Welcome to the Nexus of Ethics, Psychology, Morality, Philosophy and Health Care

Welcome to the nexus of ethics, psychology, morality, technology, health care, and philosophy
Showing posts with label CRISPR. Show all posts
Showing posts with label CRISPR. Show all posts

Tuesday, March 29, 2022

Gene editing gets safer thanks to redesigned Cas9 protein

Science Daily
Originally posted 2 MAR 22

Summary:

Scientists have redesigned a key component of a widely used CRISPR-based gene-editing tool, called Cas9, to be thousands of times less likely to target the wrong stretch of DNA while remaining just as efficient as the original version, making it potentially much safer.

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Scientists have redesigned a key component of a widely used CRISPR-based gene-editing tool, called Cas9, to be thousands of times less likely to target the wrong stretch of DNA while remaining just as efficient as the original version, making it potentially much safer.

One of the grand challenges with using CRISPR-based gene editing on humans is that the molecular machinery sometimes makes changes to the wrong section of a host's genome, creating the possibility that an attempt to repair a genetic mutation in one spot in the genome could accidentally create a dangerous new mutation in another.

But now, scientists at The University of Texas at Austin have redesigned a key component of a widely used CRISPR-based gene-editing tool, called Cas9, to be thousands of times less likely to target the wrong stretch of DNA while remaining just as efficient as the original version, making it potentially much safer. The work is described in a paper published today in the journal Nature.

"This really could be a game changer in terms of a wider application of the CRISPR Cas systems in gene editing," said Kenneth Johnson, a professor of molecular biosciences and co-senior author of the study with David Taylor, an assistant professor of molecular biosciences. The paper's co-first authors are postdoctoral fellows Jack Bravo and Mu-Sen Liu.


Journal Reference:

Jack P. K. Bravo, Mu-Sen Liu, et al. Structural basis for mismatch surveillance by CRISPR–Cas9. Nature, 2022; DOI: 10.1038/s41586-022-04470-1

Monday, January 20, 2020

Chinese court sentences 'gene-editing' scientist to three years in prison

Huizhong Wu and Lusha Zhan
kfgo.com
Originally posted 29 Dec 19

A Chinese court sentenced the scientist who created the world's first "gene-edited" babies to three years in prison on Monday for illegally practising medicine and violating research regulations, the official Xinhua news agency said.

In November 2018, He Jiankui, then an associate professor at Southern University of Science and Technology in Shenzhen, said he had used gene-editing technology known as CRISPR-Cas9 to change the genes of twin girls to protect them from getting infected with the AIDS virus in the future.

The backlash in China and globally about the ethics of his research and work was fast and widespread.

Xinhua said He and his collaborators forged ethical review materials and recruited men with AIDS who were part of a couple to carry out the gene-editing. His experiments, it said, resulted in two women giving birth to three gene-edited babies.

The court also handed lesser sentences to Zhang Renli and Qin Jinzhou, who worked at two unnamed medical institutions, for having conspired with He in his work.

The info is here.

What Is Prudent Governance of Human Genome Editing?

Scott J. Schweikart
AMA J Ethics. 2019;21(12):E1042-1048.
doi: 10.1001/amajethics.2019.1042.

Abstract

CRISPR technology has made questions about how best to regulate human genome editing immediately relevant. A sound and ethical governance structure for human genome editing is necessary, as the consequences of this new technology are far-reaching and profound. Because there are currently many risks associated with genome editing technology, the extent of which are unknown, regulatory prudence is ideal. When considering how best to create a prudent governance scheme, we can look to 2 guiding examples: the Asilomar conference of 1975 and the German Ethics Council guidelines for human germline intervention. Both models offer a path towards prudent regulation in the face of unknown and significant risks.

