Category Archives: Human Genetic Engineering

Each year, fungal infections destroy at least 125 million tons of the world's five most important crops -rice, wheat, maize, soybeans and potatoes- a quantity that could feed 600 million people. Fungi are not only a problem in the field, but also produce large losses in the post-harvest stage: during product storage, transport or in the consumer hands. Also, it should be noted that some fungi produce mycotoxins, substances capable of causing disease and death in both humans and animals. Farmers use fungicides to treat fungal infections, but these are not always 100% effective and, moreover, consumer demands pesticide-free products.

Like humans, plants have developed defense strategies to protect themselves against pathogen attacks. Now a team from the Centre for Research in Agricultural Genomics (CRAG), in Spain, has found that the regulation of the protein activity in the plant by the mechanism known as SUMOylation is crucial for the plant protection against fungal infections.

The study, which has just been published in the specialized journal Molecular Plant, is the result of a collaboration between two CSIC researchers at CRAG: Maria Lois, expert in protein regulation, and Mara Coca, expert in plant immune responses to pathogen infection. As Maria Lois explains, "the results of this research will be used to develop new strategies for crop protection against fungal infection."

SUMOylation: difficult to study but essential for living organisms

SUMO protein binding to other cellular proteins (SUMOylation) is a key process for many cellular functions. For example, in animals, some cancers and neurodegenerative diseases are associated to a defective SUMOylation. In plants, it is known that SUMO conjugation regulates plant development and their responses to environmental stresses.

However, until now SUMOylation roles have been difficult to study because, its complete inhibition causes plant death at the seed stage. To overcome these limitations, Maria Lois' research group has developed a new tool to inhibit the SUMOylation only partially, so the plant can develop normally. Using genetic engineering techniques, the CRAG researchers introduced in the plant a small protein fragment that partially inhibits the SUMOylation.

Plants more susceptible to fungal infections

Using this new approach, CRAG's team found that plants with compromised SUMOylation showed an increased susceptibility to necrotrophic fungal infections by Botrytis cinerea and Plectosphaerella cucumerina. "These two fungi cause plant death and feed on dead tissues. Botrytis cinerea is a geographically widespread fungus which infects many species of plants. It is well known for viticulturists because it produces both the noble rot and the grey rot in wine grapes, affecting the wine quality. Plectosphaerella cucumerina is a model of study, but is also an important pathogen of vegetable crops such as melon" explains the CSIC researcher at CRAG, Maria Coca.

In addition, the researchers observed that shortly after the fungal infection, protein SUMOylation was decreased in the infected plants. This observation suggested that the necrotrophic fungi reduce protein SUMOylation as a mechanism of pathogenicity. Thus, this study opens new opportunities for developing novel strategies for crop protection against pathogenic fungi, as well as for the development of more specific fungicides

A new strategy useful for plants and animals

The strategy designed by Maria Lois' team to partially inhibit the SUMOylation has been key in this study, but it is expected that its applications will go much further. "This new approach will allow us to better understand SUMOylation-regulated processes and, most importantly, it is a tool that can be easily implemented in agronomically important plants, even in those with high genetic complexity, such as wheat," explains Lois. "We believe that there are still many important SUMOylation functions to discover, and we have designed a molecular tool that will be helpful in this regard," the researcher adds.

Indeed, Maria Lois has already taken steps for transferring the knowledge gained from her plant SUMOylation studies to the field of human health. These activities have been supported by the European Research Council (ERC) and by the Government of Catalonia through the respective programs and Proof-of-Concept and Llavor.

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Key mechanism in the plant defense against fungal infections - Science Daily

Picture this: The year is 2167, and climate change has caused temperatures to rise to a level so high that the human race can longer sustain itself.

That's part of the premise behindGenetic Drift,an immersive theatre production produced by Boca del Lupo and created by Jesse Richardson-award winning Pi Theatre.

Built on the speculative fiction concept introduced by Boca del Lupo and the Performance Corporation's Expedition Series,Genetic Driftanswers the question, "how will climate change affect the world 150 years in the future?"

