Category Archives: Genetic Engineering

The approach is generic enough that you could theoretically apply it to other flowering plants. Blue roses, anyone? There are broader possibilities, too. While the exact techniques clearly won't translate to other lifeforms, this might hint at what's required to produce blue eyes or feathers. And these color changes would be useful for more than just cosmetics. Pollinating insects tend to prefer blue, so this could help spread plant life that has trouble competing in a given habitat.

Just don't count on picking up a blue bouquet. You need a permit to sell any genetically modified organism in the US, and there's a real concern that these gene-modified flowers might spread and create havoc in local ecosystems. The research team hopes to make tweaked chrysanthemums that don't breed, but that also means you're unlikely to see them widely distributed even if they do move beyond the lab. Any public availability would likely hinge on a careful understanding of the flowers' long-term impact.

Here is the original post:
Genetic engineering creates an unnaturally blue flower - Engadget - Engadget

Some of the most powerful technologies ever invented whichcan literally change human life at the DNAlevel aremoving forward with very little societal discussion or sufficient regulatory oversight. Technology Review is now reporting an attempt in the US to use CRISPR to genetically modify a human embryo. From the story:

The first known attempt at creating genetically modified human embryos in the United States has been carried out by a team of researchers in Portland, Oregon,Technology Reviewhas learned.

The effort, led by Shoukhrat Mitalipov of Oregon Health and Science University, involved changing the DNA of a large number of one-cell embryos with the gene-editing technique CRISPR, according to people familiar with the scientific results

Now Mitalipov is believed to have broken new ground both in the number of embryos experimented upon and by demonstrating that it is possible to safely and efficiently correct defective genes that cause inherited diseases.

Although none of the embryos were allowed to develop for more than a few daysand there was never any intention of implanting them into a wombthe experiments are a milestone on what may prove to be an inevitable journey toward the birth of the first genetically modified humans.

It may begin with curing disease. But it wont stay there. Many are drooling to engage in eugenic genetic enhancements.

So, are we going to just watch, slack-jawed, the double-time marchto Brave New World unfoldbefore our eyes?

Or are we going to engage democratic deliberation to determine if this should be done, and if so, what the parameters are?

Considering recent history, I fear I know the answer.

And NO: I dont trust the scientists to regulate themselves.

Mr. President: We need a presidential bioethics/biotechnology commission now!

Originally posted here:
Human Genetic Engineering Begins! - National Review

Roses are red, but science could someday turn them blue. Thats one of the possible future applications of a technique researchers have used to genetically engineer blue chrysanthemums for the first time.

Chyrsanthemums come in an array of colours, including pink, yellow and red. But all it took to engineer the truly blue hueand not a violet or bluish colourwas tinkering with two genes, scientists report in a study published on July 26 inScience Advances. The team says that the approach could be applied to other commercially important flowers, including carnations and lilies.

Consumers love novelty, says Nick Albert, a plant biologist at the New Zealand Institute for Plant & Food Research in Palmerston North, New Zealand. And people actively seek out plants with blue flowers to fill their gardens.

Plenty of flowers are bluish, but its rare to find true blue in nature, says Naonobu Noda, a plant researcher at the National Agriculture and Food Research Organization near Tsukuba, Japan, and lead study author. Scientists, including Noda, have tried to artificially produce blue blooms for years:efforts that have often produced violet or bluish huesin flowers such as roses and carnations. Part of the problem is that naturally blue blossoming plants arent closely related enough to commercially important flowers for traditional methodsincluding selective breedingto work.

Most truly blue blossoms overexpress genes that trigger the production of pigments called delphinidin-based anthocyanins. The trick to getting blue flowers in species that arent naturally that colour is inserting the right combination of genes into their genomes. Noda came close in a 2013 studywhen he and his colleagues found that adding a gene from a naturally blue Canterbury bells flower (Campanula medium) into the DNA of chrysanthemums (Chrysanthemum morifolium) produced a violet-hued bloom.

Noda says he and his team expected that they would need to manipulate many more genes to get the blue chrysanthemum they produced in their latest study. But to their surprise, adding only one more borrowed gene from the naturally blue butterfly pea plant (Clitoria ternatea) was enough.

