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Posts Tagged ‘CRISPR

Science Policy Around the Web July 2nd, 2020

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By Mary Weston, PhD

Source: Wikimedia

The line is forming for a COVID-19 vaccine. Who should be at the front?

With the possibility of COVID vaccines becoming available as soon as next fall, the debate over who will receive the initial doses has begun. Last week, a committee that provides vaccine recommendations to the CDC met to deliberate vaccine prioritization. 

Those risking their health for others in essential roles, such as high-risk health care workers and first responders, will receive the earliest vaccine doses. However, for subsequent groups, the ethics surrounding vaccine prioritization are difficult and complicated. Prioritization is a balance between what is best for society and protecting the health of an individual says Dr. Bruce Gellin, former director of the US National Vaccine Program and current lead at the nonprofitSabin Vaccine Institute

Who else should get these early doses? The virus has disproportionately affected the elderly, arguing they should be high on the list. However, older people typically have the weakest immune response to vaccines and ensuring those who get the early doses develop immunity is important. Alternatively, perhaps groups working in professions/environments that drastically increase their infection risk should be vaccinated early. However, these groups tend to be younger and healthier, such as prisoners, meat packers, and grocery store workers. Additionally, there is the complex issue surrounding the disproportionate effect of COVID-19 on certain ethnic groups.  Should they get special consideration? What about those who are poor, who likely have less access to healthcare and live in more crowded conditions, or teachers that work indoors with big groups of children?

One conclusion made by the committee is that pregnant women, who typically are last to get a new vaccine because of concerns of possible harm to the fetus, may be high on the list due to an increased risk of severe illness from COVID-19. 

Both the CDC and the WHO are rapidly working to develop their own schemes for vaccine distribution. Initial outlines indicate they are listing high-risk healthcare workers as the first group. The WHO’s plan has subsequent tiers involve prioritize select groups including general health care workers, the elderly, pregnant women, and people with co-morbidities that increase their COVID-19 risk. However, these are just guidelines and many of the details/classifications need to be established. Additionally, since data surrounding COVID-19 changes so rapidly, these recommendations could be modified to reflect current knowledge.

Vaccine prioritization debates are challenging and the “right” answer is difficult to determine. These conversations have just started and will likely continue until vaccines are widely available. 

(Jon Cohen, Science Magazine)

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July 2, 2020 at 6:17 pm

Science Policy Around the Web June 30th, 2020

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By Maria Disotuar, (MPH, PhD)

Image from Zeiss Microscopy on Flickr

CRISPR gene editing in human embryos wreaks chromosomal mayhem

The CRISPR-Cas9 gene-editing system has been known to produce unwanted DNA deletions, otherwise known as “off target” mutations. These mutations typically occur far from the target site and are generally easily detected via genome-wide assays. Recently, three separate laboratories found that CRISPR can cause unwanted mutations near or at the target site of human embryos. Previously, these types of observations had only been reported in mouse embryos and human cell lines. 

Using CRISPR to modify human embryos is a controversial topic. Changes to human DNA could be passed down to other generations and unwanted mutations could be catastrophic. In fact, it was not too long ago that a Chinese scientist sparked international outrage for using CRISPR to create the first gene-edited human babies. Yet, globally, scientists agree that a better understanding of the gene-editing technology could revolutionize medicine in situations where there are no other medical alternatives. 

Kathy Niakan of the Francis Crick Institute in London was the first to report that 22% of the 18 genome-edited embryos in her lab had unwanted mutations in close proximity to the target-site. The mutations consisted of  large deletions of thousands of DNA bases. Not long after, Dieter Egli of Columbia University in New York City reported that when trying to correct a mutation for blindness in the lab, about 50% of the embryos either lost large fragments of the chromosome or completely lost the chromosome of the target-site. Finally, Shoukhrat Mitalipov of Oregon Health and Science University in Portland reported similar results with mutations leading to loss of more than 100 base pairs in the embryos. 

Although the studies have not yet been peer-reviewed, they highlight the potential dangers of CRISPR technology due to a lack of understanding in the scientific community. Importantly, from a bioethics perspective, these studies underscore the need to tread cautiously as we move forward with CRISPR gene-editing technology.   

