Posts by Katherine Drabiak, J.D.

The Problem of Transparency and Human Genome Editing

Posted on Jun 4, 2016


In the past several weeks, human genetic modification has been dominating headlines.  This time, the controversy surrounded the closed door meeting between 130 scientists, attorneys, entrepreneurs, and government officials to discuss the creation of a synthetic human genome.  The project, called “Human Genome Project-Write Testing Large Synthetic Genomes in Cells” aims to synthesize a complete human genome in a cell line within ten years, with the future goal of translating such basic science into clinical applications.  Rather the modifying the human genome through editing technology such as CRISPR, synthetic creation would allow scientists to make extensive and radical changes throughout the genome.


According to one of the co-organizers, Harvard Geneticist George Church, the meeting merely constituted a “thought experiment” and the organizers made an executive decision to close the meeting to the public, asserting they would subsequently publish the discussion from the meeting in a prominent scientific journal that required a pre-publication embargo on publicly sharing the content of the meeting.


Stanford’s Drew Endy not only declined to attend based on the meeting’s intentional secrecy, but posted to his Twitter a copy of the meeting invitation, which stated the organizers instituted the media ban as a mechanism avoid media scrutiny and “to permit attendees to speak freely and candidly.”  Endy, along with Northwestern’s Laurie Zoloth published a response in Cosmos Magazine noting that “when the first people at the table mostly have significant and direct material interests in the proceeding, everyone, not just those in the room, risk out-of-control competition between public and private interests, ethical conflicts of interest, and temptations to manipulate human subject consent.”


Endy advocated for “pluralistic, public, and deliberative discussions” to encourage transparency of purpose and content.  Marcy Darnovsky  from The Center for Genetics and Society posited the meeting served as a step to privatize efforts toward genetic modification.  According to the Center for Genetics and Society, billionaire attorney and entrepreneur Randal Kirk plans to expand his empire of life sciences corporations focused on genetic modification (projects that currently include genetically modified salmon, genetically modified mosquitoes, and human gene therapy research) to include research projects designed to synthetically create human ova and alter the human germline.


We have seen the impact of closed meetings and the power by which interested stakeholders with deep pockets and a vested interest in promoting a technology can direct public opinion like a puppet master through strategic media campaigns, assert “conclusions” professing basis in scientific evidence, proclaim consensus despite the existence of divisive questions within the scientific community, and strong arm regulation and policy without public transparency.  Perhaps most problematically, few members of the public are even aware of this complex history behind the curtain of genetically modified food so eloquently and meticulously presented by attorney Steven Druker in Altered Genes, Twisted Truth In his book, Druker raises several notable points, each of which are pertinent to the discussion relating to human genetic modification: we must analytically examine the current state of science rather than accepting inflated promises, comprehend the danger of failing to consider unintended effects within the organism and its ecosystem, and scrutinize the implication of inherent unpredictability when altering genetic structures.


Indeed, the Committee on Science Technology, and Law Policy and Global Affairs at the International Summit on Human Gene Editing noted that the current gene editing technology CRISPR is highly unpredictable: it can alter DNA at other unintended locations other than its target, which would impact genetic structure and function at other locations on the genome.  This process could activate other genes including cancer causing genes,  inactivate essential genes, or cause chromosomal rearrangements.  One team from Guangzhou Medical University China who conducted gene editing on non-implantable embryos using CRISPR reported dismal preliminary results: only 4 of the 26 embryos the team used produced the desired mutation that scientists believe confers HIV resistance and the embryos demonstrated signs of mosaicism.  Furthermore, Geneticist Eric Lander observed inducing this particular mutation simultaneously confers an increased risk of West Nile virus and aptly summarized: “We are terrible predictors of the consequences of the changes we make…we don’t understand the genome enough to make changes in the long run.”


Despite a United Nations prohibition on the modification of the human genome and other nations that legally prohibit human genetic modification, the US does not have federal regulations prohibiting human genetic modification, whether achieved through genome editing or synthetic human genome creation.  It is also foreseeable that any obstacles arising out of federal funding limitations could be easily circumvented though private funding or successful lobbying to ease or even erase such restrictions.


