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Science Policy Around the Web September 30th, 2019

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By Allison Dennis B.S.

Image by Gerd Altmann from Pixabay 

23andMe, moving beyond consumer DNA tests, is building a clinical trial recruitment business

Clinical trials are often criticized for poor patient recruitment that inadequately represents patients from minorities, e.g., women of reproductive age, racial minorities, underserved patient populations and people with rare genetic diseases. To fight this, 23andMe feels that its vast database of patients comfortable enough to trade their genetic information and a small bit of spit to learn more about their genetic predisposition to disease and heritage could be a much-needed recruiting tool for those enrolling patients in clinical trials, and one they would be willing to pay for. 

23andMe can mine the database of their 8 million potential research participants to identify which customers fit the needed demographics and genetic profiles relevant for studying a particular drug. For example, 23andMe found about 7,500 carriers of a rare mutation in the gene LRRK2, a potential target being pursued by GlaxoSmithKline to prevent the progression of Parkinson’s disease. In patient populations, this mutation is only found in one in a thousand people, meaning it would take years to identify enough participants to enroll in a trial. With enough potential participants to choose from trial managers are hoping to to recruit local patients, allowing them to overcome the costs of paying for patient travel and ease the stress patients experience by spending extended time away from home.

To augment the diversity of their database, 23andMe has launched programs to provide free genetic analysis to people whose four grandparents were born in the same country. The Global Genetics Project focuses on underrepresented countries like Mali, Tajikistan, and Paraguay, while the African Genetics Project focuses on the ethnic and tribal groups of countries such as Cameroon, Ghana, Libera, and Senegal. By starting with the genomes of people with clearly known ancestry to better define the genetic differences common to them, 23andMe is hoping it will be able to improve its unravelling of more complicated genetic lineages. A greater diversity of enrollees is sure to appeal to clinical trial recruiters, who are trying to meet FDA guidelines designed to enhance the diversity of clinical trial populations.

It remains to be seen how receptive 23andMe customers will be to being targeted for participation in clinical trials. Many of the 8 million may not have fully realized that consenting to genetic research would potentially extend to drug companies paying for their data. However, for many people, the possibility of playing a role in the discovery of cures for genetic diseases may outweigh privacy concerns and any initial discomfort from being singled-out. 

(Rebecca Robbins, STAT News)

NIH reveals its formula for tracking foreign influences

NIH’s extramural research program is struggling to find the balance between curbing inappropriate information sharing, fostering the international collaboration recognized as necessary for the global pursuit of science and maintaining some level of ease in the grant application process. The grants that are distributed by NIH are won following review by a panel of experts, composed of about 27,000 reviewers recruited to serve on committees by NIH each year. It is believed that some reviewers have violated NIH policy by sharing the confidential contents of grant applications with international colleagues. The data and research approaches described in grant applications is proprietary and often has the potential to result in patents in addition to publications. 

A more complicated scheme concerning officials involves international researchers setting up labs in parallel, one in the US to win grant money, and one in a foreign country where the grant winner wishes to benefit from any emerging intellectual properties stemming from the funded research. Such an arrangement allows US funded discoveries to be transferred to another country without any oversight from the US government. 

It is difficult to clearly spot scientists unfairly leveraging their role in NIH grant giving activities. While grant reviewers are not supposed to share any parts of the application, it is common for researchers to share grants with trainees in their lab, sometimes seeking relief from the burden of review by having junior researchers take the first look, other times viewing it as a needed opportunity for future grant-seekers to become familiar with the process. Grant applicants routinely have joint appointments with international institutions. This is acceptable if clearly disclosed when they seek funding from NIH. 

In the past the issue has been treated as a regulatory hot potato, NIH requires grant seeking institutions certify the grantee listed on the application, institutions rely on the assumption that foreign scientists would be denied visas by the US Department of state if they were thought to have improper ties to their home countries. Of course, citizens that are US citizens are at risk of behaving improperly as well. NIH is taking the next sixth months to develop a risk-based approach to flag potential conflicts with reviewers. As a first step they are considering moving grant reviews to a read-only online portal to prevent any untracked distribution of downloaded applications. 

 (Jeffrey Mervis, Science)

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October 1, 2019 at 11:32 am

Science Policy Around the Web – June 18th, 2019

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By Allison Dennis, B.S.

Source

Congress is debating-again-whether genes can be patented

The last time the U.S. government issued an official guidance on human gene patenting, it was from the Judicial Branch in 2013. By a unanimous decision, the Supreme Court ruled that two genes whose DNA sequence can be used to predict the probability of a patient developing breast or ovarian cancer, BRCA1 and BRCA2, could not be patented. Companies are still free to pursue patents manipulating or mitigating the effects of specific genes, but the ruling invalidated the patents held by Myriad Genetics for these two genes and opened the door for clinical labs to begin widely testing patient samples for mutations across a wide variety of disease predicting genes that might have otherwise been patented.

