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Gene editing- Regulatory and ethical challenges

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By: Chringma Sherpa, Ph.D.

Image by Colin Behrens from Pixabay 

When power is discovered, man always turns to it. The science of heredity will soon provide power on a stupendous scale; and in some country, at some point, perhaps, not distant, that power will be applied to control the composition of a nation. Whether the institution of such control will ultimately be good or bad for that nation, or for humanity at large, is a separate question.

William Bateson, English biologist who coined the term “genetics.”

On November 25, 2018, in an allegedly leaked YouTube video, He Jiankui, a scientist at the Southern University of Science and Technology in Shenzhen, China, revealed the birth of the first gene-edited babies using a technology called CRISPR. There has been a general consensus in the scientific community that heritable changes should not be made to prevent the off-target and unwanted genetic changes artificially produced in an individual during gene editing to be passed on to his/her offspring(s). He became the first scientist to publicly violate this consensus resulting in an international scandal and criminal/ethics investigations into both He and his collaborators.

In the wake of He’s CRISPR-babies scandal, scientists worldwide are debating on the ethical and regulatory measures that would discourage another wayward and rogue scientist like He from attempting such an irresponsible feat.  At the 2nd international summit on human gene editing that convened two days after He’s video became public, He presented his work. The summit was well attended by ethicist and journalist besides scientists. At the summit, David Baltimore of the California Institute of Technology, who chaired the organizing committees for both the 1st and 2nd international summits on human gene editing read one of the conclusions from the 1st summit held at Washington DC in 2015 – “It would be irresponsible to proceed with any clinical use of germline editing unless and until (i) the relevant safety and efficacy issues have been resolved, based on appropriate understanding and balancing of risks, potential benefits, and alternatives, and (ii) there is broad societal consensus about the appropriateness of the proposed application”. Baltimore called He’s work outright irresponsible on the basis of the statement from the 1st summit. At the summit, many other ethical and safety-related questions were raised which He failed to answer or did not answer convincingly. 

He’s scandal has driven various organizations to draft new guidelines and sanctions aimed at preventing unethical and unapproved use of genome editing.  China has imposed new laws requiring human gene editing projects to be approved by China’s health ministry first to avoid fines and blacklists. Both the 2nd human gene editing summit and the WHO panel that convened in March 2019, have proposed a central registry of human gene-editing research and called for an international forum/ committee to devise guidelines for human gene editing based on common norms and differences of opinions between countries.  To allow time for the creation and effective implementation of new regulations, the WHO also called for a global moratorium on heritable editing of human eggs, sperm, or embryos for the next five years. Supporting the WHO panel’s recommendations, Francis Collins, director of the National Institute of Health, said that “NIH strongly agrees that an international moratorium should be put into effect immediately”. However, not all scientists are in favor of a moratorium, as they believe it might stifle the growth of a technology that might be safe and beneficial in the near future. Jennifer Doudna of the University of California, Berkley, one of the co-inventors of CRISPR gene editing, says that she prefers strict regulation that precludes the use of germline editing until scientific, ethical, and societal issues are resolved over a moratorium. David Baltimore agrees with Doudna stating that the word moratorium was intentionally not used in both the human gene editing summits as a moratorium would be hard to reverse.  Science historian Ben Hurlbut of Arizona State University, who had numerous discussions with He before Lulu and Nana were created, thinks a blanket moratorium on clinical germline editing would have prevented He from proceeding. Both the two human gene editing summits and a 2015 essay by Baltimore, Doudna, and 16 co-authors had already outlined numerous guidelines for clinical germline editing. According to Hurlbut, He weighed these criteria and believing that his procedure met all the guidelines proceeded. A categorical prohibition of germline editing would not have allowed him to use his subjective judgment and act out of self-interest. 