(Heidi Ledford, Nature) 

World’s second-deadliest Ebola outbreak ends in Democratic Republic of the Congo

Since 2018, the Democratic Republic of the Congo has been battling the second-deadliest Ebola outbreak in the world. In less than two years, the virus infected more than 3000 people and killed 66% of these individuals. Despite the political instability and civil unrest of the region, there was significant progress in vaccination and treatment programs. This was the first time a vaccine for Ebola was widely distributed in an affected region. In fact, 300,000 people received the vaccine if they had been in close proximity to someone with Ebola. As a result, more than 80% of individuals vaccinated did not contract the virus or they developed a very mild case of the disease. Importantly, two antibody-based drugs were proven to reduce deaths in clinical trials. Thus, individuals who were hospitalized soon after being infected were able to receive the drugs if they gave consent. 

On June 1st, Equateur, a northern region of the country reported a new Ebola outbreak of 18 people and now local leaders are hoping to use the same tools and strategies to combat the virus. However, from a geographical and economical standpoint,  the region is difficult to access by car and the economic hardships lead people from the region to travel to other cities to engage in trade practices. Officials worry that this will lead to a wider and faster spread of the virus. Additionally, due to the coronavirus outbreak there is concern that researchers and health professionals stationed in the country have shifted their attention to fighting Covid-19. 

(Amy Maxmen, Nature

Written by sciencepolicyforall

June 30, 2020 at 10:15 am

Science Policy Around the Web March 24th, 2020

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By Maria Disotuar, PhD

Image from Flickr

The Secretive Company That Might End Privacy as We know It

Have you heard of the start-up company Clearview AI? If not, you’re not alone. Most individuals have not heard about this tiny company, and yet it’s bound to transform our privacy and the world. Clearview is a facial recognition application founded by Hoan Ton-That, an Australian computer programmer and part-time model. The app allows users to upload a picture of a stranger and then it searches a database containing more than 3 billion images scraped from social media sites such as Facebook, Venmo, YouTube, and Instagram. The search results provide images of the stranger and direct links to the photos. The app software also has the capability to be paired-up with augmented-reality glasses which means you could identify anyone on the street and know who they are and where they live in seconds. 

For now, the app has only been distributed to Homeland Security, the FBI, local cops, and a few companies for security purposes. These individuals have used the app to solve a series of murder, identify theft, and kidnapping cases. Yet, experts are concerned about future implications of the app and some argue it should be banned all together. Currently, the app has not been tested by an independent party and so there is no data to determine the rate of false or positive matches. Importantly, these types of apps tend to be controversial because they tend to deliver false matches for certain ethnic groups, particularly individuals of color. To date, there is no clear indication about if or when Clearview will be made publicly available, however, experts like Al Gidari, a privacy professor at Stanford University note that without a strong federal privacy law Clearview could end anonymity as we know it. 

(Kashmir Hill, The New York Times

CRISPR treatment inserted directly into the body for the first time

For the first time in history, CRISPR-Cas9 gene-editing has been directly administered into a clinical trial patient to treat Leber’s congenital amaurosis 10 (LCA10), a rare genetic eye disorder that often leads to blindness in infancy. Typically, clinical trials that use CRISPR edit the genome of cells removed from the body. The CRISPR elements are introduced into the cells and then these cells are transplanted into the patient. In this case, however, the CRISPR elements are injected directly into the eye and used to remove the mutation in the gene CEP90 that results in LCA10.

This is not the first time gene editing has been used directly on a clinical trial patient. In 2018, Sangamo Therapeutics used an older gene editing system called zinc-finger nucleases to alleviate the symptoms of Hunter’s syndrome, a metabolic disease that can lead to organ damage. The results of the trial showed that the therapy was not effective. CRISPR, however, is more powerful and easier to use and design in the laboratory. Scientists hope direct insertion of CRISPR elements will remove the DNA mutation and lead to reactivation of the inactive photoreceptors. 

Yet, this landmark event does not come without challenges. There are inherent safety and efficacy concerns when using this type of technology directly on an individual. The challenge with direct application is getting the CRISPR system to edit the correct place and understanding if the system made unwanted off-target edits. For now, the first volunteers to get the therapy will receive a small dose to test for efficacy and later they will receive larger doses to minimize any health risks.  