This weekend at the American Society of Law, Medicine and Ethics Annual Heath Law Professors Conference Law Professor John Robertson repeated Church’s label, asserting that we are likely to see “exciting” efforts to “correct disease” fairly soon but efforts for enhancement are a distant “thought experiment.”  I disagree.   Corporations need not offer perfectly accurate technology, but instead appeal to a market by advertising a product’s technological promise.  As we’ve seen in current genomic technologies, this translates into technology premised upon manufacturer advertisements of accuracy and validity which may or may not produce the desired advertised outcome.


The community of interested stakeholders must rise as a leader to promote thoughtful governance, particularly given the transnational and global nature of this research.  Public transparency of the scientific community’s goals and agendas are imperative given our current juncture-  private corporations are poised to create synthetic ova, presently occurring experiments create chimeras integrating human DNA into animals, and Bill Skarnes of the Wellcome Trust Sanger Institute predicts the utilization of human genetic modification for clinical use in humans within the next five years.  Failing to intervene with prudent regulation at this juncture will have unimaginable and irreversible consequences.



Read More

Media Misstates the Message: Investigate CDC Whistleblower’s Claims

Posted on Apr 22, 2016

Media headlines are abuzz around the decision to pull the documentary Vaxxed: from Conspiracy to Cover-Up from the Tribeca Film Festival.  As a disclaimer, I have not viewed the film.  What is deeply troubling, however, is how numerous media outlets (here and here) have misconstrued the film’s message calling for an examination of vaccine safety and efficacy.  Instead, headlines and news content repeat erroneous assertions that are contrary to scientific evidence and focus exclusively on the controversial Dr. Andrew Wakefield as a red herring. (If you are interested in learning the full story about the Wakefield controversy and the role of the media, you can read it in this book).   Both the science and the law relating to vaccination are nuanced and evolving.  When vaccines go through the approval process at the FDA, approval is premised upon data submitted by the vaccine manufacturer showing that the product is safe, effective, and its benefits outweigh the risks.  Glossing over this complex process and improperly labeling any questions pertaining to safety and efficacy as “anti-vaccine” effectively stunts the scientific process as an evolution and pursuit of developing knowledge.

Based on its website, the film intends to address statements made by Dr. William Thomson PhD, senior scientist at the CDC who revealed he was instructed by fellow CDC senior scientists to eliminate highly unfavorable data from studies they conducted examining links between vaccination and neurological injury.  The conclusions of these studies (DeStefano 2004, Thompson 2007,  Price 2010)  have been widely cited and touted by Dr. Paul Offit MD as “definitive” proof demonstrating vaccine safety.  What did that excluded data show?  According to conversations between Thompson and biology Professor Dr. Brian Hooker PhD, the data demonstrated a substantial differential rate of adverse reactions to the MMR vaccine based on sex and race: African American boys who received the vaccine according to the American Academy of Pediatric Schedule had a 3.4 fold increase in risk of autism.  Barry published a book summarizing conversations he had with Thompson including full transcripts of lengthy discussions related to alleged data manipulation and conflicts of interest between industry and the CDC.  You can read a summary written by attorney Robert Kennedy Jr. JD LLM here and the book containing full transcripts here.

Not only is this statistic alarming, but what’s more concerning is lack of mainstream media coverage and public knowledge of this incident and other information that calls into questions vaccine safety from a variety of angles.    CBS Reporter Sharyl Attkisson has referred to the topic of vaccine safety and efficacy as the “most censored and misreported story of the century.” To find that information requires digging through other media channels, such as Attkisson’s website, attorney Robert Kennedy Jr. JD LLM’s work, MIT Senior Research Scientist Stephanie Seneff PhD’s findings, or assessments by physicians Dr. Mark Hyman MD and  Dr. Kelly Brogan MD.

Combing through the research rather than accepting the common meme reveals numerous safety questions about which there has been no open dialogue pertaining to studies demonstrating: long term central nervous system damage including seizures, learning disabilities, and neurological disorders; an increased risk of severe allergies and asthma; the onset of chronic arthritis; and death.  Further, numerous studies (examples here and here) and federal whistleblower claims against Merck point to compelling evidence undermining assumptions of efficacy and the veracity of manufacturer claims of efficacy prior to FDA submission for approval.  Such evidence threatens the massive profits of the global vaccine market, which constituted estimated $24 billion in 2014 (see here and here).