The modern debate over CRISPR editing is not the first time the scientific community has come together to discuss game-changing biological technologies, and it is heavily informed by two prior events. In 1970, Paul Berg and his postdoctoral researcher David Jackson used the recombinant DNA technology to create the first chimeric DNA. This invention created an uproar among the scientists and the general public who feared that this technology would lead to the creation of uncontrollable and destructive superbugs, the exaggerated versions of which can be seen in some science fiction movies. Yielding to the opinions and sentiments of the fellow scientists, Berg held himself from cloning such recombinant DNAs and in 1974, he pleaded for a voluntary moratorium on certain kinds of recombinant DNA research until their safety issues have been resolved.  He also moved quickly to organize the Asilomar conference (Asilomar II) in 1975 that bore semblance to the 2nd human gene editing conference in that it invited not only the scientists but lawyers, ethicists, writers, and journalists to weigh in on the risk-benefit analysis of the Recombinant DNA technology. On the recommendation of Asilomar conference, Donald Fredrickson, then director of the National Institutes of Health (NIH), initiated the formation Recombinant DNA Advisory Committee (RAC) to act as a gatekeeper of all research that involved recombinant DNA technology. The scope of the committee, which was composed of stakeholders, including basic scientists, physicians, ethicists, theologians, and patients’ advocates was later expanded to encompass the review and approval of human gene therapy research. Due to the redundancies of regulatory oversights between the US Food and Drug Administration (FDA) and RAC, RAC was reinstated as only an advisory body providing advice on the safety and ethical issues associated with emerging biotechnologies in 2019.

While this is a successful example of scientific self-regulation, the second event resulted in a major setback in the field of gene therapy. On September 13, 1999, Mark Batshaw and James Wilson of University of Pennsylvania supervised the administration of adenovirus to an 18-year-old Jesse Gelsinger in a gene therapy clinical trial. Gelsinger died of liver and kidney failure and brain damage three days later. Like the birth of CRISPR babies, Gelsinger’s death was an instance where new technology was used prematurely without a thorough assessment of its safety profile. It is suspected that both the clinical applications headed by He and Wilson might also have been motivated by fame and financial gain; He and Wilson both had financial stakes in private biotechnology companies that would benefit from these human trials. In the aftermath of Gelsinger’s death, Wilson was banned from carrying out FDA regulated clinical trials for the next five year, nearly all gene therapy trials were frozen, and many biotechnology companies carrying out these trails went bankrupt. This was a dark period in the history of gene therapy, and it would take almost another decade of introspection, reconsideration, and more basic experimentation for gene-therapy to re-emerge as a viable therapeutic strategy.

Figure 1: The regulatory status of human germline gene modification in various countries. Thirty-nine countries were surveyed and categorized as “Ban based on legislation” (25, pink), “Ban based on guidelines” (4, faint pink), “Ambiguous” (9, gray), and “Restrictive” (1, light gray). Non-colored countries were excluded in this survey. Adapted from Araki, M. and Ishii, T (2014): “International regulatory landscape and integration of corrective genome editing into in vitro fertilization” Reproductive Biology and Endocrinology, 2014 12:108

Scientists at both the Asilomar and human gene editing conferences passionately debated the safety of the relevant technologies but deliberated on the discussion of the big ethical issue associated with these technologies – the ultimate creation of designer babies. That gene editing sits on the slippery slope to eugenics was recognized since the days of Charles Darwin and Gregor Mendel when the study of genes and heredity was still in its infancy and the discovery of DNA as the genetic material was half a century away. One of the earliest proponents of genetic manipulation for human benefits was Francis Galton, Charles Darwin’s cousin. Galton proposed an unnatural and accelerated selection of beneficial traits by marriage between people of desirable traits. The danger that someday some rogue scientists might use germline gene editing technology in favor of eugenics lurks in the mind of those who understand the potential of the currently available gene editing technologies. However, more fearful is the idea that the wave of positive eugenics would soon give way to negative eugenics – elimination of undesirable traits as it did around World War II as exemplified by the famous case of Carrie Buck, a woman who was designated “mentally incompetent” and involuntarily sterilized. 

Various countries have their own regulation and legislation on germline editing to prevent any backlash from this powerful technology. Figure 1 presents a summary of the regulatory landscape of germline gene modification surveyed in thirty-nine countries by Araki Motoko and Tetsuya Ishii.  In the US, Congress has shown strong support against germline gene editing. In 1996, it passed a rider as part of the annual appropriations bill that prohibits the use of federal funds for any research involving human embryo. In another appropriations bill passed in 2015, Congress banned the FDA from considering applications involving the therapeutic modification of the human germline. 

Human gene editing holds great promises in treating many life-threatening and previously intractable diseases. Only when this discipline of science is held to high ethical standards and regulated sensibly at international, national, and a personal level, shall we reap the benefits of this powerful technology.

