Category: CRISPR

Geneticists Have Used CRISPR Gene Editing to Create Crops That Grow More Food

Better Crops, Better Yield

Crops and vegetables were among the first to be used in testing how effective CRISPR-Cas9 can be. Now, researchers from Cold Spring Harbor Laboratory (CSHL) in New York have used today’s most efficient gene editing tool to push the envelope of agricultural crop yield. In their study, published in the journal Cell, the CSHL scientists developed a method to edit the genome of tomatoes using CRISPR.

Specifically, the researchers edited trait variations or major components known to affect yield rates in crops. These traits include the size of the fruit, its branching architecture, and the overall shape of the plant. They used CRISPR-Cas9 to make multiple cuts inside three genome sequences in tomatoes. These sequences are called promoters, which are DNA areas close to the genes that regulate when, where, and at what level the actual “yield” genes become active. The CSHL scientists were able to induce a wide range of changes in the three targeted traits mentioned by introducing multiple sets of mutations on the promoter gene sequences.

“What we demonstrated with each of the traits was the ability to use CRISPR to generate new genetic and trait variation that breeders can use to tailor a plant to suit conditions,” lead researcher and CSHL professor Zachary Lippman said in a press release. “Each trait can now be controlled in the way a dimmer switch controls a light bulb.”

Editing Our Way Through Hunger

Some might ask why target regulatory sequences instead of the actual “yield” genes. Well, the researchers found that this method yielded significantly better results. They were able to achieve a subtler impact on the quantitative traits. “Traditional breeding involves great time and effort to adapt beneficial variants of relevant genes to the best varieties, which must continuously be improved every year,” Lippman explained.

“Our approach can help bypass this constraint by directly generating and selecting for the most desirable variants controlling gene activity in the context of other natural mutations that benefit breeding,” he added. “We can now work with the native DNA and enhance what nature has provided, which we believe can help break yield barriers.”

How CRISPR Works: The Future of Genetic Engineering and Designer Humans
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This isn’t the first time CRISPR has been used to improve crop yield. Indeed, the agricultural applications of CRISPR not only obvious. According to CRISPR-Cas9 developer Jennifer Doudna, agricultural use is greatly needed. Crops genetically modified using CRISPR could hypothetically solvet the world hunger. This new CSHL method, which can be used in all food, feed, and fuel crops — staples such as rice, maize, sorghum, and wheat — can definitely contribute.

“Current rates of crop yield increases won’t meet the planet’s future agricultural demands as the human population grows,” said Lippman. “One of the most severe limitations is that nature hasn’t provided enough genetic variation for breeders to work with, especially for the major yield traits that can involve dozens of genes. Our lab has now used CRISPR technology to generate novel genetic variation that can accelerate crop improvement while making its outcomes more predictable.”

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A Closer Look at the Human Gene Editing Lab

The Gene Editing Process

In a lab at Oregon Health & Science University, biologist Shoukhrat Mitalipov and a team of experts have been exploring and learning how to edit the DNA in human embryos efficiently and safely. This month, they announced their successful edit and correction of a mutation which causes a heart condition that can be fatal — hopefully the first landmark step of many on the road to preventing thousands of genetic diseases with editing.

To edit an embryo, a researcher will begin by taking a human egg and monitoring it on a computer screen. They will then inject, with a pipette, donor sperm and CRISPR, microscopic chemical sequences that act as a gene-editing tool, that is designed to make the precise desired edit. CRISPR then goes to work, slicing the target defect from the DNA. After this editing process, the scientists place the embryos created using the process in an incubator and monitor them.

Image Credit: Oregon Health & Science University
Image Credit: Oregon Health & Science University

Mitalipov and the team believe that the editing process finally started to work when they began to inject the sperm and CRISPR into the egg simultaneously. Waiting until the embryos were already created produced results that were less accurate and more likely to be plagued by dangerous mutations. And, while the team isn’t totally certain on how the process works, they believe that the slice CRISPR makes as it targets defects triggers the repair process in the embryo.

Incredible Potential, Mixed Feelings

Thus far, the results from this study appear to be promising. However, many questions in the scientific community about the technique itself and the underlying ethics of the process remain. For example, the technique has not yet been reproduced by other teams, and some scientists believe that the data doesn’t support the conclusions Mitalipov and the team are claiming.

Others are more concerned that this kind of technology has not been proven safe. worried that less careful scientists might rush ahead too quickly and attempt to make babies before the technique has been proven to work and be safe. Any change to the genome, or germline editing, could be passed along for generations, perpetuating mistakes and even potentially leading to the development of new diseases. Harvard Medical School Dean George Daley told NPR, “I think it would be professionally irresponsible for any clinician to use this technology to make a baby. It’s just simply too early. It would be premature.”

Still, others are critical of the technique from an ethical standpoint, arguing that scientists editing embryos are “playing God,” and pushing the field toward selling the ability to create designer babies to parents who can afford the technology. “I think it’s extraordinarily disturbing,” Marcy Darnovsky, head of the watchdog group the Center for Genetics and Society, told NPR. “We’ll see fertility clinics advertising gene editing for enhancement purposes. We’ll see children being born who are said to biologically superior.”

Mitalipov and the team acknowledge these criticisms and agree, specifically, that the technique requires reproduction and further testing and should be used for medical purposes only. However, they point out the amazing potential that the technology has to improve our world and the quality of human life. Mitalipov thinks the process may eventually be able to wipe out many genetic diseases:

“[There are] about 10,000 different mutations causing so many different conditions and diseases,” he said to NPR. “We’re talking about millions of people affected. So I think the implications are huge.”

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The 10 Most Significant Scientific Discoveries Of the Year (So Far)

The year 2017 has catapulted us into a science-fiction future, from human cell regeneration for growing organs, to banishing genetic disease through breakthrough gene-editing techniques and recycling orbital rockets — and it’s only August at the time of writing. A lot has happened in the last eight months; scientific breakthroughs have made our lives safer, easier and more enjoyable. And the scientific community is only getting started.

Researchers and scientists around the globe have worked tirelessly to bring us this future, so it’s worthwhile to take a step back and applaud their tremendous efforts. The world of tomorrow is being shaped as you read this, so let’s have a look at ten of the biggest stories in science of this year, so far.

Scientists Successfully Edited the First Human Embryo Ever in The U.S.

Image Source: Getty Images

Jul 27, 2017: Researchers in Portland, Oregon have achieved a significant breakthrough in gene-editing technology. Taking advantage of the revolutionary gene- editing technique, CRISPR, a gene linked to heart conditions was successfully “deleted” from a human embryo.

Read the full story here.

 

Scientists Have Finally Created Metallic Hydrogen

Image Source: Harvard University

January 27, 2017: For the first time in the wold, scientists created metallic hydrogen by applying almost five million atmospheres of pressure to liquid hydrogen. That’s about five million times the pressure we experience at sea level, and 4,500 times that at the bottom of the ocean. It is the first time a state of hydrogen has existed in a metallic state on Earth. In its metallic state, hydrogen could act as a genuine superconductor and could revolutionize everything from energy storage to rocketry.

Read the full story here.

 

Scientists Discovered an Alien Planet That’s The Best Candidate for Life As We Know It

Image Source: NASA Ames/JPL-Caltech/T. Pyle

On April 19 this year scientists at the European Organisation for Astronomical Research (ESO) found the best candidate for extraterrestrial life so far. The super-Earth named LHS 1140b was found in the habitable zone of a dim star 40 light-years away from Earth. It receives about half as much sunlight from its star, LHS 1140, as the Earth does from the Sun.

“This is the most exciting exoplanet I’ve seen in the past decade,” author Jason Dittmann of the Harvard-Smithsonian Center for Astrophysics said in an ESO press release. “We could hardly hope for a better target to perform one of the biggest quests in science — searching for evidence of life beyond Earth.”

Read the full story here.

 

A World First CRISPR Trial Will Edit Genes Inside the Human Body

Image Source: National Institute of Allergy and Infectious Diseases, National Institutes of Health

June 1, 2017: In one of the biggest scientific breakthroughs of 2017, scientists used the gene-editing technology CRISPR (the most accessible gene-editing technique so far) inside the human body for the very first time. A new human trial aimed to remove the human papillomavirus (HPV) by applying a gel that carries the necessary DNA coding to the cervixes of 60 women to disable the tumor growth mechanism.

Read the full story here.

 

Breakthrough Initiative Will Grow Organs and Regenerate Human Tissue

Image Source: Wake Forest Baptist Medical Center

May 1, 2017: Major strides have been made in the field of regenerative medicine. The Wake Forest Institute for Regenerative Medicine is currently leading projects to speed up the development of artificially growing human tissue and even organs in a lab to help patients worldwide. These new initiatives may one day repair nerve damage and even grow entire limbs and organs.

Read the full story here.

 

DeepMind Has Taught an AI to Do Something Quite Remarkable

Image Source: DeepMind/YouTube

July 11, 2017: Google’s artificial intelligence subsidiary DeepMind published a paper illustrating the way they are teaching AI computer agents to navigate complex environments. It may look funny to us, but it’s a big step forward for autonomous AI movement.

Read the full story here.

 

SpaceX’s Historic Launch Proves Recycled Rockets Are the Future of Space Exploration

March 30, 2017: SpaceX made space launch history in March by successfully relaunching and re-landing a used Falcon 9 rocket booster via rocket descent. This is the stuff of old-school scifi. Already having been the cheapest orbital rocket system, this breakthrough brought the affordability down even more — a saving of more than $18 million per launch.

Read the full story here.

 

This Fluid-Filled Bag Lets Lambs Develop Outside the Womb. Humans Are Next.

Image Source: Children’s Hospital of Philadelphia

April 26, 2017: Physicians at the Children’s Hospital of Philadelphia have managed to imitate a woman’s uterus using a synthetic device in order to prevent mortality and disease of prematurely born children younger than 37 weeks.

Read the full story here.

 

A New Breakthrough in Quantum Computing is Set to Transform Our World

Image Source: Getty Images

July 28, 2017: A 51-qubit quantum computer was unveiled to the world at the 2017 International Conference on Quantum Technologies in Moscow, paving the way for a number of new possible applications of the technology.

Read the full story here.

 

Google’s AlphaGo Proves Its Mettle Against a Team of Five

 Image Source: AlphaGo/Deep Mind

May 29, 2017: After beating a human in the Computer Go game in 2016, Alphabet Inc.’s Google DeepMind computer took on five more of the world’s best human professional Go players and defeated them in earnest.

Read the full story here.

We’ve seen it for ourselves; whatever negativity 2017 might bring the world, this year has been one incredible leap after the other — and it’s still Summer.

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Here’s Everything You Need to Know About the Recent Human Gene Editing Trial in the US

Gene Editing In Embryos

Recently, scientists achieved a world first using the genetic editing tool, CRISPR, when they corrected a genetic mutation that causes heart failure in viable human embryos. This means that certain genetic defects may be relatively simple to correct in the near future. The issue that really has people talking, though, is the fact that the same tool could potentially be used to enhance healthy embryos, altering physical traits such as appearance or mental traits like intelligence.

However, the authors of the study firmly point out that the technology’s purpose is to save lives. “This is for [the] sake of saving children from horrible diseases,” lead author Dr. Shoukhrat Mitalipov explained in a Nature podcast. With this “milestone” achieved, humanity is getting closer, Dr. George Church confirmed to The Scientist.

The work in this study solved past problems with embryo editing including the issue of mosaicism, which happens when “fixed” cells contain a mix of the new, repaired DNA and older, damaged DNA. It also conquered the issue of unintended problems in the DNA being passed down in the germline. The technique that made the difference was injecting the CRISPR setup right into the fertilized embryo or egg cell about to be fertilized. It can then be degraded after it does its work, rather than floating around on plasmids in cells where it can do damage over time.

Future Applications

This discovery is significant for anyone suffering from hereditary, genetic diseases. For people with fatal diseases such as Huntington’s, for example, carrying certain genes means they are certain to get the disease, and a 50/50 chance of passing it on. For this reason, many people with Huntington’s don’t have children. If this discovery pans out, these patients won’t have to worry about passing on a genetic disorder.

How CRISPR Works: The Future of Genetic Engineering and Designer Humans
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Of course the specter of the “designer baby” is always raised in this context — but the study demonstrates that the way the cells repair the genes in question, researchers can’t add anything that wasn’t already present in the DNA. In other words, repair is possible, but not adding limitless “super” traits.

Regulations And Benefits

Nevertheless, there are critical voices in the fray: former molecular biologist Dr. David King (also founder of independent genetic engineering watchdog group Human Genetics Alert) said in an editorial in The Guardian that, “In fact, the medical justification for spending millions of dollars on such research is extremely thin: it would be much better spent on developing cures for people living with those conditions.” King believes that despite medical cures being the original motivation for developing genome editing, the creation of “designer babies” for the very wealthy is inevitable — as is the deepening class stratification caused by this modern eugenic drive.

In any event, there is significant work left to be done before CRISPR could be used in clinics. Scientists want to increase its accuracy and precision, for one thing. Furthermore, IVF clinics already screen out genetic disease and other abnormalities before implanting embryos; to justify the cost of using CRISPR, it would need to show more benefits unachievable otherwise.

Either way, now is probably the time to start grappling with the ethical issues surrounding CRISPR. Waiting until it is possible to use it — and dying people are waiting for it — seems shortsighted. In any event, more dialogue and research only stands to help resolve the societal issues that remain.

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Researchers Used CRISPR to Manipulate the Social Activities of Ants

Ants Marching

Researchers have used the CRISPR technique to manipulate the social activities of ants for a study that will be published in Cell. Two independent teams knocked out the orco (odorant receptor coreceptor) gene in entire colonies of ants, which negated their ability to perceive pheromone signals they use to communicate. Without those cues, they began to exhibit asocial behaviors like leaving the safety of the nest and declining to aid efforts to hunt for food.

Ants possess a whopping 350 genes for odorant receptors, but as they all need to liaise with the orco gene to be effective, they could all be knocked out at once. The two teams chose different ants based on two distinct strategies for proliferating this edit among the colony.

One group chose a species that has no queens, instead procreating using unfertilized eggs that mature as clones, producing ants that are genetically identical. CRISPR was used to edit lone eggs, which produced an entire colony with the desired modification.

Meanwhile, the other team of researchers selected a species known for an unusual trait that sees worker ants graduate to the role of egg-laying pseudoqueen in the event that the former queen dies. The chosen worker ant had its genetic makeup modified being converted into a pseudoqueen and prompted to spawn a new colony.

Superorganism Socialization

The social interactions of ants are fascinating because of the way a colony acts as a single entity. And as such, these amalgamate superorganisms can potentially tell us a lot about the way we humans interface with one another.

How CRISPR Works: The Future of Genetic Engineering and Designer Humans
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The researchers observed that disabling the orco gene resulted in certain substructures from the ants’ central processing centers going missing. These parts of the brain are essential to their olfactory communications, and it’s not known exactly why they disappeared. Symptomatically, this is analogous to a number of human mental disorders.

The hope is that further research into the biochemistry of ant colony behavior could reveal more about disorders that affect social communication, like depression or schizophrenia. If we can better understand this process as it occurs in an ant’s brain, and then that of the invisible hand moving the colony as superorganism, we might shine a light on how similar changes that affect mammals.

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11 Incredible Things CRISPR Has Helped Us Achieve in 2017

We All Dream to Splice the Genes

The CRISPR//Cas9 gene editing tool has quickly earned a reputation as a revolutionary technology, and its merits support the clout. This year has, in fact, seen so many CRISPR-related breakthroughs that it’s worthwhile to take a step back and take in all of the many accomplishments.

1. This week, circulating reports about the successful application of gene-editing human embryos in the US were confirmed by a research paper published in Nature. The researchers “corrected” one-cell embryo DNA to remove the MYBPC3 gene — known to cause hypertrophic cardiomyopathy (HCM), a heart disease that affects 1 in 500 people.

2. This year, scientists successfully used gene editing to completely extract HIV from a living organism, with repeated success across three different animal models. In addition to the complete removal of the virus DNA, the team also prevented the progress of acute latent infection.

3. Semi-synthetic organisms were developed by breeding E.coli bacteria with an anomalous six-letter genetic code, instead of the normal four-base sequence. Additional gene editing was implemented to ensure that the new DNA molecules were not identified as an invasive presence.

4. The CRISPR method successfully targeted the “command center” of cancer — called the hybrid fusion — which leads to abnormal tumor growths. A “cut-and-paste” method allowed the creation of a cancer-annihilating gene that shrinks tumors in mice carrying human prostate and liver cancer cells.

5. Scientists also slowed the growth of cancerous cells, by targeting Tudor-SN, a key protein in cell division. It’s expected that this technique could also slow the growth of fast-growing cells.

6. Gene editing techniques have also made superbugs kill themselves. By adding antibiotic resistant gene sequences into bacteriophage viruses, self-destructive mechanisms are triggered which protect bacteria.

7. Gene editing may even make mosquito-born diseases an extinct phenomenon. By hacking fertility genes, scientists have gained the ability to limit the spread of mosquitoes — a success they credit to CRISPR’s ability to make multiple genetic code changes simultaneously.

8. Using CRISPR, researchers have edited out Huntington’s disease from mice, pushing the symptomatic progression of the condition into reverse. Experts expect this promising technique to be applied to humans in the near future.

9. Outside of the medical field, CRISPR might also provide a more abundant and sustainable biofuel. By connecting several gene-editing tools, scientists engineered algae that produce twice the biofuel material as wild (or “natural”) counterparts.

Flickr: Sarah Fulcher

10. Very recently, the first-ever “molecular recorder” was developed — a gene editing process that encodes a film directly into DNA code — and with this ability, scientists embedded information into an E.coli genome.