Insurance claims filed in 2004 indicate that only one in four women received a BRCA mutation test before being diagnosed with cancer. By 2014, more than 60% of these tests were administered diagnostically, allowing women confirmed to be at risk to pursue prevention and early detection of breast and ovarian cancer before developing either. The effect of the 2013 Supreme Court ruling to dramatically reduce testing costs in combination with technological developments and public health awareness have been attributed to this shift.

Now lawmakers in the legislative branch are weighing in. Senators Thom Tills and Chris Coons filed a bipartisan draft bill that would expand the types of inventions eligible for a U.S. patent to include previously restricted subject matter falling under “abstract ideas,” “laws or nature,” or “natural phenomenon,” which could be interpreted to include human genes. While Tillis has since made clear that it was “was never the intent” to again give companies ownership over single human genes, the changes could allow companies to limit examination of specific genetic variants like those most likely to cause disease. Supporters of the bill feel it is necessary to provide companies with sufficient intellectual property to incentivize their research into isolated natural products. Many point to less-restrictive patent codes abroad, which they feel put the U.S. at a disadvantage.  

Following two weeks of Congressional hearings, and a letter signed by 170 scientific organizations, nine nobel prize winners along with 74 leading physicians and scientists have weighed in by urging lawmakers to more carefully consider the proposed changes. The level of concern or eagerness expressed for the bill seems largely up to the interpretation of the reader, suggesting that much more work is needed for the bill to achieve its stated goal of reducing frustration and confusion generated by the Supreme Court rulings.

(Megan Molteni, Wired Magazine)

Federal Grants Restricted To Fighting Opioids Miss The Mark, States Say

Of the 70,237 drug overdose deaths captured by the CDC in 2017, nearly a third involved cocaine, psychostimulants, which include MDMA and methamphetamine, or both. The CDC cites “changes in the drug supply, mixing of substances with or without the user’s knowledge, and polysubstance use” as emerging threats. Yet the opioid-focused way grant money is allocated may be restricting the ability of states to adapt.

At the frontlines of the opioid epidemic are state officials dedicated to making the most of federal grants designed to offer struggling states a financial lifeline. For example in 2017, Arizona used funds from a State Targeted Response grant to train 9,197 individuals in Naloxone usage and purchase 8,798 Naloxone kits, allowing first responders to perform 5,649 overdose reversals. Many states are using the money to implement the hub-and-spoke model, first developed and demonstrated to be effective by Vermont, in which intensive addiction treatment is offered at a limited number of hubs connected by a local network of outpatient addiction programs and primary care physicians. Through this structure, the hub-and-spoke model can make at least one licensed mental health or addiction counselor accessible per 100 patients.

While the framework provided by the hub-and-spoke model may intuitively help address addiction beyond the specific use of opioids, they rely on Medication Assisted Treatment, an intervention that has only been approved for opioid addiction. Similarly the use of Novaxalone is only effective in reversing opioid overdoses, in the case of cocaine overdose it is ineffective. Additional research is underway to develop parallel treatments for other substances, but these efforts have been eclipsed by the national focus on opioids.  

In 2017, opioids accounted for less than half of the overdoses suffered in eleven states, including Pennsylvania, Texas, and California. This may point to the effectiveness in opioid specific treatment, but it also the persistent dangers of drug-use. Currently, the funding opportunities are insufficient to address the gaps in the mental health system needed to more completely help patients living with addiction. The pathways leading to drug-abuse, no matter the current drug of choice, may provide a common point of intervention resilient against the so called “emerging threats” of substance abuse.

However, similar to the shift seen as users transitioned from OxyContin to Heroin, public health fear that the next shift will turn to drugs not classified as opiods and therefore ineligible to be combated with the funds. In 2017, eleven states

(Carmen Heredia Rodriguez, Elizabeth Lucos, and Orion Donovan-Smith, Kaiser Health News)

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June 18, 2019 at 5:22 pm

Mapping the Human Exposome: Understanding the “E” after the “G”

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By: Bryan Bassig, Ph.D.

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Source: Pixabay

 

Current efforts to maximize our understanding of the known interplay between genetic and environmental factors in disease etiology have the potential to inform future research priorities and disease management and prevention

Defining the concept of the ‘exposome’

It is now commonly accepted that the etiology of most chronic diseases is a combination of genetics and environmental exposures, and most likely the interaction of these factors (“G” x “E”). The breadth of environmental exposures that have been implicated in chronic disease risk is substantial and includes personally modifiable factors including smoking and dietary choices as well as exposures that likely require policy interventions on a more universal scale, such as reducing air pollution. Substantial investments to map and characterize the human genome have led to an explosion of population-based studies that seek to understand the specific genetic variants that are associated with a wide variety of disease phenotypes. This in turn has generated great enthusiasm in applying these identified variants to personalized disease risk management and treatment. Whereas current discussion of the role of genetics in population-based health has already begun to move from discovery to translation with ongoing personalized medicine initiatives, our understanding of how to comprehensively measure the totality of environmental factors (broadly defined as non-genetic factors) that shape disease risk at a population-based level has generally lagged behind that of genetics.