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May 29, 2019 at 9:25 am

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Science Policy Around the Web – May 3rd, 2019

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By: Allison Dennis B.S.

Image by Ashley Smith from Pixabay

A More Humane Livestock Industry, Brought to you by CRISPR

Innovations sparked by germline editing in livestock are poised to help farmers make rapid improvements in the care and treatment of their animals by helping overcome inefficiencies genetically. Livestock industries use animals specifically bred to maximize their use and often require or prefer animals of a particular gender. Male cattle produce more meat. Female cows produce milk. Female chickens lay eggs. Known as “the dirty secret” of the dairy industry, farmers under financial pressure may kill male calves soon after birth to avoid the costs of raising them further. Every year, 6 billion male chicks, which hold no economic value for egg production, are killed within a day of hatching. The egg industry is seeking to prevent this, and in June of 2016, the United Egg Producers, a group that represents more than 95% of egg production in the United States, stated their goal of “eliminating the culling of day old male chicks by 2020 or as soon as it is commercially available and economically feasible.”

Scientists are racing to offer these industries solutions by harnessing the power of the gene editing technology CRISPR to genetically engineer animals to break the 50-50 gender rule. Mark Tisard, a geneticist at the The Commonwealth Scientific and Industrial Research Organization, Australia’s national science agency, is using CRISPR to engineer male eggs to glow red under fluorescent light, allowing farmers to repurpose male eggs for vaccines or feed production before the chick has developed. Across the world, the startup eggXYt in Israel is taking a similar approach, making male eggs glow yellow. Alison Van Eenennaam, an animal geneticist at UC Davis, is exploring the possibility of using CRISPR to produce all male herds of beef cattle from the point of conception.

While pre-determining gender remains a major goal, gene-editing has already been used to introduce a gene for slick hair that helps cattle handle heat better in warm climates. Scientists have successfully used CRISPR to produce pigs that are resistant to the PRRS virus, which causes respiratory disease and reproductive failure, costing farmers in the United States half a billion dollars a year. 


The reception of these technologies in the United States remains unclear. Most recently, in January 2017, the FDA drafted rules that would put genetically altered animal products through the same safety and efficacy testing undertaken for new drugs. However, since then, the USDA has clarified that plants produced through genome editing will not be subject to additional regulation if they could conceivably been developed through traditional breeding methods. Those looking to harness the power of these types of genetic modifications for livestock are hoping to see this attitude expanded to animal products.

(Gregory Barber, Wired Magazine)

House Democrats move to resurrect Congress’s science advisory office

At the helm of American society is a group of appointed representatives racing to keep abreast of a deluge issues stemming from technological innovation. A draft of the 2020 Legislative Branch funding bill that was approved by its subcommittee on April 30th offers potential relief in the form of re-establishing the Office of Technology Assessment (OTA). The OTA was originally established in 1972 to provide congressional staff with deep and comprehensive analysis of technical issues to aid in the crafting of public policy, independent from lobbyists and activists. At that time, Anti-Ballistic Missiles and Super Sonic Travel were the technologies stirring up media frenzies. However, the OTA was eliminated in 1995 to reclaim $21 million for the congressional budget. The $3.9 billion dollar proposed budget for 2020 included only $6 million for its revival.

Currently, the Congressional Research Service (CRS) is tasked with keeping Congress informed on technical issues ranging from gene editing to artificial intelligence. In January 2019, recognizing the need for greater technical assistance, the US Government Accountability Office (GAO) established the Science, Technology Assessment, and Analytics team to conduct technology assessments and provide technical assistance directly to Congress. The proposed budget would support these efforts by providing CRS and the GAO an additional $24 million and $26 million respectively. However, some believe that there is still a need for the OTA in spite of these new teams. Representative Sean Casten testified to fund the OTA as he believes there is still a need to “fulfill the forward looking, deep-dive, technical assessments of new scientific and technological developments once provided by OTA.” Representative Mark Takano also expressed support, stating “In the ecosystem of legislative support organizations, OTA plays a unique role. No other entity has the capacity and expertise to provide in-depth and forward-looking analysis of complex, technical issues informed by an understanding of how Congress works.” 