11. Last but not least, and on the macro-scale, the US Defense Advanced Research Projects Agency (DARPA) invested $65 million in a project called “safe genes,” designed to improve the accuracy and safety of CRISPR editing techniques. In addition to serving the public interest of avoiding accidental or intentional (cue ominous music) misuse, the seven research teams will remove engineered genes from environments to return them to baseline “natural” levels.

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CRISPR Skin Grafts Could Replace Insulin Shots For Diabetes

The Potential of CRISPR

The potential of the gene editing tool CRISPR just seems to keep growing and growing, and the latest experimental use of the technology is creating skin grafts that trigger the release of insulin and help manage diabetes.

Researchers have successfully tested the idea with mice that gained less weight and showed a reversed resistance to insulin because of the grafts (high insulin resistance is a common precursor to type 2 diabetes).

In fact, the team from the University of Chicago says the same approach could eventually be used to treat a variety of metabolic and genetic conditions, not just diabetes – it’s a question of using skin cells to trigger different chemical reactions in the body.

“We didn’t cure diabetes, but it does provide a potential long-term and safe approach of using skin epidermal stem cells to help people with diabetes and obesity better maintain their glucose levels,” says one of the researchers, Xiaoyang Wu.

Image Source: Immunofluorescence image of a skin graft. Image: University of Chicago

If you’re new to the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) phenomenon, it’s a new and innovative way of editing specific genes in the body, using a biological copy and paste technique: it can do everything fromcut out HIV virus DNA to slow the growth of cancer cells.

For this study, researchers used CRISPR to alter the gene responsible for encoding a hormone called glucagon-like peptide-1 (GLP-1), which triggers the release of insulin and then helps remove excess glucose from the blood.

Treating Diabetes

Type 2 diabetes comes about due to a lack of insulin, also known as insulin resistance.

Using CRISPR, the GLP-1 gene could be tweaked to make its effects last longer than normal. The result was developed into skin grafts that were then applied to mice.

Around 80 percent of the grafts successfully released the edited hormone into the blood, regulating blood glucose levels over four months, as well as reversing insulin resistance and weight gain related to a high-fat diet.

Significantly, it’s the first time the skin graft approach has worked for mice not specially designed in the lab.

“This paper is exciting for us because it is the first time we show engineered skin grafts can survive long term in wild-type mice, and we expect that in the near future this approach can be used as a safe option for the treatment of human patients,” says Wu.

Human treatments will take time to develop but the good news is that scientists are today able to grow skin tissue very easily in the lab using stem cells, so that won’t be an issue.

If we can make it safe, and patients are happy with the procedure, then the researchers say it could be extended to treat something like haemophilia, where the body is unable to make blood clots properly.

Any kind of disease where the body is deficient in specific molecules could potentially be targeted by this new technique. And if it works with diabetes, it could be time to say goodbye to needles and insulin injections.

Other scientists who weren’t directly involved in the research, including Timothy Kieffer from the University of British Columbia in Canada, seem optimistic.

“I do predict that gene and cell therapies will ultimately replace repeated injections for the treatment of chronic diseases,” Kieffer told Rachel Baxter at New Scientist.

The findings have been published in Cell Stem Cell.

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Researchers Used CRISPR to Successfully Increase HIV Resistance in Animals

Engineering a Mutation

Of the many diseases that have plagued humanity, HIV is proving to be one of the trickiest to cure. The virus’ ability to remain hidden in latent reservoirs makes eliminating it particularly challenging, which is why Chinese researchers decided to test a different approach. Instead of developing a drug to fight HIV, they’re working on a way to make cells immune to the virus.

How CRISPR Works: The Future of Genetic Engineering and Designer Humans
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In a study published in Molecular Biology, a team led by Hu Chen of the 307 Hospital of the Chinese People’s Liberation Army and Hongkui Deng of the Peking University Stem Cell Research Center used CRISPR/Cas9 to induce a homozygous mutation in a gene called CCR5, which encodes receptors in immune cells.

Previous studies have shown that this mutation of CCR5 can prevent HIV from entering cells, but only a small percentage of people have it naturally. Using CRISPR/Cas9, the researchers edited human fetal liver hematopoietic stem/progenitor cells (HSPCs), which were then engrafted into mice. Their research showed that this targeted approach of editing CCR5 was effective at making T-cells more resistant to HIV.

Powerful Potential

While this study isn’t the first to use edited stem cells to develop HIV-resistance in immune cells, it is the first example of using CRISPR to edit CCR5. “One of the advantages of CRISPR is its high efficiency on difficult to transfect cells,” Cheng and Deng told The Scientist. Using the remarkable method, they achieved a 21 to 28 percent efficiency in editing CCR5.

This isn’t surprising since CRISPR is considered the most effective and efficient gene-editing tool available. One of the most recent and remarkable demonstrations of its precision was the first-ever editing of a human embryo in the U.S.. The tool even gives us the ability to revive extinct species (if we wanted to).

As for this CCR5 study, Kamel Khalili from Temple University told The Scientist that expectation should remain in check: “[It] may not be a complete cure because the virus itself is not eliminated and may shift to using the CCR4 or another receptor to spread.” However, he did add, “CCR5 seems to be the one Achilles heel of HIV. There may be some other targets, but for now, it’s the best target.”

HIV affects more than 36.7 million people worldwide, 1.8 million of whom are younger than 15 years old. An approach that helps humans develop a resistance or immunity to it could be our best chance at future eradication.

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First U.S. Human Embryo Gene Editing Experiment Successfully “Corrects” a Heart Condition

Correcting Mutant Genes

Last week, reports circulated  that doctors had successfully edited a gene in a human embryo — the first time such a thing had been done in the United States. The remarkable achievement confirmed the powerful potential of CRISPR, the world’s most efficient and effective gene-editing tool. Now, details of the research have been published in Nature.

The procedure involved “correcting” the DNA of one-cell embryos using CRISPR to remove the MYBPC3 gene. That gene is known to cause hypertrophic cardiomyopathy (HCM), a heart disease that affects 1 out of 500 people. HCM has no known cure or treatment as its symptoms don’t manifest until the disease causes sudden death through cardiac arrest.

How CRISPR Works: The Future of Genetic Engineering and Designer Humans
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The researchers started with human embryos created from 12 healthy female donors and sperm from a male volunteer who carried the MYBOC3 gene. The defective gene was cut out using CRISPR around the time the sperm was injected into the eggs.

As a result, as the embryos divided and grew, many repaired themselves using the non-edited genes from the genetic materials of the female donors, and in total, 72 percent of the cells that formed appeared to be corrected. The researchers didn’t notice any “off-target” effects on the DNA, either.

The researchers told The Washington Post that their work was fairly basic. “Really, we didn’t edit anything, neither did we modify anything,” explained Shoukhrat Mitalipov, lead author and a researcher at the Oregon Health and Science University. “Our program is toward correcting mutant genes.”

A [Controversial] New Era?

Basic or not, the development is remarkable.“By using this technique, it’s possible to reduce the burden of this heritable disease on the family and eventually the human population,” Mitalipov said in an OHSU press release.

However, gene editing is a controversial area of study, and the researchers’ work included changes to the germ line, meaning the changes could be passed down to future generations. To be clear, though, the embryos were allowed to grow for only a few days and none were implanted into a womb (nor was that ever the researchers’ intention).

In fact, current legislation in the U.S. prohibits the implantation of edited embryos. The work conducted by these researchers was well within the guidelines set by the National Academies of Sciences, Engineering, and Medicine on the use of CRISPR to edit human genes.

University of Wisconsin-Madison bioethicist Alta Charo thinks that the benefits of this potential treatment outweigh all concerns. “What this represents is a fascinating, important, and rather impressive incremental step toward learning how to edit embryos safely and precisely,” she told The Washington Post. “[N]o matter what anybody says, this is not the dawn of the era of the designer baby.”

Before the technique could be truly beneficial, regulations must be developed that provide clearer guidelines, according to Mitalipov. If not, “this technology will be shifted to unregulated areas, which shouldn’t be happening,” he explained.

More than 10,000 disorders have been linked to just a single genetic error, and as the researchers continue with their work, their next target is BRCA, a gene associated with breast cancer growth.

Mitalipov hopes that their technique could one day be used to treat a wide-range of genetic diseases and save the lives of millions of people. After all, treating a single gene at the embryonic stage is far more efficient that changing a host of them in adults.

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Scientists Just Successfully Edited the First Human Embryo Ever in The U.S.

A New Age in Human Evolution

By now, most of us know what CRISPR gene editing is. At the very least, we have heard of this revolutionary technology that allows us to alter DNA—the source code of life itself. One day, CRISPR could allow us to delete genes in order to eradicate genetic diseases, add in new genes in order to vastly improve various biological functions, or even genetically modify human embryos in order to create an entirely new class of humans…of super humans.

But first, we have a lot of research to do.

And that brings us to today. Reports from MIT were just released which assert that the very first attempt at creating genetically modified human embryos in the United States has been carried out by a team of researchers in Portland, Oregon.

“So far as I know this will be the first study reported in the U.S.,” Jun Wu, who played a role in the project and is a collaborator at the Salk Institute, said to MIT.

According to MIT, the work was led by Shoukhrat Mitalipov, who comes from the Oregon Health and Science University. Although details are scarce at this point, sources familiar with the work assert that the research involved changing the DNA of one-cell embryos using CRISPR gene-editing. Further, Mitalipov is believed to have broken records in two notable ways:

  1. He broke the record on the number of embryos experimented upon.
  2. He is the first researcher to ever conclusively demonstrate that it is possible to safely and efficiently correct defective genes that cause inherited diseases.

This is notable because, despite the fact that it has been around for several years now, CRISPR is still an incredibly new tool—one that could have unintended consequences. As previous work published in the journal Nature Methods revealed, CRISPR-Cas9 could lead to unintended mutations in a genome. However, the work was later reviewed by researchers at another institution and the findings were brought into question. It remains to be seen whether the original study will be corrected or retracted, but this development highlights the importance of peer review in science.

In this regard, Mitalipov’s work brings us further down the path to understanding exactly how CRISPR works in humans, and reveals that is it possible to avoid both mosaicism (changes that are taken up not by only some of the cells of an embryo, as opposed to all of them) and “off-target” effects.

A Long Road to Travel

It is important to note that none of the embryos were allowed to develop for more than a few days, and that the team never had any intention of implanting them into a womb. However, it seems that this is largely due to ongoing regulatory issues, as opposed to issues with the technology itself.

In the United States, all efforts to turn edited embryos into a baby—to bring the embryo to full term—have been blocked by Congress, which added language to the Department of Health and Human Services funding bill that forbids it from approving any such clinical trials.

How CRISPR Works: The Future of Genetic Engineering and Designer Humans
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Yet, the potential of the CRISPR-Cas9 system as a gene editing technology is undeniable. As previously mentioned, it has seen success in developing possible cancer treatments, in making animals disease-resistant, and it has even shown promise in replacing antibiotics altogether.

This new work adds to the promise of CRISPR, and stands as an important step toward the birth of the first genetically modified humans.

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New DARPA Initiatives Aim to Improve Safety and Efficiency of CRISPR Gene Editing

DARPA “Safe Genes” Program

Last week, the US Defense Advanced Research Projects Agency (DARPA) created a program called “Safe Genes” with an award of a $65 million in research funding. Seven research teams will share the funding, all dedicated to the broader goal of improving the accuracy and safety of CRISPR gene editing techniques. DARPA’s stated goals include improving the understanding of gene editing technologies, more predictably harnessing them for beneficial uses, and addressing issues of intentional or accidental misuse that could caused potential health and security problems.

Image Credit: DARPAImage Credit: DARPA[/caption]The “Safe Genes” program sets forth three technical objectives, and each of the seven teams housed under the program will be assigned at least one of them. DARPA sets forth these objectives as follows: “develop genetic constructs — biomolecular “instructions” — that provide spatial, temporal, and reversible control of genome editors in living systems; devise new drug-based countermeasures that provide prophylactic and treatment options to limit genome editing in organisms and protect genome integrity in populations of organisms; and create a capability to eliminate unwanted engineered genes from systems and restore them to genetic baseline states.”The seven teams from different research institutions will be focusing on different areas of research, from developing an “on and off” switch for genome editing in bacteria, insects, and mammals in order to take aim at diseases like malaria, to safeguarding genomes by detecting, preventing, and reversing radiation-induced mutations. This kind of work, improving our understanding of CRISPR and how it works, will ideally help settle spats about whether the technique causes mutations and other scientifically controversial issues. The ethical and safety components of the project may also defuse controversies about using CRISPR to revive extinct species or create new ones.

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Sexual Reproduction and Natural Selection Work Together to Protect the Gene Pool

The Purging Role of Sex

In a new paper published by Science, Alexey Kondrashov, Professor of Ecology and Evolutionary Biology at the University of Michigan, along with the co-authors of the study, have proposed that a discrepancy between the predicted amount mutations in a species and the actual number is explained by sexual intercourse compounding mutations. When mutations combine and interact, it expedites the time it takes for natural selection to work against negatively mutated individuals.

The study first calculated the theoretical mutation rate of humans and wild fruit flies. Then, it amassed data from around 2,000 people and around 300 flies, in order to ascertain the proportion of real-world individuals with mutations. They found that the real world ratio was far lower than the theoretical one.

Shamil Sunyaev, a co-director of the project, told Phys.Org that this lead them to believe that “natural selection against highly damaging genetic mutations is ongoing in humans, and that it is aided by synergistic interactions between different parts of the human genome.” Essentially, mutation does not work in isolation, but different mutations can impact and worsen each other.

Human Evolution: A Timeline of the Near and Far Future [INFOGRAPHIC]
Click to View Full Infographic

Mashaal Sohail, lead author on the study, went on to state that “sex had to come about in a species such as our own to allow for more effective natural selection because the mutation rate is too high to sustain otherwise.” Sex is the mechanism through which we combine mutations and therefore speed up the rate at which these mutations are eliminated, as they are exposed to other mutations that increase their effect.

This phenomena is called synergistic (or narrowing) epistasis, and the researchers concluded that it is has a more positive evolutionary effect than asexual reproduction, as it allows an organism to eliminate multiple mutations — that are the result of sexual genome mixing — in the death of a single organism that is no longer able to reproduce — or even reach the reproductive stage — due to stacked mutations.

New Perspectives on Natural Selection and CRISPR

The implications of this study are twofold. First, it gives a causal mechanism that explains why humans continue to reproduce at such a rapid rate — a key question in the field of population genetics. According to the study, rapidly multiplying may in fact be an efficient means of mutation purging.

It also explains why there were fewer people and flies with lots of detrimental mutations. Natural selection continues to exert its influence in a world of effective medicine and adequate infrastructure.

The study, if it proves correct, would change the previous concept of genetic mutations, which saw them as manifesting and being purged on a micro level, with each being eliminated one by one.

This shift in perception towards a synergistic model has serious ramifications on the theories behind gene editing processes like CRISPR. CRISPR functions according to the logic of the micro alteration proposed above, making individual changes in the genome with the hope of altering one aspect or mutation.

This finding shows, however, that genes work in synchronicity, and therefore an alteration in one could be the first domino to fall in a chain reaction, leading to wholly unexpected consequences. It gives ammunition to the scientists who are arguing that CRISPR does cause unexpected genetic mutations in a recent dispute over a paper published in Nature Methods.

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Scientists Just Encoded a GIF into the DNA of Bacteria Using CRISPR

DNA Storage

Researchers working to test the potential and limits of DNA storage have used CRISPR to insert an animated image or GIF into the genomes of live E. coli bacteria. They converted each individual pixel in the GIF into nucleotides, the components of the DNA molecule.

The ability to convert bits of information into nucleotides would make it possible to save massive amounts of data in microscopic molecules and carry them with you — even embedded in your skin. Harvard University geneticist George Church, who is leading the team behind the GIF insertion experiment, believes all of this is possible within the realm of this exciting area of research.

The five frame GIF of a horse and rider was placed into the live bacteria frame by frame. The researchers then simply needed to sequence the bacteria’s DNA to retrieve the data and reconstruct the animation. Using this method, their reconstruction was 90 percent accurate. Given that it’s possible to extract and sequence DNA from hundreds of thousands of years into Earth’s past, DNA storage is a durable way to store tremendous amounts of information in a compact space.

The other notable achievement to take away from this success with the horse and rider GIF is that the researchers were able to store and retrieve the data in the DNA of a living organism, despite the constant dynamism of live cells which change, divide, move, and die. Previous DNA storage experiments have been confined to synthetic DNA.

*5* Scientists Just Used CRISPR to Encode a GIF into Bacteria

Future Directions

Next up, the team will be exploring “living sensors” for DNA storage that are sensitive to their environment. Study researcher Seth Shipman commented to MIT Technology Review, “What we really want to make are cells that encode biological or environmental information about what’s going on within them and around them.”

Although the dream of mass DNA storage within our bodies won’t be realized anytime soon, the technique is already proving valuable to researchers. For example, scientists may be able to use DNA storage devices with sensory capabilities to record the molecular events that occur as neurons form during brain development. According to what Shipman told MIT Technology Review, researchers will be able to place these “hard drives” in bacteria, allowing them to record processes or events of interest, and then sequence their DNA to reap the informational rewards.

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Researchers Refute Study That Claims CRISPR Causes Unexpected Mutations

Wrongfully Accused?

A study published earlier this year warned scientists of potential complications in their work with CRISPR/Cas9, but after review by researchers at another institution, the findings of that study are being brought into question. The original paper was published by a team at Columbia University Medical Center (CUMC) in May of this year in the journal Nature Methods.

In the study’s original press release, co-author Stephen Tsang said: “We feel it’s critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR, including single nucleotide mutations and mutations in non-coding regions of the genome.” The researchers had sequenced the genomes of mice whose genes had previously been editing using CRISPR in an attempt to cure their blindness. The genomes revealed there were 1,500 single-nucleotide mutations and over 100 larger deletions,= and/or insertions in two of the mice which had been modified using the gene-editing technique.