Pi Theatre's artistic director, Richard Wolfe, was tasked with coming up with an answer to that question.

"I thought, possibly, in the face of climate change, were going to have to adapt to something quite extreme," he said in an interview with the Straightat Boca del Lupo's micro performance space on Granville Island.

"Hows that going to happen? Well, perhaps through genetic engineering, because just recently, with CRISPR technology, they are now able to remove and splice in DNA from other places into human embryos," he added.

For Wolfe and writer Amy Lee Lavoie, this meant introducing a character from the future.

Played by Thomas Jones, Gary 3 is a human/creature hybrid who has been forcibly kidnapped from the future and brought to modern times for the viewing pleasure of audience members.

"The role is challenging in that it's not an entirely human character, so getting your head and your body around how this creature with some other DNA spliced into it actually physically moves and communicates was difficult," said Jones. "That, and also to imagine what his perspective is when being confronted with people like us, today."

For Keltie Forsythe, who plays the voice of Lucy the computer,the technology that's responsible for bringing Gary to present day, Genetic Driftoffers viewers a chance not to watch a show, but to really experience it.

"We hope [the audience] will be sucked in by Garyhe's a charming guy," she says. "We hope that they'll feel some things around Gary,and what hes going through 150 years into the future as this kind of genetically-engineered creature, and the kind of alienation he feels."

Curious about how Boca del Lupo and Pi Theatre made it happen? Check out an exclusive preview ofGenetic Driftin the video below.

Genetic Driftplays at Boca del Lupo's Fishbowl on Granville Island from April 5 to 8. Find tickets here.

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In Genetic Drift, mutant humans are the answer to surviving extreme ... - Straight.com

Dr. Luhan Yang, chief scientific officer at eGenesis, says she wants to pay back to society with her work in genetic engineering.

CAMBRIDGE Where other people see bacon, biologist Luhan Yang sees lifesaving organs hundreds and thousands of them, pig livers and pig kidneys and diabetes-curing pancreases, and possibly hearts and lungs, all growing inside droves of pampered swine.

More established scientists than Yang have dreamed of creating animal organs that are suitable for transplantation into people waiting for a human donor. But until recently, experts said it would take decades to genetically alter pig organs to make them work safely in people. Most dreamers gave up.

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Giving up is not in Yangs lexicon. Urgency is. In her native China, she told STAT, 2 million people need organ transplants, and people are dying before they get one.

The intensely driven 31-year-old has a few things going for her that other would-be pioneers did not. As a Harvard graduate student, Yang was a lead author of a breakthrough 2013 study on the genome-editing technology CRISPR-Cas9. And in 2015, she cofounded the biotech company eGenesis with her mentor, legendary Harvard bioengineer George Church, with whom shes also worked on trying to resurrect the Ice Age wooly mammoth through genetic legerdemain. From eGenesiss tiny headquarters in Kendall Square, she intends to use CRISPR to accomplish what the worlds largest drug companies failed to do despite investing billions of dollars: create designer pigs whose organs can be transplanted into people.

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Luhan is a remarkable person, Church said, and a force of nature.

She better be. Daunting hurdles stand between where biology is now and where it needs to be to make transplantable pig organs. The old problems of infection and rejection of another species organs seem almost quaint compared to those facing eGenesis.

Theres the challenge of CRISPRing an unprecedented number of genes without compromising the viability of the designer pigs and without introducing aberrant edits. And of optimizing mammalian cloning, which is how the company creates the pigs. And of persuading investors and doctors that xenotransplantation, as the process is called, is safe, effective, ethical and lucrative.

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Yang, eGenesiss chief scientific officer, has already made enormous strides, both scientific and financial. In 2015, she and colleagues in Churchs lab used CRISPR to eliminate from pig cells 62 genes so potentially dangerous their very existence nixed previous efforts to turn pigs into organ donors. Last month, eGenesis announced that it had raised $38 million from investors. The next hurdle: get the surrogate-mother sows that are pregnant with genetically altered embryos to give birth to healthy piglets.

Her work has the potential to change the face of transplantation and to save countless lives, said Dr. James Markmann, chief of transplant surgery at Massachusetts General Hospital.

