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Limits of gene editing

Limits of gene editing


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I was reading some articles about CRISPR and the world of gene editing, but then a lot of questions for which I couldn't find any answer online came into my mind. Those are all about how far can we edit an organism. So here is the general question, followed by some other to narrow down a little bit this broad subject:

What are the limits of gene edition?

  1. Can one edit the genes in its entire body? (as a human, or a multicellular organism)
  2. What are the risks? I heard that some people who did try gene therapy ended up having some of their modified cells turned into cancer. Was is because of gene incompatibility or because of error during the gene editing process?
  3. Can we go as far as adding some chromosomes or changing an entire chromosome? For example, if a male human would like to change their sex, could they switch all their Y to an X?

EDIT: I decided to accept the answer from @MattDMo. However, I'm still interested in some development (clues with other technologies… )


Your question is very broad, but I'll try to address each of your points briefly.

  1. It would be nearly impossible to edit the genes in every cell of a human being or other complex organism simply due to the number (and accessibility) of cells. A full-grown human has in the neighborhood of 30 trillion cells - 30,000,000,000,000. Cells in locations such as the brain and central nervous system are protected by the blood-brain barrier, which would keep most gene therapy vectors from accessing those cells. There are other reasons why editing each cell in the body is virtually impossible, such as vectors accumulating in the liver, but this is one of the main ones.

  2. Cancer is indeed a risk from gene therapy in general, although DNA editing technologies like CRISPR in particular have a lower risk due to thTe circumstances surround exactly how the therapy is delivered to the nucleus of the cell where DNA resides. Other risks include potentially serious or fatal systemic inflammation due to an immune reaction to the viral vector which carries the CRISPR "machinery". Off-target effects can occur due to the wrong cells being targeted (although this risk is generally lower with CRISPR). Additionally, there is the very small but non-zero chance that the genetically-engineered vector could somehow regain its native infectious capability. Newer generations of gene therapy have significantly reduced this chance, however.

  3. Very briefly, no. DNA is made up of "letters" (A, T, C, and G) called bases or base pairs, and typical CRISPR constructs only operate on 10-20 bases at the most - usually it's just one or a couple that are changed. A typical human chromosome has millions of base pairs encompassing hundreds to thousands of genes, so editing, adding, or removing an entire chromosome is simply out of the realm of possibility with this technology.


Scientists Debate How Far To Go In Editing Human Genes

Nobel laureate David Baltimore of Caltech speaks to reporters at the National Academy of Sciences international summit on human gene editing, on Tuesday in Washington, D.C. Hundreds of scientists and ethicists from around the world debating how to deal with technology that makes it easy to edit the human genetic code. Susan Walsh/AP hide caption

Nobel laureate David Baltimore of Caltech speaks to reporters at the National Academy of Sciences international summit on human gene editing, on Tuesday in Washington, D.C. Hundreds of scientists and ethicists from around the world debating how to deal with technology that makes it easy to edit the human genetic code.

Global warming isn't the only vexing issue the world wrestled with this week.

While delegates gathered in Paris to discuss climate change, the International Summit on Human Gene Editing convened in Washington, D.C., to debate another conundrum: How far should scientists go when editing human DNA?

The main focus was whether scientists should be allowed to use powerful new genetic engineering techniques to edit genes in human eggs, sperm or embryos — an extremely controversial step that raises a host of thorny safety and ethical issues.

At the end of the meeting Thursday, conference organizers concluded it would be "irresponsible to proceed" with any attempt to create a pregnancy or a baby from human eggs, sperm or embryos that have been altered, because of safety and ethical concerns.

But "intensive basic" research is "clearly needed and should proceed" to explore the safety and potential benefits of editing that kind of DNA, the committee said in a statement.

"That statement is our answer to the question of whether there should be a ban" on any further research, said David Baltimore, a Nobel Prize-winning biologist who chaired the committee.

Notably, the organizers didn't rule out the possibility that gene editing someday could be used to create humans, as "scientific knowledge advances and societal views evolve."

The organizers called for the creation of a ongoing forum to continue to assess the state of the research and society's readiness.

Nearly 500 scientists, doctors, bioethicists, legal experts, historians, patient advocates and others convened for the summit, which was sponsored by the U.S. National Academy of Sciences, U.S. National Academy of Medicine, Chinese Academy of Sciences and the U.K.'s Royal Society.

An international committee organized by the U.S. academies attended the summit as part of its fact-finding process for issuing recommendations for possible guidelines for gene editing. Those are expected next year.

The meeting was convened because of rising concerns sparked by the development of gene-editing techniques such as CRISPR-Cas9. These techniques allow scientists to make very precise changes in DNA much more easily than ever before.

Scientists believe the new techniques will produce many benefits, such as finding new ways to prevent and treat diseases, including AIDS, cancer and Alzheimer's.

But the ability to edit DNA so easily is also raising many fears, especially about the prospect of changing human DNA from the the very start. Scientists explored how altering sperm, eggs and embryos could yield important new insights into basic human biology and development, and help prevent and treat many inherited diseases, including Huntington's disease, cystic fibrosis and Tay-Sachs disease.