How CRISPR Works: The Future of Genetic Engineering and Designer Humans
Click to View Full Infographic

In their study, the researchers attributed these genetic anomalies to the use of CRISPR — but a team of researchers from Harvard University and MIT have reviewed the paper and are challenging that attribution. In a paper published in bioRxiv — a pre-print server for biology research which is not a peer reviewed journal — the researchers pointed out the CUMC study had several serious problems. The most glaring of which, the Harvard and MIT researchers argue, is that the mutations found in the mice that were attributed to CRISPR were more likely than not already present in those mice before they were exposed to the gene-editing technique.

The third mouse whose genome had been edited with CRISPR did not demonstrate the mutations, and was also not as genetically similar as the two mice who did. The Harvard and MIT research team argue that this supports the theory that the mutations in the pair of mice were not caused by CRISPR. It should be noted that this criticism comes from a small study that was not peer reviewed.

The Importance of Peer Review

The team’s goal in refuting the research is to make sure the rest of the scientific community is reminded of the lasting impact claims that are not well supported by data can have. “Given these substantial issues, we urge the authors to revise or re-state the original conclusions of their published work so as to avoid leaving misleading and unsupported statements to persist in the literature,” the team explained in their paper.

The peer review process is essential to scientific disciplines other than biology and genetics, of course. Whether researchers are making claims about climate change, artificial intelligence, or medical treatments, rigorous review of their methods, data, and analysis by other scientists who are doing similar work is essential. This process ensures that the research — and the way it is presented — is accurate, of high quality, and will be useful not only to the scientific community, but to the general public.

For teams who have spent months — if not years — heavily focused on a single study, trial, or data set, it can be very easy to lose sight of the bigger picture. Peer review offers research teams the chance to address inconsistencies, data that doesn’t add up, and conclusions that make assumptions or inferences that aren’t supported by the data.

While there have certainly been instances where teams have intentionally fabricated data in order to mislead their peers and the public, most members of the scientific community do not mislead intentionally. But that’s why the peer review process is so important. It remains to be seen if the team at CUMC plans to revisit, or possible retract, their paper in light of the response.

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Stanford’s Final Exams Pose Question About the Ethics of Genetic Engineering

Stanford’s Moral Pickle

When bioengineering students sit down to take their final exams for Stanford University, they are faced with a moral dilemma, as well as a series of grueling technical questions that are designed to sort the intellectual wheat from the less competent chaff:

If you and your future partner are planning to have kids, would you start saving money for college tuition, or for printing the genome of your offspring?

The question is a follow up to “At what point will the cost of printing DNA to create a human equal the cost of teaching a student in Stanford?” Both questions refer to the very real possibility that it may soon be in the realm of affordability to print off whatever stretch of DNA you so desire, using genetic sequencing and a machine capable of synthesizing the four building blocks of DNA — A, C, G, and T — into whatever order you desire.

*2* Stanford Entrance Questions Ethics of Genetic Engineering

The answer to the time question, by the way, is 19 years, given that the cost of tuition at Stanford remains at $50,000 and the price of genetic printing continues the 200-fold decrease that has occurred over the last 14 years. Precursory work has already been performed; a team lead by Craig Venter created the simplest life form ever known last year.

The Ethics of Changing DNA

Stanford’s moral question, though, is a little trickier. The question is part of a larger conundrum concerning humans interfering with their own biology; since the technology is developing so quickly, the issue is no longer whether we can or can’t, but whether we should or shouldn’t. The debate has two prongs: gene editing and life printing.

With the explosion of CRISPR technology — many studies are due to start this year — the ability to edit our genetic makeup will arrive soon. But how much should we manipulate our own genes? Should the technology be a reparative one, reserved for making sick humans healthy again, or should it be used to augment our current physical restrictions, making us bigger, faster, stronger, and smarter?

The question of printing life is similar in some respects; rather than altering organisms to have the desired genetic characteristics, we could print and culture them instead — billions have already been invested. However, there is the additional issue of “playing God” by sidestepping the methods of our reproduction that have existed since the beginning of life. Even if the ethical issue of creation was answered adequately, there are the further questions of who has the right to design life, what the regulations would be, and the potential restrictions on the technology based on cost; if it’s too pricey, gene editing could be reserved only for the rich.

It is vital to discuss the ethics of gene editing in order to ensure that the technology is not abused in the future. Stanford’s question is praiseworthy because it makes today’s students, who will most likely be spearheading the technology’s developments, think about the consequences of their work.

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This New Gene-Editing Technique Can Spot CRISPR’s Mistakes

Editing The Editor

The CRISPR gene-editing tool is already in use by scientists all over the world who are racing to cure deadly diseases by editing the genomes of patients. However, as human trials for various treatments are slated to begin, we still face the hurdle of ensuring that any errors in CRISPR edits won’t causing problems. Scientists from The University of Texas at Austin may have come up with a possible solution. They’ve developed something that works like a predictive editor for CRISPR: a method for anticipating and catching the tool’s mistakes as it works, thereby allowing for the editing of disease-causing errors out of genomes. 

How CRISPR Works: The Future of Genetic Engineering and Designer Humans
Click to View Full Infographic

Scientists have already learned how to use CRISPR to edit errors in almost any genome — and it’s these errors that can cause a wide range of diseases. Many forms of cancer, Huntington’s disease, and even HIV can be targeted using CRISPR. That being said, it’s not a perfect solution. Just as the autocorrect on your smartphone can cause you to send an unintentional and embarrassing text message, CRISPR can “correct” something that was actually right — the consequences of which can make it a dangerous mistake. One that actually causes a disease as opposed to an embarrassing social gaffe.

The researchers developed a method for quickly testing a CRISPR molecule against a person’s entire genome, rather than only the target area, in order to predict other segments of DNA the tool might accidentally interact with. This new technique functions like an early warning system, giving doctors a chance to more closely tailor gene therapies to specific patients, while ensuring they are effective and safe.

“If we’re going to use CRISPR to improve peoples’ health, we need to make sure we minimize collateral damage, and this work shows a way to do that,”Stephen Jones, UT Austin postdoctoral researcher and co-lead author of the study, told the UT News.

More Accurate Predictions

This research will also allow scientists to improve their own predictive skills when it comes to CRISPR molecule behaviors — even without genome testing. This is because the work is actually revealing the “rule book” CRISPR molecules follow when they choose targets.

One CRISPR molecule the team tested, Cascade, targets DNA sequences but pays less attention to every third letter in the sequence. “So if it were looking for the word ‘shirt’ and instead found the word ‘short,’ it might be fine with that,” Jones said, explaining the significance of the quirk to the UT News.

As researchers master these rules, they will be able to develop better predictive models for CRISPR therapies. This will make the technique faster and cheaper, which will in turn render personalized gene therapies more accessible to more patients. Most important of all, it will also help make the entire process far safer.

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Is Getting Genetically Engineered a Human Right?

Paying For Cures

CRISPR, a gene editing tool, is at the heart of numerous new medical treatments and technologies. Some of the incredible uses of CRISPR we’ve seen in the past year alone include editing phages to kill antibiotic-resistant bacteria; targeting cancer’s “command center” in mice, boosting survival rates from 0 to 100 percent; repairing the gene defects that cause sickle cell disease; and copying the T-cells of naturally HIV-immune individuals.

However, even as CRISPR moves toward clinical trials and practical use, its future remains unclear. This is due to the extreme cost of CRISPR treatments; most people simply cannot afford them, and whether insurance carriers will pay the tab is uncertain. Some insurance companies have already implemented no coverage policies for gene therapies; the American healthcare system is ever-changing, and it’s seeming increasingly likely that these extremely expensive therapies might be out of reach even for people with insurance.

How CRISPR Works: The Future of Genetic Engineering and Designer Humans
Click to View Full Infographic

StatNews reports that oncologist and author Dr. Siddhartha Mukherjee, who wrote the bestseller Emperor of All Maladies, told the American Society of Clinical Oncology in spring that the world would soon be divided “into the rich who can afford personalized cancer treatment and the poor who cannot.” The case of Glybera, a gene therapy infamously called “the most expensive drug in the world,” adds more credence to this concern. At a whopping $1.4 million per patient, Glybera was sold only once in Germany, abandoned in the EU, and never came to the US market due to its cost.

Much of the issue arises as we try to treat and cure rare diseases, which the United States defines as diseases that affect fewer than 200,000 people and the European Union defines as one that affects fewer than 1 in 2,000 people. However, cumulatively, rare diseases effect an estimated 25 to 30 million Americans, and there could be up to 7,000 rare diseases.

Funding Research Matters

The tension comes at the nexus between multiple market forces: drug companies who want to invest in research and profit from their investment; insurance companies who must maximize profit for shareholders while insuring as many people as possible; governments and leaders with different policies about intervention into the system; scientists who may have independent interest in conducting research but must find a way to fund it; and patients (some with insurance, some without) who are interested or, in some cases, desperate for treatments and cures. How to relieve the tension and allow science to progress in the best way for the most people is a difficult question, but various experts have ideas.

University of Alberta law and policy expert Tania Bubela suggests to StatNews that insurers should be allowed to reimburse drug companies for gene therapies before they receive FDA approval, requiring them to amass more data before increasing drug costs to full price. Another partial solution might be to grant CRISPR licenses one gene at a time rather than issuing exclusive patents on tools like CRISPR. Other creative intellectual property strategies have been proposed by the Rare Genomics Institute. Pediatric oncologist Stuart Orkin and Phillip Reilly, a Third Rock Ventures partner, along with FDA commissioner Scott Gottlieb, advocate for spreading insurer payments to companies out over years of time contingent upon the drug’s continued performance, a sort of annuities structure; this would recognize the value in paying for even expensive drugs rather than years of care and treatment for expensive diseases.

Some form of government intervention is probably inevitable, according to most experts. The US Orphan Drug Act, for example, facilitates the development of treatments and drugs for rare diseases; Orkin and Reilly argue that funds from the Act could pay for gene therapies. The 2009 Biologics Price Competition and Innovation Act made generic biologics, called biosimilars, possible. However, generic forms of CRISPR are not likely to come for decades. Where does this leave us?

StatNews writer Jim Kozubek frames the ultimate issue, suggesting two possible outcomes. “One of two things will happen: either we will embrace a national health care system with broad access but that severely limits expensive new drugs, gene therapies, and CRISPR-based biologics; or these treatments will be available to only the wealthiest among us who can pay for them, a dystopian vision which is perverse but perhaps more realistic considering the pressures for a return on investment.”

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Scientists Want to Genetically Engineer Heat-Resistant Cows to Survive Climate Change

Can Cows Take the Heat?

The University of Florida Institute of Food and Agricultural Sciences (UF/IFAS) has proposed a plan to make cows more resistant to the temperature increase caused by global warming. The proposal has received a three-year, $733,000 federal grant.

The scientists’ plan aims to retain the quality meat cows provide while increasing the efficiency of the process in spite of a changing climate. The first step is conducting research on cows that already handle the heat pretty well. By studying the Brangus cow, researchers hope to identify how it regulates its body temperature, which allows it thrive in hotter climates. Once identified, researchers could use a gene editing tool to give that ability to other breeds.

Dr Rachel Mateescu, associate professor in the UF/IFAS department of animal sciences, told Digital Trends:

“Heat stress is a principal factor limiting production of animal protein and negatively affecting health and welfare of cattle in subtropical and tropical regions, and its impact is expected to increase dramatically due to climate change […] the ability to cope with heat stress is imperative to enhance productivity of the U.S. livestock industry and secure global food supplies.”

*3* Plan to Make Cows Heat Resistant Receives Funding

What Humans Can Learn

That a venture like this received funding is a sign of two things that many in the scientific community have been well aware of, but that they may not have yet connected: the rate at which the climate is changing, and the potential of gene editing software.

Climate change is fundamentally changing our world. It’s even changing the genetics of several species — including humans — as well as altering the function of entire ecosystems.

As funding for this research is contingent on viability, it’s also a chance to demonstrate the rapid progress made in gene editing software, which has been catalyzed by CRISPR. Since its first demonstration in 2013, an enormous amount of research has been conducted using it. The future of gene editing with CRISPR’s help looks bright, too: many trials have or are set to begin this year, including attempts to modify viruses to kill antibiotic resistant bacteria and revive extinct species.

While it seems more logical to reduce global warming rather than try to deal with its consequences, should the preventative method fail, the only solutions that we could turn to are those previously reserved for the realms of science fiction, like changing our genetic makeup — or migrating to another planet.

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A New Gene-Editing Breakthrough Could Forever Change Life on Earth

CRISPR

The discovery of the gene-editing technology CRISPR came, in part, from Jennifer Doudna, a biochemist at the University of California, Berkeley. “It’s very profound,” she told NBC News. “It means that we can control human evolution now.”

With collaborator Emmanuelle Charpentier, Doudna was able to harness a curiosity in the DNA of certain bacteria and help turn CRISPR into the world’s most accessible gene-editing technology. The discovery is detailed in Doudna’s new book titled “A Crack in Creation.”

The Dangers of Gene-Editing

In the book, Doudna says that the days of costly, complicated processes to edit DNA are over. We’re now in an age of CRISPR, and it’s a profoundly simple technique. Doudna compares CRISPR to word-processing software that allows someone to correct a typo in a hefty document.

At the Innovative Genomics Institute in Berkeley where Doudna is executive director, teams of scientists are working to find new approaches to treating disorders like cancer, sickle cell anemia, and some forms of blindness. But CRISPR isn’t limited to Doudna’s lab. Its low cost and ease of use have helped the technology proliferate to labs all over the world.

hiv crispr-cas9 gene editing hiv cure
Image Source: National Institute of Allergy and Infectious Diseases, National Institutes of Health

At UT Southwestern in Dallas, Dr. Eric Olson is chasing a cure for Duchenne muscular dystrophy. At an insectary at UC Irvine, Dr. Anthony James has created mosquitoes that can pass on malaria resistance to some of their offspring. At the Salk Institute in La Jolla, Calif., CRISPR is being used to pursue a gene-engineered pig with transplantable human organs.

But with the thrill of discovering such a powerful tool came a somber realization. Doudna describes a nightmare: “Hitler was leaning forward and looking at me very intently. And he said, ‘So please tell me about the CRISPR technology.’ And I just felt this chill running down my back.”

Doudna knows better than anyone that with the power to alter evolution comes a daunting responsibility: Make sure it doesn’t get misused.

This Gene-Editing Breakthrough Could Change Life on Earth was originally published by NBC Universal Media, LLC on June 15, 2017 by Munir Atalla and Brenda Breslauer. Copyright 2017 NBC Universal Media, LLC. All rights reserved.

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Scientists Modify Viruses with CRISPR to Kill Antibiotic-Resistant Bacteria

CRISPR-Powered Viruses

Earlier this month, the annual CRISPR 2017 conference was held at Montana State University. Attendees were the first to hear about successes companies have had using CRISPR to engineer viruses to kill bacteria. One of the most exciting potential application for these viruses, called bacteriophages, would be killing bacteria that have become resistant to antibiotics. At least two of the companies aim to start clinical trials of these engineered viruses within 18 to 24 months.

The use of bacteriophages isn’t new. In the past, they have been isolated in the wild and purified for use. Although bacteriophages are regarded as being safe and effective for use in humans, because they are found in the wild, research on them has been sluggish. New discoveries can’t be patented, and furthermore, these discoveries can also be transient, because bacteria can, and often do, rapidly evolve.

However, using CRISPR to engineer them is definitely innovative. It renders viruses uniquely lethal to the most dangerous bacteria in the world, and initial tests saved the lives of mice who were infected with antibiotic-resistant infections that would have ultimately killed them, explained conference speaker Rodolphe Barrangou, chief scientific officer of Locus Biosciences.

This ability has lead researchers from at least two companies to use CRISPR in an attempt to turn the tables on antibiotic-resistant bacteria. Both companies cite treating bacterial infections linked to serious diseases as their primary goal. Eventually, they intend to engineer viruses that would allow them to do much more by taking a precision approach to the human microbiome as a whole. The idea would be to selectively remove any bacteria that occur naturally and have been associated with various health conditions. This could be anything from autism to obesity — and possibly even some forms of cancer.

How CRISPR Works: The Future of Genetic Engineering and Designer Humans
Click to View Full Infographic

Self-Destruct Switches

One company, Locus, is using CRISPR to send DNA that will create modified guide RNAs to find pieces of the antibiotic-resistance gene. After the virus infects the bacterium and the guide RNA connects with the resistance gene, the bacterium produces a phage-killing enzyme called Cas3. This is the bacterium’s usual response, only in this instance, it destroys its own antibiotic-resisting genetic sequence. Over time Cas3 destroys all of the DNA, and the bacterium dies.

Another company, Eligo Bioscience, is taking a slightly different approach. The team chose to insert the DNA that creates guide RNAs (this time with the bacterial enzyme Cas9), which removes all genetic replication instructions. Cas9 then severs the DNA of the bacterium at a specific place, and that cut triggers the self-destruct mechanism in the bacterium.

The third approach, by Synthetic Genomics, involves creating “supercharged” phages that contain dozens of enzymes. Each enzyme offers its own unique set of benefits, including the ability to camouflage the phages from the human immune system by breaking down proteins or biofilms.

Despite these promising results thus far, there will be challenges to bringing successful engineered phages to market. For example, there is a risk that phages could actually spread genes for antibiotic-resistance to non-resistant bacteria. Another potential issue is that it might take a very large number of phages to treat an infection, which in turn could trigger immune reactions that would sabotage the treatment.