Given the interplay and contributions of both “G” and “E” in disease processes, research and financial investments in one component but not the other likely lead to less efficiency in capturing the interindividual variation that exists in disease etiology and treatment and survival. An increasing recognition of this point over the last decade has propagated several research initiatives aimed at greater understanding of environmental factors in disease etiology, including efforts to understand the human “exposome.” Investment in these initiatives from a scientific funding standpoint has the potential to significantly improve exposure science and may in theory inform population-based health research strategies.

The concept of the human exposome was first conceived by epidemiologist Dr. Christopher Wild, a former director of the International Agency for Research on Cancer, in 2005. The concept has since gained traction within the research community. The idea behind the exposome is to complement the advances that have been made in understanding the human genome by characterizing the full spectrum of environmental exposures that occur from conception to death with an understanding that these exposures are both dynamic in nature and broad in scope. Indeed, a full “mapping” of the exposome as originally conceived by Dr. Wild and subsequently by others would include an ability to measure all internal (e.g. endogenous hormones and metabolites) factors as well as exogenous exposures that are either specific to the individual (e.g. smoking/alcohol, diet) or more universal in nature (e.g. built environment, climate). These exposures would be captured or measured at various “snap shots” throughout life, ideally corresponding to key time points of biological development such as in utero, childhood, and early adulthood. In contrast to traditional exposure assessment in population-based studies, which rely on questionnaires or targeted biological measurements of a limited number of chemicals that have been selected a priori, innovative technologies that take an agnostic and more comprehensive approach to measuring internal biomarkers (e.g. “omics”) or lifestyle-related factors (e.g. using smart phones to log physical activity patterns) would be needed for full characterization. Ideally, this would represent the “cumulative level of all cumulative exposures” in the human body.

Implementation: Progress, Potential, and Challenges

Implementation of the exposome paradigm is still in its relative infancy and current discussions are primarily focused on the scope of the initiative that is achievable within the parameters of scientific funding and infrastructure. For instance, in the absence of large prospective cohort studies that include collection of repeated samples or exposure information from people over multiple timepoints, application of the exposome paradigm is still possible but may be limited to fully characterizing the internal and external environment using samples or measurements taken at a single timepoint. While the current focus is on scientific implementation of this paradigm, the potential long-term translatable implications of exposome research can be imagined. From the standpoint of environmental regulation, agencies that conduct risk assessments of environmental exposures evaluate a series of questions including the dose-response relationship of these exposures with biologic effects or disease risk, and whether certain factors like age at exposure influence susceptibility. Application of the exposome framework provides a mechanism to potentially better characterize these questions as well as to evaluate multiple exposures or “mixtures” when making regulatory decisions. This potential however would need to be balanced in view of the existing regulatory framework and the need to develop guidelines for interpreting the expansive and complex datasets.   

While any application of the exposome paradigm to public health or clinical utilization would be an incredibly daunting challenge, a 2012 study published in Cell described this theoretical potential. The case study presented findings from a multiomic analysis of a single individual over 14-months in which distinct biologic changes and omic profiles were observed during periods when the individual was healthy relative to periods when he developed viral illness and type 2 diabetes. The authors concluded that the observed profiles were a proof of principle that an integrative personal omics profile could potentially be used in the future for early diagnostics and monitoring of disease states. While the study did not integrate data on external environmental exposures, further incorporation of these factors into the omic framework may provide evidence of distinct signatures that differ according to exposure status.

Current efforts to advance the exposome field have been bolstered by several initiatives including a 2012 report by the National Academies that described the future vision and strategy of exposure science in the 21st Century. Exposome-related research is also a major goal of the 2018-2023 strategic plan offered by the National Institute of Environmental Health Science (NIEHS), and the agency has supported two exciting exposome research initiatives. These include the HERCULES (Health and Exposome Research Center: Understanding Lifetime Exposures Center) research center at Emory University that is on the front lines of developing new technologies for evaluating the exposome, and the Children’s Health Exposure Analysis Resource (CHEAR) to encourage the use of biological assays in NIH-funded studies of children’s health.