Former Congressman Rush Holt similarly tried to revive the OTA in 2015, only asking for 2.5 million dollars, but his amendment was defeated 248 to164. The 2020 funding bill next heads to the full House Appropriations Committee for markup before representatives get a chance to vote.

(David Malakoff, Science)



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May 3, 2019 at 11:20 am

Science Policy Around the Web – March 15, 2019

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By: Allison Dennis. B.S.

Image by Gabriela Sanda from Pixabay 

A Genetic Mutation Might Explain Why Birth Control Can Fail

Hormonal contraceptives have been increasingly embraced as an effective tool for family planning since their approval for contraceptive use by the FDA in 1960Fewer than 1 in 100women will get pregnant in a year when using the contraceptive pill correctly, but the cause of the few unintended pregnancies remaines a mystery. 

To ask if there was a genetic reason why hormonal contraceptives might be ineffective at preventing pregnancy for some women, researchers measured the amount of etonogestrel in the blood of women using the etonogestrel contraceptive implant (Nexplanon). While the findings of this small study were not significant, the researchers did observe that women carrying a mutation in their CYP3A7gene had lower concentrations of etonogestrel in their blood. Of the women with mutation, 28% had etonogestrel levels lower than what is needed to suppress ovulation. Only 9% of women without the mutation had critically low levels. The CYP3A7 gene produces a fetal enzyme, responsible for breaking down excessive steroid hormones in the developing fetus. Usually the gene is turned off in adulthood, but genetic mutations can result in it staying active throughout one’s life, possibly leading women with these mutations to break down the etonogestrel being supplied by the Nexplanon implant. 

To begin capturing the ability of particular genetic variants to predict which patients will or will not respond to particular medication, experience adverse events, or need a particular dose, the FDA maintains a list of drugs whose use may be complicated by particular Pharmacogenomic Biomarkers. Only one of the 232 on the list is a hormonal contraceptive, listed because women carrying a particular mutation may respond negatively to one of its inactive ingredients, not because it is less effective for these women. The etonogestrel study is the first to associate particular genetic variants with birth control performance. As researchers delve into the complicated intersection between genetic differences and drug responses their discoveries promise to lead to better outcomes for all those seeking effective family planning options. 

(Megan Molteni, Wired Magazine)

New call to ban gene-edited babies divides biologists

The birth of genetically modified children is now possible thanks to technologies like the genome-editing CRISPR-Cas9which can introduce heritable changes in germline cells, including human sperm, eggs, and embryos. In November 2018, He Jiankui’s demonstrated the technique by orchestrating the birth of two babies whose genomes were altered between in vitro fertilization and implantation. He Jiankui’s experiment may have shown editing the human germline was possible, but it did not address the safety or efficacy of the genetic changes for his two inaugural patients. While many view He Jiankui’s experiment as prematureand possibly illegal, it has undeniably brought discussions of the appropriate use of the technology to a forefront. 

On March 13th, a group of prominent scientists and international specialists published a call for a global moratorium on clinically making genetically modified children. The first step, as they see it should be setting a deadline before which all clinical use of germline editing will be put on hold. They suggest five years from now. During this time, they propose that nations engage in “discussions about the technical, scientific, medical, societal, ethical, and moral issues that must be considered.” Technical issues arise from the need to demonstrate germline editing as safe and efficacious. Scientifically, the long-term effects of specific genetic enhancements or corrections must be understood. Many potential changes imagined to be possible may not be medically necessary. As for societal, ethical and moral considerations, the authors stress the importance of carefully weighing “the appropriateness of altering a fundamental aspect of humanity.” The commentary acknowledges that not all nations will be ready to proceed at the same rate but suggests that any nation that does decide to proceed only do so after consulting broadly with other countries and allowing their public to reach societal consensus that the next step is appropriate. 

The motivation of the authors’ is clear. “We’re trying to force the spotlight on what comes next,” said co-author Eric Lander, President of the Broad Institute. To what extent international consensus can be built surrounding what the National Institutes of Health calls“a crucial moment in the history of science: a new technology offers the potential to rewrite the script of human life”  remains to be seen.

(Jon Cohen, Science Magazine)

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March 15, 2019 at 4:00 pm

Science Policy Around the Web – December 18, 2018

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By: Janani Prabhakar, Ph.D.

