilities that range from mild to severe.[vii]

Such a person may often appear removed from social interaction becoming an “isolated self.”[viii]  The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) uses a broad definition of “autism spectrum disorder” that includes what were once distinct diagnostic disorders such as autistic disorder and Asperger syndrome.[ix]  ASD affects four times more males than females and symptoms usually manifest by the age of three.[x]\

The March of Dimes estimates that 6% of children born worldwide each year will have a serious birth defect that has a genetic basis.[xi]  The occurrence of ASD varies but is thought to be as high as 1% of the population.[xii]  Unlike diseases such as Cystic Fibrosis or Tay Sachs Disease for which carrier testing exists, the genetics of ASD is not yet well understood.  Geneticists such as Dr. Scherer suspect as many as 100 different genes may be associated with ASD.  Over 100 genetic disorders can exhibit features of ASD such as Rett Syndrome and Fragile X Syndrome, further complicating the diagnosis and understanding of ASD.  Dr. Scherer estimates that a subset of “high- impact” genes are involved in 5-20% of all ASD Diagnosis.[xiii]  Danielle Rizzo’s children were found by Dr. Scherer to carry two mutations associated with ASD.[xiv]

Despite the fact that genetic screening is available for many diseases, the United States does not require any genetic screening for gamete donors.  Under federal law, sperm banks in the United States are regulated by the Food and Drug Administration which requires donors of reproductive cells or tissue to undergo testing for certain enumerated communicable diseases such as HIV, Hepatitis B and C, chlamydia, and gonorrhea.[xv]  “Sexually intimate partners,” however, are exempted from such screening.[xvi]  The FDA also requires that an establishment that conducts donor screening must also review the donor’s medical records and social behavior for increased risk for communicable disease and conduct a physical exam of the donor.[xvii]  Retesting of donors is required after six months for any subsequent donations.[xviii]

Sperm banks in the U.S. are also not required to limit the number of semen samples sold or to keep track of live births resulting from their donors.  And no law prohibits a man from donating to as many sperm banks as he likes.  For example, a donor in Michigan who donated his semen twice a week between 1980 and 1994 had fathered at least 400 children by 2010.[xix]  A mother of a donor child was able to trace at least 150 half-siblings to her son using web-based registries.[xx]  Danielle Rizzo discovered that her donor, H898, was still being sold by at least four sperm banks, despite receiving calls and letters warning them of her experience.[xxi]  With the popularity of DNA home testing kits such as 23andMe and Ancestry.com as well as voluntary donor registries such as Donor Sibling Registry, even more children from donors like H898 are likely to be discovered.

In addition to the FDA rules mandating screening for communicable disease, the American Society for Reproductive Medicine (“ASRM”) advises sperm banks only include donors who are between the ages of 18-40 and provide a psychological evaluation and counseling to prospective donors performed by a mental health professional. [xxii]   The industry group recommends genetic testing for cystic fibrosis of all donors and other genetic testing that is indicated by the donor’s ethnic background.  The group does not recommend a chromosomal analysis of all donors.

The American College of Obstetricians and Gynecologists (“ACOG”) as well as ASRM recommend limiting the number of children born to a single gamete donor. [xxiii]  While populations will vary, to limit the possibility of consanguinity, AGOG recommends a maximum of 25 children born from a single donor per population of 800,000.[xxiv]  The challenge in setting limits on the number of children born to a sperm donor lies in obtaining the information and keeping updated records.  Many women purchase sperm from banks across the country and even the globe with no legal incentive to inform a sperm bank of any resulting children or their health status.  Sperm banks are also unlikely to share information with donors regarding the number of their semen vials sold let alone any children that result.

Despite the lack of a federal mandate, most sperm banks voluntarily screen for genetic defects.[xxv]  However, like ASD, many diseases that are thought to have a hereditary component cannot be tested for and clinicians and patients are forced to rely on the donor to give truthful and accurate medical and family histories as well as the banks to accurately document such information.

Like Danielle Rizzo, another mother of two children diagnosed with ASD conceived with donor H898’s sperm filed a lawsuit against Idant Labs including claims for fraud, negligent misrepresentation, strict products liability, false advertising, deceptive business practices, battery, and negligence.[xxvi]  Danielle Rizzo settled her claims against Idant’s parent company Daxor Co. in 2017 for $250,000 though she alleges it is a fraction of the estimated $7 million in care that will be needed for both of her children.[xxvii]

Similar lawsuits were filed against Xytex, a sperm bank based in Atlanta, Georgia, regarding sperm it sold from Donor #9623 named Chris Aggeles who was advertised as having a genius level IQ of 160 pursing a PhD in neuroscience engineering.[xxviii]   In fact, the donor at the time was a high school drop out with a history of mental disorders including schizophrenia, bipolar disorder, and narcissistic personality disorder and a criminal record.[xxix]  He had been a donor at Xytex for fourteen years. The plaintiffs claimed the company did not verify any of the information the donor had given them but Xytex claims it discloses to prospective clients that any representations by the donor were his alone.[xxx]  Recently nine families with 13 children conceived with sperm from Aggeles settled their claims for wrongful birth, failure to investigate, and fraud.[xxxi]

Despite monetary damages awarded in settlement of these lawsuits, a case filed in the Third Circuit against Idant was dismissed because the court found the argument of liability based on quality of sperm to be indistinguishable from New York’s prohibition against wrongful life claims.[xxxii]  “The difficulty B.D. now faces and will face are surely tragic, but New York law, which controls here, states that she ‘like any other [child], does not have a protected right to be born free of genetic defects.’”  Idant in this case had sold the sperm of Donor G738 to a mother in Pennsylvania whose daughter was diagnosed as a Fragile X carrier.