Ideally, though, if clinical trials go well, engineered phages could provide humans with a powerful weapon in the fight against superbugs. A fight that has, thus far, included a variety of strategies. Whenever it happens, it wouldn’t be soon enough: this past January, the Centers for Disease Control (CDC) reported that a patient died from a superbug that was resistant to all 26 antibiotics available in the US.

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A World First CRISPR Trial Will Edit Genes Inside the Human Body

Uninvasive CRISPR

A new CRISPR trial, which hopes to eliminate the human papillomavirus (HPV), is set to be the first to attempt to use the technique inside the human body. In the non-invasive treatment, scientists will apply a gel that carries the necessary DNA coding for the CRISPR machinery to the cervixes of 60 women between the ages of 18 and 50. The team aims to disable the tumor growth mechanism in HPV cells.

The trial stands in contradistinction to the usual CRISPR method of extracting cells and re-injecting them into the affected area; although it will still use the Cas9 enzyme (which acts as a pair of ‘molecular scissors’) and guiding RNA that is typical of the process.

How CRISPR Works: The Future of Genetic Engineering and Designer Humans
Click to View Full Infographic

20 trials are set to begin in the rest of 2017 and early 2018. Most of the research will occur in China, and will focus on disabling cancer’s PD-1 gene that fools the human immune system into not attacking the cells. Different trials are focusing on different types of cancer including breast, bladder, esophageal, kidney, and prostate cancers.

Modifying Our World

The study, if it succeeds, will be promising for sufferers of HPV and act as a milestone in the CRISPR process. Although HPV is not necessarily cancerous, it can cause cervical cancer. In the U.S. alone, there are more than 3 million new infections every year. Although there is a vaccine for the virus, currently, once you have it you can never get rid of it.

More generally, the CRISPR process could be nothing short of a miracle: if it passes all medical tests it wouldn’t just make medicine a whole new kettle of fish, it would reinvent the kettle…and the fish, for almost any field. It is cheaper than other gene editing therapies, and could potentially save millions of lives by curing diseases we can only deal with therapeutically like cancer, diabetes and cystic-fibrosis. Crops could be altered more effectively using the process. Drugs and materials that were never possible before could be pioneered.

However, it is still extremely nascent technology, and many fear that there could also be a host of unexpected consequences. Recently, it has been found that it causes hundreds of unexpected mutations in DNA. While these concerns are valid, more research is necessary. Which is why the upcoming studies over the next few years are so vital to the future of our health.

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CRISPR Gene Editing May Cause Hundreds of Unintended Mutations in DNA

Potential Hazards

Gene editing is a relatively new technology, and no other method currently available is as fast, precise, and efficient as CRISPR-Cas9. It has had unprecedented success in a number of fields, particularly in medicine—allowing scientists to edit HIV out of living organisms and engineer an end to malaria through the modification of mosquitoes.

Chinese scientists asserts that they’ve already used CRISPR on a human being, and clinical trials are in the mix in many locals (including the United States). Given the expected widespread use of CRSIPR in the world of tomorrow, researchers from the Columbia University Medical Center (CUMC) are offering a word of caution. A study published in the journal Nature Methods revealed that CRISPR-Cas9 can lead to unintended mutations in a genome.

“We feel it’s critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR, including single nucleotide mutations and mutations in non-coding regions of the genome,” co-author Stephen Tsang, from CUMC, said in a press release.

In the study, Tsang’s team sequenced the genome of mice that they had previously used CRISPR on in an attempt to cure their blindness. They looked for all possible mutations, even those that might have changed just a single nucleotide. The researchers discovered a staggering 1,500 single-nucleotide mutations and over 100 larger deletions and insertions in the genomes of two of the recipients.

To better understand the difference between single nucleotide changes and larger deletions, see the below infographic:

Refining Methods

The study isn’t suggesting a wholesale ban on CRISPR—not even close. After all, CRISPR was found to be effective in the mice they used it on. Instead, the scientists are offering caution, and calling for a clearer method of checking for mutations, deletions, or insertions into genomes. They propose doing whole-genome sequencing instead of relying on computer algorithms, which didn’t detect any of the mutations they discovered in the study.

“We hope our findings will encourage others to use whole-genome sequencing as a method to determine all the off-target effects of their CRISPR techniques and study different versions for the safest, most accurate editing,” Tsang said.

“[P]redictive algorithms seem to do a good job when CRISPR is performed in cells or tissues in a dish, but whole genome sequencing has not been employed to look for all off-target effects in living animals,” added co-author Alexander Bassuk, from the University of Iowa.

The potential of the CRISPR-Cas9 system as a gene editing technology is undeniable. As previously mentioned, already, it has seen success in developing possible cancer treatments, in making animals disease-resistant, and has shown promise in even replacing antibiotics altogether.

It has also been used to program living cells into digital circuitry. Among its more exciting — and perhaps dangerous(?) — applications is nothing short of a Jurassic Park-esque revival of extinct species. There seems to be no limit to what CRISPR can do.

However, as this research reveals, in order to realize the full potential of gene editing, and to ensure that living organisms aren’t harmed as a result of the edits that we make to DNA—the source code of life itself—we must advance slowly and with careful scrutiny.

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In Just a Few Short Years, CRISPR Has Sparked a Research Revolution

There’s a revolution happening in biology, and its name is CRISPR.

CRISPR (pronounced “crisper”) is a powerful technique for editing DNA. It has received an enormous amount of attention in the scientific and popular press, largely based on the promise of what this powerful gene editing technology will someday do.

CRISPR was Science magazine’s 2015 Breakthrough of the Year; it’s been featured prominently in the New Yorker more than once; and The Hollywood Reporter revealed that Jennifer Lopez will be the executive producer on an upcoming CRISPR-themed NBC bio-crime drama. Not bad for a molecular biology laboratory technique.

Two of the CRISPR co-inventors, Emmanuelle Charpentier (middle-left) and Jennifer Doudna (middle-right), rubbing elbows with celebs after receiving the 2015 Breakthrough Prize in Life Sciences. Image Credit: Breakthrough Prize Foundation, CC BY-ND

CRISPR is not the first molecular tool designed to edit DNA, but it gained its fame because it solves some longstanding problems in the field. First, it is highly specific. When properly set up, the molecular scissors that make up the CRISPR system will snip target DNA only where you want them to. It is also incredibly cheap. Unlike previous gene editing systems which could cost thousands of dollars, a relative novice can purchase a CRISPR toolkit for less than US$50.

Research labs around the world are in the process of turning the hype surrounding the CRISPR technique into real results. Addgene, a nonprofit supplier of scientific reagents, has shipped tens of thousands of CRISPR toolkits to researchers in more than 80 countries, and the scientific literature is now packed with thousands of CRISPR-related publications.

When you give scientists access to powerful tools, they can produce some pretty amazing results.

The CRISPR revolution in medicine

The most promising (and obvious) applications of gene editing are in medicine. As we learn more about the molecular underpinnings of various diseases, stunning progress has been made in correcting genetic diseases in the laboratory just over the past few years.

Take, for example, muscular dystrophy — a complex and devastating family of diseases characterized by the breakdown of a molecular component of muscle called dystrophin. For some types of muscular dystrophy, the cause of the breakdown is understood at the DNA level.

In 2014, researchers at the University of Texas showed that CRISPR could correct mutations associated with muscular dystrophy in isolated fertilized mouse eggs which, after being reimplanted, then grew into healthy mice. By February of this year, a team here at the University of Washington published results of a CRISPR-based gene replacement therapy which largely repaired the effects of Duchenne muscular dystrophy in adult mice. These mice showed significantly improved muscle strength — approaching normal levels — four months after receiving treatment.

Using CRISPR to correct disease-causing genetic mutations is certainly not a panacea. For starters, many diseases have causes outside the letters of our DNA. And even for diseases that are genetically encoded, making sense of the six billion DNA letters that comprise the human genome is no small task. But here CRISPR is again advancing science; by adding or removing new mutations — or even turning whole genes on or off — scientists are beginning to probe the basic code of life like never before.

CRISPR is already showing health applications beyond editing the DNA in our cells. A large team out of Harvard and MIT just debuted a CRISPR-based technology that enables precise detection of pathogens like Zika and dengue virus at extremely low cost — an estimated $0.61 per sample.

Using their system, the molecular components of CRISPR are dried up and smeared onto a strip of paper. Samples of bodily fluid (blood serum, urine, or saliva) can be applied to these strips in the field and, because they linked CRISPR components to fluorescent particles, the amount of a specific virus in the sample can be quantified based on a visual readout. A sample that glows bright green could indicate a life-threatening dengue virus infection, for instance. The technology can also distinguish between bacterial species (useful for diagnosing infection) and could even determine mutations specific to an individual patient’s cancer (useful for personalized medicine).

In Just a Few Short Years, CRISPR Has Sparked a Research Revolution
Feng Zhang, another co-inventor of CRISPR technology, discussing its safety and ethical ramifications. Image Credit: AP Photo/Susan Walsh

Almost all of CRISPR’s advances in improving human health remain in an early, experimental phase. We may not have to wait long to see this technology make its way into actual, living people though; the CEO of the biotech company Editas has announced plans to file paperwork with the Food and Drug Administration for an investigational new drug (a necessary legal step before beginning clinical trials) later this year. The company intends to use CRISPR to correct mutations in a gene associated with the most common cause of inherited childhood blindness.

CRISPR will soon affect what we eat

Physicians and medical researchers are not the only ones interested in making precise changes to DNA. In 2013, agricultural biotechnologists demonstrated that genes in rice and other crops could be modified using CRISPR — for instance, to silence a gene associated with susceptibility to bacterial blight. Less than a year later, a different group showed that CRISPR also worked in pigs. In this case, researchers sought to modify a gene related to blood coagulation, as leftover blood can promote bacterial growth in meat.

You won’t find CRISPR-modified food in your local grocery store just yet. As with medical applications, agricultural gene editing breakthroughs achieved in the laboratory take time to mature into commercially viable products, which must then be determined to be safe. Here again, though, CRISPR is changing things.

A common perception of what it means to genetically modify a crop involves swapping genes from one organism to another — putting a fish gene into a tomato, for example. While this type of genetic modification — known as transfection — has actually been used, there are other ways to change DNA. CRISPR has the advantage of being much more programmable than previous gene editing technologies, meaning very specific changes can be made in just a few DNA letters.

White Agaricus bisporus mushrooms with no browning are more visually appealing. Image Credit: Olha Afanasieva/Shutterstock.com

This precision led Yinong Yang — a plant biologist at Penn State — to write a letter to the USDA in 2015 seeking clarification on a current research project. He was in the process of modifying an edible white mushroom so it would brown less on the shelf. This could be accomplished, he discovered, by turning down the volume of just one gene.

Yang was doing this work using CRISPR, and because his process did not introduce any foreign DNA into the mushrooms, he wanted to know if the product would be considered a “regulated article” by the Animal and Plant Health Inspection Service, a division of the U.S. Department of Agriculture tasked with regulating GMOs.

“APHIS does not consider CRISPR/Cas9-edited white button mushrooms as described in your October 30, 2015 letter to be regulated,” they replied.

Yang’s mushrooms were not the first genetically modified crop deemed exempt from current USDA regulation, but they were the first made using CRISPR. The heightened attention that CRISPR has brought to the gene editing field is forcing policymakers in the U.S. and abroad to update some of their thinking around what it means to genetically modify food.

New frontiers for CRISPR

One particularly controversial application of this powerful gene editing technology is the possibility of driving certain species to extinction — such as the most lethal animal on Earth, the malaria-causing Anopheles gambiae mosquito. This is, as far as scientists can tell, actually possible, and some serious players like the Bill and Melinda Gates Foundation are already investing in the project. (The BMGF funds The Conversation Africa.)

Most CRISPR applications are not nearly as ethically fraught. Here at the University of Washington, CRISPR is helping researchers understand how embryonic stem cells mature, how DNA can be spatially reorganized inside living cells, and why some frogs can regrow their spinal cords (an ability we humans do not share).

It is safe to say CRISPR is more than just hype. Centuries ago we were writing on clay tablets — in this century we will write the stuff of life.

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New CRISPR Technique Targets and Destroys Cancer’s Command Center

The Age of CRISPR

The past several months have been no less than astounding ones for the CRISPR gene-editing tool. In September, 2016, researchers in Germany discovered a way to use CRISPR to edit out cancer mutations. In November, Chinese researchers used CRISPR technology on a person for the first time. Then, in January if this year, researchers uncovered two distinct anti-CRISPR proteins that could lead to a CRISPR “off switch” and greater control over the gene editing tool in human subjects.

How CRISPR Works: The Future of Genetic Engineering and Designer Humans
Click to View Full Infographic

Now, researchers from the University of Pittsburgh have used CRISPR to target cancer’s “command center,” increasing survival rates and shrinking aggressive tumors without harming healthy cells in mice. The method targets fusion genes, mutations that develop when two distinct genes combine into a single, hybrid gene — one that often leads to cancer. They published their results in Nature Biotechnology earlier this week.

The team transplanted human liver and prostate cancer cells into mice, and then used the CRISPR fusion gene targeting tool to treat them. The control group’s treatment targeted fusion genes that weren’t present in their bodies — making it ineffective. Their tumors grew nearly 40 times larger, and spread to other parts of the body in most cases. None of the control group survived the test period.

The treatment for the experimental group targeted fusion genes that were present in their tumors, and the tumors shrunk by up to 30 percent and didn’t spread. Most impressively, all of the animals that received the experimental treatment survived to the end of the test — representing an increase in survival rate from 0 to 100 percent.

Remission — Or Elimination?

The fact that these fusion genes are genetically unique makes them an easy target for CRISPR, which can target them and replace them with something else. In this case, researchers replace them with genes that kill cancer, ensuring healthy cells stay well — something chemotherapy can’t do.

Via Pixabay
Credit: Pixabay

While these dramatic results are exciting, they do not necessarily mean that the treatment will be effective in people, and no plans for clinical trials have been announced as of yet. Before the treatment is tested in humans, the researchers hope to improve it. Although the current research demonstrates that the technique can force the cancer cells into remission, the scientists want to test whether it could entirely wipe the cancer out instead.

“This is the first time that gene editing has been used to specifically target cancer fusion genes,” Jian-Hua Luo, lead author of the study, said in a press release. “It is really exciting because it lays the groundwork for what could become a totally new approach to treating cancer. Other types of cancer treatments target the foot soldiers of the army. Our approach is to target the command center, so there is no chance for the enemy’s soldiers to regroup in the battlefield for a comeback.”

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There’s Never Been a More Exciting Time to Work in the Biological Sciences

Daria Hazuda, Merck’s vice president of infectious disease discovery and chief scientific officer of MRL Cambridge Exploratory Science Center, is a 25-year industry veteran.

That means the researcher has been in drug discovery — the earliest stage of the drug development process — long enough to see her fair share of successes, like the development of treatments for HIV, as well as failures.

But of all the years of innovation and cutting-edge ideas she’s experienced, she told Business Insider that right now is the best time to be in the field.

“Today is the most exciting time to be in the biological sciences,” she told Business Insider.

That’s for a few reasons, she said.

  • There’s been an explosion of new research on the microbiome, or the microorganisms that live in and on our bodies that play a role in our overall health, compared to five years ago when there was just a trickle of new developments.
  • Then there’s CRISPR, the groundbreaking gene-editing tool that could one day manipulate cells to create new therapies.
  • There’s also been better research on the immune system, which in turn is helping build a better understanding of infectious diseases, Hazuda said.
  • Research into infectious disease biology, the research Hazuda works on, is now expanding beyond pathogens (the bacteria, viruses or other organisms that cause disease). Now, Hazuda and other researchers are learning more about entire “constellations of organisms,” such as mosquitoes or zebra fish. These external creatures could be an important piece of human health, even if they’re not inside the body, she said.
Why a scientist who’s worked in the drug industry for 25 years thinks ‘today is the most exciting time to be in the biological sciences’ [Kelsey]
UC Davis College of Engineering/flickr

But even with these developments, there’s still a lot we don’t know about the biological sciences, Hazuda said. It’s why her employer Merck set up a video in which the company asked people what inventions they can’t wait for. Very few mentioned new ways to treat diseases.

“It’s important for people to understand that there are still amazing discoveries that are yet to be made,” she said. “What looks crazy today will become routine in the future.”

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A New “CRISPR Pill” Makes Bacteria Destroy Its Own DNA

Targeted and Edible

As antibiotic resistance continues to grow, scientists are desperately trying to figure out how to best fight bacterium like Clostridium difficile, which can cause fatal infections in hospitals and nursing homes. C. difficile has been ranked by the U.S. Centers for Disease Control and Prevention (CDC) as a top drug-resistant threat responsible for about 15,000 deaths per year. Several means are being explored to counter the pandemic, the most recent coming from a project funded by the National Institute of Health.

*3* This CRISPR Pill Could Replace Antibiotics
Clostridium difficile. Credit: CDC

The proposed solution uses CRISPR, the world’s most precise and efficient gene editing technology currently available. Jan-Peter van Pijkeren, a food scientist from the University of Wisconsin-Madison, is creating a probiotic cocktail that patients can swallow as a liquid or pill.

The cocktail of bacteria will include a bacteriophage – a virus that infects bacteria – capable of carrying a customized, false, CRISPR message to C. difficile. This message would cause C. difficile to make lethal cuts to its own DNA.

Better Than Antibiotics

Currently, this probiotic is still in its early stages, according to van Pijkeren, and is yet to be tested on animals. Luckily, similar studies have proven the effectiveness of bacteriophage-delivered CRISPR in killing bacteria. However, researchers still have some concerns.

How CRISPR Works: The Future of Genetic Engineering and Designer Humans
Click to View Full Infographic

“The downside of antibiotics is they are a sledgehammer that depletes and destroys the gut microbial community,” van Pijkeren said to the University of Wisconsin-Madison. “You want to instead use a scalpel in order to specifically eradicate the microbe of interest.”