As the field of exposomics matures, there will undoubtedly be several issues that arise that intersect both scientific and policy-related considerations as described by Dr. Wild and others involved in this field. These include but are not limited to:

  1. a) Cross-discipline education and training opportunities: The exposome paradigm encompasses multiple scientific disciplines, including laboratory sciences, bioinformatics, toxicology, and public health. Given the traditional model of graduate programs in science, which generally focus on distinct subfields, new educational and/or training programs that provide cross-disciplinary foundations will be critical in training the next-generation of scientists in this field.
  2. b) Data accessibility and reproducibility: Given its expansive nature and the inherent interindividual variation of non-genetic factors, full characterization of the exposome and associations between exposures and disease may require large international teams of researchers that have central access to the expansive, complex datasets that are generated. Unlike the human genome, the dynamic nature of the internal and external environment will require extensive reproduction and validation both within and across different populations.
  3. c) Funding and defining value: Fully implementing the exposome paradigm from an epidemiological research perspective would likely require profound investments in study infrastructure and laboratory technology. The discontinuation of the National Children’s Study, which originally intended to enroll and follow 100,000 children from birth to 21 years of age in the United States, illustrates the challenges associated with conducting large longitudinal research projects. These demands would need to be balanced with justifying the added value and potential for future utility along the same lines as genomics. The comprehensive understanding of non-genetic determinants of disease risk from a research standpoint, however, is the natural precursor to any discussion of utility.
  4. d) Communication of research findings: The field of genomics has matured to the point that consumers can now obtain personalized reports and risk profiles of their genome from companies like 23andMe and Ancestry.com. It is theoretically possible that this commercial model could be extended in the future to other types of biomarkers such as the metabolome, yet the dynamic nature and current lack of clarity regarding the disease relevance of most non-genetic biomarkers would create considerable challenges in interpreting and conveying the data.

Conclusions

The underlying principles of the exposome were originally conceived by Dr. Wild as a mechanism to identify non-genetic risk factors for chronic diseases in epidemiologic studies. While the increasing number of exposome research initiatives are primarily focused on this scientific goal, challenges remain in the implementation. It is likely too early to project what the future public health and/or clinical utility of this paradigm, if any, may be. Nevertheless, continued investments in this area of research are critical to understand the “missing pieces” of disease etiology and to ideally inform preventive measures and/or disease management in the future.  

 

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November 21, 2018 at 9:55 pm

Insect Allies and the role of DARPA in scientific research

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By: Ben Wolfson, Ph.D.

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Source: Pixabay

 

Last month, a Pentagon research program called Insect Allies burst into the public conversation after a team of research scientists and legal scholars published an article detailing their concerns and critiques of the project in Science magazine. Insect Allies is run by the Defense Advanced Research Projects Agency (DARPA), and was announced in 2016 with the stated goal of “pursuing scalable, readily deployable, and generalizable countermeasures against potential natural and engineered threats to the food supply with the goals of preserving the U.S. crop system”. As indicated by its eponymous project name, the Insect Allies research program seeks to develop insects that carry gene editing viruses, allowing for rapid genetic modification of plant food sources. The Insect Allies program exemplifies both the pros and cons of DARPA work. The described project leapfrogs current technological paradigms, promoting a next stage of synthetic biology work. However at the same time, it seeks to create a technology with problematic potential military applications. The battle between basic research and the development of military technologies is one that has dogged DARPA since its inception. As the theoretical and empirical knowledge in the fields of genetic modification and synthetic biology improve, it is imperative that novel technologies are developed with the appropriate ethical and moral oversight and that scientists consider the ramifications of their work.

Origins and Changes of DARPA

Science and the military have long been interwoven, a process that was formalized in the U.S. in the past century. In 1947, President Truman created the Department of Defense, in part to fund scientific research. A decade later President Eisenhower highlighted the importance of science in national defense with the creation of the Advanced Research Projects Agency (renamed DARPA in 1972). DARPA’s creation was in direct response to the launch of Sputnik by the Soviet Union, and given the mission statement of “preventing technological surprises like Sputnik, and developing innovative, high-risk research ideas that hold the potential for significant technological payoffs”.

In its early years, DARPA funded significant amounts of basic and foundational research that did not have immediate applications. However, in 1973 Congress passed the Mansfield Amendment, preventing the Defense Department from funding any research without “a direct and apparent relationship to a specific military function or operation”. The amendment was contentious at the time of its passing, with Presidential Science Advisor Lee DuBridge telling a congressional subcommittee that the amendment had negatively affected the quality of research projects because it is not possible to prove the relevance of a project, and therefore it is wrong to prevent an agency from funding basic research it sees as valuable. Passage of the amendment fundamentally reshaped the U.S. research funding landscape, and projects consisting of upwards of 60% of DOD research funds were cancelled or moved to other agencies. In place of basic research DARPA has shifted to funding research with direct military applications. These projects have often fallen into the realm of “dual-use” technologies, having both civilian and military uses. Successful examples of this strategy include funding projects that evolved into the internet and Global Positioning Systems (GPS). Current research span from projects with clear civilian applications, such as a multitude of projects researching the next generation of medical technologies, to those that are weapons research with purely military potential.