But altering the so-called germline in this manner has long been considered off-limits. That's because such changes can be passed down to future generations. Mistakes could inadvertently introduce new diseases into the human gene pool.

Another fear is that taking this step would open the door to designer babies — creating children who are smarter, taller, smarter or have other supposedly desirable traits.

During his opening remarks, Baltimore referred to Aldous Huxley's 1932 book Brave New World. "The warning implicit in his book is one that we should take to heart today as we face the prospect of new and powerful means to control the nature of the human population," Baltimore said.

Another speaker, Daniel Kevles, a Yale University medical historian, reminded the audience that eugenics was once widely accepted in the United States. "Eugenics was not unique to the Nazis it happened everywhere," Kevles said.

Many scientists stressed that they are nowhere near having the ability to genetically engineer complex traits. But one prominent geneticist speculated that attempts to enhance the human race could start with medical research.

Harvard Medical School's George Church listens to a discussion about the safety and ethics of human gene editing at a summit meeting Tuesday. Susan Walsh/AP hide caption

Harvard Medical School's George Church listens to a discussion about the safety and ethics of human gene editing at a summit meeting Tuesday.

"I think enhancement will creep in the door in terms of treating serious diseases," said George Church of Harvard University. The ability to improve memory might start with research aimed at treating Alzheimer's disease, for example, Church said.

There seemed to be general agreement that the safety concerns make it far too early to try to make a baby using eggs, embryos or sperm with edited DNA. But there is a split about what should be allowed short of that.

Some, such as Catholic bioethicist Hille Haker of Loyola University in Chicago, called for a moratorium on any experiments, at least until scientists have more time to understand how to use the new gene-editing techniques and society has more time to debate the complex issues they raise.

Others feared a moratorium would stymie a promising field at an important moment. They argued that basic studies in the lab should proceed.

"We all have an inescapable moral duty: to continue with scientific investigation to the point at which we can make a rational choice," said John Harris, a professor of bioethics at the University of Manchester in England. "It seems to me, consideration of a moratorium is the wrong course. Research is necessary."

But Jennifer Doudna of the University of California, Berkeley, a pioneer in the development of CRISPR-Cas9, repeated her position that research involving the technique should proceed cautiously.

One of the most emotional moments occurred when Sarah Gray of the American Association of Tissue Banks addressed a panel of scientists from the audience. Choking back tears, Gray described how her son suffered before dying of a genetic disorder six days after he was born. "If you have the skills and the knowledge to fix these diseases," Gray said, "then freaking do it."


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USDA revised regulations of GMO and gene edited plants. Here’s what it means.

Credit: University of Pennsylvania

USDA oversight from 1987 to the present

To understand the USDA’s new regulation of GE plants, it is important to know how the agency has regulated GE plants since 1987. USDA regulates the import, interstate movement, and environmental release of GE plants under its legal authority to manage “plant pests” under the Plant Protection Act. A “plant pest” is any organism “that can directly or indirectly injure, cause damage to, or cause disease in any plants or plant product.” Under USDA regulations, a GE plant has been considered a “potential” plant pest if any of its newly introduced DNA came from an organism on USDA’s list of plant pests, or if the method of introducing DNA into the plant’s genome involved an organism on USDA’s list of plant pests. For example, if a GE plant was developed using the plant pest Agrobacterium to introduce new DNA, as many are, it was regulated. However, if the same DNA were introduced using the gene-gun method of transformation, USDA would not regulate the GE plant.

Under those regulations (found at 7 CFR part 340), developers were required to submit their GE plant products to one of three oversight processes before environmental release.

The first process, known as “notification,” is used to regulate field trials of low-risk GE plants. The applicant provides the USDA with information detailing its trial and the agency has 30 days to decide whether to permit the trial to proceed. As many as 1,000 field trials are authorized yearly using this procedure.

The second process is “permitting,” which requires a more detailed application for any outdoor planting (e.g., field trial) of higher-risk GE plants. After reviewing the application, USDA may issue a permit authorizing the release. The USDA has issued hundreds of permits since 1987.

The third process involves a “petition for non-regulated status,” where a developer requests the USDA to determine—based on evidence from field trials—that the GE plant presents no plant pest risk and no longer requires regulation. The petition process is the primary path to commercialization and more than 140 plants have been deregulated.

For each regulatory process, the USDA is ensuring that the GE plant is not going to become a plant pest and cause harm to agricultural interests.