CRISPR is ideal for this use because such drugs would be very specific to the user. They could kill a single species of germ while leaving good bacterial untouched. In contract, regular antibiotics kill off both good and bad bacteria, leading to resistance. If proven successful, CRISPR could become, not just the world’s most effective gene editing tool, but also the best bacteria-killing technology available. While this is a long way off, it still gives hope to thousands.

“As long as we house patients together in a hospital or in a nursing home and we give a lot of them antibiotics we’re going to have a problem with C. difficile,” says Herbert DuPont, director of the Center for Infectious Diseases at the University of Texas to MIT Technology Review. 

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CRISPR Gives Us the Power to End Diseases and Remake Species

Could vs Should

In 2013, some 200 million humans suffered from malaria, and an estimated 584,000 of them died, 90 percent in Africa. The vast majority of those killed were children under age 5. Decades of research have fallen short of a vaccine for this scourge. A powerful new technique that allows scientists to selectively edit entire genomes could provide a solution, but it also poses risks—and ethical questions science is only beginning to address.

The technique relies on a tool called a gene drive, something scientists have discussed since 2003 but which has only recently become possible. A gene drive greatly increases the odds that a particular gene will be inherited by all future generations. Genes occasionally evolve the ability naturally, but if we could engineer it deliberately, small interventions could have enormous impact, giving scientists the power to eradicate diseases, remove invasive species, and wholly remake the natural landscape.

One proposed use of a gene drive would alter the genetic code of a few mosquitoes that carry the malaria parasite, ensuring that the ‘Y’ chromosome would always be passed on. The result is a male-only line that systematically topples the population’s gender balance. Once started, a carefully implemented gene drive could eradicate the entire malaria-causing Anopheles species.

“Its advantage over vaccines is that you don’t have to go out and inject every person at risk,” says George Church, a geneticist at the Wyss Institute at Harvard Medical School. “You simply have to introduce a small number of mosquitoes into the wild, and they do all the work. They become your foot soldiers, or your cadre of nurses.”

The question becomes ‘Should we?’ rather than ‘Can we?’ To what extent do scientists have the right to work on problems where, if they screw up, it could affect us all? – Kevin Esvelt

But because gene drives spread the adaptation throughout an entire population, some scientists are concerned that the technology is advancing before we have a conversation about the best ways to use it wisely – and safely.

“Of all the species that cause human suffering, the malarial mosquito is arguably number one,” says Kevin Esvelt, a researcher at the Wyss Institute. “If a gene drive would allow us to eradicate malaria the way we eradicated smallpox, that’s a possibility we at least need to consider. At the same time, this raises questions of, who gets to decide? Given the urgency of problems like malaria, we should probably be talking about it now.”

The Machinery of Gene Drives

Interest in gene drives’ potential has intensified since 2012, when scientists developed the gene-editing technique known as CRISPR (for DNA sequences called clustered regularly interspaced short palindromic repeats). Derived from a bacterial defense strategy, CRISPR is a search, cut-and-paste system that works in any cell. It uses an enzyme to home in on a specific nucleotide sequence, slice it, and replace it with others of the scientists’ choosing. CRISPR is cheap and precise, making gene drives viable.

In normal sexual reproduction, offspring inherit a random half of genes from each parent. By encoding the CRISPR editing machinery in a genome along with whatever new trait you’d want to include, you would ensure that any offspring not only have the new mutation, but the tools to give that same trait to the next generation, and so on. The gene then drives through an entire population exponentially.

“It would be as if in your family, all of your daughters and sons insisted that all of their daughters and sons would have the same last name. Then your name would spread throughout the population,” Church says.

Mosquitoes reproduce quickly, making them an ideal target for CRISPR modification, Esvelt says. If the mutation reduced mosquitoes’ offspring or rendered males sterile, the population could be wiped out in a single season—along with the parasite that causes malaria.

This would require more work to isolate the genes involved, however. The technique also needs to become more efficient, Church says. The enzyme that hunts down target DNA sequences sometimes misses its mark, which could introduce unintended—and harmful—changes in the genome that spread throughout the species.

Genetic Upgrades or Risks

These ethical and safety concerns came into stark relief in April, when Chinese scientists reported editing the genomes of human embryos. The embryos were already non-viable, meaning they would not have resulted in live birth. CRISPR-mediated changes to their chromosomes were unsuccessful, and resulted in several off-target mutations, according to the researchers, led by Junjiu Huang at Sun Yat-sen University in Guangzhou, China. The paper set off a firestorm of controversy and calls for a moratorium on such research, including from the National Academies and the White House Office of Science and Technology Policy.

“We should be very concerned about the prospect of using these gene editing techniques for altering traits that are passed on,” says Marcy Darnovsky, executive director of the Center for Genetics and Society, a California-based nonprofit. “If you think about how that could—or perhaps would—likely play out in the social, political, and commercial environment in which we all live, it’s easy to see how you could get into hot water pretty quickly. You could have wealthy people purchasing genetic upgrades for their children, for instance. It sounds like science fiction.”

Even if gene drives are only used in pests, ethical questions still loom large. Eliminating a whole mosquito species could make way for new pests, or disrupt predators who feast on the insects, Esvelt says. And there could be human consequences, too. David Gurwitz, a neuroscientist at Tel Aviv University in Israel, wrote in an August 2014 letter to the journal Science that gene drives could also be used for nefarious purposes.

“Just as gene drives can make mosquitoes unfit for hosting and spreading the malaria parasite, they could conceivably be designed with gene drives carrying cargo for delivering lethal bacteria toxins to humans. Other scary scenarios, such as targeted attacks on major crop plants, could also be envisaged,” he wrote. He called for elements of CRISPR editing techniques to stay out of the scientific literature. In an email, he said he is “amazed at the lack of public discussion” to date on gene drive use.

Offense vs. Defense

In part because it is so inexpensive—the reagents and plasmid DNA used in CRISPR modification can be had for under $100, Church says—the method has spread through labs around the world like wildfire. “It’s hard to keep people from doing things that are simple and cheap,” he says. It has been shown to work in at least 30 organisms, according to Esvelt. As CRISPR use becomes more common, Esvelt, Church and their colleagues have aimed to develop ways to ensure its safety.

If one modified organism escapes from a lab and is able to breed with a wild relative, its altered gene would quickly spread through the entire population, making containment especially important. In April 2014, Esvelt, Church and a team of scientists published a commentary in Science suggesting methods for preventing accidental gene drive releases, such as conducting experiments on malarial mosquitoes in climates where no Anopheles relatives live. Esvelt also suggests CRISPR itself could be used to reverse an accidental release, by simply undoing the edit.

In April 2015, Church and colleagues and a separate team led by Alexis Rovner and Farren Isaccs of Yale University reported two new ways to generate modified organisms that could never survive outside a lab. Both approaches make the altered organism dependent on an unnatural amino acid they could never obtain in the wild.

Turning this concept inside out could yield engineered pests or weeds that succumb to natural substances that don’t harm anything else, Esvelt says. Instead of modifying crops to resist a broad-spectrum herbicide, for instance, gene drives could modify the weeds themselves: “You could create a vulnerability that did not previously exist to a compound that would not harm any other living thing.”

But any containment methods would have to follow the law, which remains murky, he says. Absent a national policy—which Darnovsky says should come from Congress—scientists should be talking about how, and when, CRISPR should be used.

“The question becomes ‘Should we?’ rather than ‘Can we?’” Esvelt says. “To what extent do scientists have the right to work on problems where, if they screw up, it could affect us all?”

Darnovsky, who notes that scientists have only just begun to understand the machinery of life as it evolved over millions of years, argues that scientists should not monopolize discussions about the use of CRISPR.

“We need to develop habits of mind, or habits of social interaction, that will allow for some very robust public participation on the use of these very powerful technologies,” she says. “It’s the future of life. It’s an issue that affects everybody.”

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Genetic Engineering Can Help Us Save Animals’ Lives

Manipulating Genetics With or Without CRISPR

From tackling cancer to eradicating single-gene mutations, the CRISPR/Cas9 gene editing tool is often portrayed as the eighth wonder of the world by many. We look to CRISPR regarding how it affects us as a species, but the implications of the CRISPR Cas-9 system extend far beyond just humanity. The gene editing tool’s precision and efficacy can be implemented in manipulating the genetics of our agriculture as well as animals. It would be wrong, however, to think that this is humanity’s first attempt at the genetic manipulation of crops and pets alike—to be fair, we have been doing it since the inception of human civilization itself.

Thirty thousand years ago, our ancestors were the first individuals to manufacture genetically modified organisms (GMOs) before it was cool. Through selective breeding or artificial selection, wild wolves in East Asia were selected for docility. With more obedient animals at their side, humans from 32,000 BCE could optimize their hunter/gatherer lifestyles. After several millennia, the artificially-selected wolves began to resemble the dogs we see today. Crops weren’t spared from our genetic coercion either. In fact, humans had domesticated several forms of wheat since 7800 BCE. However, our greatest success in genetic modification through artificial selection comes from corn. Corns is derived from a wild grass known as teosinte, which only occurred when humans at the time selectively planted corn kernels that displayed desirable traits. Over time, this behavior reconciled the five-gene difference between corn and teosinte and led to the desirable crop that we use to this day.

It’s clear that humanity’s days of artificial selection aren’t behind us, as most major crops today are genetically engineered for our benefit. Rather than waiting around a few thousand years for evolution to do its work, we are now able to immediately manipulate the genetic information of organisms; an idea first executed in 1973 by Stanley Cohen, Herbert Boyer, Annie Chang, and Robert Helling to provide anti-bacterial resistance to a certain strain of bacteria. Since then, gene editing has exploded in all directions. Thanks to genetic engineering, we now dehorn cattle, produce disease-resistant pigs, and herd goats that grow longer hair, all in the name of productivity.

CRISPR and Animal Regulation: Do We Need It?

So how does CRISPR work? Unlike other gene editing tools in the past, CRISPR works to propagate sequences through generations at a 97% effectiveness rate. The system is naturally found in viruses, but researchers were able to manipulate the tool to essentially work as a copy and paste function for any desirable genetic information. The advent of CRISPR is revolutionizing business, with corporations taking advantage of the easy-to-use genetic engineering to even edit pets to sell. However, while CRISPR does essentially accelerate mankind’s ability to artificially select traits for organisms that we find beneficial, people like David Ishee, a Mississippi kennel operator, believe that we can reverse the negative side effects of artificial selection—particularly hyperuricemia (an abnormally high level of uric acid in the blood) in Dalmatians. While David feels that it’s a relatively simple request to utilize gene editing in the hopes of ameliorating a human-caused condition in the breed of dogs, the U.S. Food and Drug Administration (FDA) feels differently.

Ishee, and many others like him who wish to genetically modify animals, face the FDA’s newly drafted regulations from January 2017. While Ishee’s plan to modify the malfunctioning genes of Dalmatians and re-insert them into healthy sperm before fertilization isn’t outlawed by the FDA, its distribution is.

If Ishee manages to produce healthy Dalmatians without the disease, he would not be able to sell or distribute them for breeding purposes, according to the FDA. With that said, Ishee’s hope of spreading his movement far and wide might just be curtailed by government regulation.

The new measures by the FDA might just be a response to the emerging fear that CRISPR and other gene editing techniques can be utilized as weapons of mass destruction. While there are those who don’t intend on adhering to the regulations, hoping the new administration would absolve them entirely, there are others like Ishee who are stonewalled against even starting their projects. However, the benefits of being able to use CRISPR on animals’ DNA could be huge; just looking at dogs and cats alone, selective breeding has introduced some unfortunate side effects. We could help our pets live longer, more comfortable lives in the future. Dalmatians shouldn’t have to suffer because humans wanted a dog that had spots, and perhaps we can undo some of the damage we’ve done in the name of purebred dogs and cats. Scientists and others who want to use this technology also argue that doing this is completely different than splicing two animals’ DNA together, for example.

What about you? Do you feel this is the FDA’s responsibility?

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CRISPR Is Rapidly Ushering in a New Era in Science

A Battle Is Waged

A battle over CRISPR is raging through the halls of justice. Almost literally. Two of the key players in the development of the CRISPR technology, Jennifer Doudna and Feng Zhang, have turned to the court system to determine which of them should receive patents for the discovery of the technology. The fight went public in January and was amplified by the release of an article in Cell that many argued presented a one-sided version of the history of CRISPR research. Yet, among CRISPR’s most amazing feats is not its history, but how rapidly progress in the field is accelerating.

A CRISPR Explosion

CRISPR, which stands for clustered regularly-interspaced short palindromic repeats, is DNA used in the immune systems of prokaryotes. The system relies on the Cas9 enzyme* and guide RNA’s to find specific, problematic segments of a gene and cut them out. Just three years ago, researchers discovered that this same technique could be applied to humans. As the accuracy, efficiency, and cost-effectiveness of the system became more and more apparent, researchers and pharmaceutical companies jumped on the technique, modifying it, improving it, and testing it on different genetic issues.

Then, in 2015, CRISPR really exploded onto the scene, earning recognition as the top scientific breakthrough of the year by Science Magazine. But not only is the technology not slowing down, it appears to be speeding up. In just two months — from mid-November, 2015 to mid-January, 2016 — ten major CRISPR developments (including the patent war) have grabbed headlines. More importantly, each of these developments could play a crucial role in steering the course of genetics research.

CDC Global

Malaria

CRISPR made big headlines in late November of 2015, when researchers announced they could possibly eliminate malaria using the gene-editing technique to start a gene drive in mosquitos. A gene drive occurs when a preferred version of a gene replaces the unwanted version in every case of reproduction, overriding Mendelian genetics, which say that each two representations of a gene should have an equal chance of being passed on to the next generation. Gene drives had long been a theory, but there was no way to practically apply the theory. Then, along came CRISPR. With this new technology, researchers at UC campuses in Irvine and San Diego were able to create an effective gene drive against malaria in mosquitos in their labs. Because mosquitos are known to transmit malaria, a gene drive in the wild could potentially eradicate the disease very quickly. More research is necessary, though, to ensure effectiveness of the technique and to try to prevent any unanticipated negative effects that could occur if we permanently alter the genes of a species.

Muscular Dystrophy

A few weeks later, just as 2015 was coming to an end, the New York Times reported that three different groups of researchers announced they’d successfully used CRISPR in mice to treat Duchenne muscular dystrophy (DMD), which, though rare, is among the most common fatal genetic diseases. With DMD, boys have a gene mutation that prevents the creation of a specific protein necessary to keep muscles from deteriorating. Patients are typically in wheel chairs by the time they’re ten, and they rarely live past their twenties due to heart failure. Scientists have often hoped this disease was one that would be well suited for gene therapy, but locating and removing the problematic DNA has proven difficult. In a new effort, researchers loaded CRISPR onto a harmless virus and either injected it into the mouse fetus or the diseased mice to remove the mutated section of the gene. While the DMD mice didn’t achieve the same levels of muscle mass seen in the control mice, they still showed significant improvement.

Writing for Gizmodo, George Dvorsky said, “For the first time ever, scientists have used the CRISPR gene-editing tool to successfully treat a genetic muscle disorder in a living adult mammal. It’s a promising medical breakthrough that could soon lead to human therapies.”

Blindness

Only a few days after the DMD story broke, researchers from the Cedars-Sinai Board of Governors Regenerative Medicine Institute announced progress they’d made treating retinitis pigmentosa, an inherited retinal degenerative disease that causes blindness. Using the CRISPR technology on affected rats, the researchers were able to clip the problematic gene, which, according to the abstract in Molecular Therapy, “prevented retinal degeneration and improved visual function.” As Shaomei Wang, one of the scientists involved in the project, explained in the press release, “Our data show that with further development, it may be possible to use this gene-editing technique to treat inherited retinitis pigmentosa in patients.” This is an important step toward using CRISPR  in people, and it follows soon on the heels of news that came out in November from the biotech startup, Editas Medicine, which hopes to use CRISPR in people by 2017 to treat another rare genetic condition, Leber congenital amaurosis, that also causes blindness.

Gene Control

January saw another major development as scientists announced that they’d moved beyond using CRISPR to edit genes and were now using the technique to control genes. In this case, the Cas9 enzyme is essentially dead, such that, rather than clipping the gene, it acts as a transport for other molecules that can manipulate the gene in question. This progress was written up in The Atlantic, which explained: “Now, instead of a precise and versatile set of scissors, which can cut any gene you want, you have a precise and versatile delivery system, which can control any gene you want. You don’t just have an editor. You have a stimulant, a muzzle, a dimmer switch, a tracker.” There are countless benefits this could have, from boosting immunity to improving heart muscles after a heart attack. Or perhaps we could finally cure cancer. What better solution to a cell that’s reproducing uncontrollably than a system that can just turn it off?

CRISPR Control or Researcher Control

But just how much control do we really have over the CRISPR-Cas9 system once it’s been released into a body? Or, for that matter, how much control do we have over scientists who might want to wield this new power to create the ever-terrifying “designer baby”?

The short answer to the first question is: There will always be risks. But not only is CRISPR-Cas9 incredibly accurate, scientists didn’t accept that as good enough, and they’ve been making it even more accurate. In December, researchers at the Broad Institute published the results of their successful attempt to tweak the RNA guides: they had decreased the likelihood of a mismatch between the gene that the RNA was supposed to guide to and the gene that it actually did guide to. Then, a month later, Nature published research out of Duke University, where scientists had tweaked another section of the Cas9 enzyme, making its cuts even more precise. And this is just a start. Researchers recognize that to successfully use CRISPR-Cas9 in people, it will have to be practically perfect every time.