Anthocyanins can turn petals red, violet or blue, depending on the pigments structure. Noda and his colleagues found that genes from the Canterbury bells and butterfly pea altered the molecular structure of the anthocyanin in the chrysanthemum. When the modified pigments interacted with compounds called flavone glucosides, the resulting chrysanthemum flowers were blue. The team tested the wavelengths given off by their blossoms in several ways to ensure that the flowers were truly blue.

The quest for blue blooms wouldn't only be applicable to the commercial flower market. Studying how these pigments work could also lead to the sustainable manufacture of artificial pigments, says Silvia Vignolini, a physicist at the University of Cambridge, UK, who has studied themolecular structure of the intensely blue marble berry.

Regardless, producing truly blue flowers is a great achievement and demonstrates that the underlying chemistry required to achieve 'blue' is complex and remains to be fully understood, says Albert.

This article is reproduced with permission and wasfirst publishedon July 26, 2017.

Read the original:
True Blue Chrysanthemum Flowers Produced with Genetic Engineering - Scientific American

Naonobu Noda/NARO

Giving chrysanthemums the blues was easier than researchers thought it would be.

Roses are red, but science could someday turn them blue. Thats one of the possible future applications of a technique researchers have used to genetically engineer blue chrysanthemums for the first time.

Chyrsanthemums come in an array of colours, including pink, yellow and red. But all it took to engineer the truly blue hue and not a violet or bluish colour was tinkering with two genes, scientists report in a study published on 26 July in Science Advances1. The team says that the approach could be applied to other commercially important flowers, including carnations and lilies.

Consumers love novelty, says Nick Albert, a plant biologist at the New Zealand Institute for Plant & Food Research in Palmerston North, New Zealand. And people actively seek out plants with blue flowers to fill their gardens.

Plenty of flowers are bluish, but its rare to find true blue in nature, says Naonobu Noda, a plant researcher at the National Agriculture and Food Research Organization near Tsukuba, Japan, and lead study author. Scientists, including Noda, have tried to artificially produce blue blooms for years: efforts that have often produced violet or bluish hues in flowers such as roses and carnations. Part of the problem is that naturally blue blossoming plants arent closely related enough to commercially important flowers for traditional methods including selective breeding to work.

Most truly blue blossoms overexpress genes that trigger the production of pigments called delphinidin-based anthocyanins. The trick to getting blue flowers in species that arent naturally that colour is inserting the right combination of genes into their genomes. Noda came close in a 2013 study2 when he and his colleagues found that adding a gene from a naturally blue Canterbury bells flower (Campanula medium) into the DNA of chrysanthemums (Chrysanthemum morifolium) produced a violet-hued bloom.

Noda says he and his team expected that they would need to manipulate many more genes to get the blue chrysanthemum they produced in their latest study. But to their surprise, adding only one more borrowed gene from the naturally blue butterfly pea plant (Clitoria ternatea) was enough.

Anthocyanins can turn petals red, violet or blue, depending on the pigments structure. Noda and his colleagues found that genes from the Canterbury bells and butterfly pea altered the molecular structure of the anthocyanin in the chrysanthemum. When the modified pigments interacted with compounds called flavone glucosides, the resulting chrysanthemum flowers were blue. The team tested the wavelengths given off by their blossoms in several ways to ensure that the flowers were truly blue.

The quest for blue blooms wouldn't only be applicable to the commercial flower market. Studying how these pigments work could also lead to the sustainable manufacture of artificial pigments, says Silvia Vignolini, a physicist at the University of Cambridge, UK, who has studied the molecular structure of the intensely blue marble berry.

Regardless, producing truly blue flowers is a great achievement and demonstrates that the underlying chemistry required to achieve 'blue' is complex and remains to be fully understood, says Albert.

Read more:
'True blue' chrysanthemum flowers produced with genetic engineering - Nature.com

July 27, 2017 Which is more disruptive to a plant: genetic engineering or conventional breeding?

It often surprises people to learn that GE commonly causes less disruption to plants than conventional techniques of breeding. But equally profound is the realization that the latest GE techniques, coupled with a rapidly expanding ability to analyze massive amounts of genetic material, allow us to make super-modest changes in crop plant genes that will enable farmers to produce more food with fewer adverse environmental impacts. Such super-modest changes are possible with CRISPR-based genome editing, a powerful set of new genetic tools that is leading a revolution in biology.