Up until 2011, every GE plant tested outdoors either submitted a notification or received a permit, and all commercialized plants satisfactorily completed the petition process. Then, in 2011, the USDA established a process whereby GE seed developers could ask the agency whether the GE plants they were developing required regulation, or whether they were exempt because they did not involve any plant pest components. The USDA responded to these “Am I regulated?” inquiries stating whether the GE plant was not regulated and could be planted without oversight. By the end of 2019, USDA determined that more than 85 plants did not fall within its regulatory authority and are exempt from oversight. So, over the last eight years, we have seen a decrease in how many GE plants USDA regulates.[1]

Revised regulations in 2020

The new rule (called the Sustainable, Ecological, Consistent, Uniform, Responsible, Efficient, (SECURE) Rule), which will be implemented over the next 18 months, applies to organisms produced through “genetic engineering,” which is defined to include “techniques that use recombinant, synthesized, or amplified nucleic acids to modify or create a genome.” This broad definition includes classical genetic engineering, which add one or more new genes to organism (transgenics, or what consumers consider GMOs), and newer gene editing techniques such as CRISPR, which can make edits within an organism’s existing genome.

While the definition captures all GE plants, the USDA exempts many of them from any oversight. First, it exempts products with a single sequence deletion, substitution, or addition (if the addition is from the plant’s gene pool). Second, it exempts any GE plant that has the same “plant-trait-mechanism of action” as any GE plant previous regulated by the USDA. This means that if the USDA previously regulated a GE plant, such as an glyphosate-tolerant variety of corn, a new GE glyphosate-tolerant corn is exempt if it employs the same mechanism of action (meaning it biologically operates the same way to provide tolerance). Developers can self-determine whether they qualify for these exemptions confirmation of their self-determination from the USDA is not required and the agency need not be informed.

If a GE plant is not exempt, the developer can either: (1) apply for a permit if the GE plant has potential plant pest risks or (2) seek a Regulatory Status Review (RSR). The RSR starts with an initial 180-day process where the USDA determines if the GE plant has any plausible plant pest risks. That initial RSR step is a closer look at the GE plant than the current “am I regulated?” process, but less detailed than the process used for “petitions for non-regulated status.” The USDA stated that the initial review does not require any plant-specific “laboratory or field-test data.” If the USDA decides there are no plausible risks, it sends a letter to the developer stating the plant is not regulated and publishes the letter on its website. If the USDA cannot conclude that there are no plausible risks, then the developer can either: (1) request that the USDA conduct the second part of the RSR, which is detailed evaluation of potential plant pest risks that can take up to 15 month) or (2) apply for a permit. The more lengthy and detailed RSR evaluation is comparable to the current “petition for non-regulated status” process and ends in the USDA determining either that the GE plant is not regulated or that it needs a permit. If a developer receives a permit from the USDA, any outdoor planting (e.g. a field trial or a commercial planting) is subject to restrictions to prevent inadvertent release into the environment and any adverse plant pest impacts. These are the same restrictions that virtually all GE plants were subject to prior to 2012 under the notification and permitting processes. Only GE plants that receive permits have any continued USDA oversight.

Worrisome aspects of SECURE

The exemptions are one worrisome aspect of the new SECURE rule. First, they are not supported by scientific evidence showing that these categories of GE plants do not pose risks. Instead, the USDA states that since a single deletion, substitution or addition produces a plant that could be achieved by conventional breeding methods, and because conventionally bred plants have not raised plant pest risks, gene-edited plants that are the same as products that could be achieved through conventional breeding will not pose plant pest risks. The problem with this argument is that a science-based regulatory system should base its oversight on whether the plant possesses traits that make it a potential plant risks, not the plant’s method of production. One reason the USDA revised its rules was to focus on the properties of a product, not how it was developed, yet that is the very approach these exemptions enshrine. While many, if not most, plants with a single deletion may not present any plant pest risks, if one does, shouldn’t USDA regulate it?

The second concern is that the developer self-determines if its product qualifies for an exemption. This sets up an inherent conflict of interest because developers have financial incentives to determine themselves exempt. While some developers will diligently determine the regulatory status of a GE plant, others may not. In addition, when a developer self-determines its product is exempt, neither the USDA nor the public know that the GE plant is being released into the environment and entering the food supply because there is no requirement to notify the agency of one’s self-determination. If the USDA does not know which GE plants are self-determined as exempt, how can it confirm that the determination is correct?

Positive aspects of SECURE

One positive of the new rule is the agency’s decision to limit the exemptions to single edits. The USDA reasons that while a single edit mimics a product that can be produced through conventional breeding methods, the same is not true for products with multiple edits. Therefore, if a developer makes two or more edits, the developer must apply for a permit or ask for an RSR. The first gene edited commercial product in the US—Calyxt’s high oleic soybean, which the USDA exempted under the “am I regulated?” process—would not be exempt under the new rules because it has two edited genes. If most gene-edited products end up having two or more edits, the exemptions may have limited applicability.

While multi-edited products are not automatically exempt, the USDA is likely to find in the initial step of the RSR process that many do not pose any plausible plant pest risk. So the result may be the same—these products are not regulated. However, at least the initial RSR determination (instead of a developer self-determination), is made public, so stakeholders will know which multi-edited products are entering the market.