But that raises the second question: Can we trust all scientists to do what’s right? Unfortunately, this question was asked in response to research out of China in April, in which scientists used CRISPR to attempt to genetically modify non-viable human embryos. While the results proved that we still have a long way to go before the technology will be ready for real human testing, the fact that the research was done at all raised red-flags and shackles among genetics researchers and the press. These questions may have popped up back in March and April of 2015, but the official response came at the start of December when geneticists, biologists and doctors from around the world convened in Washington D. C. for the International Summit on Human Gene Editing. Ultimately, though, the results of the summit were vague, essentially encouraging scientists to proceed with caution, but without any outright bans. However, at this stage of research, the benefits of CRISPR likely outweigh the risks.

Global Panorama/Flickr

Big Pharma

“Proceed with caution” might be just the right advice for pharmaceutical companies that have jumped on the CRISPR bandwagon. With so many amazing possibilities to improve human health, it comes as no surprise that companies are betting, er, investing big money into CRISPR. Hundreds of millions of dollars flooded the biomedical start-up industry throughout 2015, with most going to two main players, Editas Medicine and Intellia Therapeutics. Then, in the middle of December, Bayer announced a joint venture with CRISPR Therapeutics to the tune of $300 million. That’s three major pharmaceutical players hoping to win big with a CRISPR gamble. But just how big of a gamble can such an impressive technology be? Well, every company is required to license the patent for a fee, but right now, because of the legal battles surrounding CRISPR, the original patents (which the companies have already licensed) have been put on hold while the courts try to figure out who is really entitled to them. If the patents change ownership, that could be a big game-changer for all of the biotech companies that have invested in CRISPR.

Upcoming Concerns?

On January 14, a British court began reviewing a request by the Frances Crick Institute (FCI) to begin genetically modified research on human embryos. While Britain’s requirements on human embryo testing are more lax than the U.S. — which has a complete ban on genetically modifying any human embryos — the British are still strict, requiring that the embryo be destroyed after the 14th day. The FCI requested a license to begin research on day-old, “spare” IVF embryos to develop a better understanding of why some embryos die at early stages in the womb, in an attempt to decrease the number of miscarriages women have. This germ-line editing research is, of course, now possible because of the recent CRISPR breakthroughs. If this research is successful, The Independent argues, “it could lead to pressure to change the existing law to allow so-called “germ-line” editing of embryos and the birth of GM children.” However, Dr. Kathy Niacin, the lead researcher on the project, insists this will not create a slippery slope to “designer babies.” As she explained to the Independent, ““Because in the UK there are very tight regulations in this area, it would be completely illegal to move in that direction. Our research is in line with what is allowed an in-keeping in the UK since 2009 which is purely for research purposes.”

Woolly Mammoths

Woolly Mammoths! What better way to end an article about how CRISPR can help humanity than with the news that it can also help bring back species that have gone extinct? Ok. Admittedly, the news that George Church wants to resurrect the woolly mammoth has been around since last spring. But the Huffington Post did a feature about his work in December, and it turns out his research has advanced enough now that he predicts the woolly mammoth could return in as little as seven years. Though this won’t be a true woolly mammoth. In fact, it will actually be an Asian elephant boosted by woolly mammoth DNA. Among the goals of the project is to help prevent the extinction of the Asian elephant, and woolly mammoth DNA could help achieve that. The idea is that a hybrid elephant would be able to survive more successfully as the climate changes. If this works, the method could be applied to other plants and animal species to increase stability and decrease extinction rates. As Church tells Huffington Post, “the fact is we’re not bringing back species — [we’re] strengthening existing species.”

And what more could we ask of genetics research than to strengthen a species?

*Cas9 is only one of the enzymes that can work with the CRISPR system, but researchers have found it to be the most accurate and efficient.

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The First Results of Gene Editing in Normal Embryos Have Been Released

Viable Editing

One of the most fascinating and promising developments in genetics is the CRISPR genome editing technique. Basically, CRISPR is a mechanism by which geneticists can treat disease by either disrupting genetic code by splicing in a mutation or repairing genes by splicing out mutations and replacing them with healthy code.

Researchers in China at the Third Affiliated Hospital of Guangzhou Medical University have successfully edited genetic mutations in viable human embryos for the first time. Typically, to avoid ethical concerns, researchers opt to use non-viable embryos that could not possibly develop into a child.

*5* Researchers Release Successful Results of First Genetic Edit of Viable Embryos
Source: pixabay

Previous research using these non-viable embryos has not produced promising results. The very first attempt to repair genes in any human embryos used these abnormal embryos. The study ended with abysmal results, with fewer than ten percent of cells being repaired. Another study published last year also had a low rate of success, showing that the technique still has a long way to go before becoming a reliable medical tool.

However, after experiencing similar results with using the abnormal embryos again, the scientists decided to see if they would fare better with viable embryos. The team collected immature eggs from donors undergoing IVF treatment. Under normal circumstances, these cells would be discarded, as they are less likely to successfully develop. The eggs were matured and fertilized with sperm from men carrying hereditary diseases.

Disease Sniper

While the results of this round of study were not perfect, they were much more promising than the previous studies done with the non-viable embryos. The team used six embryos, three of which had the mutation that causes favism (a disease leading to red blood cell breakdown in response to certain stimuli), and the other three had the mutation that results in a blood disease called beta-thalassemia.

The researchers were able to correct two of the favism embryos. In the other, the mutation was turned off, as not all of the cells were corrected. This means that the mutation was effectively shut down, but not eliminated. It created what is called a mosaic. In the other set, the mutation was fully corrected in one of the embryos and only some cells were corrected in the other two.

These results are not perfect, but experts still do find potential in them. “It does look more promising than previous papers,” says Fredrik Lanner of the Karolinska Institute. However, they do understand that results from a test of only six embryos are far from definitive.

Gene editing with CRISPR truly has the possibility to revolutionize medicine. Just looking at the development in terms of disease treatment, and not the other more ethically murky possible applications, it is an extremely exciting achievement.

Not only could CRISPR help eradicate hereditary disease, but it is also a tool that could help fight against diseases like malaria. There is a long road ahead for both the scientific and ethical aspects of the tech. Still, the possible benefits are too great to give up now.

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Scientists Assert That Modern Society is Transforming the Biological Evolution of Our Species

The Evolution of Humankind

Humans are constantly evolving, but scientists are thinking about how environmental changes and social behaviors may increase the rate of evolution in the years to come.

Gregory Cochran, an anthropologist the University of Utah, told Scientific American that through his work analyzing over 3 million DNA sequences, “We found very many human genes undergoing selection. Most are very recent, so much so that the rate of human evolution over the past few thousand years is far greater than it has been over the past few million years.”

Culture is one factor: due to increasing globalization, the 7,000 languages that the world speaks today could whittle down to just a hundred. In terms of climate change, darker skin may prove to be an evolutionary advantage — as more melanin protects humans from the dangerous UV rays that penetrate our atmosphere. Even the human physique could evolve in response to the changes of our environment; taller and slimmer bodies may prove better at managing increased heat.

Genetic mutations may also cause physical changes. It could be as subtle as a new eye color — or having the ability to see a hundred times more colors than before.It could also be a more drastic and unique ability, like the human body becoming able to digest new materials.

via AsapSCIENCE

Artificial Selection

Geoffrey Miller, an evolutionary psychologist at the University of New Mexico, told National Geographic News that he thinks Darwinian evolution is speeding up in part due to our interactions with technology:

“The more advanced the technology gets, the greater an effect general intelligence will have on each individual’s economic and social success, because as technology gets more complex, you need more intelligence to master it.”

Natural evolutionary changes take thousands of years, but human-influenced changes will have a broader and more immediate impact. Breakthroughs in technology, which have made it possible to combine human biology with machines, could alter human evolution in ways we haven’t even considered yet: we already have bionic eye implants that could restore sight, and advanced prosthetics that can translate thought into motion.

Thanks to CRISPR, we now have the ability to modify DNA with such precision that we could use it to one day alter DNA and ensure the health of future babies, and maybe even completely eliminate undesirable traits. This however, leaves room for the possibility of limiting humans’ genetic diversity such that a single disease could actually wipe out the entire human race. While it’s certain that advances in technology have altered how we live now, the future remains uncertain — but with that comes near-limitless possibilities.

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For the First Time Ever, Biologists Have Genetically Modified Ants

Hacking Social Insect Colonies

Social insects are particularly difficult to modify genetically because of their social nature. Modification of an individual genome is typically ineffective because a single female queen usually does all the laying. Therefore, the edited eggs are rejected by workers and fail to survive. Social insects also experience a complex, drawn-out lifecycle, so creating many genetically modified offspring within a reasonable amount of time has been impossible.

However, these problems were recently addressed by a team at The Rockefeller University in New York City, who combined CRISPR technology with clonal raider ants. CRISPR is a gene editing technique that can modify any region of any genome accurately, without harming other genes. It works by modeling bacterial response to invading DNA—or even your computer’s copy-paste functions. When bacteria encounter an invading DNA source, they can copy and incorporate pieces of the foreign DNA into its genome as “spacers” between the short DNA repeats. Scientists harnessed that ability and turned CRISPR into a gene-editing tool, which can add or delete genes, activate dead genes, or control the activity level of genes.

Unlike most ants, clonal raider ants lack a queen. Instead, each ant creates perfect clones of itself by laying its own unfertilized eggs. The team saw the answer in CRISPR, which would allow them to target specific genes and inject the edited DNA back into the eggs.

*4* World’s First Genetically Modified Ants Unveiled, Transforming Our Understanding of Biology
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Injecting edited DNA back into the unfertilized clonal raider ant eggs would allow the team to breed genetically modified strains of ants almost instantly—but only if it works. It took the team 10,000 tries over the course of two years, but they finally got it right.

Ants, Interrupted

Clonal raider ants have to follow scent paths (and they have over 350 odorant receptors with which to do so), so the team targeted an olfactory gene first: orco. The theory was that by knocking out the ants’ ability to follow scent paths they would disrupt critical social behaviors. The goal? To see what would happen if they did. As predicted, knocking out orco rendered the GM ants restless and unable to follow scent paths. However, there were more long-term, serious consequences, too.

The transgenic ants displayed differences in both behavior and brain anatomy. Young clonal raider ants typically spend their first month with their nest-mates, motionless. The transgenic ants skipped this stage and wandered aimlessly, failed to follow trails, and otherwise did not exhibit the social behaviors that allow ant colonies to function cohesively. Typical ants lay six eggs every two weeks, but the transgenics laid only once in that same period of time. Finally, the transgenics had a shorter lifespan of only 2 to 3 months, compared to the usual 6 to 8 month lifespan.

Typical ants have clusters of nerve endings of each type of odorant receptor called glomeruli in their brains. In transgenic ants, the glomeruli never formed.

Researchers also tried knocking out orco in fruit flies, which did not have the same effect. However, knocking out the equivalent gene in mice did. These results suggest a future line of research: comparing and contrasting brain development in different species in order to assess how brains evolve to manage complex social behaviors. The researchers hope the clonal raider ant will become a model organism for study of the origin and evolution of animal societies.

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Gene Editing Could Make You Smarter

Importing Intelligence

The gene editing technology CRISPR/Cas9 has paved a new path forward for us – from eliminating disease and fixing pests, to restoring lost abilities – the process is expected to graduate us into a new age of medicine. But it begs the question, can we make ourselves better? Can we improve our intelligence in the advent of gene engineering?

The answer might just be a resounding yes.

The Cognitive Genomics Project is focused on understanding the origin of intelligence within our own genome. It’s lead by BGI, a non-profit research group based in Shenzhen, China, that was founded in 1999. The organization is currently conducting a gene-trait association study of g, a general factor of intelligence. General intelligence is defined by three prominent categories: stability, heritability, and predictive powers. In short, the study is collecting genetic data from over 20,000 individuals who have an IQ above 150, and looking for patterns in their genes.

While this might seem relatively straightforward, it’s actually a complex and difficult task. That’s because general intelligence does not follow mendelian, single-gene genetics. Researchers cannot simply look for specific mutations in specific genes, as they do for diseases like Huntington’s Disease or Cystic Fibrosis. Rather, intelligence is more similar to traits like eye color and hair color that involve multiple genes in inheritance patterns that we are just beginning to understand.

No Gene Editing Needed?

It remains to be seen how effective gene editing can be at influencing traits like personality and intelligence in people whose brains have already been formed. One way we could avoid the gene editing process entirely is by genetically designing intelligence into our children from conception. We could utilize in vitro fertilization and carefully process the genetic information of each embryo produced for genetic preferences.

If the Cognitive Genomics Project provides significant data supporting the correlation between particular parts of the genome and intelligence, then parents can look for these genetics sequences in potential embryos and select the embryos with the desired traits. This method would increase the probability of intelligent children without having to edit particular genome sequences.

While the ethics of human genetic engineering continue to be debated, we may be closer to a more intelligent humanity than ever before.

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Should Gene Editing Be a Human Right?

Genetic Editing for All

We are all subject to the genetic lottery. That’s how it’s always been, and for a while, we thought that was how it would always be.

Then, in 2014, a gene-editing technology called CRISPR was introduced. With CRISPR, geneticists could edit sections of the genome to alter, add, or remove parts of the DNA sequence. To date, it is by far the easiest way we’ve found to manipulate the genetic code, and it is already paving the way for more efficient and effective treatments of conditions with a genetic component. However, the technology brings with it the potential to manipulate and remove simply “unwanted” genes.

Crispr Cas 9
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While most of the proposed CRISPR applications are focused on editing somatic (non-reproductive) cells, altering germline (reproductive) cells is also a very real possibility. This prospect of editing germline cells and making changes that would be passed on from generation to generation has sparked a heated ethical debate.

The potential to change someone’s DNA even before they are born has led to claims that CRISPR will be used to create “designer babies.” Detractors were appalled at the hubris of science being used to engineer the human race. Supporters, on the other hand, are saying this ability should be a human right.

Rigging the Game

To be fair, most advocates of genetic editing aren’t rallying for support so CRISPR can be used to create a superior human race. Rather, they believe people should have free access to technology that is capable of curing diseases. It’s not about rigging the genetic game — it’s about putting the technique to good use while following a set of ethical recommendations.

To that end, a panel made up of experts chosen by the National Academy of Sciences and the National Academy of Medicine released a series of guidelines that essentially gives gene editing a “yellow light.” These guidelines supports gene editing on the premise that it follows a set of stringent rules and is conducted with proper oversight and precaution.

Obviously, genetic enhancement would not be supported under these guidelines, which leaves some proponents miffed. Josiah Zaynor, whose online company The ODIN sells kits allowing people to conduct simple genetic engineering experiments at home, is among those who are adamant that gene editing should be a human right. He expressed his views on the subject in an interview with The Outline:

We are at the first time in the history of humanity where we can no longer be stuck with the genes we are dealt. As a society we have begun to see how choice is a right, but for some reason when it comes to genetics, some people think we shouldn’t have a choice. I can be smart and attractive, but everyone else should be ugly, fat, and short because those are the genes they were dealt and they should just deal with it.

However, scientific institutions continue to caution against such lax views of genetic editing’s implications. Apart from the ethical questions it raises, CRISPR also faces opposition from various religious sects and legal concerns regarding the technology. Governments seem divided on the issue, with nations like China advancing research, while countries like the U.K., Germany, and the U.S. seem more concerned about regulating it.

The immense potential of gene editing to change humanity means the technology will continue to be plagued by ethical and philosophical concerns. Given the pace of advancement, however, it’s good that we’re having this debate on what and who it should be used for right now.

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A Major Organization Just Endorsed Human Genetic Modification

Sometime not necessarily too far from now, the first humans whose DNA has been intentionally edited by scientists could very likely be born.

The technologies that make that theoretically possible have existed for some time now and in the past few years, new discoveries have made genetic editing tools far simpler, cheaper, and more accurate — though they still aren’t precise enough to use safely on human embryos that will be carried to term.

Still, that reality is close enough that the scientists who work closely with these tools have said that guidelines for this research are urgently needed. And on February 14, the National Academy of Sciences and the National Academy of Medicine issued a report that outlines the circumstances under which research into editing human embryos could be permitted.

“Although heritable germline genome editing trials must be approached with caution … caution does not mean prohibition,” the National Academy committee said in a statement.

That’s a big statement. Right now, the US Food and Drug Administration (FDA) prohibits any research that would include germline genome editing; a number of other countries also prohibit similar research.

These groups are hesitant because “heritable germline genome editing” is a world-changing sort of thing. It means that researchers would go into the unique genetic blueprint for a person before they are born and make changes and substitutions, snipping out code for traits they don’t want and potentially replacing them with something else. Then, all of these changes would be passed on if that person had children, meaning that we’d have introduced manually edited genes into the wild.

The National Academies panel convened to assess this is concluding that under certain circumstances, that may be okay.

Still, even if the panel thinks that research and trials into human genome editing should go forward, the cases for which they think this should be permitted are very limited, for now at least.

dna cut and paste crispr
Samantha Lee/Business Insider

The Sorts of Changes We Might See

After evaluating the issue for a year, the National Academies panel concluded that clinical trials involving inheritable changes to the genome could be allowed, so long as they treat or prevent genetic diseases that we have no other way of dealing with.

This could make a huge difference for the cases where it’s basically a certainty that parents will pass a devastating disease on to a child. Specific diseases that might fit this category include the blood disorder beta thalassemia, cystic fibrosis, and sickle-cell anemia. But those cases are very rare.

Perhaps more interestingly, the researchers leave open the possibility of using genetic editing to remove or replace mutations that make people susceptible to other diseases. They mention mutations of BRCA1 and BRCA2, which can increase risks for breast and ovarian cancers. Edits like that could help remove mutations that make people more likely to get many forms of cancer, Alzheimer’s disease, and other conditions. This could have a far-rippling effect on human health in the long run.