The Insect Allies program

Agriculture is one of the predominant industries in the U.S., making the U.S. a net exporter and world’s largest supplier of a variety of agricultural products including beef, corn, wheat, poultry and pork. The importance of American agriculture to both national security and the security of its global allies and trade partners is well recognized by national security officials, especially in the context of climate change and the potential for growing scarcity. The primary threats to agriculture are disease and weather related events. While these can be mitigated through pesticides, clearing of crops, quarantine, and selective breeding, current strategies are both destructive and time consuming.

The Insect Allies program has three focus areas; viral manipulation, insect vector optimization, and selective gene therapy in mature plants. Through application and combination of these technologies Insect Allies would function by genetically modifying already growing plants through utilization of “horizontal environmental genetic alteration agents (HEGAAs). Traditionally, genetic modification involves changing the genes of a parent organism and propagating its offspring. This process is essentially the same as the selective breeding practiced in agriculture for generations. While this is effective, it is a time-consuming practice as you must breed successive generations of your population of interest.

Through HEGAAs, Insect Allies completely revamp the process. Instead of creating a population of interest from scratch, HEGAAs allow scientists to modify an existing population. If you wanted to create a pesticide-resistant crop, the traditional strategy would be to insert the gene for pesticide resistance into one plant and then collect its seeds and use them to grow an entire field of pesticide resistant plants. With HEGAA technology, farmers could make an already grown field resistant by modifying each individual plant on a broad scale.

Criticism of the Insect Allies program

The authors of the Science article critique the Insect Allies program over a variety of issues, ranging from biological to ethical or moral dilemmas. The article raises issue with both the use of wide-scale genetic modification technologies as well as with the application of insects as vectors as opposed to already existing technologies such as overhead spraying. The use of wide-scale genetic modification is a line which has yet to be crossed, and currently lacks a regulatory path. While research into gene modifying technology is ongoing and real-world tests inevitable, these tests are a contentious issue that is currently being debated. Moreover, agricultural products modified by HEGAAs have no current path to the market. The combination of seemingly little thought in the program towards the regulation that would be necessary for the described application of their technology as well as the existence of lead the authors to suspect that Insect Allies is being developed for other means. While a population of gene-modifying insects could be used to help U.S. crops survive weather-changes or pesticides, they could also potentially be applied to crops of other nations in war. Biological Weapons were banned in 1972, and currently no nations have (publicly) developed them.While the technologies being developed by Insect Allies are described as “for peaceful means”, the stated goals are achievable through already existing technologies. Furthermore, international competition with Insect Allies may accelerate crossing the line between wartime and peacetime technology.

Soon after publication of the Science article, Dr. Blake Bextine, program manager for Insect Allies, released a statement refuting many of these points. He stated that DARPA moved into agricultural work as it is an important aspect of both national and international security, and that the work falls under DARPA’s charter to develop fundamentally new technologies that leapfrog existing capabilities. Moreover, he affirmed that Insect Allies has no plan for open release, and that regulatory systems would be developed and had been planned since the start of the program.

What does the future hold

The Science article’s authors note that they would be worried about Insect Allies whether it was under a civilian or military purview, but it is impossible to ignore the implications of synthetic biology and genetic modification research to the military. DARPA’s strategy of generating high-risk, high-reward research is both effective and engrained into the DNA of the organization, however so is the fact that DARPA is a defense organization.

When DARPA was founded (as ARPA), it was to promote high-risk scientific research that would increase U.S. soft power internationally. After the Mansfield amendment, these goals were shifted towards applied research instead of basic, and with them a focus on defense-oriented research. An advantage of basic research is that it takes time to develop, allowing the findings, and their ramifications, to percolate throughout the global scientific community. The quintessential example of this is regulation of recombinant DNA technologies. Soon after recombinant DNA technology was developed, the 1975 Asilomar Conference was held to establish voluntary guidelines that would ensure the safety of a game-changing scientific technology. As synthetic biology technological development has accelerated, the discussion around the regulation of synthetic biology and genetic modification technology has also begun, and is currently ongoing.

While it is impossible to argue with the massive benefits that civilian applications of DARPA developed technologies have provided, synthetic biology and genetic modification technologies have the potential to enact immense changes globally. The environment and application of a technology has a huge potential to influence its use and the way it is viewed by the public for generations. Insect Allies program states that it is focusing on developing insect-based HEGAAs technologies as a means of pushing development of gene-editing technologies to increase food security in a transparent manner that promotes open published research. It is critical that the Insect Allies program is held to this standard, and that regulation by the global scientific community is allowed to impact the direction and application of these potentially game-changing technologies.

 

 

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November 15, 2018 at 11:22 am

Unlinking databases is not enough to unlink identity from genetic profiles

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By: Allison Dennis B.S.