Potential impacts

The USDA states that one goal of its revisions is to provide “regulatory relief,” and the final rule clearly achieves that. Many GE plants that historically required containment for field trials through either the notification or permitting process will no longer be subject to any substantive regulation. They either will be exempt or deemed to have no plausible plant pest risks through the initial step of the RSR process. What this means in practice is that GE plant developers (both private developers and academic scientists) can conduct field trials without any confinement conditions that ensure the GE plants do not persist in the environment after the trial is completed. The USDA stated in its proposed rule that it hopes developers voluntarily continue confinement measures, but that may or may not happen. GE plants have escaped from field trials with USDA oversight in the past and the likelihood of that happening will only increase without USDA oversight. That could mean new proteins inadvertently entering our food supply before they are deemed safe for human consumption. Experimental GE plants persisting in the environment after a field trial is concluded could also harm non-target organisms. Finally, if an unregulated GE plant escapes from a field trial and enters the export market, it could result in rejection of the US commodity because the experimental plant has not been approved in the importing country.

The final rule also fails to provide needed transparency on GE plants that will be commercialized. The USDA, food industry and consumers will be at the mercy of developers to make public information about products that they have deemed exempt. How will the food industry know which foods contain GE plants to ensure they are complying with export market legal requirements? How will food manufacturers and retailers answer questions from consumers asking whether their products contain ingredients from GE or gene-edited plants? If consumers are unable to access information about which GE plants are commercialized, will they become skeptical about those products and their safety? The lack of transparency inherent in the rule could result in international trade problems and misinformed consumers.

GE plants have provided benefits to farmers, the environment and consumers and are likely to continue to do so in the future. However, the USDA rule could impact the food industry’s acceptance of those products and fuel consumer suspicions about biotech crops and foods.

[1] While the USDA is the primary agency regulating GE plants, the FDA and EPA regulate subsets of GE plants. If a GE plant is used for food or feed, the FDA regulates it under a voluntary consultation process set up under the Federal Food, Drug and Cosmetic Act. If a GE plant produces a pesticide, the EPA regulates it as a plant-incorporated protectant under the Federal Insecticide, Fungicide, and Rodenticide Act.

This article ran at Cornell Alliance for Science website and has been republished here with permission. Follow the Alliance for Science on Twitter @ScienceAlly


An on-off switch for gene editing

Now, in a paper published online in Cell on April 9, researchers describe a new gene editing technology called CRISPRoff that allows researchers to control gene expression with high specificity while leaving the sequence of the DNA unchanged. Designed by Whitehead Institute Member Jonathan Weissman, University of California San Francisco assistant professor Luke Gilbert, Weissman lab postdoc James Nuñez and collaborators, the method is stable enough to be inherited through hundreds of cell divisions, and is also fully reversible.

“The big story here is we now have a simple tool that can silence the vast majority of genes,” says Weissman, who is also a professor of biology at MIT and an investigator with the Howard Hughes Medical Institute. “We can do this for multiple genes at the same time without any DNA damage, with great deal of homogeneity, and in a way that can be reversed. It’s a great tool for controlling gene expression.”

The project was partially funded by a 2017 grant from the Defense Advanced Research Projects Agency to create a reversible gene editor. “Fast forward four years [from the initial grant], and CRISPRoff finally works as envisioned in a science fiction way,” says co-senior author Gilbert. “It’s exciting to see it work so well in practice.”

Genetic engineering 2.0

The classic CRISPR-Cas9 system uses a DNA-cutting protein called Cas9 found in bacterial immune systems. The system can be targeted to specific genes in human cells using a single guide RNA, where the Cas9 proteins create tiny breaks in the DNA strand. Then the cell’s existing repair machinery patches up the holes.

Because these methods alter the underlying DNA sequence, they are permanent. Plus, their reliance on “in-house” cellular repair mechanisms means it is hard to limit the outcome to a single desired change. “As beautiful as CRISPR-Cas9 is, it hands off the repair to natural cellular processes, which are complex and multifaceted,” Weissman says. “It’s very hard to control the outcomes.”

That’s where the researchers saw an opportunity for a different kind of gene editor — one that didn’t alter the DNA sequences themselves, but changed the way they were read in the cell.

This sort of modification is what scientists call “epigenetic” — genes may be silenced or activated based on chemical changes to the DNA strand. Problems with a cell’s epigenetics are responsible for many human diseases such as Fragile X syndrome and various cancers, and can be passed down through generations.

Epigenetic gene silencing often works through methylation — the addition of chemical tags to to certain places in the DNA strand — which causes the DNA to become inaccessible to RNA polymerase, the enzyme which reads the genetic information in the DNA sequence into messenger RNA transcripts, which can ultimately be the blueprints for proteins.

Weissman and collaborators had previously created two other epigenetic editors called CRISPRi and CRISPRa — but both of these came with a caveat. In order for them to work in cells, the cells had to be continually expressing artificial proteins to maintain the changes.

“With this new CRISPRoff technology, you can [express a protein briefly] to write a program that’s remembered and carried out indefinitely by the cell,” says Gilbert. “It changes the game so now you’re basically writing a change that is passed down through cell divisions — in some ways we can learn to create a version 2.0 of CRISPR-Cas9 that is safer and just as effective, and can do all these other things as well.”