Here is an excerpt:

Beyond this key distinction, the potential risks and consequences—both to individuals and society—of human genome editing are relevant to ethical considerations of nonmaleficence, beneficence, justice, and respect for autonomy and are thus also relevant to the creation of an appropriate regulatory model. Because genome editing technology is at its beginning stages, it poses safety risks, the off-target effects of CRISPR being one example. Another issue is whether gene editing is done for therapeutic or enhancement purposes. While either purpose can prove beneficial, enhancement has potential for abuse.
Moreover, concerns exist that genome editing for enhancement can thwart social justice, as wealthy people will likely have greater ability to enhance their genome (and thus presumably certain physical and mental characteristics), furthering social and class divides. With regards to germline editing, a relevant concern is how, during the informed consent process, to respect the autonomy of persons in future generations whose genomes are modified before birth. The questions raised by genome editing are profound, and the risks—both to the individual and to society—are evident. Left without proper governance, significant harmful consequences are possible.

The info is here.

Sunday, November 24, 2019

Is biohacking ethical? It’s complicated. A new Netflix series explains why.

A baby’s hand sporting a UPC barcode on its wrist holds onto an adult’s finger.Sigal Samuel
www.vox.com
Originally posted October 22, 2019

Here is an excerpt:

Biohacking raises a lot of questions with huge ethical implications. Should biohacking yourself be a human right or should your control over your own body be curtailed — possibly even criminalized — if it’s risky to you or others? (Many biohacking pursuits exist in a legal gray zone but are not yet outright illegal, or not enforced as such. Some new gene therapies profiled in Unnatural Selection, like Jackson Kennedy’s, are approved by the Food and Drug Administration.) Will biohacking enhance life for all of us equally or will it widen the gap between haves and have-nots?

Perhaps we’d do best to strictly limit the use of new technologies like CRISPR. But then again, given that people are dying and these technologies might help, can we morally afford to not use them?

Ethical objections to biohacking

While some people who engage with biohacking view themselves as part of the scientific establishment and often voice ethical concerns about technologies like CRISPR, others have a strong anti-establishment streak.

Unnatural Selection assigns uneven weight to different camps — proponents of the new technologies get more airtime than their critics, perhaps because it’s more visually interesting to watch people inject themselves with new DNA than it is to watch finger-wagging bioethicists warn about risks.

The info is here.

Wednesday, November 20, 2019

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

CRISPR-Cas9 gene editing complex, illustration.Heidi Ledford
nature.com
Originally posted October 21, 2019

For all the ease with which the wildly popular CRISPR–Cas9 gene-editing tool alters genomes, it’s still somewhat clunky and prone to errors and unintended effects. Now, a recently developed alternative offers greater control over genome edits — an advance that could be particularly important for developing gene therapies.

The alternative method, called prime editing, improves the chances that researchers will end up with only the edits they want, instead of a mix of changes that they can’t predict. The tool, described in a study published on 21 October in Nature1, also reduces the ‘off-target’ effects that are a key challenge for some applications of the standard CRISPR–Cas9 system. That could make prime-editing-based gene therapies safer for use in people.

The tool also seems capable of making a wider variety of edits, which might one day allow it to be used to treat the many genetic diseases that have so far stymied gene-editors. David Liu, a chemical biologist at the Broad Institute of MIT and Harvard in Cambridge, Massachusetts and lead study author, estimates that prime editing might help researchers tackle nearly 90% of the more than 75,000 disease-associated DNA variants listed in ClinVar, a public database developed by the US National Institutes of Health.

The specificity of the changes that this latest tool is capable of could also make it easier for researchers to develop models of disease in the laboratory, or to study the function of specific genes, says Liu.

The info is here.

Wednesday, October 23, 2019

The Moral Choices on CRISPR Babies

Sheldon Krimsky
The American Journal of Bioethics
Published online September 26, 2019

In late November 2018, Chinese scientist Dr. He Jiankui announced at the Second International Summit on Human Genome Editing in Hong Kong that he had used CRISPR/Cas 9 gene editing on two female embryos that were brought to term through an in vitro fertilization (IVF) pregnancy. The world scientific community was ill-prepared for the announcement since the moral issues surrounding the editing of human embryos were under discussion but hardly resolved. The recommendation of the 12-member organizing committee of the 2015 International Summit on Human Gene Editing in Washington, DC, stated that it would be irresponsible to undertake any clinical use of germline editing unless and until the safety and efficacy issues were resolved and there was a broad consensus on the specific application, and that such use could proceed only under appropriate regulatory oversight (International Summit on Human Genome Editing 2015). Similar recommendations were made by the National Academies of Sciences, Engineering, and Medicine. This editorial gives two reasons for genetically modifying embryos and three reasons against it.