As New York University School of Law Research Scholar Mary Holland JD has noted, the law recognizes vaccines’ risks despite appropriate manufacturing and administration.  Vaccines are classified as “unavoidably unsafe” products; that is, they will necessarily expose some individuals to risk of injury and death.  In 1986 Congress passed the National Childhood Vaccine Injury Act as a means to shield manufacturers from mounting liability claims via private litigation while compensating victims of vaccine injury.  In 2011,  the Supreme Court in Bruesewitz v. Wyeth held that the Act preempts all design-defect claims against vaccine manufacturers, which precludes injured parties from seeking private remedy from the manufacturer.

In a powerful dissent, Justice Sotomayor stated:

“Vaccine manufacturers have long been subject to a legal duty, rooted in basic principles of products liability law, to improve the designs of their vaccines in light of advances in science and technology… the majority’s decision leaves a regulatory vacuum in which no one—neither the FDA nor any other federal agency, nor state and federal juries—ensures that vaccine manufacturers adequately take account of scientific and technological advancements. This concern is especially acute with respect to vaccines that have already been released and marketed to the public. Manufacturers, given the lack of robust competition in the vaccine market, will often have little or no incentive to improve the designs of vaccines that are already generating significant profit margins.”

Excluding information such as Thompson’s allegations from both public and policy discussions has implications for determining the extent and acceptability of risk for adverse events.  Notably, it also disables consideration of the risk of adverse events based on distinct classes and differential responses based on sex, genetic variation, or use during pregnancy.  FDA’s regulatory structure assumes that until a vaccine is given to the general population, all potential adverse events cannot be anticipated.  Many vaccines undergo Phase IV studies and the FDA relies upon the Vaccine Adverse Event Reporting System (VAERS) to identify adverse events after marketing begins.  According to former FDA Commissioner Dr. David Kessler MD, since VAERS’s inception in 1990 about 35.2 million adverse events have been reported, yet Kessler estimated only this accounts for only 1% of all serious adverse events that occurred.

Without an open and frank conversation about the meaning of evidence demonstrating increased risks or decreased efficacy, we face as a society troubling public health implications for which as Justice Sotomayor warned,  no one will be held accountable.

Read More

Read the Fine Print Before You Send Your Spit to 23andMe

Posted on Apr 7, 2016

Our genomic sequence constitutes the most sensitive and personal of information: uniquely identifying us, revealing our propensity to develop certain diseases and conditions, and exposing familial connections of close genetic relatives. In recent years, Big Data has taken firm hold in numerous sectors, revolutionizing the volume and velocity at which businesses can collect, curate, and use digital information. Consumers can track what they eat, their fertility, whether they are exercising, and how much they are sleeping. Combining these pieces of data with genomic and health information such as family history, health conditions, disease state, and demographic information constitutes a gold mine for scientific research.

23andMe capitalized on the quantified self movement and consumers’ effusive willingness to collect and share personal data, transforming it into a highly profitable venture. Within the past year, 23andMe rapidly reinvigorated its business model, introducing Food and Drug Administration-compliant Carrier Screening Reports as part of its new Personal Genome Service, introduced on online recruitment platform for disease specific research cohorts, and publicized multimillion dollar partnerships with pharmaceutical giants such as Genentech.

In numerous media interviews, 23andMe CEO and cofounder Anne Wojcicki beams with positivity about how this model will revolutionize health care; empowering consumers with an awareness of the secrets of their genome while accelerating the speed of research and drug discovery. As one article in theSan Francisco Chronicle characterized it, “23andMe wants to do for health what Google has done for the search: make massive quantities of information digital, accessible, and personal.” 23andMe made this vision a reality by digitalizing and compiling genotypic-phenotypic data into a searchable format for interested investigators to run queries in its Research Portal, an online searchable database of over genotyped individuals with more than 225 million phenotypic data points, including demographic, clinical information, and family history.

An exciting prospect for research scientists, but also attractive to many other business as well. The sheer amount of information 23andMe’s database makes it appealing to a number of external parties, including data brokers, the pharmaceutical industry, employers, health insurers, and law enforcement. Entities may want to use the data for predictive modeling and draw inferences to market a product, decide suitability for employment, deny life insurance coverage, or target suspects pursuant to a criminal investigation. These uses of the data pose significant informational risks: shame, embarrassment, discrimination, or being subjected to law enforcement investigations. Perhaps surprisingly, many of these secondary uses of the data are currently permitted by law.