Building the switch

To build an epigenetic editor that could mimic natural DNA methylation, the researchers created a tiny protein machine that, guided by small RNAs, can tack methyl groups onto specific spots on the strand. These methylated genes are then “silenced,” or turned off, hence the name CRISPRoff.

Because the method does not alter the sequence of the DNA strand, the researchers can reverse the silencing effect using enzymes that remove methyl groups, a method they called CRISPRon.

As they tested CRISPRoff in different conditions, the researchers discovered a few interesting features of the new system. For one thing, they could target the method to the vast majority of genes in the human genome — and it worked not just for the genes themselves, but also for other regions of DNA that control gene expression but do not code for proteins. “That was a huge shock even for us, because we thought it was only going to be applicable for a subset of genes,” says first author Nuñez.

Also, surprisingly to the researchers, CRISPRoff was even able to silence genes that did not have large methylated regions called CpG islands, which had previously been thought necessary to any DNA methylation mechanism.

“What was thought before this work was that the 30 percent of genes that do not have a CpG island were not controlled by DNA methylation,” Gilbert says. “But our work clearly shows that you don’t require a CpG island to turn genes off by methylation. That, to me, was a major surprise.”

CRISPRoff in research and therapy

To investigate the potential of CRISPRoff for practical applications, the scientists tested the method in induced pluripotent stem cells. These are cells that can turn into countless cell types in the body depending on the cocktail of molecules they are exposed to, and thus are powerful models for studying the development and function of particular cell types.

The researchers chose a gene to silence in the stem cells, and then induced them to turn into nerve cells called neurons. When they looked for the same gene in the neurons, they discovered that it had remained silenced in 90 percent of the cells, revealing that cells retain a memory of epigenetic modifications made by the CRISPRoff system even as they change cell type.

They also selected one gene to use as an example of how CRISPRoff might be applied to therapeutics: the gene that codes for Tau protein, which is implicated in Alzheimer’s disease. After testing the method in neurons, they were able to show that using CRISPRoff could be used to turn Tau expression down, although not entirely off. “What we showed is that this is a viable strategy for silencing Tau and preventing that protein from being expressed,” Weissman says. “The question is, then, how do you deliver this to an adult? And would it really be enough to impact Alzheimer’s? Those are big open questions, especially the latter.”

Even if CRISPRoff does not lead to Alzheimer’s therapies, there are many other conditions it could potentially be applied to. And while delivery to specific tissues remains a challenge for gene editing technologies such as CRISPRoff, “we showed that you can deliver it transiently as a DNA or as an RNA, the same technology that’s the basis of the Moderna and BioNTech coronavirus vaccine,” Weissman says.

Weissman, Gilbert, and collaborators are enthusiastic about the potential of CRISPRoff for research as well. “Since we now can sort of silence any part of the genome that we want, it’s a great tool for exploring the function of the genome,” Weissman says.

Plus, having a reliable system to alter a cell’s epigenetics could help researchers learn the mechanisms by which epigenetic modifications are passed down through cell divisions. “I think our tool really allows us to begin to study the mechanism of heritability, especially epigenetic heritability, which is a huge question in the biomedical sciences,” Nuñez says.


Paper: Congress Must Clarify Limits of Gene Editing Technologies

University of Illinois at Urbana-Champaign

CHAMPAIGN, IL &mdash Genome editing of human embryos represents one of the most contentious potential scientific applications today. But what if geneticists could sidestep the controversy by editing sperm and eggs instead?

According to a new paper co-written by a University of Illinois at Urbana-Champaign legal expert who studies the ethical and policy implications of advanced biotechnologies, how the next Congress decides to handle the issue will affect the science, ethics, and financing of genome editing for decades to come.

Although there are a number of statutes and federal appropriation riders that take as their bioethical center the human embryo, none exist that govern the editing of "gametes"&mdashthat is, sperm and eggs, said Jacob S. Sherkow, a professor of law at Illinois.

"The current federal funding ban is predicated on a concept of bioethics that focuses on the embryo, and that's because there's widespread recognition in US society that embryos have a certain moral salience that other biological components don't," he said. "But with advances in biotechnology, you can get around that. You can sidestep editing embryos by editing sperm and eggs, instead.

Regardless of how one thinks about whether embryos should get special bioethical status in this context, you have to understand that the same technology can now be used on sperm and eggs. So federal funding bans on genetically editing embryos with technologies such as CRISPR may not extend to future generations of the technology&mdashand those future generations are coming quickly."

In the paper, Sherkow and co-authors Eli Y. Adashi of Brown University and I. Glenn Cohen of Harvard Law School discuss how the editing of sperm and eggs differs from embryos from a bioethical and U.S. legal perspective.

"This is particularly timely for two reasons," he said. "One, genome-editing technology is getting more effective, cheaper, and safer to use every day and two, this is an election year. We're going to seat a new Congress in January, and whether to continue down this path is something that the new Congress is going to have to decide."

The main statute that prohibits the clinical use of heritable genomic editing is an annually renewed Congressional appropriations rider first put into law in 2015.