The summary of arguments for and against genetically modifying embryos is here.

Tuesday, October 22, 2019

Is Editing the Genome for Climate Change Adaptation Ethically Justifiable?

Lisa Soleymani Lehmann
AMA J Ethics. 2017;19(12):1186-1192.

Abstract

As climate change progresses, we humans might have to inhabit a world for which we are increasingly maladapted. If we were able to identify genes that directly influence our ability to thrive in a changing climate, would it be ethically justifiable to edit the human genome to enhance our ability to adapt to this new environment? Should we use gene editing not only to prevent significant disease but also to enhance our ability to function in the world? Here I suggest a “4-S framework” for analyzing the justifiability of gene editing that includes these considerations: (1) safety, (2) significance of harm to be averted, (3) succeeding generations, and (4) social consequences.

Conclusion

Gene editing has unprecedented potential to improve human health. CRISPR/Cas9 has a specificity and simplicity that opens up wide possibilities. If we are unable to prevent serious negative health consequences of climate change through environmental and public health measures, gene editing could have a role in helping human beings adapt to new environmental conditions. Any decision to proceed should apply the 4-S framework.

The info is here.

Monday, September 9, 2019

China approves ethics advisory group after CRISPR-babies scandal

Hepeng Jia
Nature.com
Originally published August 8, 2019

China will establish a national committee to advise the government on research-ethics regulations. The decision comes less than a year after a Chinese scientist sparked an international outcry over claims that he had created the world’s first genome-edited babies.

The country's most powerful policymaking body, the Central Comprehensively Deepening Reforms Commission of the ruling Chinese Communist Party, headed by President Xi Jinping, approved at the end of last month a plan to form the committee. According to Chinese media, it will strengthen the coordination and implementation of a comprehensive and consistent system of ethics governance for science and technology.

The government has released few details on how the committee will work. But Qiu Renzong, a bioethicist at the Chinese Academy of Social Science in Beijing, says it could help to reduce the fragmentation in biomedical ethics regulations across ministries, identifying loopholes in the enforcement of regulations and advise the government on appropriate punishments for those who violate the rules.

The info is here.

Wednesday, July 31, 2019

US Senators Call for International Guidelines for Germline Editing

Jef Akst
www.the-scientist.com
Originally published July 16, 2019

Here is an excerpt:

“Gene editing is a powerful technology that has the potential to lead to new therapies for devastating and previously untreatable diseases,” Feinstein says in a statement. “However, like any new technology, there is potential for misuse. The international community must establish standards for gene-editing research to develop global ethical principles and prevent unethical researchers from moving to whichever country has the loosest regulations.” (Editing embryos for reproductive purposes is already illegal in the US.)

In addition, the resolution makes clear that the trio of senators “opposes the experiments that resulted in pregnancies using genome-edited human embryos”—referring to the revelation last fall that researcher He Jiankui had CRISPRed the genomes of two babies born in China.

The info is here.

Saturday, July 6, 2019

Congress weighs dropping ban on altering the DNA of human embryos used for pregnancies

Embryonic cell divisionSharon Begley and Andrew Joseph
www.statnews.xom
Originally posted June 4, 2019

A congressional committee is expected to vote on Tuesday to drop a ban on altering the genomes of human embryos intended for pregnancies, which could open the door to creating babies with genetic material from three people or with genomes that have been modified in a way that would be inherited by their descendants, as China’s “CRISPR babies” were.