Yang is not only confident of success, she also sees eGenesiss xeno work as a sort of trial run for even bolder goals. In 2016, she helped conceive Genome Project-write, whose aims include assembling a synthetic human genome from off-the-shelf parts and because, really, as long as youre making a human genome, why not? doing it better than nature.

By starting from scratch, she wonders, could we make the human genome cancer-resistant? ... Or make it virus-resistant? ... There is a great opportunity that xeno can tell us what would happen in humans after dramatic genome engineering.

But if eGenesis is to succeed in making designer pigs, let alone paving the way for new and improved humans, Yang will need to fix the miscarriage problem.

On a frigid March morning, Yang is holding her monthly meeting with Church and the companys half-dozen employees, getting updates on the designer-pig pipeline and lighting a fire under her team. The big conference table in the windowless basement room is strewn with 8.5-ounce cans of Wild Jujube Drink and snacks that Yang brought back from her Lunar New Year visit to China, where she spent five days with her parents and visited eGenesiss pig colony.

The highlight of the month, biologist Marc Guell tells Yang, is that surrogate mother pigs didnt reinfect fetuses with PERVs. Thats crucial, because the memorably named infectious agents, short for porcine endogenous retroviruses, could cause tumors, leukemia, and neuronal degeneration if transplanted into patients. To make xenotransplantation succeed, PERVs have to go.

PERV genes are interwoven into the genome of pig cells, so eGenesis scientists start their work with CRISPR-Cas9, which has made editing organisms genomes so simple high-schoolers can do it. It takes far more expertise, however, to remove dozens of PERV genes at once, as eGenesis does in pig fibroblasts, which are connective-tissue cells.

EGenesis ships batches of these cells to China, where each de-PERVed pig cell is fused with a pig ovum whose own DNA has been removed. The ova, which now contain only the PERV-free genome, start dividing and multiplying, beginning the journey to becoming pig fetuses. The embryos are implanted into surrogate mothers and, if all goes well, born 114 days later. (Yang wont say how many sows are or have been pregnant.) Unfortunately, all has not gone well.

The anti-PERV work is only the start of the changes eGenesis is making to pig genomes. Its scientists are also slipping into the pig ova up to 12 human genes to make the pig organs more human-like, Yang said in an interview. One gene, she said, would shield its organs from attack by the human immune system; another would revamp its coagulation system to reduce the risk of clots.

Thats a ton of genetic handiwork for one little pig to handle, and early signs are it might be too much.

One batch of embryos all died, Yang said, possibly because their chromosomes had gotten scrambled by either the genetic changes or the lab manipulations. Another batch had a lot of miscarriage, she said.

There are other concerns, scientists noted at the March meeting. Sometimes PERVs are found in the embryos before theyre implanted into surrogate mothers. The problem, Yang says as she leaps to the front of the conference room, is that removing the DNA-containing nuclei from pig ova isnt always complete; occasionally some of an ovums own PERV-infested genes remain behind, so the embryo created from it also has PERVs, genetic analyses showed.

Yang grills her team. How prevalent is this? May I see the genetic profile again? What can we do quickly to correct the protocol? A gene that was inserted to protect other genes is the problem, she says with finality. Maybe we should pause this one and look for other solutions. Its better to figure out where the problem comes from, then we dont have the problem anymore.

A clue to how Yangs mind works is that she counts. Ask her about the ethical issues around xenotransplantation and she will immediately tell you there are three, then elaborate on them. Ask her what characteristics make up the entrepreneurial spirit and she will say there are four, then reel them off. Colleagues say she has an uncanny knack for working backward from an ultimate goal and breaking it into a manageable sequence of steps.

She darts down corridors, speaks quickly, hates waiting, and expects others to move at her speed. Some colleagues call her impatient. Biologist Dong Niu, who worked in the Church lab and is now at eGenesis, joined Yang on a recent blitz of apartment hunting. Yang set such a breakneck pace, Niu said, I couldnt even watch.