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Source: Pixabay

 

The efficacy of law enforcement is an issue of public safety. Advances in medicine are a matter of personal wellbeing. Knowing more about one’s unique genetic heritage is a point of curiosity. As all of these spheres delve further and further into DNA sequencing, the ubiquity of personal genetic information is increasingly becoming an issue of privacy. The emerging nature of DNA technology has left us with three major types of DNA databases separated by their use: medical, forensic, and recreational. Each is governed by its own sets of rules, set by federal law, state law, and user agreements. Under specific circumstances data can be intentionally shared for other uses. However, the technological limitations that kept these databases separated in the past may be nearing erosion.

Medical

By congregating and comparing the genomes of people with and without a specific disease through DNA databanks, researchers can discover small glitches in the DNA of affected patients. Identifying the genetic changes that disrupt the normal functions of the body allows researchers to begin designing therapeutics to correct deficiencies or developing genetic tests to diagnose specific diseases, possibly before symptoms have appeared. The potential for medical databases have prompted government led initiatives such as All of Us to amass genetic information from a diverse group of 1 million Americans, which will be queried for medical insights. Already, the Cancer Genome Atlas, maintained by the US National Institutes of Health, contains deidentified genetic data from tumor and normal tissues from 11,000 patients and is openly searchable for research purposes. Foundation Medicine, a private company that provides doctors and patients with genomic profiles of tumor samples to inform treatment options, has stockpiled data from over 200,000 samples. Foundation Medicine shares these data through collaborative agreements and business partnerships with members of the oncology research community and pharmaceutical companies.

Medical DNA databanks, while masking a patient’s name, may link to an individual’s medical history. Because researchers often do not know what parts of the genome will reveal key clues, the genetic data contained in these databases is rich. Often researchers look at how the frequency of single nucleotide changes at hundreds of thousands of places in the genome differ between people affected and unaffected by a particular disease.

The medical benefit of compiling and sharing genomic information is carefully balanced against privacy concerns by Federal regulation. The Genetic Information and Nondiscrimination Act of 2008 (GINA) prohibits employers and health insurers from requesting access to an individual’s or family’s genetic information. The Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule mandates that health-care providers not disclose an individual’s genetic information. The NIH Genomic Data Sharing Policy limits access to individual-level genetic information held in their databases, including the Cancer Genome Atlas, to approved scientific researchers. Despite these safeguards, genetic information contained within medical databases can be identified and provided to law enforcement following a court order in extreme cases.

Forensic

Forensic DNA databases contain searchable genomic profiles for the critical task of identification by law enforcement and military experts. U.S. Federal law allows law enforcement officers to collect and store DNA profiles on anyone they arrest, including those detained by immigration enforcement. Since 1998, the Federal Bureau of Investigation has hosted the national Combined DNA Index System (CODIS), which currently contains 16.8 million offender and arrestee profiles. Unlike medical databases, which can contain a wealth of information, CODIS profiles are limited to a set of 20 places in the genome where the number of times a small sequence of DNA is repeated varies between individuals. The unique combination of these 20 lengths place the probability of two unrelated people sharing a profile at roughly 1 in 1 septillion, and were intentionally selected to not reveal any medically relevant parts of the genome.

The creation of CODIS was authorized by Congress through the DNA Identification Act of 1994, which mandated privacy protection standards. As a safeguard, the database profiles are associated with specimen identification numbers rather than any personal information. The system can only be accessed in physically secure spaces and is restricted to use by criminal justice agencies specifically for the purpose of law enforcement. Only after a match has been found from a query and the candidate match has been confirmed by an independent laboratory will the identity of the suspected perpetrator be revealed, and even then only to the agencies involved in the cases. The Scientific Working Group on DNA Analysis Methods (SWGDAM) continues to recommend revisions to these standards for security and confidentiality issues. Despite housing a relatively unrevealing type of genetic information, CODIS goes above and beyond the privacy protections provided by many recreational and medical databases.

Recreational

Individuals are increasingly turning to direct-to-consumer genetics testing, driven by their curiosity to discover their genetic heritage and to gain some insight into their genetic traits. These tests contain a wealth of information drawn from single nucleotide changes across more than 500,000 parts of the genome. The most popular tests are offered by AncestryDNA and 23andMe, who manage data according to Privacy Best Practices established by the industry. These practices include removing names and demographic identifiers from genomic records, storing identifying information separately if retained, using encryption, limiting access, and requiring consent for third party sharing. As the records are presumed to contain medically relevant information, all identified samples are governed by the same HIPAA and GINA regulations that govern medical tests. 23andMe has amassed a database of over 5 million genetics profiles. AncestryDNA has over 10 million, greatly rivaling the size of forensic and medical databases.

Direct-to-consumer genetics testing companies often sell de-identified genetic data to pharmaceutical and diagnostic development companies for research purposes. Those that follow the Privacy Best Practices established by the industry only do so for users who have consented to participate in research, and GINA expressly prohibits these companies from sharing an individual’s genetic information with potential employers or health insurers.