Both mothers of the children diagnosed with ASD from donor H898’s sperm left professional careers to care for their children and alleged severe financial losses as a result.[xxxiii]  Donor H898, however, was not a party to the suits nor were any other establishments selling vials of his semen and therefore not bound to any settlement agreements reached which might restrict future donations.  Since lawsuits only offer the possibility of damages and other relief after an injury has occurred and some jurisdictions, like New York, will not even consider claims related to defective sperm, policies that focus on avoiding harm prior to insemination should be considered.

Because screening is not available for many diseases that likely have a strong genetic component, the family and medical history of donors becomes critical as a secondary method of screening.  Sperm banks could require signed, sworn affidavits from donors attesting to the truthfulness and accuracy of the information they provide to encourage more accurate reporting by donors.  Many banks claim they run criminal background checks on donors but they could also verify claims of employment and education with a simple phone call.  Laws mandating a cap on the number of vials an individual may donate make sense in light of the vast numbers of children possibly being conceived from popular donors.  It may also be time for sperm banks in the U.S. to follow the example of the UK which allows children conceived from donor gametes to obtain medical information from donors at age 16 and the full name, date of birth, and address of their donors at age 18.[xxxiv]  In the age of DNA testing, social media, and cyber stalking, anonymity may be unrealistic.  If sperm banks do not tighten their internal policies for screening donors, more avoidable tragedies are likely to occur.

Laurie Rosenow in an attorney and former Senior Fellow at the Institute for Science, Law & Technology.

 

[i] Rizzo v. Idant Labs, Case No. 17-cv-00998, N.D. Ill. Jan 31, 2017.

[ii] Id.  See also, Arianna Eunjung Cha, “The Children of Donor H898,” Wash. Post, Sept. 14, 2019.

[iii] Id.  See also, Doe v. Idant Labs, complaint filed NY State Supreme Court, Civil Branch, June 2016.

[iv] Cha, “The Children of Donor H898.”

[v] Id.

[vi] Id.  Dr. Scherer also noted, however, that the donor could have other biological children who are not affected.

[vii] Yuen, R.K.C. et al, “Whole Genome Sequencing Resource Identifies 18 New Candidate Genes for Autism Spectrum Disorder,”  20 Nat. Neurosci., 602-611 (2017).

[viii] “What Does the Word ‘Autism’ Mean? WebMD, available at https://www.webmd.com/brain/autism/what-does-autism-mean#1.

[ix] Autism Spectrum Disorder, Diagnostic Criteria, Centers for Disease Control, available at https://www.cdc.gov/ncbddd/autism/hcp-dsm.html.

[x] Yuen et al, “Whole Genome Sequencing Resource Identifies 18 New Candidate Genes for Autism Spectrum Disorder.”  For examples of common behaviors found in children with ASD, see National Institute of Mental Health. Autism Spectrum Disorder Overview, available at https://www.nimh.nih.gov/health/topics/autism-spectrum-disorders-asd/index.shtml.

[xi] March of Dimes Global Report on Birth Defects 2006, available at https://www.marchofdimes.org/global-report-on-birth-defects-the-hidden-toll-of-dying-and-disabled-children-full-report.pdf

[xii] Anney, Richard et al, “A Genome-wide Scan for Common Alleles Affecting Risk for Autism,” Hum. Mol. Gen. Vol. 19, No. 20, p. 4072-4082 (2010).

[xiii] Cha, “The Children of Donor H898.”

[xiv] The genetic mutations found in her sons were MBD1 and SHANK1, Cha, “The Children of Donor H898,” Washington Post, Sept. 14, 2019.

[xv] 21 C.F.R. Sec. 1271.75.

[xvi] 21 C.F.R. Sec. 1271.90.

[xvii] 21 C.F.R. Sec. 1271.50 (2006).  See also, https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/what-you-should-know-reproductive-tissue-donation.  Donor screening consists of reviewing the donor’s relevant medical records for risk factors for, and clinical evidence of, relevant communicable disease agents and diseases.  These records include a current donor medical history interview to determine medical history and relevant social behavior, a current physical examination, and treatments related to medical conditions that may suggest the donor is at increased risk for a relevant communicable disease.

[xviii] 21 C.F.R. Sec. 1271.85 (d).

[xix] Newsweek Staff, “Genetic Lessons from a Prolific Sperm Donor,” Newsweek, Dec. 15, 2009, also available at https://www.newsweek.com/genetic-lessons-prolific-sperm-donor-75467.  See also, Hayes, Daniel, “9 Sperm Donors Whose Kids could Populate a Small Town,” Thought Catalog, Jan. 13, 2016, available at https://thoughtcatalog.com/daniel-hayes/2016/01/9-sperm-donors-whose-kids-could-populate-a-small-town/.