(Heidi Ledford, Nature)

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March 24, 2020 at 9:04 am

Science Policy Around the Web February 25th, 2020

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By Andrew Wright BSc

Image by CheapStockImage_com from Pixabay

Humans are a bigger source of climate-altering methane, new studies suggest

One of the holes in modern climate research is an appropriate estimate of newly emerging positive-feedback loops and their planetwide impact. One such phenomenon that has been previously put forward is the “clathrate gun” hypothesis, which theorizes that an increasingly warm environment will be capable of releasing crystallized methane frozen in arctic permafrost and shallow waters. This would, in turn, lead to more warming and more methane release, potentially causing a catastrophic runaway warming event. However, recent studies have suggested that arctic deposits of ocean-bound methane are less sensitive to warming than previously thought and new data from the University of Rochester seems to confirm that idea in terrestrial deposits of crystalline methane as well.

In order to assess the effect of different global average temperatures on release of methane from natural sources, researchers took advantage of radioactive carbon isotope levels (like carbon-14) in ice core samples that marked the last climate transition; during the most recent ice age thousands of years ago. Since carbon-14 is formed by solar radiation, if methane was released from large underground and underwater sources following the last warming it should have shown a smaller percentage of carbon-14 than methane sampled from when the earth was much cooler. Instead, levels of carbon-14 were similar across samples, suggesting that an increase in release of crystalline methane did not occur.

 Importantly, another study was able to demonstrate with the same technique that the large increase in methane emissions following the industrial revolution were almost entirely anthropogenic. In fact, they demonstrated that the amount of naturally generated methane was generally in agreement with the estimates of those levels from the last ice age, which would mean that most modern methane release is from human consumption. While this does provide stark evidence of the increasing level of methane that is being released from industrial sources, it also means that ultimately the amount of methane that acts as a greenhouse gas can be controlled though inter-governmental policy corrections.   

(Warren Cornwall, Science)

African killifish may hold key to stopping aging in humans

While many forms of anti-aging research have focused on telomerases and stem-cell therapies, an increasing emphasis is being put on diapause, the phenomenon of biological suspension. When diapause is induced, often during developmental periods and in response to environmental pressure, organisms largely cease cellular activity and do not age. The mechanisms of this process were generally unknown, but research from Stanford University has started to elucidate them. Here, researchers focused on the African killifish, the eggs of which can enter diapause in response to months-long droughts.

After inducing diapause in killifish embryos, researches analyzed which genes and proteins were more active. They found that a particular protein called CBX7 was greatly increased.  To determine the function of this protein, researchers generated a genetically modified killifish with impaired CBX7-encoding genes using the gene-editing tool CRISPR-Cas9.  Genetically modified animals showed changes in genes that regulated metabolism, muscle development and maintenance, hormones, and neurotransmitters. They also experienced muscle atrophy within a month of diapause and were not able to maintain diapause for as long. 

While this research is far from being applicable in humans, it is a step closer than nematodes like C. Elegans, or the beloved extremophile known as the tardigrade, or “waterbear”.  Still, the study raises the prospect of another avenue of research that might limit or pause aging in other living systems. 

(Nicola Davis, The Guardian

Written by sciencepolicyforall

February 25, 2020 at 11:14 am

Science Policy Around the Web January 7th, 2020

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By Ben Wolfson, PhD

Image by mcmurryjulie from Pixabay 

What CRISPR-Baby Prison Sentences Mean for Research

Chinese scientist He Jiankui came to prominence last year after claiming he had used CRISPR/Cas9 to genetically edit human embryos to confer resistance to HIV-1. Twin girls with the mutation were born in October of 2018, and He’s work was confirmed by Chinese investigators in February of 2019.

Now, after a trial held in secret, He has been sentenced to three years in prison for “illegal medical practice” by a Chinese court. Two of He’s colleagues were also charged and given shorter prison sentences. All three were leveled fines, and will be prevented from conducting research using human reproductive technology.

These actions set an important precedent for regulation of human gene editing, however Chinese scientists also worry that they may result in restrictions for research into genetic modification that is not as ethically dubious. They worry that it may become difficult to get approval to use gene editing tools in clinical trials, as well as making funding for these sorts of research experiments more difficult to get. 