There are also limits to prevent law enforcement from abusing recreational genetics testing companies. While there is the potential for someone to submit a sample that is not their own, the AncestryDNA service agreement stipulates that users only provide their own sample, and 23andMe expressly disallows “law enforcement officials to submit samples on behalf of a prisoner or someone in state custody.” Moreover, their tests have been specifically designed to make collection of a third parties’ sample difficult. For instance, the 23andMe test requires an amount of saliva needing 30 minutes to generate, preventing illicit collection.

While companies go to great lengths to protect the information contained in their databases, most companies will provide individuals with their own complete profiles when requested. The allure of mapping family connections has lead millions of genealogical hobbyists to openly contribute their re-identified genomic DNA to searchable online databases. The most famous searchable database is GEDmatch, which currently contains about one million profiles. The platform allows users to upload their own genome to retrieve high probability matches of other user’s profiles. A level of privacy is maintained by only sharing small pieces of the genome, allowing complete profiles to remain obscured. However, GEDmatch’s user agreement emphasizes that rather than use encryption, they store data in a format that “would be very difficult for a human to read” and allow volunteers access to the data. Additionally, they specifically welcome “DNA obtained and authorized by law enforcement” for inclusion in their database. The wealth of information publicly hosted on sites like GEDmatch have provided a unique opportunity for other types of DNA databanks to share information and blur the lines of privacy.

Database Cross-Linking

The use of GEDmatch by law enforcement marks an important seachange in genetic privacy. In the past, medical and recreational databases were only occasionally queried by law enforcement, who were seeking specific profiles. However in April 2018, in a desperate search for leads to solve a cold case, law enforcement officers utilized a nearly 40-year old rape-kit to develope a genetic profile. While previous searches over the decades had been limited to the FBI database and the perpetrator’s 20 CODIS loci law enforcement officials were able to undertake a blind and expansive search by uploading the complete profile to the GEDmatch database, which ultimately lead to a third cousin of the man who would be charged with 12 murders.

These types of searches have the power to exonerate or implicate criminals, as a 100% match is undeniable. While only just starting to be used, for someone of European ancestry living in the United States the odds are as high as 60% that a genetic relative can be identified from a database similar to GEDmatch. A public opinion poll conducted shortly after April 2018, revealed that the majority of respondents approved of searches of recreational databases by law enforcement, especially to identify perpetrators of violent crimes.

Scientists have already laid the theoretical groundwork that could allow law enforcement to link a suspect’s profile in a medical or recreational database using the limited 20 CODIS markers from a crime-scene sample. Portions of the genome that share close physical proximity along a chromosome are more likely to be inherited together, allowing statistical predictions to be made about which pieces are most likely to occur together. Although the two types of profiles do not contain the same markers, scientists can predict which marker profiles most likely came from the same individual.

While the use of these tactics might be supported for the purpose of identifying violent criminals, it also puts medical privacy at risk. Despite the de-identification of genomic profiles, scientists have demonstrated reasonable success in tracking down a person’s identity given a genetic profile, a genealogical database such as GEDmatch, and information on the internet.

As DNA databases develop in their depth of information and coverage of individuals, the ability to link records to individuals grows. A lack of compatibility will not be enough to keep medical genomic information sequestered from criminal profiles. Industry standards and user agreements must be discussed and strengthened to safeguard the genetically curious.

 

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November 8, 2018 at 10:14 am

Science Policy Around the Web – April 3, 2018

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By: Allison Dennis, B.S.

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source: pixabay

Gene Editing

CRISPR’d Food, Coming Soon to a Supermarket Near You

The United States Department of Agriculture has given a green light to plant breeders to use gene-editing technology to produce plant varieties that could have been made the old fashioned way. Traditionally, simple changes in genes have been cultivated in crops through selective breeding over generations, which relies on the naturally occurring mutations in the genome to produce new traits. In more recent history, would-be crop innovators rapidly introduced DNA changes to crop genes through mutagens such as radiation, vastly increasing the chances of producing a desirable genetic change in the next generation.

The first product of the gene-editing tool CRISPR-Cas9 to officially go unregulated was a variety of white button mushrooms whose genome was edited to resist browning. The mushroom was engineered by making a small deletion in its polyphenol oxidase gene, preventing the organism from making the enzyme that interacts with oxygen in the air to form melanins, think of that green bowl of guacamole on your counter slowly turning brown. Since this process did not introduce any new genetic material, the USDA ruled that it would not be regulated.

The USDA and FDA are currently drafting policy to oversee whether foods derived by this impossibly-sped-up-but-otherwise-natural method of crop development will need to be specifically labeled to inform the consumer. However US Secretary of Agriculture Sonny Perdue has made clear that under his direction the “USDA seeks to allow innovation when there is no risk present.”