The prohibition on modifying the DNA of embryos for reproduction (as opposed to doing so in basic research that stops short of pregnancies) has been attached to bills that fund the Food and Drug Administration since December 2015. But last month, a House appropriations subcommittee approved a version of an FDA spending bill without the amendment, or rider — amid worldwide condemnation of the CRISPR babies experiment last year and calls by leading scientists for a global moratorium on creating gene-edited babies.

“People don’t appreciate that this is the only piece of legislation in the United States that stands between us and genetically engineered children,” said science historian J. Benjamin Hurlbut of Arizona State University, who supports a “global observatory” to track uses of CRISPR, the powerful genome-editing technology.

The info is here.

Friday, June 28, 2019

‘We as a species need to come to terms’ with CRISPR technology

Ashley Turner
www.CNBC.com
Originally posted May 21, 2019

Here is an excerpt:

Former FDA Commissioner Scott Gottlieb said Tuesday that He’s research was a “horrible experiment and it established a horrible precedent.” Gottlieb said He’s experiment risked causing people to “rightfully” turn away from the science.

Gottlieb said he has yet to see any compelling arguments in favor of human germline editing.

Paul Dabrowski, CEO of Synthego, a genome engineering company, agreed the scientific community is not yet ready for germline editing. He wondered whether allowing parents to choose to genetically alter their future children can be ethical if they’re not the one who is having their DNA changed.

“How do you make sure you can align the person who is consenting and the person who is taking the risk?” Dabrowski asked.

Stanford’s Hurlbut said there are risks to editing DNA, as those traits can then be passed down to future generations. Editing certain genes can also cause changes in other genes, according to Hurlbut.

“We want to be very careful, nature is a profound balance and if we intervene in a way that is not profound we can upset things,” Hurlbut said.

The info is here.

Thursday, March 21, 2019

China’s CRISPR twins might have had their brains inadvertently enhanced

Antonio Regalado 
MIT Technology Review
Originally posted February 21, 2019

The brains of two genetically edited girls born in China last year may have been changed in ways that enhance cognition and memory, scientists say.

The twins, called Lulu and Nana, reportedly had their genes modified before birth by a Chinese scientific team using the new editing tool CRISPR. The goal was to make the girls immune to infection by HIV, the virus that causes AIDS.

Now, new research shows that the same alteration introduced into the girls’ DNA, deletion of a gene called CCR5, not only makes mice smarter but also improves human brain recovery after stroke, and could be linked to greater success in school.

“The answer is likely yes, it did affect their brains,” says Alcino J. Silva, a neurobiologist at the University of California, Los Angeles, whose lab uncovered a major new role for the CCR5 gene in memory and the brain’s ability to form new connections.

“The simplest interpretation is that those mutations will probably have an impact on cognitive function in the twins,” says Silva. He says the exact effect on the girls’ cognition is impossible to predict, and “that is why it should not be done.”

The info is here.

Wednesday, March 6, 2019

Stanford investigates links to scientist in baby gene-editing scandal

Guardian staff and agencies
The Guardian
Originally posted February 7, 2019

Stanford University has begun an investigation following claims some of its staff knew long ago of Chinese scientist He Jiankui’s plans to create the world’s first gene-edited babies.

A university official said a review was under way of interactions some faculty members had with He, who was educated at Stanford. Several professors including He’s former research adviser have said they knew or strongly suspected He wanted to try gene editing on embryos intended for pregnancy.

The genetic scientist sparked global outcry after he claimed in a video posted on YouTube in November 2018 that he had used the gene-editing tool Crispr-Cas9 to modify a particular gene in two embryos before they were placed in their mother’s womb. He – who works from a lab in the southern Chinese city of Shenzhen – said the twin girls, known as Lulu and Nana, were born through regular IVF but using an egg that was modified before being inserted into the womb. He focused on HIV infection prevention because the girls’ father is HIV positive.

The info is here.

Wednesday, February 6, 2019

Are scientists’ reactions to ‘CRISPR babies’ about ethics or self-governance?