[xx] Meraz, Jacqueline, “One Sperm Donor; 150 Offspring,” New York Times, Sept. 5, 2011, also available at https://www.nytimes.com/2011/09/06/health/06donor.html.

[xxi] Cha, “The Children of Donor H898.”

[xxii] “Recommendations for Gamete and Embryo Donation,” 99 Fertility and Sterility 1, p.47-62,  Jan. 2013,  available at, https://www.fertstert.org/article/S0015-0282(12)02256-X/fulltext#sec1.  See also, https://www.reproductivefacts.org/news-and-publications/patient-fact-sheets-and-booklets/documents/fact-sheets-and-info-booklets/third-party-reproduction-sperm-egg-and-embryo-donation-and-surrogacy/

[xxiii] ACOG Committee Opinion: Genetic Screening of Gamete Donors, Int’l Jour. Gyn & Obst. 60 (1998) 190-192, available at https://obgyn.onlinelibrary.wiley.com/doi/abs/10.1016/S0020-7292%2897%2990229-0

[xxiv] Id.

[xxv] See, e.g. California Cryobank, one the of the largest sperm banks in the United States: https://www.cryobank.com/services/genetic-counseling/donor-screening/

[xxvi] Doe v. Idant Labs, complaint filed N.Y. State Supreme Ct., June 2016, available at https://www.donorsiblingregistry.com/sites/default/files/Rizzo%20complaint.pdf.

[xxvii] Cha, Ariana Eunjung, “Danielle Rizzo’s Donor-conceived Sons Both Have Autism.  Should Someone be Held Responsible?” Wash. Post, Oct. 3, 2019, available at https://www.washingtonpost.com/health/2019/10/03/danielle-rizzos-sons-donor-conceived-sons-both-have-autism-should-someone-be-held-responsible/

[xxviii] Johnson, Joe, “UGA Employee at Center of Sperm Bank Fraud,” Athens Banner-Herald, Sept. 3, 2016.

[xxix] Id.  See also, Van Dusen, Christine, “A Georgia Sperm Bank, a Troubled Donor, and the Secretive Business of Babymaking,” Atlanta Magazine (March 2018), also available at https://www.atlantamagazine.com/great-reads/georgia-sperm-bank-troubled-donor-secretive-business-babymaking/ (Feb. 13, 2018).

[xxx] Djoulakian, Hasmik, “The “Outing” of Sperm Donor 9623,” Biopolitical Times, June 30, 2016, available at https://www.geneticsandsociety.org/biopolitical-times/outing-sperm-donor-9623.  See also, Johnson, Joe, “UGA Employee at Center of Sperm Bank Fraud,” Athens Banner-Herald, Sept. 3, 2016.

[xxxi] Hersh & Hersh law firm, “Major Settlement of Sperm Bank/Deceptive Business Practice Case,” available at https://hershlaw.com/success-2/.  See also, Khandaker, Tamara, “Lawsuit Alleges Sperm Bank’s Genius Donor Was Actually a Schizophrenic Ex-Con,” Vice News, Apr. 15 2016, available at https://www.vice.com/en_us/article/neykmx/lawsuit-alleges-sperm-banks-genius-donor-was-actually-a-schizophrenic-ex-con

[xxxii] D.D. v. Idant Labs, (3rd Cir. 2010).

[xxxiii] Doe v. Idant Labs, Complaint; Cha, “The Children of Donor H898.”  See also, Cha, “Danielle Rizzo’s Donor-conceived Sons Both Have Autism.”

[xxxiv] Human Fertilitisation and Embryology Authority, “Rules Around Releasing Donor Information,” available at https://www.hfea.gov.uk/donation/donors/rules-around-releasing-donor-information/.

The Thin Red Line of Predictive Genetic Testing in the Military

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Bryan Helwig

By Bryan Helwig, PhD

A military segregated by genetics? The possibility is more reality than science fiction and an issue I encountered while leading a research team for the Department of Defense.  Recent advances in science and technology have produced genetic tests that are low cost, easily performed and able to produce significant amounts of genetic information about individuals. Once confined only to scientific experiments, the general public now has options to trace their family origins from a cheek swab, detect genetic abnormalities prior to birth from a sample of the mother’s blood, and determine their genetic profile using saliva.

Since the mid-1990s the Department of Defense has required that all new recruits provide a DNA sample that can be used for identification purposes. Now, advances in genetic technology are helping to identify genes profiles associated with a predisposition to post-traumatic stress disorder (PTSD) or suicide. The use of genetic testing in this manner is considered predictive genetic testing.

Proponents of predictive genetic testing in the military note the invaluable role testing provides in keeping armed forces safe. Critics contend that mandatory genetic testing is an invasion of privacy and a violation of civil liberties. These individuals contend that the Genetic Information Nondiscrimination Act (GINA) of 2008, which protects civilians from job-related discrimination based on genetic test results, should also apply to military personnel.  Specifically, §202 and §203 prohibit employment discrimination practices based on genetic information. With few exceptions, §203 reads “it shall be an unlawful employment practice for an employer to request, require, or purchase genetic information with respect to an employee or a family member of the employee . . . “ However, the military is a unique environment in which the needs of the unit are a higher priority than those of the individual, complicating the application of civilian policies such as GINA to members of the armed forces.