Related Article: Trends in Genetics: A Tale of Two Decades

According to Sherkow and his colleagues, the rider was initially dropped into an appropriations bill with little discussion. The language was briefly removed last year, prompting a debate about whether it applied to certain mitochondrial-replacement therapies and ought to be reinserted.

"The debate was firmly centered on the editing of embryos, but no legislator considered whether the language also applied to the editing of sperm and eggs," Sherkow said. "And there are strong arguments to be made that the plain text of the rider does not apply to sperm and eggs."

If the appropriations rider doesn't apply to editing sperm and eggs, then those who believe that such editing is just as problematic as editing embryos "should seek to alter the rider to make it apply to sperm and egg editing, as well," Sherkow said.

"Some of the ethical concerns raised about editing embryos are applicable to editing sperm and eggs while others are not," he said. "Objections to embryonic gene editing due to the need to destroy human embryos in research and clinical applications are quite different for sperm and eggs."

Those who have opposed the destruction of embryos, including members of some religious communities, haven't raised similar objections to sperm and egg editing, Sherkow said.

"Proponents of embryonic personhood claims emphasize that the genetic code of the early embryo is set at the time when sperm and egg form a zygote. But sperm and egg editing occurs before that moment, toppling the claim that editing gametes alters 'a person,' and is really more analogous to selecting a sperm or egg donor."

At the same time, policymakers should be heartened by the notion that "we don't necessarily have to stop research on these technologies because now we have the ability to do it in gametes as opposed to embryos," said Sherkow, who also is an affiliate of the Carl R. Woese Institute for Genomic Biology.

"The new Congress that's seated in January should pay attention to the development of genome editing technologies like these, and should be more attuned to the extent of what limits it wants to put on research, given that such research can proceed without some of the moral trappings that have jammed prior Congresses," he said. "For those who think that there are important differences between embryos and gametes, this may offer an opportunity to develop a different regulated pathway for sperm and egg editing."

- This press release was originally published on the Illinois News Bureau


Pros of Gene Editing

The pros of gene editing simply denote the advantages of genetic modification. Some pros of gene editing in agriculture are increased crop yields, reduced costs for food or drug production, reduced need for pesticides, enhanced nutrient composition and food quality, resistance to pests and disease, greater food security, and medical benefits to the world’s growing population.

In term of biology, it’s useful to cure and prevent genetic diseases using different techniques related to this field.

CRISPR has become one of the most dominant genes editing instruments now which can adjust diseases causing qualities in embryos brought to term-evacuate the defective hereditary code of that individual’s future relatives also.

This is truth be told, the greatest transformation in gene editing till the date. Late advancements found in gene editing have not just presented various energizing potential outcomes for human progression yet brought up troublesome moral issues about building an architect people.

1. Tackling and Defeating Diseases:

Generally, fatal and troublesome illnesses on the earth have opposed decimation. Various gene mutations that people endure will end simply after effectively mediate and hereditarily engineer the people to come.

Cancer therapeutics: New immunotherapy can be created utilizing hereditary altering that can treat disease. Adjustment of T-cells utilizing CRISPR can find and kill cancer cells.

Drug Research: Genetic cosmetics can possibly accelerate the medication disclosure process. A portion of the medication creators are as of now consolidating CRISPR innovation in tranquilize research and revelation stage.

Inherent Diseases: With genetic editing, the researcher can anticipate innate ailment to stream to the posterity. Diabetes and cystic fibrosis can likewise be disposed of.

2. Extend Lifespan

Genome altering could broaden the human life expectancy. People life expectancy has just shot up by various years and researchers are as of now living longer and more. Hereditary engineering could make our time on Earth even long.

There are explicit, basic ailments and ailments that can grab hold further down the road and can wind up murdering us sooner than should be expected. Genetic editing can invert most fundamental purposes behind the body’s common decay on a phone level.

Which means, it can radically improve both the range and the personal satisfaction later on.

3. Growth In Food Production and Its Quality:

Gene editing can design nourishment that can withstand brutal temperatures and that are stuffed loaded with quite a few supplements.

Furthermore, it could likewise be the response to satisfy the substantial nourishment needs that are still not met in numerous nations. Genetically modified crops have the quality of high yield and more nutrients.

4. Pest Resilient Crops

Genome editing can address pest and nutrition challenges facing agriculture. Instead of using tons of insecticides and pesticides, the plan can be protected in a healthier way. The use of pesticides after harvesting or while cultivating may ultimately harmful but the genome editing method reduces the risk of its potentiality.

5. Positive Medicine Outcome

One of the best pros in gene editing is positive medicine outcome. As a builder knows the strength as well as weak points of buildings constructed under his supervision, scientists are already known about modified genes. It means they can easily discover appropriate medicine and technique.

6. Gene therapy creates permanent results

Gene therapy creates permanent results. Gene therapy offers the plausibility of a lasting solution for any of the more than 10,000 human diseases brought about by a deformity in a single gene.

Among these maladies, the hemophilias speak to a perfect objective and concentrates in the two creatures and people have given proof that a changeless remedy for hemophilia is inside reach.