If we get to the point that it’s possible to safely and completely remove these sorts of dangerous mutations, the conclusion the panel arrived at may allow for edits that prevent disease in this way. They don’t think this would be the same as making “enhancements,” which they say should not be allowed at this time, though they call for public discussion of those possibilities.

Still, there are obstacles to overcome before this happens. For now it’s hard to apply a genetic editing tool (like CRISPR) to an early embryo and have it make all the changes to a genome that you want (and no unwanted extra changes). When you let that editing tool loose it seeks out the segments of DNA you are targeting to eliminate or replace, but it may miss some of those segments or accidentally cut something else. These tools are becoming more and more accurate, but they aren’t good enough that scientists would feel comfortable implanting an edited embryo yet.

Even once those tools are perfected, the panel is saying a go-ahead with trials seems permissible. It is not recommending that this technology should immediately go into wide use. Plus, the FDA would have to allow these sorts of procedures for this to happen in the US and it’s unclear if that will happen anytime in the near future.

The basic implication of this is clear though. We know that these tools are improving and we’re using them more and more. In some places, like Sweden, the UK, and China, researchers have already started editing (or have received permission to edit) embryos — some viable, some not, but none that they plan to implant yet. All of this will further improve the accuracy of these tools, to the point it may at some point be possible to make all the changes to a genome that we want with no unwanted side effects.

Once that’s done, the first “designed” babies could — or will — be born. If all goes well and these guidelines are followed, they’ll be healthier and free of a disease that could or would have been devastating.

The question that many have is whether we’ll see edits that happen for other purposes, to make babies smarter or stronger, not just healthier. The research the committee wants to allow wouldn’t permit those sorts of changes. But it would prove that they are indeed possible.

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Gene Editing is Leading to a New Age in Human Health and Longevity

The Magic Of Gene Editing

Advances in medicine and technology are revolutionizing what it means to be human. By providing us with gene editing tools, such as CRISPR, we’re well on our way to personalizing the medical revolution.

CRISPR provides a way for us to alter gene expression in particular cells, based on need. Up until recently, the process was very difficult to execute. It took many years to develop precision when altering gene expression. With the latest technology, the desired precision can be obtained in just a few weeks. CRISPR, and other technologies like it, are shaping the future of medicine.

When all possible treatments had failed, the parents of Layla, a 1-year-old with leukemia, sought help from new technology developed by Cellectis — a biopharmaceutical company based in Paris, France. The gene editing therapy, which was still experimental, had been utilized once before in a patient with HIV.

Layla and her parents have immunologist Waseem Qasim and his team to thank. While the treatment was approved for Layla under her particular circumstance, the Great Ormond Street Hospital for Children NHS Trust in London intends to continue the trial in 10 to 12 patients in the upcoming year. Several months after the procedure, Qasim notes Layla is doing well.

How Gene Editing Works

crispir_home
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Physicians and scientists worked together to give Layla immune cells from a healthy donor that had been modified with a gene editing tool. In this case, TALEN — a DNA-cutting enzyme — was utilized to modify the donor T-cells so that they would not attack Layla’s own cells. In order for the treatment to work, a patient’s immune system is essentially destroyed and replaced with the modified cells. However, this is not a permanent fix: it’s just a temporary solution until a matching T-cell donor can be found.

While Layla’s doctors believe she is in remission, only time will tell if this was a “one-off” fix or a case that may need revisiting. Additional trials are needed so physicians and scientists can better understand how gene-editing can benefit patients, and treat diseases other than cancer.

Treating cancer isn’t the full extent of gene editing by any means: we can halt the spread of malaria by looking at mosquitos, bring back species gone extinct by the unforgiving hand of human industrialization, or even restore vision in patients.

With the gene editing, it seems the possibilities are only the beginning.

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U.S. Scientists Have Backed the Genetic Modification of Human Embryos

Gene Editing

Since the debate about the moral ramifications behind CRISPR began, the scientific community’s stance has generally leaned towards caution versus support. Researchers recognize the potential, but gene editing and its implications on the future of the human race are so massive – it’s not something to be taken lightly.

Screen Shot 2017-02-15 at 9.59.26 AM
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A new report from the National Academy of Sciences (NAS) however, shows how the scientific community is beginning to soften their stance on the subject. Co-Chair of the study committee Alta Charo points out:

Human genome editing holds tremendous promise for understanding, treating, or preventing many devastating genetic diseases, and for improving treatment of many other illnesses. However, genome editing to enhance traits or abilities beyond ordinary health raises concerns about whether the benefits can outweigh the risks, and about fairness if available only to some people.

The paper also goes on to support germ-line engineering, a process that allows people to have biological children while ensuring that they don’t pass on serious genetic diseases to their offspring – but only if there are no reasonable alternatives available. To that end, scientists are calling for more stringent regulations. They concede that global prohibition of the technique is not practical, especially in the interest of safety and efficacy.

“Genome editing research is very much an international endeavor, and all nations should ensure that any potential clinical applications reflect societal values and be subject to appropriate oversight and regulation,” said committee co-chair Richard Hynes, Howard Hughes Medical Institute Investigator and Daniel K. Ludwig Professor for Cancer Research, Massachusetts Institute of Technology. “These overarching principles and the responsibilities that flow from them should be reflected in each nation’s scientific community and regulatory processes.”

Risks and Moral Dilemmas

The biggest concern that experts have over gene editing is anchored on the very real possibility that it will be used to create designer babies. All efforts now are centered on using CRISPR to prevent inherited disease. But who’s to say that the same principles won’t be used to engineer traits like strength, beauty, or intelligence?

That said, what if only some people have access to this tool in the future? Could it create a social divide between engineered babies and naturally born ones? The risks also aren’t entirely known. While rare, there are instances where CRISPR edits DNA in unintended places, which could result in unforeseen consequences.

Of course, we’re still pretty far off from a designer baby being born. Right now, the gene editing technique is still being tested in animals, and it will take a significant amount of time and research before it will be ready for humans. But that’s not to say that we shouldn’t already be having a conversation about where this advancement will take us.

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Scientists Have Created Genetically Modified Cows That Are Resistant to Deadly Disease

CRISPR Cows

Bovine tuberculosis is a disease that affects cows, but can also be transmitted to human beings and other animals. While the disease is well-controlled in most countries, there are still cases of cattle fatalities due to bovine tuberculosis in developing countries. The situation is made worse when the drug-resistant strain of the disease surfaced.

Researchers from the Northwest A&F University in China have given cows a better fighting chance. Using the world’s most effective gene editing tool called CRISPR, the researchers inserted a gene that’s associated with tuberculosis resistance into 20 cows. Of these, 11 cows lived past 3 months and showed greater resistance to tuberculosis compared to their unmodified.

“I think this is a very neat study that demonstrates the feasibility of introducing a desired gene of interest via a potentially safer way,” said Suk See De Ravin from the U.S. National Institutes of Allergy and Infectious Diseases, who wasn’t involved in the study.

CRISPR-Cas9 has been widely studied and applied in a good number of studies, and is so far the most efficient and cheapest method we have to insert or cut into specific locations in an organism’s genome. The Chinese team, however, applied a new version of this technique that’s potentially safer. Instead of cutting both strands of DNA, their method inserts a gene at a desired location in the cow genome into a single snip within only one strand of DNA.

“Here, we report the first application of single Cas9 nickase (Cas9n) to induce gene insertion at a selected locus in cattle,” according to the study published in the journal Genome Biology. But “obviously further studies to demonstrate the safety of the outcome are necessary,” De Ravin added.

Credits: Yuanpeng Gao, et al./Northwest A&F University
Credits: Yuanpeng Gao, et al./Northwest A&F University

Safe Cows are Safer

The study is yet another example of how CRISPR-Cas9 can be applied in agriculture and is also a solution to a longstanding problem. According to De Ravine, we now have the ability to raise animals with improved resistance to infections. This could dramatically reduce the overuse of antibiotics in livestock.

Moreover, the inserted gene seems to be already found naturally in some cattle, said Chuck Sattler, VP of genetic programs at cow-breeding company Select Sires. CRISPR simply made these naturally occurring changes happen faster, and in a more specific manner.

For the first time, we have cows resistant to tuberculosis. These transgenic cows reduce the transmission of tuberculosis through milk, a problem that remains in developing countries. In the U.S., pasteurization processes have “pretty much eliminated tuberculosis risk from milk, though the faddish enthusiasm for raw milk and cheeses… has reintroduced that risk,” said Harry Malech, chief of the National Institutes of Allergy and Infectious Diseases.

Being able to use CRISPR to turn cows into tuberculosis resistant cattle opens up the possibility of being able to do the same for other livestock. It could also lead to the elimination of other cow-related diseases that get transferred to humans. For now, however, these transgenic cattle still needs approval from the U.S. Food and Drug Administration.

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First-Ever Semi-Synthetic Organism Opens The Door to New Forms of Life

 

A Happy Separation

What was once thought to be possible only through nature is now being created in the lab. Scientists from The Scripps Research Institute (TSRI) announced today that they have successfully created the first-ever, fully stable semi-synthetic living organism.

In 2014, TSRI professor Floyd Romesberg and his colleagues led a study which resulted in the synthesis of a DNA base pair. A feat of its own, the team was now able to take those natural bases (A, G, C, T), and assemble a completely new bacterium. Their findings are published in the journal Proceedings of the National Academy of Sciences.

Photo Credit: The Scripps Research Institute/Madeline McCurry-Schmidt

This goes beyond previous methods of creating stable single-celled organisms, as these bacteria hold an extra pair of synthetic bases in their genetic makeup called X and Y. Cell division was difficult to achieve in this past experiment as the bacterium would divide, but would not hold the synthetic base pair during the process. With this new experiment, TSRI graduate student Yorke Zhang and American Cancer Society postdoctoral fellow Brian Lamb were able to find a way for the organism to retain the base pairs.

First, they modified a tool called a nucleotide transporter, which makes it possible for the synthetic base pair to be copied across the cell membrane (when originally attempted in 2014, it made the semisynthetic organism very sick). This modification helped lead them to their success, allowing for an easier division while maintaining the X and Y bases. They then optimized their Y to make it more easily recognizable during the process.

Finally, the researchers used CRISPR-Cas9 as a sort of “spell check.” CRISPR-Cas9’s original role in bacteria is to act as an immune response. When there is a threat such as a virus, it can essentially cut and paste the genome from the invading virus onto itself, and use it on the offense if it returns.

Through this novel technique, they prevented X and Y as being seen as invaders by CRISPR-Cas9. When the synthetic base pairs were dropped, the bacterium remained unharmed during and after dividing. Even after 60 divisions, their organism kept X and Y in its genome. “We can now get the light of life to stay on,” said Romesburg. “That suggests that all of life’s processes can be subject to manipulation.”

Creating Life From Scratch

The findings of Romesburg and his colleagues are groundbreaking. However, there are no plans to use this knowledge to create multicellular organisms. Romesburg emphasized that he works solely with single-celled organisms. This means that, at least currently, there are no applications for the bacterium.

But we are one step further towards creating organisms that use and mimic our own biological processes. Although we are far off from assembling new organisms entirely from the ground up, this group of scientists is far from done with this research. They hope to figure out how their genetic code can be transcribed into RNA, which would provide the foundation for the next steps going forward.

This could be the groundwork for the future creation of organisms, but it could also provide more meaningful understanding of our own biology and universe.

 

 

 

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Gene Editing Could End Mosquito-Borne Disease

Fever Reducing Editing

Each year, mosquitos carrying the dengue fever virus (DENV) infect about 390 million people across the world. Symptoms of the fever are often similar to other viral infection (headaches, nausea, fatigue, etc.) but can develop into more serious issues such as massive bleeding, shock, and death. The virus is responsible for the deaths of nearly 25,000 people worldwide, each year.

dengue-mos_m2216653
CDC

Researchers have been working painstakingly to develop ways to combat the mosquitos that carry the virus. Now, researchers from Johns Hopkins University have published their work on how mosquitos can be genetically engineered to resist DENV. The study has been published in PLOS Neglected Tropical Diseases.

Mosquitos’ own immune systems also try to fight the virus off upon infection. There are specific proteins known as ‘Dome’ and ‘Hop’ that activate after infection to kickstart the immune process. The new work shows how the researchers were able to turn on this immune response as soon as the would-be host ingests infected blood, much sooner than the natural response.

Scientists engineered the bugs to express either Dome or Hop sooner and the results were very promising. The viral counts of DENV were reduced by 78.18 percent for those engineered to express Dome, and a remarkable 83.63 percent for Hop.

Engineering the Resistance

The rise of the gene editing technique known as CRISPR has given epidemiologists new hope that many of these mosquito-borne illnesses can be combatted on a molecular level. Other diseases, such as malaria, are currently being targeted by genetic engineers. However, genetic engineering brings about its own set of ethical and practical concerns.

Extra diligence must be exhibited if researchers want to both prove the effectiveness of these and similar methods, as well as convince the public of their safety. Just this past election, Florida voters passed a resolution to allow the release of genetically modified mosquitos to combat the Zika virus.

As stated by the researchers of the dengue fever study, there is hope in genetic engineering, “Recently developed powerful mosquito gene-drive systems that are under development are likely to make it possible to spread pathogen resistance in mosquito populations in a self-propagating fashion, even at a certain fitness cost.”

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Future Health: 2017’s Most Exciting Medical Advances

The transition from one year to the next is always a little uncertain – an uneasy blend of anxiety and optimism, it’s also a time of retrospection, introspection, and even a little tentative prognostication. And since the latter is our stock-in-trade at Futurism, we believe now is the perfect time to look ahead at what 2017 has in store for us.

Last year was a remarkable year in medicine. We saw continued development and refinements of CRISPR/Cas-9 gene-editing technology, lab-grown “mini-brains” were created to study the neurological effects of Zika and other disorders, a successful womb transplant was performed in the US, and the FDA approved the first artificial pancreas. Pretty remarkable advances—but 2017 promises to usher in more of the same.

Here’s our list of some of the many wonderful advances in medicine we can look forward to in 2017.

Techno-Medicine

Sophisticated technologies have always had an important role to play in medicine, with each year adding extraordinary new tools to the physician’s medicine bag—2017 will be no exception.

We can, for instance, expect further improvements in the technology of robotic surgery. In addition to the currently available da Vinci Surgical System, look to see competition from the new surgical robot system developed by the partnership of Google and Johnson & Johnson. These new systems will parlay advances in software, miniaturization, and robotics to allow for minimally invasive surgeries on the most delicate elements of human anatomy.

health article image
The robotic da Vinci Surgical System. (Credit: Intuitive Surgical)

Another untapped (or very minimally tapped) technological frontier in medicine involves the use of artificial intelligence (AI)—which seems to touch upon just about every field nowadays. IBM’s Watson has already displayed a keen diagnostic eye, and machine learning and deep learning programs have been used to predict everything from when a patient will die to where the next major disease outbreak will occur.

We can expect the application of AI to medicine to only increase in the coming year, when the need to cull through and assimilate enormous quantities of medical data—whether on an individual or large-scale, societal basis—will become critical. Meanwhile, the danger that potentially flawed machine learning programs will supplant rather than merely supplement human medical judgment will also become much more than just an abstruse, academic question for medical ethicists.

A Pharmacological Revolution

But 2017 won’t be just about robots and artificial intelligence. It’s likely that some of the less visually spectacular medical technologies will yield the most astonishing medical breakthroughs. Drug research, for instance, is poised to take off in 2017—especially with immunotherapeutic treatments for cancer.

According to Stanley Marks, chairman of the UPMC CancerCenter, it is these treatments—which marshal the body’s immune system to attack and destroy cancerous cells—that represent the single most promising new front in the war on cancer. Using checkpoint inhibitor drugs and CAR (chimeric antigen receptor) T-cell therapies, it’s become possible to mobilize the body’s own immune system to fight the cancer.

The method involves extracting T-cells from the patient’s own blood, and genetically engineering them to recognize, attach to, and neutralize tumorous cells. It’s already had promising results in fighting some leukemias, so we can look forward to more research on these remarkable “living drugs” in 2017.

Further drug advances to look out for in the coming year include: a vaccine for HIV beginning Phase II trials, the use of the dissociative anesthetic ketamine to target treatment-resistant depression, new drugs and therapies based on the microbiome, and even a new female libido booster that’s up for approval.

Gene-Editing Comes of Age

The revolutionary CRISPR/Cas-9 gene-editing technology has disrupted biology like nothing else—and bids fair to transform it from a slow, imprecise science to something approaching the precision of the physical sciences. What 2017 holds for gene-editing technology is anyone’s guess—it’s even possible that the Chinese, or some other nation with laxer standards than are currently permitted in the U.S., might begin a more widespread use of the technique in human subjects.

Despite the reasonable ethical qualms, it’s inevitable that the CRISPR/Cas-9 method will be extended to human use, and 2017 will very likely be the year we see this happen. Look for active measures, such as more extensive trials in the cancer-fighting uses of the technology (for example, in the CAR T-cell therapies we mentioned above), or scientists using it to eradicate pathogenic human DNA viruses like HIV or herpes.

But expect passive measures, too, such as simply learning how Alzheimer’s and other neurodegenerative diseases progress, or even non-medical agricultural and industrial uses for the technology. As Nicola Patron of the Earlham Institute sagely observes, “Understanding what DNA sequences do is what enables us to solve problems in every field of biology from curing human diseases, to growing enough healthy food, to discovering and making new medicines, to understanding why some species are going extinct.”

The bottom line: 2017 is looking to be an exciting year, in all avenues of research and discovery, but particularly in medicine.  And if all the above wasn’t exciting enough for you—you can look forward to capping it off with what might be the world’s first head transplant.

Disembodied heads or not, you can read all about the latest developments here at Futurism.