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Source: Pixabay

How will we outsmart A.I. Liars?

Click bait, such as the new SNAP_R bot, is becoming increasingly sophisticated. Researchers at ZeroFOX, a security company in Baltimore, designed SNAP_R to fool users to click on links in tweets that could lead to hazardous sites. While this was just a proof of concept and did not actually lead users to such sites, the findings are striking about human click behavior: SNAP_R elicited a click 66% of the time, on par with hand-crafted phishing attempts. The bot was designed using neural networks that learned to write phishing messages through tweets, Reddit posts, and other online hacks. Improvements in machine learning methods will allow these types of networks to become smarter and smarter and learn from larger amounts of data that include human specific behaviors through text analyses. Thus, a more powerful network can take advantage of the nuances of human behavior to manipulate innocent users much easier. There are examples of this already in place that are not nefarious, such as Apple’s Siri or Amazon’s Alexa. These platforms use neural networks to learn and decode voice data and generate sounds as well as images in response. Another example is Google’s Duplex system,  an A.I. that can call restaurants and make reservations for you. With advances in language systems, future bots can respond in a more nuanced, almost unrecognizable (as A.I.) manner. Experts believe that with the many global advances in A.I., “we face a machine-learning arms race.” While there are many advances in these types of networks, we are still figuring out methods to detect those that are malicious. The current standard is that of individual responsibility, or the “onus is on the individual” approach. In essence, each person should view every bit of news from an online source with distrust. While at present this is the best standard, it is less easy to control and measure than algorithms that could detect pernicious machine learning algorithms. While these are currently being developed, It will be some time before they can be implemented. The problem is, undoubtedly, complex.

(Cade Metz, New York Times)

 

China orders medical team to stop gene-editing project

Late in November, Dr. He Jiankui announced that he had used CRISPR to change the genomes of twin girls born through IVF. This news made headway and received significant criticisms from universities and government organizations across the world. On November 29th, China’s government ordered a halt to this approach by the medical team, stating with a large global consensus that it was too early to make permanent changes to DNA. Gene editing holds promise for helping individuals with genetic illnesses and studies are currently underway to modify the genome using CRISPR in these individuals. However, little is known about the risks of altering DNA in eggs, sperm, or embryos. To do so outside of laboratory research has been described as a huge violation of research ethics. Currently, Dr. Jiankui plans to release all his raw data for independent verification. This research has brought to light questions about the acceptable risks in conducting research with high impact. There are standard, clear ethical guidelines that many argue Dr. Jiankui should have known he was in violation of. Recently, the journal Nature named Dr. Jiankui in its top 10 people who mattered in science in 2018 list because of the important questions about morality and ethics his work brings to the scientific arena. The topics under discussion include how researchers evaluate the ethical considerations and the policies in place that regulate those considerations – should these be re-evaluated?

 

(Marilynn Marchione, The Christian Science Monitor)

 

 

 

 

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December 18, 2018 at 4:52 pm

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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 – June 10, 2017

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By: Allison Dennis, BS

Source: pixabay

Animal Testing

Lack of Clarity Puts Chemical Safety and Animal Welfare at Odds

In the lineup of American stereotypes, the health-nut who cares about the chemicals in his shampoo is often the same person who cares if that shampoo was tested on animals or not. However, a bill signed June 22, 2016, known as the Frank R. Lautenberg Chemical Safety for the 21st Century Act, may be placing those two views at odds. The bill requires the U.S. Environmental Protection Agency (EPA) to implement a risk-based process to evaluate the safety of chemical substances currently being used in the marketplace and approve the use of new chemicals before their introduction. The bill was passed with bipartisan support and offered EPA the new-found power to fully regulate the use of well-known carcinogens like asbestos.

Yet the pathway forward for the EPA is daunting. More than 62,000 substances find their way into and onto our bodies through the products we use and our environment. While many of these substances have become associated with disease over time, how can the EPA certify the risks associated with different exposures to varying amounts of each substance on such an extensive list? The Act itself suggested that once the EPA has evaluated the existing information on the 62,000 substances currently in use, it spend the next twelve months triaging chemicals according to their potential risk. Next, the highest priority chemicals will be evaluated on a three-year deadline to develop knowledge of their toxicity and guidelines for their regulation. Ultimately, by clearly cataloging the risk of common chemicals the Frank R. Lautenberg Chemical Safety for the 21st Century Act promises to greatly reduce the amount of animal testing needed in the long-term.