She pushes colleagues to accomplish tasks now, if not sooner, and when she asks a coworker to explain a scientific detail, she says, Were short of time; just get to the point.

Yet colleagues sing her praises, saying she motivates them and brings extraordinary passion and a laser focus to her work. Whenever you have a question, she has an answer, almost before you get it out, said Niu.

Yang was born and grew up in a small town in a mountainous region of southwest China. Her parents were ordinary working-class people, she said, her father a government employee and her mother an accountant.

In 2004, as a high school senior, she was chosen for Chinas four-person team in the 15th International Biology Olympiad, held in Australia. Yang was one of 16 contestants to win a gold medal, coming in 13th.

After majoring in psychology at Peking University, Yang entered graduate school at Harvard, where she rotated through three labs before joining Churchs. It was a crash course not only in biological engineering but also in what success means.

I think my generation of Chinese, we are very aggressive and very optimistic, Yang said. Sometimes I think we all want to be successful and to find a shortcut to be successful, because the competition [for academic success in China] is so fierce.

The different worldviews and value systems she saw at Harvard, she said, made me open my eyes and reassess what kind of person I want to be. I want to pay back to society.

Yang stumbled out of the gate in Churchs lab, nearly failing her PhD qualifying exams because her English was so poor. It was her first academic setback, but in relating the story, Yang betrayed no more emotion over the experience than if it had been another gene she had to CRISPR. George asked the committee to let me pass with the condition that he would spend more time with me for English training, Yang said.

She played point on some of the labs most important experiments. In 2012, she and postdoctoral fellow Prashant Mali teamed up on CRISPR-Cas9, a molecular complex that bacteria use as a primitive immune system; other scientists had recently gotten it to cut specific locations on DNA floating in test tubes. Mali and Yang got a single cluster of CRISPR molecules to edit multiple genes in human and mouse cells in one fell swoop, a breakthrough published in early 2013. Although Mali and Yang had equal billing as first authors, the paper is always referred to as Mali et al. Yang said that doesnt bother her.

Soon after, physicians approached Church about using CRISPR to alter the genomes of pigs so their organs would not be rejected by the human immune system. The very question was a triumph of hope over experience. In the 1990s, a handful of drug companies, including Novartis, had collectively spent north of $2 billion to use genetic manipulation to make human-friendly pig organs.

She said she feels a strong sense of responsibility to help the millions waiting for organs in her homeland: I regard myself as a Chinese scientist. Something that can potentially solve a huge health care and social problem for China and for the world? I feel it is a privilege to work on that.

With hundreds of labs catching CRISPR fever since 2013, most experiments have altered one or two genes at a time, maxing out at five. Yangs challenge was audacious: To knock out all the PERVs would require a tenfold improvement.

But if we could make it work, she said, the impact would be huge.

They did, and it has been. In 2015 the Church lab announced it had CRISPRd out 62 PERV genes in pig kidney cells growing in lab dishes. It was a record, and it still stands.

George always encouraged me to think bigger, Yang said.

Determined as she is to make xenotransplantation succeed, Yang also sees it as opening a back door for me to push the limit of [genomic] technology. For one thing, xenotransplantation requires large-scale genome engineering, she said. In addition to knocking out PERVs, which is relatively easy, making organ-donor pigs requires inserting large chunks of human DNA into the pig genome.

Our ability to knock in a large fragment of DNA is still limited, Yang said.

Working out how to do it in the pigs would point the way toward, say, adding copies of the cancer-fighting gene p53 into a persons genome.

Thats why I love xeno, she said. Its a platform to help us assess technology.

Yang has immersed herself in the ethical issues around xenotransplantation, but they havent slowed her pursuit of transplantable pig organs.

Some scholars argue that it is morally wrong to value human life more than animals, but so many people are eating pork every day, Yang said. As for playing God the argument that it is unethical to change a pig in the way that genome-editing does she retorts that the highest moral standard is human life. I think its a personal choice whether you use a pig organ or die. But you shouldnt prevent other people from using it.