Military duty is characterized by physical demands and exposure to environments that are unpredictable and often extreme. As a result, work in military environments can result in manifestation of genetic abnormalities that would remain unknown without diagnostic genetic testing in which screening occurs for specific genes that are diagnostic for a condition.

During the last five years, the expansion of genetic testing has been proposed. An advisory panel of independent scientists produced the JASON report in 2010 recommending “The DoD should establish policies that result in the collection of genotype and phenotype data, the application of bioinformatics tools to support the health and effectiveness of military personnel, and the resolution of ethical and social issues that arise from these activities.” The idea is robust and one I frequently encountered during my career directing a Biomedical Research Laboratory for the Department of Defense.

The focus of my team’s work was to better understand how and why the human body responds in extreme environments. For instance, the expression of a subset of genes allows for adaptation to high altitude, low-oxygen environments such as the mountains. Although not as well established, a similar set of genes also may be advantageous to prolonged work in hot and cold environments. Thus, predictive genetic screening in the military could be used to identity individuals that would have advantageous or disadvantageous physiological responses to hot, cold or high-altitude environments. In addition, the JASON report proposes the use of predictive genetic testing to identify service members at increased risk of blood coagulation abnormalities, bone fracture risk, tolerance to sleep deprivation and over two hundred other health-related phenotypes of interest to the military.

Although not widely recognized, each of us undergoes a diagnostic genetic test at birth for phenylketonuria, more commonly known as PKU, an inborn error of protein metabolism that can have profound negative affects on development if not identified early in life. In comparison, the use of predictive genetic screening is in its infancy. Genetic tests are highly accurate in quantifying gene expression, however use of the results in a predictive capacity is less accurate and often over-exaggerated by the media.

For instance, a genetic profile that affords natural protection in a hot environment is likely to be comprised of up and down regulation of hundreds or even thousands of genes. Some genes may be affected by health status, nutrition, sleep, etc. Thus, the use of predictive genetic testing requires identification of stable gene profiles that serve as accurate predictors of health status and only change expression in the environment being studied. Additionally, many scientists cite a two-fold change in gene expression as significant.  However, a two-fold change is arbitrary and not always indicative of a significant physiological impact. Despite rapid expansion of genomic technology, the reliability of predictive gene profiling remains nascent.

Despite the scientific gaps, legal and ethical issues need to be addressed before genetic testing achieves an accuracy allowing its use en masse. Initial efforts should focus on privacy, including modification of GINA to protect privacy of military members in a way that is similar to the general public. Secondly, if GINA cannot be modified, discussions regarding new policies associated with predictive genomic testing that address the intersection of military personnel privacy and mission readiness should be encouraged. Instrumental will be deciding how broadly predictive genetic testing should be used by the Department of Defense. Conversations must also include updated policies regarding the handling or even destruction of DNA samples and specimens after military service ends and related rules for governing the almost fifty million samples in the Department of Defense Serum Repository (DoDSR). Such policy decisions should be balanced with the knowledge that the DoDSR is the largest repository of samples in the world and its use in understanding disease has been substantial.

Some service members refused to provide DNA for inclusion in the DoDSR and the punishment was harsh, including court martial, a reduction in rank and loss of pay. The Hawaii District Court held that requiring DNA samples from service members does not violate the Fourth Amendment right to be free from unreasonable searches [Mayfield v. Dalton, 901 F. Supp. 300 (D. Haw. 1995), vacated as moot, 109 F. 3d 1423 (9th Cir. 1997)]. Objection to inclusion may become more common if predictive genetic testing is used without privacy protection. The military must revisit the thin red line between privacy and military needs; a line that currently favors minimizing individual needs.

Standard informed consent required whenever biological samples are obtained must also be re-evaluated to better reflect the current practices. Informed consent forms should be re-written, allowing the service member to give different levels of permission regarding future use of their DNA beyond the required baseline diagnostic screening and identification purposes. Importantly, this option must be revocable at any time, during or after their military career. The military should also consider the alternative of an external third party to perform predictive genetic screening, the results remaining private, and released only as required by strict criteria. Regardless of the results, policies must be in place to prevent discriminatory practices related to genetic results in military and post-military career advancement.

The military benefit to the Warfighter from genetic testing is significant and, if used responsibly, can help protect a soldier’s health. However, many ethical and legal hurdles exist that must be resolved before predictive genetic testing becomes mainstream.  Conversations addressing such issues need to occur now; the issues are central to protecting the privacy of those who keep us safe.

Bryan Helwig, PhD is a first-year law student at Chicago-Kent College of Law (Class of 2017) with an interest in the intersection of intellectual property, genetics and privacy. During the five years preceding law school he directed a Biomedical Research Lab for the Department of Defense.