In the meantime, however, the companies that use to-be-regulated substances in their products may be inclined to undertake independent toxicity testing, collecting enough data to guarantee that their favorite substances meet the low-risk criteria and avoid a drawn-out evaluation. Defining toxicity requires careful experimentation, which can sometimes be carried out in human cells outside of the body, but often require evaluation in animals. Animal rights groups like the Human Society find concern with the lack of transparency in the pre-prioritization process. They fear the eagerness of companies to provide data without any clear guidelines about how that data will be evaluated or what substances will require extensive evaluation could result in extensive and unnecessary animal testing. Further they suggested that the EPA require any new pre-approval data obtained by companies to be collected using non-animal methods. (Maggie Koerth-Baker, FiveThirtyEight)

CRISPR

Small Study may Reveal Big Concerns over CRISPR-Based Therapy

A one-page letter published in Nature Methods last week reports unexpectedly high levels of unintended changes to the genomes of mice that underwent a CRISPR-based therapy. Since it’s renaissance as a therapeutic tool in 2012, CRISPR has occupied the imaginations of scientists, doctors, patients, investors, and ethicists. CRISPR technology provides a relatively straight-forward and reproducible means to gene editing on the cellular level, but its applications to create heritable mutations in the human germ line is on hold until more is understood about the long-term effects such treatments would have.

The original study sought to explore potential long-term effects of germline manipulation by CRISPR in a mouse model. Guide RNA along with the Cas9 enzyme were injected into mouse zygotes, which introduced a correction in a mutation in the rd1 gene of otherwise blind mice. Initiating this change before the first cell division enabled this corrected mutation to be inherited by all cells arising in the developing mouse, consequently restoring the ability for the eyes to develop normally. In a follow-up experiment described in their one page letter, the researchers looked for mutations in the genomic DNA of two CRISPR-treated adult mice compared with a control mouse, revealing over 2,000 unintended mutations following CRISPR treatments. None of these mutations appeared to affect the mice, suggesting that deep genomic sequencing may be required to reveal unanticipated changes in an outwardly healthy mouse. Further, the nature of these unintended mutations offered few clues explaining how they might have occurred.

This result stands in contrast with other reports quantifying the extent of these unintended changes, which found CRISPR to be highly specific. While the CRISPR-Cas9 system has been observed to sometimes alter off-target regions of the genome, this activity can usually be curbed through the careful design and evaluation of the guide RNA. The limitations of this small study have been discussed extensively since its publication. However, the findings have sparked the need for further investigation into the long-term-whole-animal effects of germline-editing by CRISPR. As human germline-editing creeps closer to reality, the FDA will be tasked with developing an entirely new means of evaluating the safety of such technologies (Megan Molteni, Wired)

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June 10, 2017 at 11:33 am

Science Policy Around the Web – February 24, 2017

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By: Alida Palmisano, PhD

Source: usda [Public domain], via Wikimedia Commons

Public Access to Data

Lawsuit Aims to Force USDA to Repost Scrubbed Animal Welfare Records

“Put the records back on the internet.”

An article published in Science discusses a lawsuit filed on February 13 against the U.S. Department of Agriculture (USDA) by an animal law expert at Harvard University. According to the plaintiffs, USDA violated the federal Freedom of Information Act (FOIA) when it removed thousands of animal welfare inspection reports and other records from a publicly accessible website. USDA generated records that document animal facility inspections, enforcement actions, animal censuses, and other information collected by the agency in the course of enforcing the federal Animal Welfare Act.  The law covers animals in more than 7800 facilities, including zoos, roadside circuses, and research laboratories at government agencies and academic medical centers.

The decision to remove the public access to these records may have been a response to a lawsuit involving another law, the Horse Protection Act. The plaintiffs in a 2016 Texas lawsuit accused USDA of violating their rights under the Privacy Act by posting inspection documents required by the Horse Protection Act. A resulting USDA review of all its public postings led the agency to scrub from its website documents generated under both the Horse Protection Act and the Animal Welfare Act.  In the future, the agency announced, people who want access to those records will need to file a FOIA request. The agency’s most recent FOIA report states that it takes an average of 94 days for the agency to respond to a simple FOIA request and 234 days on average for more complicated requests.