As of early March, two of eGenesiss cloned and CRISPRd pig fetuses were just a few weeks from delivery, Yang said. We checked the genotype and were surprised but also delighted to see that the fetuses [in one surrogate mother] are 100 percent PERV-free.

Yang is more than ready to be a proud mother: I feel its our time.

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Cambridge company is making designer pigs with transplantable (to people) organs. - The Boston Globe

The goalposts of embryo ethics have shifted. Just two years ago, a Chinese study testing whether CRISPR-Cas9 genome editing could be used to cure beta thalassemia in human embryos was getting negative critiques. As quoted by Gina Kolata in a New York Times last June, a comment by Nobel laureate and former Caltech president David Baltimore illustrates the magnitude of the criticism:

[The study] shows how immature the science is. We have learned a lot from their attempts, mainly about what can go wrong.

Despite the criticism and disappointing results, its noteworthy that the researchers were careful to destroy all the embryos before they reached a gestational age of 14 days. Doing otherwise would have created an ethical dilemma, because going beyond 14 days would have taken the work outside of guidelines in place in all countries where such research is technically possible. Butchange may be in sight. Last week, Harvard genetic engineering pioneer George Church and colleagues published a thoughtful paper in eLife, Addressing the ethical issues raised by synthetic human entities with embryo-like features. Its a lengthy discussion, but the take-home message is that may betime to discardthe so-called 14-day rule.

As the Chinese researchers themselves pointed out, only a fraction of the embryos ended up with the genetic payload in their cells, so the technique was not adequately efficient. Furthermore, there was mosaicism: In several embryos that did get modified genetically, the change showed up in somecells, but not others. In other words, some embryonic cells were of the original, thalassemia genotype and the remainder were corrected. There also were off-target effects unintentional changes in other parts of the genome. All of this illustrated the potential danger of editing an entire organism, and germline editing, what is sometimes called heritable gene therapy changing genetic sequences that can be passed down to new generations. This meant that CRISPR, in its current form, was not reliable for correcting genetic diseases during pregnancy.

But none of this means the research should not have been conducted. For safety, the researches used human embryos that were not viable; they contained extra chromosomes, so it was not possible for them to develop into actual people. And of course, the team followed the rule about the 14 days.

As we shall see later, there is nothing magical about the 14-day mark in human embryology. But virtually every country with biotechnology advanced enough to maintain embryos outside the body has guidelines dictating that embryo research must not continue to gastrulation. This is the point when a blastula, consisting of a single layer of identical cells, reorganizes into a gastrula, consisting of three layers of cells, each of which will become a different kind of tissue. Gastrulation starts on day 15 with the appearance of whats called the primitive streak. This is the beginning of a head-to-tail orientation and over the past four decades some have given it a kind of moral status. This didnt matter much to science through the 1980s and 90s, because there was no technical capability to maintain human embryos in the lab more than a few days beyond fertilization. But things have changed. Today, researchers can maintain embryos right up through 14 days in Petri dishes. Its only on account of laws and guidelines that they dont go further. But doing socould have benefits, both for science and medicine. The question is whether things might change, now that ahigh profile genetics researcher has come forward advocating amore nuanced approach, rather thana simple cut-off point.

There is no scientific or cultural basis for giving moral status to gastrulation, and so the 14-day mark isan arbitrary point. The rule traces its birth to1979, when a board commissioned by the US Department of Health, Education, and Welfare soughta compromise position between scientists and social conservatives.

Soon after that, it was recognized that twinning splitting an embryo into two or more clones could produce a viable pregnancy only if it occurred before the primitive streak appeared. This presents a conflict for those religious people concerned with the issue of ensoulment the point at which asoul is believed to enter embryo. What happens to the soul of an embryo that splits into twins is relevant on to somebody who believes that ensoulment occurs in the early phase of development. However, religions that worry about souls dont dont align on the matter pertaining to embryos. In Islam, ensoulment occurs fairly late pregnancy, 120 days gestation being a commonly cited point. In Hinduism, the soul moves around between different animals, so there is no worry about it being created and split. Various Christians disagree on the timing of ensoulment, and in Judaism there is no talk of souls or ensoulment in connection to human development.