Individuals below the Barrier

The greatest damage to the barrier came when new technologies defined some of the acts below the germline barrier as actually impacting individuals, not the species. Recall that this barrier was built to draw a boundary with the eugenists, who were primarily interested in improving the human species, so below the barrier was the species. As technology improved, what is now obvious came into view, which is that to change a species, you must first change individuals. The moral view of the acts below the barrier began to focus on the changed individual who would be produced and largely ignored any influence that the individual would subsequently produce on the species. If there are individuals on both sides, this is a similarity, which will further weaken the barrier.

The first act below the barrier impacting an individual was the hypothetical future patient. For example, LeRoy Walters was the bioethicist who was the chair of the committee at the NIH that regulated trials of HGE. He extrapolated from the beneficent relief of suffering from disease for an existing individual on the somatic side of the barrier to a future individual on the germline side, arguing that “Affected offspring could presumably be treated by means of somatic-cell gene therapy in each succeeding generation, but some phenotypically cured patients would probably consider it more efficient to prevent the transmission of specific malfunctioning genes to their offspring, if the option were available” (26).

Similarly, somatic gene therapy pioneer Theodore Friedmann wrote that “it has been suggested that the need for efficient disease control or the need to prevent damage early in development or in inaccessible cells may eventually justify germ line therapy” (17). For example, somatic modification of the cells in an existing person’s brain is not easy, because the cells are inaccessible. However, a modified embryo would develop the genetically modified brain. There was now a person with a genetic disease upslope requiring somatic modification, and one downslope who requires germline invention to prevent the disease in the first place. If the only values are beneficence and nonmaleficence, these acts on individuals are the same, so Walters and Friedmann argue for taking down the barrier.

Far more consequential for future debate was that a different technology was now placing actual babies below the barrier. It is testimony to the incredible strength of the barrier that, at first, few saw the implications. In 1978, in vitro fertilization was invented, which did not influence the genetic qualities of the offspring. However, it was discovered in 1989 that the genetic qualities of those embryos could be evaluated using what is now called preimplantation genetic diagnosis (PGD). With PGD, a number of embryos are created and all are tested, and those with desirable genetic qualities are gestated and the undesirable discarded. This was, in effect, germline selection (not modification) of the traits of a baby and ultimately a (very small) influence on the species as the eugenicists would have desired. It changed the germline of the baby compared to what it otherwise would have been.

A few participants in the debate realized that PGD produced a baby on the slope below the germline barrier, and we again had the similar individual with a potential disease both upslope and downslope. Bioethicist LeRoy Walters predicted a scenario that would, in my terms, produce almost perfect similarity of acts on both sides of the germline barrier. A couple would like to use PGD but could not because they are opposed to destroying embryos, or are not capable of producing embryos that do not have disease. If germline modification of their embryos was performed for this couple, the goal would be to produce an individual—a healthy baby—not influence the species: “in both of these scenarios, germ-line transmission would be a foreseeable but unintended side effect of a therapeutic procedure intended primarily to cure disease in an (embryonic) individual” (27). These insights had little impact on the HGE debate because PGD was perceived to be a part of the abortion debate. As PGD became more commonplace, and could identify more traits, the stage was set for later weakening the barrier.


Ethical and regulatory reflections on CRISPR gene editing revolution

Only three years ago, scientists from the United States and Sweden invented a technology that is literally upending our view of the limits of biotechnology. It’s called CRISPR-Cas9. It’s akin to a biological word processing system that allows scientists to cut and paste DNA almost as easily as if they were editing a journal article.

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, which describes a process in nature that scientists have harnessed to snip and splice sections of DNA. To do this, they use what’s known as a slicer enzyme called Cas9.

The technology, a key part of a revolution in what is known as synthetic biology and gene editing, is a huge improvement over existing techniques. It’s much more precise, targeted and far quicker than transgenics—the classic process of moving so-called “foreign” genes from one organism into another. The public, egged on by activist NGOs, have created the erroneous perception that transgenics involves crossing a “species barrier” that in fact does not really exist in nature, and therefore poses unique ecological and ethical risks. Those fears are now embodied in restrictive legislation around genetic engineering in food—GMOs.

Transgenesis has other limitations. It is fundamentally a process of gene addition that does not harness a plant’s native genetic repertoire to create whole suites of valuable traits. These concerns have conspired to limit the use of transgenesis for creating crops with agriculturally valuable traits to a few high-profit ones, such as cotton, soybean and corn.

Genome editing sidesteps many of these concerns and has emerged as an important means through which crop improvements that increase the food supply, improve health and are good for the environment can be made. The potential for creating genes that could produce metabolites, provide resistance to stresses, increase photosynthetic efficiency to attain higher yields and other beneficial improvements are almost endless.

However, it’s not clear how new crops varieties with precisely modified genomes will be regulated, as regulatory regimes did not anticipate this kind of simple precision. The US Department of Agriculture has said it is studying CRISPR/Cas9 and will make recommendations in the near future. But recent developments suggest that plants that lack a transgene may not fall under the USDA’s regulatory authority.