A White House Invitation to Launch Precision Medicine

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By Lori Andrews

President Obama at the launch of the Initiative

Last Friday, I was a guest at the White House for President Obama’s launch of the Precision Medicine Initiative.  The goal of the Initiative is to sequence people’s genomes and read the nuances of their genes to determine how to prevent disease or more precisely treat it. The President illustrated how this would work by introducing Bill Elder, a 27 year old with cystic fibrosis. Bill has a rare mutation in his cystic fibrosis gene and a drug was fast-tracked at the FDA to target that mutation.  “And one night in 2012, Bill tried it for the first time,” explained President Obama. “Just a few hours later he woke up, knowing something was different, and finally he realized what it was:  He had never been able to breathe out of his nose before.  Think about that.”

When Bill was born, continued the President, “27 was the median age of survival for a cystic fibrosis patient.  Today, Bill is in his third year of medical school.”  Bill expects to live to see his grandchildren.

The Precision Medicine Initiative will involve sequencing the genomes of a million Americans.  Such a project would have been unimaginable if we hadn’t won the Supreme Court case challenging gene patents.  Prior to that victory, genetic sequencing cost up to $2,000 per gene due to patent royalties.  Now it will cost less than ten cents per gene.

Bill Elder at the White House event

The people who volunteer as research subjects for the project may expect cures for their own diseases.  But, even when genetic mutations are discovered, cures are a long way off.   “Medical breakthroughs take time, and this area of precision medicine will be no different,” said President Obama. And despite the fanfare surrounding genetics, researchers often find that environmental factors play a huge role in illness. At the same time the White House was preparing for the launch of the Precision Medicine Initiative, Stanford researchers and their colleagues across the globe were publishing a study in the January 15 issue of the prestigious journal Cell challenging the value of sequencing research.  Their study, “Variation in the Human Immune System is Largely Driven by Non-Heritable Influences,” tested sets of twins’ immune system markers.  The result: Nearly 60% of the immune system differences were based on the environment rather than genes.

Capturing environmental information about the million volunteers will involve invasions of their privacy as their health and behavior is categorized and quantified from every perspective.  Their genetic data will be combined with medical record data, environmental and lifestyle data, and personal device and sensor data.  If not handled properly, this data could be used to stigmatize the research participants or discriminate against them.  Will they be properly informed of the risks in advance?  Will sufficient protections be in place for their device and sensor data, which is often not covered by medical privacy laws such as HIPAA?

At the White House last Friday, President Obama said, “We’re going to make sure that protecting patient privacy is built into our efforts from day one. It’s not going to be an afterthought.” He promised that patient rights advocates “will help us design this initiative from the ground up, making sure that we harness new technologies and opportunities in a responsible way.”

Professor Andrews with Henrietta Lacks’ descendants at the White House

President Obama underscored that commitment by inviting members of Henrietta Lacks’ family to last Friday’s event. In 1951, Henrietta Lacks was dying of cervical cancer.  A researcher at Johns Hopkins University undertook research on her cells without her knowledge or consent (or that of her family).  Her immortalized human cell lines provided the basis for generations of research in the biological sciences, as well as research by commercial companies.  When her husband learned about it years later, he said, “As far as them selling my wife’s cells without my knowledge and making a profit—I don’t like it at all.”

A former Constitutional Law professor, President Obama is aware of the importance of people’s rights.  Let’s hope that his aspiration of an Initiative that guards research subjects’ autonomy and privacy will be honored by the scientists who will actually operationalize the $215 million project.

U.S. Supreme Court Liberates Breast Cancer Gene

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By Lori Andrews

Today the U.S. Supreme Court held in Association for Molecular Pathology v. Myriad Genetics, Inc., that human genes were not patentable since they are products of nature and not inventions.  This decision is great news for patients, doctors, and scientific researchers.  Some biotechnology companies might grumble about the decision, but the decision will actually stimulate innovation by pharmaceutical companies and the new generation of biotech companies.

The case involved Myriad’s patents on the human breast cancer genes known as BRCA1 and BRCA2.  Those patents made your genes Myriad’s property once they were removed from your body.  Consequently, the company could control all uses of the genes, including any diagnostic testing or research.  The U.S. Supreme Court saw the absurdity of letting a company own your breast cancer genes.  Continue reading →

Supreme Court to Hear Challenge to Patents on Human Genes

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By Lori Andrews

On April 15, the U.S. Supreme Court will hear the case Association of Molecular Pathology v. Myriad.  The question before the court is:  Are human genes patentable?

For 150 years, the Supreme Court has said that abstract ideas, laws of nature and products of nature are not patentable.  Such patents would run afoul of the progress clause of the Constitution and section 101 of the Patent Act.

In 1980, the Supreme Court in Diamond v. Chakrabarty held that genetically modified living organisms are patentable if they are markedly different than what occurs in nature.  That case reiterated that laws of nature like E = mc2 are not patentable, nor are products of nature such as plants from the wild or minerals from the ground.

Three decades after the Chakrabarty decision, the Supreme Court revisited the exception by taking a trilogy of cases.  In the first one, Bilski v. Kappos, the Court held that an abstract idea–hedging in trading energy futures–could not be patented.  In Mayo v. Prometheus, the Court held 9-0 that a law of nature–how the body responded to the administration of a drug–was not patentable.