On top of this, there are vast numbers of purely secular-minded people throughout the world, for whom the embryo ethics is less about rights of potential human beings and more about the potential of embryo-based research to create new treatments for disease that make people suffer. Nevertheless, the main idea of the 1979 guideline has spread throughout the developed world, where current restrictions on embryo research vary from country to country, but still use gastrulation as the cut-off point.

The new paper by Church and his colleagues at Harvard and the University of Groningen calls for a nuanced discussion. They talk about special individual stem cells calledsynthetic human entities with embryo-like features (SHEEFs) available to researchers that can generate the same developmental features that are attributed to a developing embryo. They think this should be the basis of future regulations. In their words:

Our proposal to base research limits for SHEEFs directly on signifying features is based on the inference that, given the engineering methods used to create SHEEFs and their potential for developmental plasticity, revising limits in this way will be the only workable way to prevent the creation of SHEEFs in morally concerning conditions. But non-synthetic embryos go through the PS stage routinely and are not generally developmentally plastic in this way, so this conclusion does not follow. A more secure conclusion would be that, if for independent reasons the revision of the 14-day rule for embryos is justified, the considerations we have outlined for SHEEFs might be relevant to what new limit might replace it.

It already has people arguing in the comments section, and that discussion is expanding. On the Scientific American blog, for example, journalist Karen Weintraub quotes a handful of people from a range of perspectives, including Rev. Tadeusz Pacholczyk, a neuroscientist and director of education at the National Catholic Bioethics Center in Philadelphia:

Now were getting into experiments that call into question some of our deepest beliefs philosophically about what it means to be human and what it means to deserve moral respect.

What will happen if guidelines are relaxed? As explained in a New York Times OpEd piece last June, even discussing this will start a debate that pits scientists against religiously motivated people, which in this case means mostly fundamentalist Christians:

This technological advance has reopened the ethical debate about the 14-day limit. Many scientists chafe at restrictions on their ability to learn more about life and potentially create breakthrough therapies. Critics, especially religious believers, are horrified because they believe that, in the words of Philippa Taylor, head of public policy at the Christian Medical Fellowship, all embryos are very young human beings.

As discussed in the last section, the belief that embryos are people is limited to Christianity, which must be placed in context of a diverse society that includes more liberal Christians, as well as Jews, Muslims, people of eastern religions, and millions of non-religious people. But if the history of stem cell policy and abortion serve as models, we can expect plenty of sanctimony and arguments rooted in questionable assumptions that the extreme Christian view represents some kind of universal ethics.

In the UK, where the first in vitro fertilization baby was born in 1978, the 14-day limit is more than a guideline. Rather, it is a strict rule, but since January it has been in the spotlight. In contrast with George Church, a handful of researchers are calling for a simple pushing back of the limit from 14 days to 28 days.

Now lets consider the long-term. Unlike in 1979, scientists today have the technical means to study embryos well into the period when different tissues and organs are forming, with potential science and medical benefits. Such benefits could come in the form of new treatments in regenerative medicine, since researchers could observe the precise genetics, cell biology, and chemistry of specific tissue and organ genesis. Progress toward an artificial womb. also would be accelerated. Furthermore, such studies could reveal the molecular biology underlying pregnancy loss through spontaneous abortion. Often these events are labeled as miscarriages, but many occur at very early gestational ages, before the woman even knows that she is pregnant. Thus, ironically, research on human embryos could end up saving future embryos from what happens when nature runs its course.

David Warmflash is an astrobiologist, physician and science writer. Follow @CosmicEvolution to read what he is saying on Twitter.

For more background on the Genetic Literacy Project, read GLP on Wikipedia.

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Time to amend human embryo research '14-day rule'? - Genetic Literacy Project

By Frank Kalman

A relatively obscure talk about genes was given at UC Santa Barbara recently by Dr. Siddhartha Mukherjee, a researcher and clinical oncologist at Columbia University and author of a Pulitzer Prize winning book, the Emperor of all Maladies: A Biography of Cancer.