Just how much information does 23andMe collect? Much more than consumers may imagine unless they read the fine print. Purchasing the test and submitting DNA creates a potentially indelible electronic record of your genomic sequence in 23andMe’s database, along with a composite mosaic of additional health, lifestyle, and consumer generated personal details. In addition to the information the consumer actively sends, 23andMe employs numerous techniques to collect and track additional details through social media, web beacons, and consumer IP addresses such as compiling personal photos, place of employment, a record of every website the consumer clicks on, and real time tracking of the consumer’s location.  23andMe uses this data internally for marketing purposes and shares the data for research if the consumer provides consent.

But- the fine print also contains a provision that permits 23andMe to unilaterally modify its privacy policy at any time, effectively changing current promised limitations. Wojcicki’s positive intentions aside, she is not the sole party controlling the data. If 23andMe follows in Google’s footsteps, then the private information may not stay private. Indeed, Google Ventures managing partner Bill Maris (a financial supporter of 23andMe) has dismissively challenged, “What are you worried about? Your genome isn’t really secret.” If 23andMe modifies its policy to widely sell consumer data without consent, the lightning nature of electronic data sharing means Pandora’s Box is open.

How is this possible? In addition to expediting the process for research, 23andMe also challenged the traditional regulatory and ethical requirements that ordinarily correspond to collecting and disseminating private genomic and health information. The massive paradigm shift to collecting genomic and health information in the commercial arena, as opposed to the health care setting, means the transaction may occur outside the scope of regulatory structures designed to ensure informed consent when subjects provide DNA and to protect health data privacy.

The HIPAA (Health Insurance Portability and Accountability Act) Privacy Rule does not apply to consumer curation of health data or any associated protections related to privacy, security, or minimizing access. Similarly, unless a commercial entity conducts research that is supported by a federal department or agency, such as NIH funding, regulations set forth in the Common Rule will not govern that entity’s practice. Even though 23andMe receives NIH funding, 23andMe currently asserts that its data-mining analysis does not constitute research on human subjects under the current version of the Common Rule because it de-identifies the data. This stance is significant because it means 23andMe believes any consent it obtains to retain, use, and share consumer data is not necessary for regulatory compliance, but rather constitutes a transactional courtesy.

The traditional informed consent dialogue intended as a means to convey risks and benefits shifts dramatically when the consent process occurs online via consumer interaction with a website clickwrap interface rather than a physical contact person from the research team. Clicking through to purchase the test constitutes an entangled package consisting of a service, agreeing to receive medical information, and research.Recent litigation over 23andMe’s model of presenting its terms reiterates that just because you don’t read the fine print does not mean you can claim those terms are unfair and erase your decision.

Consumers may be blinded by the genomic technological imperative to know and widely share their genetic profile or assuaged by notions of altruism highlighting their contribution to important scientific research. They may bypass reading the fine print, or alternatively, they may not fully appreciate the implications of the transaction. Read the policies closely, and read them carefully, to assess whether the benefits outweigh such looming informational risks.

Read more:

Read More

Laboratory Developed Tests Under Scrutiny: FDA Questions Validity and Utility of Oncotype Dx and Prolaris Tests for Personalized Cancer Treatment

Posted on Mar 8, 2016

In November 2015, FDA published a startling report, The Public Health Evidence for FDA Oversight of Laboratory Developed Tests, which enumerated serious concerns with the current framework it uses to oversee laboratory developed tests (LDTs). LDTs are tests used by physicians to diagnose disease, predict risk of disease, and guide critical therapy decisions. This report revealed grave shortcomings in test accuracy, reliability, and ability to provide clinically meaningful information to physicians and patients in a number different tests, ranging from tests to determine personalized oncology treatment, to fetal genetic tests, to tests to predict heart disease risk and pharmacogenetic response to statin therapy. The report listed that testing inaccuracies resulted in false positives, where patients were informed they had a condition they did not have, producing psychological distress and overtreatment. Other tests produced false negatives, where patient illnesses went undetected and the patient failed to receive appropriate and timely treatment.