Despite these worries, He’s imprisonment is supported by the scientific community, and represents the first big check on clinical gene editing research. Others outside of the mainstream scientific community disagree. In an Op-Ed published by Stat News, Biohacker Josiah Zayner states that as gene-editing of human embryos becomes more common, the perspective on Jiankui will shift and he will no longer be seen as having done anything wrong. 

(David Cyranoski, Scientific American)

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January 7, 2020 at 1:27 pm

Science Policy Around the Web December 6th, 2019

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By Hannah King, PhD

Image by Steve Buissinne from Pixabay 

200,000 Uninsured Americans to Get Free H.I.V.-Prevention Drugs

World AIDS Day, held annually on December 1st, has led to a flurry of AIDS-related announcements this week.

The Trump administration has released an announcement outlining how it plans to distribute HIV prevention drugs donated by the pharmaceutical company Gilead, which manufactures the drugs. These drugs will be available to 200,000 uninsured Americans who have a prescription and recent evidence of their HIV-negative status.

While other programs exist in the US to provide these drugs free of charge (including those run by cities in high-incidence areas and a program from Gilead itself) this announcement marks the first time the government has provided such HIV-prevention medicine free to individuals not enrolled in a federal health program. With 37,500 new HIV infections per year in the US, and 1.2 million Americans estimated as being at high risk for HIV-acquisition, widespread distribution of this preventative treatment is an important public health initiative. 

Access to HIV prevention and treatment medication is also a worldwide issue. In further encouraging news, an Indian drug manufacturer has announced that it will make a pediatric formulation of HIV medication, that is strawberry flavored and the size of sugar granules! The current medication is either formulated as hard tablets, or requires refrigeration, reducing either the tolerability to children or accessibility of the product. As 160,000 children are born with HIV each year, but only approximately half receive treatment, this new formulation will hopefully reduce the AIDS-related morbidity and mortality in this vulnerable population.   

(Donald G. McNeil Jr., New York Times

China’s CRISPR babies: Read exclusive excerpts from the unseen original research

Further details of the research purporting to use CRISPR to create gene-edited babies have emerged, reinforcing the “serious, unresolved safety concerns” associated with this human research. 

MIT Technology Review has released excerpts from an unpublished manuscript outlining a study by the Chinese researcher He Jiankui which describes the creation of the first gene-edited human babies. The mutation introduced into the embryos is a deletion in the gene expressing a protein called CCR5. A deletion in this CCR5 protein occurs naturally in some individuals and renders them resistant to infection with HIV – the stated rationale for this experiment. However, the manuscript shows the deletion that was introduced into the genomes of these babies is similar, but not identical to the naturally occurring deletion, and no attempt is made by the authors to validate its ability to confer HIV resistance.

Furthermore, despite the manuscript describing the experiments a “success”, the data shows the CCR5 deletion is absent in one chromosome on one of the babies, meaning she carries one copy of the functional CCR5 gene, and is still susceptible to HIV infection. Data in the manuscript, showing DNA sequencing of cells from the babies following their birth also indicates that not all cells in these babies share the same genetic code, suggesting that not all cells carry the CCR5 deletion, or that other “off-target” effects with unknown health implications may be present.

This newly available data, in addition to the many ethical concerns previously raised, further demonstrate this experiment is not the “success” nor the path forward to “control the HIV epidemic” that He Jiankui claims it to be.

(Antonio Regalado, MIT Technology Review)

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December 6, 2019 at 1:51 pm

Science Policy Around the Web October 29th, 2019

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By Allison Cross PhD

Image by Gerd Altmann from Pixabay 

Super-precise new CRISPR tool could tackle a plethora of genetic diseases

Since the first adaption of CRISPR-Cas9 for gene editing in eukaryotic cells in 2013, the hopes of using the technique to cure genetic diseases have been high.  Despite the ability of current CRISPR–Cas9 gene-editing tools to edit the human genome, successful edits are often accompanied by unintended and unpredictable errors elsewhere in the genome. However, a new method of editing, published this week in Nature, shows potential for greater control over genome editing.   

This new method of genome editing, referred to as prime editing, still uses Cas9 to recognize specific DNA sequencing in the genome.  However, instead of producing double stranded breaks, a modified Cas9 enzyme is utilized to cut only one strand of the DNA.  The cut strand of DNA (called nicked DNA) is then repaired utilizing a prime editing guide RNA, known as a pegRNA.  