It was, however, on par in terms of gravity with talks many decades ago by the founders of the A-bomb, who espoused the benefits of radiation and harnessing the atom but also spoke of the dark side of splitting the atom.

Mukherjee spoke of engineering genes, of the huge life-saving potential but also of the dark side of gene manipulation.

He began by giving background on what a gene is: a unit of hereditary information that carries information to specify biological function. You might imagine genes as a set of master instructions carried between cells and between organisms that tell it how to build, maintain, repair and reproduce itself. It controls everything about us: the color of our eyes, our height and our intellect.

Mukherjee posed this question to the audience: If you knew your unborn child had an 80 percent chance of having autism, would you abort? Would you abort at 50 percent? At 25 percent?

Until recently, scientists were only able to determine if an embryo was predisposed to a serious disease. Now technologies are evolving, such as CRISPR, which allow scientists to edit malfunctioning genes causing these diseases.

Mukherjee discussed a recently released report from the National Academy of Sciences panel that proposes guidelines for gene editing. The report proposes that human embryo editing might be permissible if there are no other reasonable alternatives for treatment or prevention, the gene(s) being altered result in a serious disease or condition, or the genes cause or strongly predispose a person to that disease or condition.

Picture a woman told that she carries a mutation in her BRCA-1 gene, so she has a 60 to 70 percent chance of developing breast or ovarian cancer during her lifetime.

Concerned that this not be a burden for her unborn children and descendants, she seeks to have the mutated gene removed.

According to the NAS panel, she doesnt automatically qualify for genetic engineering. The conditions in the report are not absolutely clear and are subject to interpretation.

Then there is the issue of genetic engineering for the purpose of enhancement. This was the scariest part of Mukherjees entire presentation human enhancement to increase a childs muscle mass and athletic ability or to boost intelligence.

The NAS panels report is firmly against the use of gene editing for human enhancements but this is where Mukherjee raises red flags. He said the rich will have the ability to conduct the testing and pay for the genetic engineering not only to avoid disease but also for enhancements.

After 50 or 500 years of this, two groups of human beings will exist the enhanced and the unenhanced.

The NAS report encourages government bodies to conduct public discussion and policy debate. Gene editing truly requires smart and strong federal regulation. We are at a very critical juncture in the history of humanity, just like we were in the 1940s with the atom.

This new gene technology could not have presented itself at a worse time. The Trump administrations chief adviser, Stephen Bannon, recently told the Conservative Political Action Conference, If you look at these cabinet nominees, they were selected for a reason, and that is destruction, destruction of the administrative state. In other words, they were selected to destroy their respective regulatory agencies.

We must be extremely grateful for Mukherjees effort to ring the alarm bell in an effort to make us aware of this critical juncture in our history. There are extremely complicated ethical questions that require extremely thoughtful solutions. They will also require strongly enforced federal regulation.

Frank Kalman is the executive director of the Kids Cancer Research Foundation in San Luis Obispo. You can contact him at [emailprotected]

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Gene technology raises ethical questions - Pacific Coast Business Times

March 8, 2017 G. William Arends Professor of Microbiology and theme leader of the IGB's Mining Microbial Genomes theme Bill Metcalf, left, with IGB Fellow Dipti Nayak. Credit: University of Illinois at Urbana-Champaign

A new study by G. William Arends Professor of Microbiology at the University of Illinois Bill Metcalf with postdoctoral Fellow Dipti Nayak has documented the use of CRISPR-Cas9 mediated genome editing in the third domain of life, Archaea, for the first time. Their groundbreaking work, reported in Proceedings of the National Academy of Sciences, has the potential to vastly accelerate future studies of these organisms, with implications for research including global climate change. Metcalf and Nayak are members of the Carl R. Woese Institute for Genomic Biology at Illinois.

"Under most circumstances our model archaeon, Methanosarcina acetivorans, has a doubling time of eight to ten hours, as compared to E. coli, which can double in about 30 minutes. What that means is that doing genetics, getting a mutant, can take monthsthe same thing would take three days in E. coli," explains Nayak. "What CRISPR-Cas9 enables us to do, at a very basic level, is speed up the whole process. It removes a major bottleneck... in doing genetics research with this archaeon.