Nina Frahm and Tess Doezema
STAT News
Originally published January 28, 2019

Here is an excerpt:

The research community widely agreed that He and his colleagues crossed an ethical line with the first inheritable genetic modification of human beings. Gene-editing experts as well as bioethicists described the transgression as being conducted by a “rogue” individual. But when leading voices such as NIH Director Francis Collins assert that He’s work “represents a deeply disturbing willingness by Dr. He and his team to flout international ethical norms,” what are they actually expressing concern about? Who determines what are the ethics of altering human life?

We believe that the alarm being sounded by the scientific community isn’t really about ethics. It’s about protecting a particular form of scientific self-governance, which the “ethics” discourse supports. What are currently treated as matters of research ethics are in fact political and social questions of fundamental human importance.

Key decisions about when and how it will be appropriate to make inheritable changes to human beings currently lie in the hands of scientists. Although ethics are repeatedly invoked, the most prominent condemnations of He’s actions don’t actually address whether it’s ethical to tinker with human life through gene editing. A largely ignored part of the story are the five “draft ethical principles” of He’s lab at the Southern University of Science and Technology of China. If the outcry from scientists was truly about ethics, we would be seeing a discussion of the relative merits of He’s ethical principles, engagement with their content, and perhaps an exploration of how to jointly achieve a better set of operating principles. Instead, the ethics of using CRISPR for germline gene editing have apparently been determined and settled among scientists, closing down a meaningful debate about the limits and opportunities of genetic engineering.

The info is here.

Tuesday, February 5, 2019

China's Latest Cloned-Monkey Experiment Is an Ethical Mess

Ryan F. Mandelbaum
www.gizmodo.com
Originally published January 19, 2019

Chinese researchers have cloned five gene-edited monkeys with a host of genetic disease symptoms, according to two scientific papers published today.

The researchers say they want to use the gene-edited macaques for biomedical research; basically, they hope that engineering sick primates will reduce the total number of macaques used in research around the world. But their experiment is a minefield of ethical quandaries—and makes you wonder whether the potential benefits to science are enough to warrant all of the harm to these monkeys.

The researchers began by using CRISPR/Cas9 to alter the DNA of a donor macaque. CRISPR/Cas9 is the often-discussed gene editing tool derived from bacteria that combines repeating sequences of DNA and a DNA-cutting enzyme in order to customize DNA sequences. Experts and the press have heralded it as an important advance due to how quickly and cheaply it can alter DNA, but recent research has demonstrated it may cause more unintended effects than previously thought.

(cut)

This research combines a ton of ethical issues into one package, from those surrounding animal rights to cloning to gene editing. As bioethicist Carolyn Neuhaus from The Hastings Center summarized her reaction to the announcement: “Whoa, this is a doozy.”

The info is here.

Friday, January 18, 2019

CRISPR in China: Why Did the Parents Give Consent?

Dena Davis
The Hastings Center
Originally posted December 7, 2018

The global scientific community has been unanimous in condemning Chinese scientist He Jiankui, who announced last week that he used the gene-editing technology called CRISPR to make permanent, heritable changes to the genes of two baby girls who were born this month in China. Criticism has focused on Dr. He’s violation of worldwide acknowledgement that CRISPR has not been proven to be safe and ready to use in humans. Because CRISPR edits the actual germline, there are safety implications not only for these two girls, but for their progeny. There is also fear, expressed by the American Society for Reproductive Medicine, that this one renegade scientist could spark a backlash that would result in overly restrictive regulation.

Largely missing from the discussion is whether the twins’ parents understood what was happening and the unproven nature of the technology.  Was the informed consent process adequate, and if so, why on earth would they have given their consent?

The info is here.

Monday, January 14, 2019

The Amazing Ways Artificial Intelligence Is Transforming Genomics and Gene Editing

Bernard Marr
Forbes.com
Originally posted November 16, 2018

Here is an excerpt:

Another thing experts are working to resolve in the process of gene editing is how to prevent off-target effects—when the tools mistakenly work on the wrong gene because it looks similar to the target gene.

Artificial intelligence and machine learning help make gene editing initiatives more accurate, cheaper and easier.