CRISPR technology presents more immediate challenges in other areas of genetics. “This discovery has triggered a veritable revolution as laboratories worldwide have begun to introduce or correct mutations in cells and organisms with a level of ease and efficiency not previously possible,” Jennifer Doudna, one of the scientists credited with harnessing the technology, wrote in an editorial published in JAMA in February.

CRISPR will certainly lead to the development of new drugs and open the door to genetic cures once seen as out of the reach of human intervention. Start-ups designed to exploit the technology are abounding. Douda herself has founded a company that recently struck a lucrative licensing deal with Novartis in a search for new drugs. But the technology has also opened the door for mischief.

In April, scientists in China reported carrying out the first experiment using CRISPR gene editing to alter the DNA of human embryos, potentially impacting the germline. Although the embryos were not viable and could not have developed into babies, the announcement ignited an outcry from scientists warning that such a step, crossed an ethical redline.

That announcement rang ethical alarm bells, and not just from precautionary-obsessed NGOs. A group of 18 prominent scientists and experts in law and ethics published a letter in Science calling for a moratorium on some uses of this technology.

“My colleagues and I felt that it was critical to initiate a public discussion of the appropriate use of this technology, and to call for a voluntary ban on human germline editing for clinical applications at the present time,” Douda wrote in an email to The Daily Beast.

“The paper was published in the center of a perfect storm,” Linzhao Cheng, a professor at Johns Hopkins University, told GENeS—the Genetic Expert News Service, an outreach project given seed funding by the Genetic Literacy Project. Cheng believes the outcry could lead to unnecessary restrictions on the CRISPR technology. “Many people are concerned that we shouldn’t be doing this, even in abnormal embryos that would arrested at the blastocyst stage [as was the case here] and otherwise would be discarded. If many people have deep concerns about doing it even in non-viable embryos then how will we ever find out whether using a normal embryo would be better or worse?”

Caution flags have also been raised about the use of CRISPR to modify wild insect and animal populations. Scientists have already used CRISPR to modify mosquitoes and the fruit fly Drosophila melanogaster in the laboratory, and have shown these changes could be spread to future generations. Unintended consequences could lead to ecosystem disruption, some scientists warn.

There are yellow warning lights ahead. The biggest one is that CRISPR could make off-target modifications in embryonic DNA and hence cause widespread damage to the genome, which could cause defects. CRISPR is so relatively simple to perform. But that does not make it foolproof. There is significant potential for these “off-target effects,” or mutations that may occur in other parts of the genome if the editing is not incredibly precise. That’s one reason why the ‘baby experiment’ was received so poorly.

“You would be insane and criminally reckless to make a baby this way without 15 to 20 years of testing and proof it was safe,” said Stanford law professor and ethics expert Henry Greely, one of the signees of the Science letter.

More controversial is the use of CRISPR in research in the human germline that does not “make babies”. Some, such as the authors of the Nature commentary on CRISPR technology, condemn even such in vitro research. Other scientists and bioethicists disagree, some vehemently. “[T]his study by Huang and co-authors was not conducted in any embryos that were ever going to be born, or indeed even had the potential to be born. While the study itself marks an important milestone, the reason it is truly extraordinary is the scientific community’s reaction to it,” wrote British biotethicists Chris Gyngell and Julian Savulescu in response to the criticism.

Far from being wrong, the research by Huang and colleagues is ethically imperative. Such research not only has the potential to provide permanent cures for genetic diseases, it also holds the potential to correct the genetic contribution to common diseases like diabetes. It even has the potential to give people the capacity to age better – some extremely people age well into 90s and 100s. Age-related disease alone kills around 30 million people per year.

The National Academy of Sciences (NAS) and its Institute of Medicine announced it will convene an international summit this fall to “explore the scientific, ethical, and policy issues associated with human gene-editing research.” In addition, NAS will appoint a multidisciplinary, international committee to study the scientific basis and the ethical, legal, and social implications of human gene editing.

Jon Entine is a Senior Fellow at the World Food Center Institute for Food and Agricultural Literacy, University of California-Davis. Follow @JonEntine on Twitter


De-extinction

Although the term sounds like it comes from a science fiction novel, it is not. Scientists are already working on bringing back animals that are extinct. The first candidate is the passenger pigeon, once a dweller of North American forests.

Using CRISPR technology, researchers plan to introduce genes from the passenger pigeons into its modern-day relative — the band tail pigeon. The hybrids will be bred for several generations until the offspring DNA matches that of the extinct species. The first generation of ‘revived’ pigeons is expected to hatch in 2022 .

Not long after, mammoths could follow . A group at Harvard is now working on bringing back the woolly mammoth that went extinct thousands of years ago.

Cover illustration by Elena Resko. Images via Shutterstock. This article was originally published in March 2019 and has since been updated to reflect changes in the field.


Watch the video: The Lieutenant Man With an Edge Gene Roddenberrys masterpiece. Starring Gary Lockwood. (September 2022).


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