In the Myriad case, the Court will be addressing the third part of the exception, dealing with products of nature.  It will address whether an “isolated” breast cancer gene is an unpatentable product of nature.  The patents at issue cover two isolated genes related to breast cancer, BRCA1 and BRCA2.  The patents define the isolated gene to include a gene sequence “removed from its naturally occurring environment.”  This claim gives Myriad the ability to control all uses of anyone’s breast cancer genes once they are removed from the body, giving Myriad the right to exert a monopoly over all BRCA1 and BRCA2 breast cancer gene testing and research.

What is a gene sequence?  It’s a series of chemical letters known as nucleic acid bases–designated by A, T, C, and G.  It is important because a single change in the letter–a typo in the sequence–can lead to a genetic disease.  To diagnose a genetic disease, a physician or laboratory compares the patient’s genetic sequence to a normal gene sequence to see if there are differences that predispose the patient to breast cancer.

The question the Supreme Court will ask, under the Chakrabarty case, is whether what Myriad patented is “markedly different” from the breast cancer genes in the body.  Myriad asserts that the isolated gene is a product of human ingenuity.  Myriad argues that it “successfully isolated the ‘BRCA’ molecules and disclosed their creation to the world. This momentous advancement required significant skill, insight, and invention on the part of Myriad’s inventors.”

Myriad also argues that isolation of the gene “depended on an enormous amount of human judgment, including how to define the beginning and end of what came to be called the BRCA1 and BRCA2 genes, and then creating isolated DNA molecules corresponding to those particular defined genes.”  Myriad also argues that by isolating the gene, it gave the gene new uses since genes in the body cannot be used for diagnosis.  It also created copies of the gene in the lab.

In contrast, the petitioners in the case argue that what Myriad patented is not markedly different from nature.  For Myriad’s gene sequence to work as a diagnostic tool, it must have the identical sequence to that of a breast cancer gene in nature.  The petitioners argue that once the unpatentable product of nature, the gene sequence, was discovered, Myriad used routine means to create copies of it and to undertake diagnostic comparisons to patients’ genes.  The Court is likely to look to a 1948 Supreme Court case, Funk Brothers Seed Co. v. Kalo Inoculant Co., in which the patent applicant combined six types of bacteria and the claimed invention was found to be an unpatentable product of nature because the bacteria “served the ends nature originally provided.”  The petitioners argue that here the isolated gene sequence merely serves the ends nature intended.

In addition to extensive briefing about whether there is sufficient human ingenuity involved to consider an isolated human gene to be a patentable invention, the affidavits and amicus briefs in the case gathered all existing data on whether gene patents encourage or discourage innovation.  Over 90 affidavits were filed, including those from Nobel Laureates.  Briefs from over 102 amicus groups were filed, including briefs from medical organizations such as the American Medical Association and patient advocacy groups such as the March of Dimes arguing for the invalidation of gene patents, and briefs from industry organizations such as the Biotechnology Industry Organization and intellectual property associations such as the American Intellectual Property Law Association arguing that gene patents are valid.  Also weighing in were prominent scientists, various companies and numerous law professors.

I filed an amicus brief in the case on behalf of medical organizations, including the American Medical Association, American College of Obstetricians and Gynecologists, and American Society of Human Genetics, providing evidence that patents on genetic sequences interfere with health care and research.

Medical organizations are concerned because gene patents increase the cost of the diagnosis and treatment of genetic diseases.  For 20 years, a gene patent holder controls any use of “its” gene. The patent holder can charge whatever it wants for any test analyzing the patented gene–even if that test uses a technology that was not invented by the patent holder.  Myriad, which holds the patent on the BRCA1 and BRCA2 genes, charges over $3,000 for its genetic test for breast cancer.  One in four laboratories has stopped performing certain genetic tests because of patent restrictions or excessive royalty costs.

The ability of a patent holder to prevent health care providers from using a patented genetic sequence denies people crucial medical information.  Most drugs only work on a percentage of patients who use them.  An asthma inhaler might only work on seven of ten people to whom it is prescribed, causing the other three to suffer symptoms of asthma and pay for an inappropriate drug until the right medication can be found.  Genetic testing can help to distinguish those people for whom a drug will work from those people for whom it will not work, but, if the same entity holds the patents on the drugs and the gene sequences, it may prevent use of the gene sequence because the identification of people for whom the drug will not work will limit the market for the drug.

One company has filed for patent protection on a genetic sequence that could be tested to determine the effectiveness of its asthma drug in a prospective patient.  The company, however, has said that it will not develop the test–or let anyone else develop the test.  While such a test would be crucial to doctors in determining which patients would benefit from the use of the asthma inhaler and which patients would benefit from a different drug or treatment, it would also diminish the market for the drug because a trial use of the asthma inhaler would no longer be needed to know if it would be an effective treatment.

For more information, listen to my interview with Minnesota Public Radio on the subject or view the video of an interview with me on the OYEZ website.