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Controlling CRISPR: Researchers May Have Found An “Off-Switch” for Gene-Editing

CRISPR Discovery

As it stands, CRISPR is a rather impressive gene editing tool and already the most precise method we have available for genetic manipulation. Studies like this recent one from UC Berkeley are helping us refine the CRISPR-Cas9 system, and now a new study published in Cell from UC San Francisco (UCSF) is offering a way to deal with some of its greatest remaining downsides.

Researchers discovered a way to switch off this gene-editing system using recently identified proteins discovered in the lab of Joseph Bondy-Denomy from UCSF’s Department of Microbiology and Immunology. These anti-CRISPR proteins could eventually improve the safety and accuracy of already very accurate CRISPR applications, and the researchers relied on a nifty little trick to discover them.

anticrispr graphic
Credit: Rauch / Cell

“Just as CRISPR technology was developed from the natural anti-viral defense systems in bacteria, we can also take advantage of the anti-CRISPR proteins that viruses have sculpted to get around those bacterial defenses,” explains the leader of the study, Benjamin Rauch.

In their research, the team looked for bacterial strains that had been infected by a known virus. They reasoned that their existence would be evidence that a bacteria’s Cas9 was not functioning properly.

“Cas9 isn’t very smart,” according to Bondy-Denomy. “It’s not able to avoid cutting the bacterium’s own DNA if it is programmed to do so. So we looked for strains of bacteria where the CRISPR-Cas9 system ought to be targeting its own genome — the fact that the cells do not self-destruct was a clue that the whole CRISPR system was inactivated.”

After examining nearly 300 strains of Listeria using Rauch’s bioinformatic approach, the team found three strains that showed this evidence. From those, they isolated four distinct anti-CRISPR proteins, and of these four, test showed that two — dubbed AcrIIA2 and AcrIIA4 — worked to inhibit the ability of SpyCas9 to target specific genomes.

A Better System

“These natural Cas9-specific ‘anti-CRISPRs’ present tools that can be used to regulate the genome engineering activities of CRISPR-Cas9,” the researchers write. They believe that with these proteins, it’s possible to avoid unintended or “off-target” gene modifications caused by keeping CRISPR’s machinery active in the body.

Of course, the next step would be to see how these proteins function in human cells. “We also want to understand exactly how the inhibitor proteins block Cas9’s gene targeting abilities, and continue the search for more and better CRISPR inhibitors in other bacteria,” Raunch explained.

Ultimately, this “off-switch” for CRISPR could prove almost as important as the system itself. “Researchers and the public are reasonably concerned about CRISPR being so powerful that it potentially gets put to dangerous uses,” Bondy-Denomy said. “These inhibitors provide a mechanism to block nefarious or out-of-control CRISPR applications, making it safer to explore all the ways this technology can be used to help people.”

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The New Cas9? Scientists Discover CasX and CasY Enzymes in Bacteria

Meet CasX and CasY

Researchers from the University of California, Berkeley have discovered new CRISPR-Cas systems, the gene-editing tool currently revolutionizing the field. In their study, which is published in Naturethe team reports that they’ve found two new bacterial Cas proteins as well as the first-ever archaeal Cas9 protein.

The researchers spent the past 10 years reconstructing the genomes of microbes they’d collected from a variety of environments — everything from groundwater and sediment to acid mine drainage biofilms and infant gut. The result of their work is a terabase-scale genomics collection of microbes. A vast majority of these were previously uncultivated, meaning that they hadn’t been grown in isolation before. This is particularly significant because the CRISPR-Cas techniques currently in use were developed from bacteria cultured in labs.

The team looked for the characteristic repeated sequences and found, as CRISPR researcher Rodolphe Barrangou told The Scientist, “gold out of the metagenomic dark matter.” Sequences that controlled the Cas9 protein were located in two archaea genomes — an interesting find, since Cas9 was previously only found in bacteria.

Furthermore, the group uncovered new CRISPR-associated proteins (Cas) among bacteria. The new proteins, which they called CasX and CasY, were composed of around 980 and 1,200 amino acids respectively. “They’re really small, especially CasX,” said Banfield. “That means it’s potentially more useful.”

A Better CRISPR System?

CRISPR, or clustered regularly interspaced short palindromic repeats, is a natural defense mechanism found in some prokaryotes. Together with the Cas protein, the system cuts and stores nonnative DNA from invaders, such as viruses. This allows the organism to retain a genetic memory of that invader, which it can then reference to quickly identify the invader if it’s encountered again in the future.

Among the numerous CRISPR-Cas programs, the class 2 system, which typically uses the Cas9 nuclease, has been studied the most, and in recent years, it has been adapted as a technique in biotechnology. Using the CRISPR-Cas9 system, scientists can target specific intervals of genetic code in living organisms and then cut and edit those genes more accurately than ever before.

Because archaea differ from bacteria biologically, finding a Cas9 protein in archaea presents an interesting new area of study in CRISPR research. Banfield believes that there may be components of the system that differ and that these differences could offer new information that could improve current biotech methods. Similarly, Rotem Sorek of the Weizmann Institute of Science in Israel sees the smaller size of the newly discovered CasX and CasY proteins to be promising since “the delivery of small genes into cells is much easier than the delivery of large genes.”

Banfield is hopeful that more useful discoveries could be found using metagenomics: “This is a case in point for what I think will be an avalanche of new proteins and pathways and systems that hold unimaginable biotechnology and medical value.”

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Evolution 2.0: Gene Editing Could Bring Extinct Species Back to Life

De-Extinction

The Anthropocene—a proposed new geological era defined by human domination of the planet—will be marked by the loss of two-thirds of wildlife on Earth. Just let that settle in a minute.

According to Living Planet Index, this is the reality we will soon be facing. The implications of this loss on our ecosystem will be significant, and have prompted scientists to look into the concept of “de-extinction,” in an effort to bring lost species back to life. Surprisingly, the idea is not far fetched as one might think.

While the idea may prompt thoughts of Jurassic Park, de-extinction is anchored on the premise of bringing back animals that the ecosystem would benefit the from the most (i.e. probably not dinosaurs). And with new advances in gene-editing technology, it might actually be possible.

To that end, ecologists from the University of California, Santa Barbara (UCSB) published guidelines that identify factors for choosing which species our planet would be best served to revive. The UCSB team focuses on three main points:

  1. Focus on recently extinct animals, rather than species we lost thousands of years ago.
  2. Select target species from guilds with low functional redundancy
  3. Only work with species that can be restored to levels of abundance that meaningfully restore ecological function.

Back to Life

Following this criteria, Jurassic Park is surely out of the running. However, the wooly mammoth could be a candidate. This species could potentially convert the Arctic tundra back to grasslands, and slow climate change. Using the DNA editing tool CRISPR, we are now actually a step closer to bringing the wooly mammoth to life. After successfully copying genes from the extinct animal, scientists spliced it into the genome of an Asian elephant.

Image Credit: Lou.gruber/ Wikipedia

From the study, published in Popular Science:

The scientists spliced genes for the mammoths’ small ears, subcutaneous fat, and hair length and color into the DNA of elephant skin cells. The tissue cultures represent the first time woolly mammoth genes have been functional since the species went extinct around 4,000 years ago.

Alongside gene editing, other possible approaches to de-extinction could be backbreeding and cloning.

“Can we thoughtfully use this tool to do real conservation?” one of the authors of the guidelines, UCSB ecologist Douglas McCauley asked. “Answering that question is going to require a lot of perspectives, not only from the geneticists who are leading the process, but also from other types of scientists — ecologists, conservation biologists, ecosystem managers.”

Polarizing opinions regarding this initiative are expected, but they will at least start a conversation among the scientific community as to how researchers can move forward in the most ecologically intelligent way possible.

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New CRISPR Technique Lets Us Probe the Darkest Corners of Biology

Two Is Better Than One

Researchers at the Weizmann Institute of Science have developed a new technique to help them understand the body’s complex and often chaotic processes, and it actually combines two technologies that are cutting-edge on their own: CRISPR and single-cell RNA sequencing.

CRISPR has certainly become quite the household name in gene editing. Its successes are well documented and now include actual human application. Single-cell RNA sequencing is a new method that’s been impacting biotechnology research. That technique involved the sequencing of RNA messenger molecules in individual cells, giving scientists a look at each cell’s molecular makeup.

“But CRISPR, on its own, is a blunt research tool, since we often have trouble observing or understanding the outcome of this genomic editing,” lead researcher Ido Amit of the Weizmann Institute of Science said in a press release. Meanwhile, single-cell RNA sequencing is a “molecular microscope,” according to Amit, that allows for the sequencing of thousands of cells of particular tissues, revealing variations in identities and functions.

Combining these tools gives researchers the ability to alter multiple target genes at once and identify the resulting changes within the cell. It required the development of new molecular techniques to allow for multiple targeting and new computational methods to analyze the different genotypes and phenotypes of groups of cells.

Credits: Weizmann Institute
Credits: Weizmann Institute

A Versatile Method

According to the researchers, a single experiment using this method can yield results that would require thousands of experiments using previous techniques, and these are results that neither method could’ve yielded on its own.  They tested the technique on immune cells in mice to examine how those cells were wired as they combatted pathogens and were able to see in high resolution the functions of the genes involved in the various immune cells as they reacted to invading pathogens.

With CRISPR as the scissor and single-cell RNA sequencing as the molecular microscope, this combination method opens up a new world in genetic engineering and will likely result in many new applications in medical research. It could possibly be used in the future to examine how cancer cells survive through mutations, which brain cells are involved in the development of disorders like Alzheimer’s, or how immune cells go through their messy decision-making process.

“We are hoping that our approach will be the next leap forward, providing, among other things, the ability to engineer immune cells for immunotherapy,” said Amit.

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Kazuo Ishiguro: Soon, We Will Be Able to Create Humans Who Are Superior to Other Humans

Dystopian Future

According to Kazuo Ishiguro, there are three areas of science that are set to transform how we live and interact with others over the next few decades: gene editing, robotics, and artificial intelligence (AI).

Ishiguro, granted, is best known as one of the most celebrated fiction writers today. He is behind the novel Never Let Me Go, the story of a dystopian future where humans are cloned to be organ donors. But the possibility of a future so fundamentally changed by scientific advancements could be more than the fruit of the author’s creativity and imagination.

Ishiguro
Kazuo Ishiguro. Credit: Jeff Cottenden

He cites CRISPR as a primary example. The discovery of this gene editing tool gives scientists the option to modify pieces of the genome, paving the way for unprecedented applications in medicine. Right now, we can replace faulty genes with working ones, which is a great accomplishment unto itself. But moving forward, as we learn more about this new technology, the option to enhance functional genes to create intellectually and physically superior humans becomes a real possibility.

Think of it as like a real world Gattaca, where society is divided into two classes. Half will be populated with humans with genetically engineered genes that makes them healthier, smarter, stronger—designer babies, essentially. And the other half, with humans whose genetic sequence has been left to chance, untouched, leaving them biologically inferior.

A New Focus on Science

Ishiguro believes we are unwittingly walking into this dystopian future because the world has yet to give science and technology more than just peripheral interest. Sure, we celebrate the headlines and acknowledge the accomplishments, but we have yet to engage in meaningful conversations about where these advancements will take us, and the kind of impact they will have on our lives.

Developments in AI and robotics for instance, mean a major part of intellectual capital will shift to what he refers to as “the Silicon Valley masters of the universe”—it will no longer be under universities or government funded labs. The lack of regulation regarding these rapid developments is also cause for concern. And of course, there is the ongoing debate about the ethics behind advancements in genetic sciences, like CRISPR.

The relevance of Ishiguro’s musings about the future comes in time for the opening of a new permanent mathematics gallery at the Science Museum in London. Included in the exhibit is the author’s father, oceanographer Shizuo Ishiguro, who created a machine that can predict coastal storm surges.

The author however, hopes that exhibits such as this will prompt more discussion about the trajectory of science and spur deeper interest. These breakthroughs have real implications that deserve to be discussed.

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For The First Time Ever, CRISPR Gene Editing Was Used in Humans. So What’s Next?

While the middle part of the 20th century saw the world’s superpowers racing to explore space, the first global competition of this century is being set in a much smaller arena: our DNA.

This month, Chinese scientists announced that they have tested the CRISPR gene-editing technique on a human for the first time, and the race is on to hone the new technology. “I think this is going to trigger ‘Sputnik 2.0’, a biomedical duel on progress between China and the United States,” Carl June, immunotherapy specialist at the University of Pennsylvania in Philadelphia, told Nature.

But while anyone with a view of the night sky could tell you what the Moon was when Neil Armstrong took his one small step on it back in 1969, not everyone has heard of CRISPR, and even fewer people understand how it works or why it’s so important.

A Brief History of Genetic Engineering

Even if it’s been a while since your last biology class, you likely know that most living organisms possess DNA. These little strands of molecules contain all of our genetic information. They determine what we look like, how our bodies function, and everything else that makes a living thing what it is.

Since the 1970s, scientists have been exploring ways to manipulate DNA. They’ve learned how to cut bits out, put chunks of code in, and generally rework these molecules to suit our needs. In 1974, they created genetically modified mice, improving researchers’ ability to conduct medical tests. In 1982, bacteria modified to produced insulin hit the market, eliminating the need for it to be sourced from animals. And ever since 1994, grocery stores have been carrying genetically modified crops, giving us access to longer-lasting, nutritionally superior foods.

As revolutionary as all this has been, genetic engineering has traditionally been expensive, complicated, and remarkably time-consuming. Then along came CRISPR.

CRISPR Uncovered

In the late-1980s, scientists noticed little repeating segments of DNA sequences that were palindromes (the same front to back). Their existence was unusual, and they named them “clustered regularly interspaced short palindromic repeats” (CRISPR). In 2005, a microbiologist figured out that these sequences essentially did for the bacteria what our immune systems do for us: protect against pathogens.

Using CRISPR, the bacteria can snip out a little piece of the pathogen that has invaded its system and store it for future reference. The next time the bacteria encountered that pathogen, it would already be prepared to defend itself. Upon further study, scientists figured out more about how the CRISPR system worked: a protein called CAS9 would make the cut in the targeted DNA after being guided directly to it by a strand of RNA.

Scientists have since found CRISPR in 40 percent of sequenced bacterial genomes and 90 percent of sequenced archaea. It wasn’t until a few years ago, however, that biochemist Jennifer Doudna and microbiologist Emmanuelle Charpentier figured out that they could use this naturally occurring system as a programmable machine to modify DNA. They published their findings in 2012, and by 2013, papers were being published showing how CRISPR could be used in labs to edit genes in humans and mice.

mutant mice
Futurism / M.S.

Faster, Cheaper Gene Editing

This new gene editing system was 99 percent cheaper than the existing methods of genetic modification and also much faster — an experiment that would have previously taken a year could be completed in just a week — so once scientists realized how CRISPR worked, they began finding beneficial ways of manipulating the system.

They figured out how to guide the CAS9 protein to the right spot in the DNA to block a gene without cutting it, and they learned how to attach a different protein to the system to activate dormant genes. Some even figured out how to get the CAS9 protein to turn a gene on or off in response to stimuli, such as certain chemicals or light.

The new system was particularly useful for researchers using live mice in their experiments. No longer would they need to spend up to two years modifying and breeding generations of mice until they arrived at those with the perfect DNA to test new medicines or treatment options. Now, they could have their perfect mouse in as little as six months. As Rudolf Jaenisch at the Massachusetts Institute of Technology (MIT) told Science, “You don’t need [skills] anymore. Any idiot can do it.”

From Mice To Men

The scientists who’ve since used CRISPR to test their theories on live animals are far from idiots, though. They’ve been smart enough to figure out how to repair the defect that causes sickle cell anemia, cut out the gene that causes HIV, and treat muscular dystrophy in live animals, all using CRISPR.

While animal testing is great for the early stages of research, though, we can never know how a human is going to react to a medication or treatment until we actually test it on humans. An estimated 80 percent of potential treatments fail in people even after they yield promising results in animals. Advances in computer processing and machine learning are improving the ability of researchers to perform in silico clinical trials, but even those can’t yet compete with the real thing.

However, the path from animal to human CRISPR testing has been fraught with controversy. While proponents are quick to point out all the good the system can do in helping us treat and even cure diseases, others are concerned about the possible implications, both moral and practical. A Pew research study this summer revealed that Americans are almost equally divided on whether “[gene editing] is meddling with nature and crosses a line we should not cross,” while only 36 percent thought the societal benefits of gene editing would outnumber the downsides.

Futurism / M.A.
Futurism / M.A.

Regulations Mount Up

Most of the world’s major governments are erring on the side of caution, enacting series of rules, regulations, and even bans on how CRISPR is used. The United States government currently prohibits funding for gene-editing research in human embryos, so CRISPR researchers won’t be using any government grants for their studies (though some are receiving funds from private donors). Earlier this year, a team in the UK was granted permission to use CRISPR on human embryos, but that’s just one team, it’s only in the pursuit of fertility treatments, and the embryos had to be destroyed after testing.

Even the scientific community is divided on the subject.

Some scientists have called for a halt to any CRISPR testing on humans until we better understand the technology, and others warn of the dangers if it falls into the wrong hands. In fact, just this month, the President’s Council of Advisors on Science and Technology (PCAST), a group of 18 scientists and scientific policy experts from a variety of disciplines, wrote a letter urging the U.S. government to prepare now for potential future bioterrorist attacks made possible by CRISPR technology.

Others scientists have argued that regulations will leave the U.S. behind countries like Sweden and China in the race to tap the potential of CRISPR, and right now, that latter group is being proven right. With one small trial on a patient suffering from an aggressive form of lung cancer, China has already made the giant leap to human CRISPR test subjects.

Now, the question isn’t so much if the U.S. can win this new global race, but whether or not the country is going to let extreme caution prevent it from even entering in time to compete.

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