In February 13’s lawsuit, the plaintiffs invoke a section of FOIA that requires agencies to make publicly available electronically all records that it has released under FOIA which “because of the nature of the subject matter, the agency determines have become or are likely to become the subject of subsequent requests for substantially the same records.” (Meredith Wadman, ScienceInsider)

Science and Immigration

Grad Students, Postdocs with U.S. Visas Face Uncertainty

While U.S. courts are busy handling President Donald Trump’s travel ban on immigration from seven majority-Muslim countries, the temporary shut down of the executive order, the appeal to reinstate the travel ban, the rejection of the immediate restoration of the ban, and more appeals and rulings, graduates and postdoctoral students already in the United States are weighing their options and trying to plan rationally in an unpredictable and fluid situation.

Many scientists in the U.S. are on student or other working visas. All these visas may not be renewable, depending on future executive orders and regulations. The dilemma “simply ruins their future. It’s a catastrophe,” says a Yemeni biologist who is on a university faculty on an H-1B, a 3-year visa for professionals. For years, lawmakers in Washington have tried to reform abuses of visa regulations by companies using visas to bring workers to the U.S. to learn the ropes, and then send the trained workers to other countries where the job can be done cheaply. The H-1B system is contentious: on one side labor advocates want the exploitation of the H-1B system to stop supporting an outsourcing business model. On the other hand, tech companies like Google and Facebook say they can’t get enough visas for top foreign talent, as the cap on the number of H-1Bs issued every year means that sometimes foreign graduates from top U.S. universities, places like the Massachusetts Institute of Technology and the University of California, Berkeley, can’t get one. The travel ban already has harmed the top universities in the U.S., stranding students, faculty and scholars abroad, and making foreign schools more attractive to some of the world’s brightest students.

In papers filed in Brooklyn federal court, the schools (that include Columbia, Duke, Harvard, Johns Hopkins, Princeton, Stanford, Yale, Massachusetts Institute of Technology and several more) said that the order blocking travel from seven predominantly Muslim countries threatens their abilities to educate future leaders from every continent. They said the executive order has “serious and chilling implications” and that the ban “casts doubt on the prospect and value of studying and working here for everyone,” the papers said. (Meredith Wadman, Richard Stone, Science)

Genetic Engineering

US Science Advisers Outline Path to Genetically Modified Babies

“Scientists should be permitted to modify human embryos destined for implantation in the womb to eliminate devastating genetic diseases such as sickle-cell anaemia or cystic fibrosis — once gene-editing techniques advance sufficiently for use in people and proper restrictions are in place. That’s the conclusion of a 14 February report from the US National Academies of Science, Engineering, and Medicine.”

The report follows a 2015 National Academies summit between scientists, ethicists, legal experts and patient groups from around the world. At the time of the meeting, given the outstanding scientific, ethical and legal questions surrounding the issue, the organizers concluded that scientists shouldn’t yet perform germline editing on embryos intended for establishing a pregnancy. However, the organizers also stated that altering human embryos for basic research was acceptable.

The latest iteration of this ongoing CRISPR debate moves the bar a little further. The report recommends restricting the technique to severe medical conditions for which no other treatment exists. Eric Lander, president of the Broad Institute of MIT and Harvard, said, “It’s a very careful, conservative position that’s just a little bit beyond an absolute bar.” In the report, the committee also called for international cooperation, strict regulatory and oversight framework, public input into decisions and long-term follow-ups of children who have edited genomes. The report adds that for now, genome editing should not be used for human enhancement, such as improving a person’s intelligence or giving them super-strength.

The report drew immediate criticism from a California-based non-profit organization called the Center for Genetics and Society. “This report is a dramatic departure from the widespread global agreement that human germline modification should remain off limits,” said Marcy Darnovsky, executive director of the center. “It acknowledges many of the widely recognized risks, including stigmatizing people with disabilities, exacerbating existing inequalities, and introducing new eugenic abuses. Strangely, there’s no apparent connection between those dire risks and the recommendation to move ahead.” (Sara Reardon, Nature)

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Written by sciencepolicyforall

February 24, 2017 at 11:23 am