The future for AI and gene technology is expected to include pharmacogenomics, genetic screening tools for newborns, enhancements to agriculture and more. While we can't predict the future, one thing is for sure: AI and machine learning will accelerate our understanding of our own genetic makeup and those of other living organisms.

The info is here.

Friday, January 4, 2019

Beyond safety questions, gene editing will force us to deal with a moral quandary

Josephine Johnston
STAT News
Originally published November 29, 2018

Here is an excerpt:

The majority of this criticism is motivated by major concerns about safety — we simply do not yet know enough about the impact of CRISPR-Cas9, the powerful new gene-editing tool, to use it create children. But there’s a second, equally pressing concern mixed into many of these condemnations: that gene-editing human eggs, sperm, or embryos is morally wrong.

That moral claim may prove more difficult to resolve than the safety questions, because altering the genomes of future persons — especially in ways that can be passed on generation after generation — goes against international declarations and conventions, national laws, and the ethics codes of many scientific organizations. It also just feels wrong to many people, akin to playing God.

As a bioethicist and a lawyer, I am in no position to say whether CRISPR will at some point prove safe and effective enough to justify its use in human reproductive cells or embryos. But I am willing to predict that blanket prohibitions on permanent changes to the human genome will not stand. When those prohibitions fall — as today’s announcement from the Second International Summit on Human Genome Editing suggests they will — what ethical guideposts or moral norms should replace them?

The info is here.

Wednesday, November 7, 2018

Japan Set to Allow Gene Editing in Human Embryos

David Cyranoski
Scientific American
Originally posted on October 3, 2018

Japan has issued draft guidelines that allow the use of gene-editing tools in human embryos. The proposal was released by an expert panel representing the country’s health and science ministries on 28 September.

Although the country regulates the use of human embryos for research, there have been no specific guidelines on using tools such as CRISPR–Cas9 to make precise modifications in their DNA until now.

Tetsuya Ishii, a bioethicist at Hokkaido University in Sapporo, says that before the draft guidelines were issued, Japan’s position on gene editing in human embryos was neutral. The proposal now encourages this kind of research, he says.

But if adopted, the guidelines would restrict the manipulation of human embryos for reproduction, although this would not be legally binding.

Manipulating DNA in embryos could reveal insights into early human development. Researchers also hope that in the long term, these tools could be used to fix genetic mutations that cause diseases, before they are passed on.

The info is here.

Monday, October 22, 2018

Why the Gene Editors of Tomorrow Need to Study Ethics Today

Katie Palmer
www.wired.com
Originally posted September 18, 2018

Two years after biochemist Jennifer Doudna helped introduce the world to the gene-editing tool known as Crispr, a 14-year-old from New Jersey turned it loose on a petri dish full of lung cancer cells, disrupting their ability to multiply. “In high school, I was all on the Crispr bandwagon,” says Jiwoo Lee, who won top awards at the 2016 Intel International Science and Engineering Fair for her work. “I was like, Crisprize everything!” Just pick a snippet of genetic material, add one of a few cut-and-paste proteins, and you’re ready to edit genomes. These days, though, Lee describes her approach as “more conservative.” Now a sophomore at Stanford, she spent part of her first year studying not just the science of Crispr but also the societal discussion around it. “Maybe I matured a little bit,” she says.

Doudna and Lee recently met at the Innovative Genomics Institute in Berkeley to discuss Crispr’s ethical implications. “She’s so different than I was at that age,” Doudna says. “I feel like I was completely clueless.” For Lee’s generation, it is critically important to start these conversations “at as early a stage as possible,” Doudna adds. She warns of a future in which humans take charge of evolution—both their own and that of other species. “The potential to use gene editing in germ cells or embryos is very real,” she says. Both women believe Crispr may eventually transform clinical medicine; Lee even hopes to build her career in that area—but she’s cautious. “I think there’s a really slippery slope between therapy and enhancement,” Lee says. “Every culture defines disease differently.” One country’s public health campaign could be another’s eugenics.

The info is here.