My interest in GE crops stems from my desire to provide more effective and sustainable plant disease control for farmers worldwide. Diseases often destroy 10 to 15 percent of potential crop production, resulting in global losses of billions of dollars annually. The risk of disease-related losses provides an incentive to farmers to use disease-control products such as pesticides. One of my strongest areas of expertise is in the use of pesticides for disease control. Pesticides certainly can be useful in farming systems worldwide, but they have significant downsides from a sustainability perspective. Used improperly, they can contaminate foods. They can pose a risk to farm workers. And they must be manufactured, shipped and applied all processes with a measurable environmental footprint. Therefore, I am always seeking to reduce pesticide use by offering farmers more sustainable approaches to disease management.

What follows are examples of how minimal GE changes can be applied to make farming more environmentally friendly by protecting crops from disease. They represent just a small sampling of the broad landscape of opportunities for enhancing food security and agricultural sustainability that innovations in molecular biology offer today.

Genetically altering crops the way these examples demonstrate creates no cause for concern for plants or people. Mutations occur naturally every time a plant makes a seed; in fact, they are the very foundation of evolution. All of the food we eat has all kinds of mutations, and eating plants with mutations does not cause mutations in us.

Knocking Out Susceptibility

A striking example of how a tiny genetic change can make a big difference to plant health is the strategy of knocking out a plant gene that microorganisms can benefit from. Invading microorganisms sometimes hijack certain plant molecules to help themselves infect the plant. A gene that produces such a plant molecule is known as a susceptibility gene.

We can use CRISPR-based genome editing to create a targeted mutation in a susceptibility gene. A change of as little as a single nucleotide in the plants genetic material the smallest genetic change possible can confer disease resistance in a way that is absolutely indistinguishable from natural mutations that can happen spontaneously. Yet if the target gene and mutation site are carefully selected, a one-nucleotide mutation may be enough to achieve an important outcome.

There is a substantial body of research showing proof-of-concept that a knockout of a susceptibility gene can increase resistance in plants to a very wide variety of disease-causing microorganisms. An example that caught my attention pertained to powdery mildew of wheat, because fungicides (pesticides that control fungi) are commonly used against this disease. While this particular genetic knockout is not yet commercialized, I personally would rather eat wheat products from varieties that control disease through genetics than from crops treated with fungicides.

The Power of Viral Snippets

Plant viruses are often difficult to control in susceptible crop varieties. Conventional breeding can help make plants resistant to viruses, but sometimes it is not successful.

Early approaches to engineering virus resistance in plants involved inserting a gene from the virus into the plants genetic material. For example, plant-infecting viruses are surrounded by a protective layer of protein, called the coat protein. The gene for the coat protein of a virus called papaya ring spot virus was inserted into papaya. Through a process called RNAi, this empowers the plant to inactivate the virus when it invades. GE papaya has been a spectacular success, in large part saving the Hawaiian papaya industry.

Aerial view of a field trial showing virus-resistant papaya growing well while the surrounding susceptible papaya is severely damaged by the virus. Reproduced with permission from Gonsalves, D., et al. 2004. Transgenic virus-resistant papaya: From hope to reality in controlling papaya ringspot virus in Hawaii. APSnet Features. Online. DOI: 10.1094/APSnetFeature-2004-0704

Through time, researchers discovered that even just a very small fragment from one viral gene can stimulate RNAi-based resistance if precisely placed within a specific location in the plants DNA. Even better, they found we can stack resistance genes engineered with extremely modest changes in order to create a plant highly resistant to multiple viruses. This is important because, in the field, crops are often exposed to infection by several viruses.

Does eating this tiny bit of a viral gene sequence concern me? Absolutely not, for many reasons, including:

Tweaking Sentry Molecules

Microorganisms can often overcome plants biochemical defenses by producing molecules called effectors that interfere with those defenses. Plants respond by evolving proteins to recognize and disable these effector molecules. These recognition proteins are called R proteins (R standing for resistance). Their job is to recognize the invading effector molecule and trigger additional defenses. A third interesting approach, then, to help plants resist an invading microorganism is to engineer an R protein so that it recognizes effector molecules other than the one it evolved to detect. We can then use CRISPR to supply a plant with the very small amount of DNA needed to empower it to make this protein.