Prime editing offers several advantages over a similar previously developed editing technique, known as base editing.  Base editing, like prime editing, does not result in double stranded DNA breaks; instead it allows researchers to make specific substitutions to the bases that make up DNA (adenine, guanine, thymine, cytosine). However, it only allows for certain subsets of single base changes to be made (C->T, G->A, A->G, and T->C).   Prime editing is more versatile, allowing for all 12 possible base-to-base changes and capable of making multi-base changes.  There is, however, a limitation to how large the changes can be using the prime editing technique.  If large insertions or deletions are desired, traditional CRISPR-Cas9 tools remain necessary.

Researchers are still evaluating how prime editing works in a variety of cells and organisms, but the initial studies published this week show promise for more versatile and precise gene editing with fewer unwanted byproducts. 

 (Heidi Ledford, Nature) 

U.S. Travel Ban Disrupts the World’s Largest Brain Science Meeting

The travel ban implemented by the Trump administration restricts U.S. travel from 7 nations; Iran, Librya, Somalia, Syria, Yemen, North Korea and Venezuela.  The ban has been a very controversial issue with wide ranging implications. After its implementation, many in the scientific community feared the ban would hurt the community by resulting in lost potential collaborators, trainees, and recruits.  

This year’s Society for Neuroscience meeting drew more than 25,000 brain scientists from around the world to Chicago this week, however, some scientists were unable to attend due to visa issues. Sepiedeh Keshavarzi, a current Australian citizen who holds an Iranian passport, was invited to give an oral presentation during the year’s meeting. Instead of attending the meeting in person, Keshavarzi instead sent a prerecorded PowerPoint presentation to the meeting after her request for a Visa to the U.S. was denied.  

With Visa problems becoming increasing common, the Society to Neuroscience created a special program aimed at helping scientists with Visa issues present their work at this year’s meeting. The program, called Science Knows No Borders, did help some scientists, like Keshavarzi, present their work; however, fewer than a dozen scientists participated in the program. 

(Jon Hamilton, NPR)

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October 29, 2019 at 2:47 pm

Science Policy Around the Web October 25th, 2019

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By Andrew Wright BSc

Image by Arek Socha from Pixabay 

NIH and Gates Foundation lay out ambitious plan to bring gene-based treatments for HIV and sickle cell disease to Africa

Following the launch of an initiative to boost gene therapy treatments of sickle cell disease last month, the National Institutes of Health (NIH) and the Bill and Melinda Gates foundation have announced a joint funding agreement of at least $100 million over the next four years to expedite a cure for both sickle cell disease and HIV and make it available in Africa. 

The current medical intervention for sickle cell disease is a bone marrow transplant, a treatment that is limited by the availability of genetically compatible donors and can be risky for adult patients. This new partnership aims to build on funding towards more effective treatments that are less restricted and more cost effective. While genetic intervention is being used in a limited clinical setting, it is still necessary to destroy a patient’s stem-cells via chemotherapy before reintroducing the patient’s genetically modified ones. Using burgeoning gene-editing techniques such as CRISPR, researchers for this initiative hope to modify targeted genes with a process more similar to a blood transfusion using replication-deficient viruses or nanoparticles to carry the molecular tools to where they need to be. This should theoretically make treatments much less expensive and more available to regions that have limited medical infrastructure and a high incidence of sickle cell disease such as sub-Saharan Africa. 

Since there is also a high incidence of HIV in sub-Saharan Africa, this initiative also aims to tackle HIV in the region using similar techniques. The current standard for treating HIV is anti-retroviral therapy, which can allow patients to live a normal life, but also must be taken every day, is expensive ($429-$10,896 per month), and does not eliminate the disease. The drive behind genetic intervention strategies comes from serendipitous case-studies when two men were cured of HIV following stem cell transplants that intentionally had white-blood cells with a weakened protein to treat their blood cancers. The NIH-Gates funding initiative will focus on strategies to weaken these proteins (called CCR5 receptors) and to directly destroy HIV genetic material.