Under the FD&C Act of 1976, FDA has the authority to regulate LDTs as medical devices, subject to registration, pre-market review, and adverse reporting to ensure the test’s analytic and clinical validity: that product is properly designed, manufactured consistently, and that the test is accurate at what it purports to predict. Up to this juncture, FDA has enforced these provisions with discretion and has not subjected certain LDTs to these regulatory requirements, so FDA has not assessed the analytic and clinical validity of certain tests that are currently on the market and relied upon by physicians. Indeed, FDA admitted concern that physicians and patients are using these LDTs without being aware that some are not FDA approved and that the FDA has not evaluated their analytic and clinical validity.

In 2014, FDA promulgated Draft Guidance Framework for Regulatory Oversight of Laboratory Developed Tests designed to phase in implementation of a more stringent regulatory approval process in the next several years. However, these classifications and requirements are not yet in place, and numerous faulty LDT tests are on the market being actively used and relied upon by physicians and patients.

Oncotype Dx and Prolaris, two LDTs recommended by the National Comprehensive Cancer Network and used by oncologists to aid in treatment protocol for breast and prostate cancer, respectively, were listed in FDA’s report. Both cancers are diseases of high visibility and frequency- almost certainly affecting someone we personally know. In the United States annually, 231,840 women are diagnosed with invasive breast cancer, and 220,800 men are diagnosed with prostate cancer. The aim of such tests lays at the heart of precision medicine– we want more effective strategies that account for individual variability that allows physicians to predict more accurately which treatment strategies for a particular disease will work.

Increasing the effectiveness of treatment, however, assumes that the oncologist’s testing tools are accurate.

Oncotype Dx, manufactured by Genomic Health, assesses 21 genes expressed in a patient’s tumor and a RNA based HER2 test, designed to detect whether the patient’s cancer is HER2 positive or negative. Genomic Health designed the HER2 RT-PCR portion of the test to provide physicians and patients personalized treatment based on this tumor profile with pharmacogenomic implications. Physicians likely believe in the test’s accuracy and reliability- both the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) incorporate Oncotype Dx into their treatment guidelines, and the highly respected New England Journal of Medicine recently published a prospective validation of the HER2 RT-PCR component.

Despite the sterling support from the medical community, the HER2 RT-PCR component is not included in ASCO’s guidelines as a test to specifically decide whether certain drugs such as Herceptin, a drug commonly used to treat HER2 positive tumors, is indicated. FDA’s report evaluated evidence set forth by a group of independent pathologists who found discrepancies in test specificity and found the test produced false negatives, missing the diagnosis of patients with HER2 positive tumors and misinforming subsequent treatment decisions. Specificity of HER2 status is imperative to guiding appropriate treatment- patients whose tumor is HER2 positive may elect to add Herceptin to the treatment protocol based on its targeted indication for treating HER2 positive cases. Alternatively, potential overtreatment of patients with Herceptin is not only ineffective, but raises significant risks including cardiomyopathy, pulmonary toxicity, and death.

FDA’s report also profiled Prolaris, manufactured by Myriad Genetics, a prostate cancer biomarker test that examines 46 genes associated with the proliferation of prostate cancer cells and prognosticates the risk of cancer progression and survival rate. FDA assessed that there was insufficient evidence for Myriad Genetics’ marketing claims and questioned the test’s ability to meaningfully improve clinical outcomes, concluding that physicians relying on this test may over or undertreat patients accordingly. This is particular disconcerting because physicians do in practice rely on the result of this test, one study showing it impacted 65% of physicians’ treatment plans. The ramifications of overtreatment of prostate cancer are also considerable. Patients who elect to undergo a radical prostatectomy face a 70% risk of impotence, 25% risk of complete incontinence, and loss of fertility.

The accuracy and validity of such LDTs constitutes a critical key in both physicians’ clinical judgment and informed decision-making by patients when diagnosing illness and deciphering appropriate corresponding care. It is imperative that both physicians and patients be aware that these tests, as well as select other widely relied upon molecular diagnostic tests, are not currently FDA approved to ensure their accuracy and reliability despite any evidence set forth by the corporation offering the LDT and rely upon them with caution.

Read More