Biohack the Planet! A New Generation of Hackers Sweep Across the Country

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Keith Syverson by Keith Syverson

The recent phenomenon of “biohacking” has been quietly gaining momentum.  In February 2010, Lori Andrews blogged about her experience at UCLA’s Outlaw Genetics conference.  Just last week, the international scientific journal Nature published an article titled “Garage Biotech: Life Hackers” describing the growing trend.  The steadily decreasing cost of molecular biology equipment has lead to a movement where amateur scientists, calling themselves biohackers, purchase equipment and set up their own molecular biology labs in their garages.  Proponents of the movement liken it to the open source movement in software.  The idea is that the “democratization of science” will bring fresh new talent to improve scientific instruments and uncover new applications for biotechnology.  At the very least, the name “biohackers” sounds cool.

Biohackers and do-it-yourself biologists come in all forms.  Geneticist Hugh Rienhoff created a home laboratory to study his ailing daughter’s rare genetic condition.  Others, like Rob Carlson, simply became frustrated with the tedious process of annually filling out grant applications to secure funding at his academic lab. The real down-and-dirty biohackers, however, are simply hobbyists with little or no formal training in molecular biology.  For example the article in Nature mentions Meredith Patterson, a computer programmer based in San Francisco California who created glow-in-the-dark yogurt by engineering a yeast strain in a garage lab.  There are growing online communities such as DIYbio where biohackers come together to share protocols and instructions for making cheaper lab equipment.  Other groups, such as the Silicon Valley-based BioCurious, are seeking to furnish a shared lab space where members of the club pay dues in exchange for classes taught by local graduate students and timeshares in the lab.

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Myriad Offers to “Gift” Its Breast Cancer Patent to Australia: What’s the Logic?

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Jake Meyer by Jake Meyer

Myriad Genetics, in mid-August, 2010, sent a letter offering to surrender its Australian BRCA1 breast cancer gene.  The letter said, “Myriad wishes to gift Australian Patent No 686004 (the Patent) to the people of Australia.”  On September 2, 2010, the Commissioner of Patents published notice of Myriad’s offer to surrender the Patent in the Australian Official Journal of Patents, and interested parties that want to be heard before the offer of surrender is accepted must submit a request within a month.

Myriad will surely claim its offer to surrender its patent is based on compassion and consideration for Australian women who have a family history of breast cancer and want genetic testing.  Not enforcing their Australian patent will allow competing labs to open and provide BRCA1 testing—perhaps at a lower cost or at higher quality.  The existence of more labs will give Australian women who wish to be tested the option of obtaining a second opinion before deciding to pursue radical surgeries, such when healthy, asymptomatic women have their breasts or ovaries removed based on a test result that suggests they are at a higher-than-normal risk of developing cancer.

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From Nude Photos to Naked Genomes: Berkeley Gets Poor Marks on Frosh Gene Tests

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Lori Andrews by Lori Andrews

What do George W. Bush, Hilary Clinton, Meryl Streep and Wendy Wasserstein have in common?  As incoming freshman to Ivy League universities, they were required to pose nude for photographs.  The goal of the project was to correct students’ posture—and to correlate posture with later life achievement.  From the Ivy League, the practice spread across the country until a female freshman at the University of Washington in Seattle challenged it.  In 1968, the program was abandoned, under criticism it was eugenic.

I attended Yale after the demise of the notorious photo program.  But when I read about U. Cal Berkeley’s recent plans for its incoming freshman, I realized Berkeley officials hadn’t learned the lesson of the posture program.  Rather than requiring nude photos of their students, Berkeley officials were planning to peer at students’ DNA.  Indeed, they were opening the door for sensitive genetic information to be made available about our future leaders–their current students.

The Scope of the Berkeley Program

Last summer, 5,000 incoming students at University of California, Berkeley received a surprise along with the packet of information about their freshman year.  Their admissions packet contained an item that looked like a Q tip and an invitation to swab the inside of their cheeks for genetic testing.  The targeted genes were involved in breaking down lactose, metabolizing alcohol and absorbing folic acid.

The program came under criticism from lawmakers, bioethicists and even the California Department of Public Health.  Now Berkeley has significantly cut back the program.  What lessons should Berkeley officials learn from this experience? 

Lessons to be Learned

1.    In the quest to be avant garde, don’t forget the basics

Berkeley officials seem to have been caught up in the novelty of the program.  “Science is moving so fast right now,” said Alix Schwartz, director of academic planning for the college’s undergraduate division. “If we assigned them a book, it would be out-of-date by the time they read it.”

Think hard about that comment.  Parents are spending up to $40,000 a year to send their children to Berkeley.  In most of their courses, students will be assigned books to read.  It would not be unreasonable for parents to ask, is it really worth $160,000 for my child to get an obsolete education?  Why don’t I just get a quickie genetic profile done on my child an put him or her in a job best on the genotype?

2.    Take responsibility for the well-being of your students

Years ago, psychology professors routinely required their students to be subjects in experiments as part of their course requirements.  Now the Code of Ethics for psychologists forbids this sort of coercion of students.  But Berkeley’s “offer” to students, although presented as voluntary, was itself coercive.  “The consent form for the project is pure marketing,” Jeremy Gruber, the president of the Council for Responsible Genetics told California lawmakers at the August 2010 hearing on the program.  The form listed speculative, unproven benefits of the testing, but none of the risks.