(Megan Molteni, Wired)

 

Personalized Medicine

Anyone Can Now Take This Breast Cancer Gene Test, But It Probably Won’t Tell You Much

The personalized DNA testing company, 23andMe has had mixed success seeking FDA approval, but may have taken a step closer medical validity this month. The FDA has approved their direct-to-consumer genetic test which can identify three variants of the BRCA1 and BRCA2 genes which are associated with an increase in the risk of developing breast and ovarian cancer. From the comfort of their home, curious patients can spit in a tube that comes at a $199 price tag to learn their result on a panel of FDA approved Genetic Health Risk reports. However, the real value of such diagnostic tests, remains a point of debate.

Because the test will only capture a subset of the known genetic markers for cancer risk, 23andMe stresses that a negative result “cannot rule out your chances of getting cancer.” In fact, most women who are diagnosed with breast or ovarian cancer have no known genetic factors. Those who receive a positive test are still advised to validate their results and seek counseling from a medical professional. The company has conceded the value for such direct-to-consumer genetic tests may be the simple act of raising awareness and inspiring them to take a more proactive role in their healthcare.

(Christie Aschwanden, FiveThirtyEight)

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April 3, 2018 at 11:47 pm

Science Policy Around the Web – October 24, 2017

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By: Jennifer Patterson-West, Ph.D.

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source: Max Pixel

Healthcare

Under Trump Rule, Nursing Home Residents May Not Be Able To Sue After Abuse

In October 2016, the Centers for Medicare and Medicaid Services (CMS) listed a final rule that prohibited pre-dispute agreements binding patients to arbitration. Subsequently, the American Health Care Association (AHCA) along with a group of nursing homes sued the CMS resulting in a preliminary injunction on the ruling. In June 2017, revised requirements for long-term care facilities that eliminated the prohibition were released by the CMS.

NPR journalist, Ina Jaffee, highlighted the major limitations of the revised requirement.  Jaffee points out that the new rule will make lawsuits by nursing home residents nearly impossible. The long-term implication is that many victims of negligent care will not have their cases heard by a jury.

The revised requirements require that “all agreements for binding arbitration must be in plain language” and that “the agreement must be explained to the resident and his or her representative in a form and manner they understand.” Senior counsel Kelly Bagby with the American Association of Retired Persons (AARP) notes that the requirement for plain language may be besides the point if that patients are required to sign these agreements.

An elder law attorney, Wendy York, noted that patients are given large stacks of papers to signs without fully comprehending the implications of what they are signing.   These patients are often recovering from a trauma, major surgery, or under the influence of mind altering medications while filling out paper work.  The new ruling would require that the “resident acknowledge that he or she understand the agreement,” however an agreement can be required for admission thereby limiting the option of a resident to refuse the agreement if they are in need of care without access to better accommodations.

These rulings could have larger implications on patient and patient advocate’s legal recourse after receiving substandard treatment. Although the new rules are an improvement on the status quo, they do not go as far as those previously proposed.  Unfortunately, it is our most vulnerable citizens that will have more limited protection under the current ruling. However, when the new rules will go into effect remains to be seen.

(Ina Jaffee, NPR)

 

Genetic Testing

A baby with a disease gene or no baby at all: Genetic testing of embryos creates an ethical morass

Increasing affordability of genomic testing has given people more access to information regarding their own genes and those of their potential offspring. Ethicists and experts are trying to consider the implications of genetic information moving into the hands of consumers. How can or should this information be used to make real-life decisions?

With respect to reproductive medicine, preimplantation genetic testing (PGT) can be used to evaluate potential diseases or disorders in in vitro fertilized (IVF) embryos.  In a 2013 federal report on fertility clinic success, PGT testing was reported for approximately 5% of IVF conceptions. However, experts suspect this figure underestimates the frequency of PGT testing and report that requests are growing. A survey of experts by STAT news relayed that “requests to transfer embryos with genetic anomalies are rare.”

The number of diseases that are tested for in prospective parents and embryos are expanding, some of these diseases have a more severe health impact than others. The question now is where to draw the line? Beyond the scope of severe diseases, patients may want to select an embryo with a specific trait.  In these cases, the physician has to decide what is within the ethical bounds of reproductive medicine.  For example, some members of the deaf or dwarfism community reject the notion that their DNA is categorized as a “genetic anomaly” and may desire a child that shares these traits.

Currently, there are no U.S regulation for these cases. However, regulations in the United Kingdom prohibit the transfer of embryos with severe abnormalities. To provide a foundation for clinicians facing these questions, an opinion was recently published from members of the American Society for Reproductive Medicine outlining potential rationales for providers to assist or decline to assist the transfer of embryos with genetic anomalies.

(Andrew Joseph, STAT)

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Written by sciencepolicyforall

October 26, 2017 at 10:05 am