(Jon Cohen, Science)

Evidence links poliolike disease in children to a common type of virus

Since 2014 more than 570 children have experienced a condition known as acute flaccid myelitis (AFM) where some suddenly lost limb control, had trouble swallowing or breathing, or ended up paralyzed. These symptoms routinely followed symptoms of a common cold, like a runny nose or fever. Up until now, the route cause behind AFM was not well understood, but recent studies of patients’ spinal fluid suggest the culprit is enterovirus. Infections from enteroviruses are common and rarely cause severe symptoms (although they can cause respiratory illness in asthmatic populations). 

Previous studies into the cause of AFM had examined enterovirus but found no trace of it in the central nervous system, where it would need to be in order to lead to loss of motor control. In the most recent study conducted by the University of California San Francisco, researchers sampled for elevated levels of antibodies in the central nervous system rather than the virus itself. They found that 69% of AFM patients had elevated antibodies against enteroviruses. There are still questions as to why only some children experience AFM when infected by enterovirus when most only experience typical symptoms.

Unfortunately, enterovirus-AFM is currently untreatable beyond post-infection physical therapy, although the lead author of the study suggests that immunoglobin therapy may help reduce the worst symptoms. Ultimately, the only way to completely prevent enterovirus-AFM infections, referred to by some as ”the new polio“,  will be a vaccine.

(Kelly Servick, Science)

Written by sciencepolicyforall

October 25, 2019 at 3:39 pm

Science Policy Around the Web August 1st, 2019

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By Andrew Wright BSc

Image by Steve Buissinne from Pixabay 

Major U.S. cities are leaking methane at twice the rate previously believed

While natural gas emits less carbon dioxide (CO2) when burned, if allowed to enter the atmosphere as methane (CH4) it can act as a greenhouse gas that is 20-80 times more potent than CO2. Some of this impact is supposed to be mitigated by the relatively low amount of leaked methane, roughly 370,000 tons in six major urban areas studied according to a 2016 report from the EPA. However, a new study in the journal Geophysical Research Letters analyzed those same metropolitan centers and found that the EPA has underestimated methane release by more than half. By taking simultaneous measurements of ethane, which appears only in natural gas supplied to homes and businesses, researchers were able to delineate the sources of leakage, as natural sources and landfills do not give off ethane. 

From their analysis, the total estimate from the six cites studies was 890,000 tons of CH4, 84% of which was from methane leaks. While the authors of the study are unsure as to why the EPA estimates are so low, they suggest it could be because the EPA only estimate leaks in the distribution system, rather than endpoint leaks in home and businesses. While these results cannot be reliably extrapolated to newer cities which may contain infrastructure more resilient to leakage, they could engender further study to gather a clearer picture of national methane release.

(Sid Perkins, Science)

 

Japan approves first human-animal embryo experiments

On March 1st the Japanese science ministry lifted a ban on growing human cells in animal embryos and transferring them to animal uteri. While human-animal hybrid embryos have been made before, functional offspring have not been allowed to develop.  The first researcher to take advantage of this new regulatory scheme is Hiromitsu Nakauch, the director of the Center for Stem Cell Biology and Regenerative Medicine at the Institute of Medical Science at the University of Tokyo and a faculty member at Stanford University. His long-term goal is to grow human organs in animals such as pigs, from which the functional organs could be extracted and transplanted into human patients. His intent is to start in an early embryonic mouse model, then a rat model, and finally a pig model with embryos that form for up to 70 days. 

This measured approach is in stark contrast to the recent controversy regarding CRISPR edited babies in China, but has still been met with a certain level of ethical skepticism. Bioethicists are particularly concerned that the human cells being injected into animal embryos, induced pluripotent stem (iPS) cells, may deviate from their intended target (in this case the pancreas) and affect the host animal’s cognition. According to Nakauchi, the experimental design, which involves eliminating the gene for the target organ and injecting human iPS cells to compensate, is such that the cells should only be involved in a specific part of the animal. 

While Nakauchi’s group used this method to successfully grow a pancreas in a rat from mouse cells, they have had limited luck putting human iPS cells into sheep embryos. Given the evolutionary distance between mice, rats, pigs, and humans it may be difficult for experimenters to produce more satisfactory results. To address this Nakauchi has suggested that he will be trying genetic editing techniques as well as using various developmental stages of iPS cells.

(David Cyranoski, Nature)

 

 

Written by sciencepolicyforall

August 1, 2019 at 12:23 pm

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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Written by sciencepolicyforall

May 29, 2019 at 9:25 am

Posted in Essays

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