The genetic testing program was replacing the “one book” program to give students a common experience to discuss.  A student entering Berkeley might feel compelled to swab rather than risk ridicule by others or marginalization by not participating.  Or worse yet, by saying “My parents wouldn’t let me send in my DNA.”

And what happens when the students started discussing the results of their tests?  Would those who were poor metabolizers of alcohol be left behind when others went to the local bar?  And, as Boston University public health professor George Annas asked, would those who had genes related to alcohol tolerance feel they could drink to excess? 

3.    Look closely at conflicts of interest

According to the consent form for the project, the students DNA sample would “become the property of the University” until its destruction and the university would “save the data for future teaching purposes and for possible publication of the aggregated data and its analysis.”  Such an approach makes one wonder if the project is being undertaken for the students’ benefit or for that of university researchers.  Indeed, the professor behind the program had formed his own genetic testing company last year.

There was also to be a writing contest where the winning students would have a chance to win further genetic testing from 23andMe, a private company that offers DNA profiling.  But should a public university be endorsing a private company?  “The FDA and Congress are currently investigating this type of testing, described as ‘snake oil’ by a member of the House Energy and Commerce Committee at a recent hearing, also described as ‘not ready for prime time’ by the Centers for Disease Control,” Gruber said at the California hearings.

4.     Check the legality of what you are doing

Berkeley planned to do the genetic testing in one of its university labs and provide the individual results to the students.  But its labs had not complied with state and federal requirements, such as the Clinical Laboratory Improvement Act, which cover any lab that provides a medical result back to a consumer.  These laws are designed to ensure the accuracy of the test results.  The university argued that it was not providing medical information and thus was not covered by the laws.  But that argument was just not credible, given the university’s position that this information could be useful to students in planning preventive measures.

Ultimately, Berkeley backed off of its program when the California Department of Public Health warned that the plan to have students’ DNA samples analyzed at an uncertified lab would violate state law.  Now, instead of offering individual test results to students, it will only post aggregate results.

Berkeley’s Poor Marks

The Berkeley administration deserves poor marks on how they handled the program.  In fact, they seemed to have flunked psychology (with a coercive program), law (not complying with statutes), biology (by not acknowledging the limits of predict
ive value in the tests they were offering), ethics (creating a potential conflict of interest) and history (not applying what had been learned from posture photos debacle).   Perhaps now they’ve learned the lesson that the use of genetic tests needs to be analyzed and contextualized–which, after all, are the hallmarks of any great college education.

A Case of Nurture over Nature

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Jake Meyer by Jake Meyer

Neuroscientist James Fallon has been studying behavioral disorders for 20 years at the University of California at Irvine, but he made his biggest discovery in his own backyard.  At a family barbeque, James's 88 year-old mother recommended to him that he find out about his father’s relatives, saying "I think there were some cuckoos back there."  What he found was a 300-year family history that included eight convicted and alleged murderers.  Among his ancestors are a man who was sentenced to death by hanging for murder in 1667 and the infamous Lizzy Borden.  Fallon was understandably concerned.  As part of a family study to determine risk of Alzheimer’s disease, he had already convinced 10 of his family members and relatives to take a brain scan and give a blood sample.  After years of studying the criminal brain, Fallon knew the signs associated with behavioral disorders, so he compared the brain scans.  Only one of the family brain scans showed the pattern of what he calls a psychopath – his own. 

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Collaboration Among Alzheimer’s Researchers As A Model For Future Genetics Research

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Jake Meyer by Jake Meyer

Researchers studying Alzheimer’s disease have been using an approach to learning about the disease rarely used in the life sciences – cooperation.  In 2003, the Alzheimer’s Disease Neuroimaging Initiative formed as a collaborative effort to find biomarkers that show the progression of Alzheimer’s disease in the brain.  Researchers from the National Institute of Health, Food and Drug Administration, the drug and medical imaging industries, and universities and non-profits have been sharing all of their data and making every finding freely accessible to the public.  The collaboration agreed that no one would either own the data or submit patent applications.  Now in 2010, the collaboration is starting to bear fruit.

The Alzheimer’s collaboration is significant for two reasons. First, the collaboration of Alzheimer’s disease research is yielding promising results for the understanding and treatment of the disease.  This collaborative approach looks to be effective – currently there are over 100 studies being conducted to test drugs that could slow the effects of the disease or cure it.  Second, this type of collaboration in the life sciences is rare, as the practice of allowing patents on the results of basic scientific research (such as human gene sequences and correlations between genetic mutations and disease) in the life sciences fields has created an incentive to not share results, but instead withhold data.  Dr. John Q. Trojanowski, an Alzheimer’s disease researcher at the University of Pennsylvania, describes how uncommon collaboration like this is in the life sciences: "It’s not science the way most of us have practiced it in our careers.  But we all realized that we would never get biomarkers unless all of us parked our egos and intellectual-property noses outside the door and agreed that all of our data would be public immediately." 

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