"Even more," continues Nayak, "with our previous techniques, mutations had to be introduced one step at a time. Using this new technology, we can introduce multiple mutations at the same time. We can scale up the process of mutant generation exponentially with CRISPR."

CRISPR, short for Clustered Regularly Interspaced Short Palindromic Repeats, began as an immune defense system in archaea and bacteria. By identifying and storing short fragments of foreign DNA, Cas (CRISPR-associated system) proteins are able to quickly identify that DNA in the future, so that it can then quickly be destroyed, protecting the organism from viral invasion.

Since its discovery, a version of this immune systemCRISPR-Cas9has been modified to edit genomes in the lab. By pairing Cas9 with a specifically engineered RNA guide rather than a fragment of invasive DNA, the CRISPR system can be directed to cut a cell's genome in an arbitrary location such that existing genes can be removed or new ones added. This system has been prolifically useful in editing eukaryotic systems from yeast, to plant, to fish and even human cells, earning it the American Association for the Advancement of Science's 2015 Breakthrough of the Year award. However, its implementation in prokaryotic species has been met with hurdles, due in part to their different cellular processes.

To use CRISPR in a cellular system, researchers have to develop a protocol that takes into account a cell's preferred mechanism of DNA repair: after CRISPR's "molecular scissors" cut the chromosome, the cell's repair system steps in to mend the damage through a mechanism that can be harnessed to remove or add additional genetic material. In eukaryotic cells, this takes the form of Non-Homologous End Joining (NHEJ). Though this pathway has been used for CRISPR-mediated editing, it has the tendency to introduce genetic errors during its repair process: nucleotides, the rungs of the DNA ladder, are often added or deleted at the cut site.

NHEJ is very uncommon in prokaryotes, including Archaea; instead, their DNA is more often repaired through a process known as homology-directed repair. By comparing the damage to a DNA template, homology-directed repair creates what Nayak calls a "deterministic template"the end result can be predicted in advance and tailored to the exact needs of the researcher.

In many ways, homology-directed repair is actually preferable for genome editing: "As much as we want CRISPR-Cas9 to make directed edits in eukaryotic systems, we often end up with things that we don't want, because of NHEJ," explains Nayak. "In this regard, it was a good thing that most archaeal strains don't have a non-homologous end joining repair system, so the only way DNA can be repaired is through this deterministic homologous repair route."

Though it may seem counter-intuitive, one of Nayak and Metcalf's first uses of CRISPR-Cas9 was to introduce an NHEJ mechanism in Methanosarcina acetivorans. Though generally not preferable for genome editing, says Nayak, NHEJ has one use for which it's superior to homologous repair: "If you just want to delete a gene, if you don't care how ... non-homologous end joining is actually more efficient."

By using the introduced NHEJ repair system to perform what are known as "knock-out" studies, wherein a single gene is removed or silenced to see what changes are produced and what processes that gene might affect, Nayak says that future research will be able to assemble a genetic atlas of M. acetivorans and other archaeal species. Such an atlas would be incredibly useful for a variety of fields of research involving Archaea, including an area of particular interest to the Metcalf lab, climate change.

"Methanosarcina acetivorans is the one of the most genetically tractable archaeal strains," says Nayak. "[Methanogens are] a class of archaea that produce gigatons of this potent greenhouse gas every year, play a keystone role in the global carbon cycle, and therefore contribute significantly to global climate change." By studying the genetics of this and similar organisms, Nayak and Metcalf hope to gain not only a deeper understanding of archaeal genetics, but of their role in broader environmental processes.

In all, this research represents an exciting new direction in studying and manipulating archaea. "We began this research to determine if the use of CRISPR-Cas9 genome editing in archaea was even possible," concludes Nayak. "What we've discovered is that it's not only possible, but it works remarkably well, even as compared to eukaryotic systems."

Explore further: Modifying fat content in soybean oil with the molecular scissors Cpf1

More information: Dipti D. Nayak et al, Cas9-mediated genome editing in the methanogenic archaeon, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1618596114

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