This approach, like susceptibility knockouts, is quite feasible, based on published research. Commercial implementation will require some willing private- or public-sector entity to do the development work and to face the very substantial and costly challenges of the regulatory process.

Engineered for Sustainability

The three examples here show that extremely modest engineered changes in plant genetics can result in very important benefits. All three examples involve engineered changes that trigger the natural defenses of the plant. No novel defense mechanisms were introduced in these research projects, a fact that may appeal to some consumers. The wise use of the advanced GE methods illustrated here, as well as others described elsewhere, has the potential to increase the sustainability of our food production systems, particularly given the well-established safety of GE crops and their products for consumption.

View original post here:
When genetic engineering is the environmentally friendly choice - Ensia

The last several decades have witnessed a remarkable increase in crop yields doubling major grain crops since the 1950s. But a significant part of the world still suffers from malnutrition, and these gains in grains and other crops probably wont be enough to feed a growing global population.

These facts have put farmers and agricultural scientists on a quest to squeeze more yield from plants (and livestock), and how to make these yield increases more sustainable. The best land is already taken and could be altered by climate changes, so new crops may have to be grown in less hospitable locations, and the soils and nutrition in existing lands need to be better preserved.

Several methods are being used to boost yields with less fertilizer or pesticides, including traditional combination techniques, marker-assisted breeding, and, of course, trans- and cis-genic modifications.

One way to get more food from a plant is through another genetic switch. It may be possible to genetically, either through hybridization, mutagenesis, or genetic engineering to alter a plant so that it transforms from an annual (one you have to replant every year) to a perennial (which you plant once and can thrive for many years).

This video from Washington State University discusses some advantages of perennial crops:

Most staples, like corn, wheat, sorghum and other grains are annuals. About 75 percent of US and 69 percent of global croplands are cereal, oilseed and legumes, and all of those are annuals, said Jerry Glover, plant geneticist at the Land Institute in Salina, Kansas, and John Reganold, a geneticist at Washington State University. This means, they wrote:

They must be replanted each year from seed, require large amounts of expensive fertilizers and pesticides, poorly protect soil and water, and provide little habitat for wildlife. Their production emits significant greenhouse gases, contributing to climate change that can in turn have adverse effects on agricultural productivity.

Perennials, meanwhile, have longer growing seasons and more extensive roots, making them more productive, and more efficient at capturing nutrients and water from the soil. Replanting isnt necessary, reducing pesticide and fertilizer use, and reducing the need to use tractors and other mechanical planters in fields. Erosion also can be reduced. Its been estimated that annual grains can lose five times more water and 35 times more nitrate than perennial grains.All plants at one time were perennials, and breeders and farmers concentrated on breeding new annuals that could meet a farmers (and consumers) needs.

Now, the table has turned. Genetics may make the annual-to-perennial transformation easier.The switch to perennials is not a new avenue of research, but its been a rocky road. Scientists in the former USSR and the US tried to create perennial wheat in the 1960s, but the offspring plants were sterile and didnt deliver on desired traits. Since then, scientists worldwide have looked at deriving perennials from annual and perennial parents using molecular markers tied to desirable traits (and the genes responsible for them). This technique, and knowing the genotypes of more and more plants, has made it possible to combine desirable genes with traditional and genetic engineering methods to find these desirable perennial plants.

Glover has pointed out that molecular markers tied to desirable traits (higher yields, disease resistance, etc.) can allow for faster breeding by determining the sources of plant variation, and that plant genomics has facilitated the combination of genes without having to field test over years at a time. Genetic modifications can also help spur this along.

Andrew Paterson, head of the plant genome laboratory at the University of Georgia, has studied for years the development of perennial sorghum one of the top five cerealon the planet. Sorghums drought resistance has made it useful as a grain and biomass source in degraded soil, and a perennial version (which has happened spontaneously twice) could reduce drought losses even to other crops. Patersons genetic analysis of wild perennials and cultivated annuals has shown the genes involved in perennial ism and offered DNA markers for more precise breeding.

Techniques like CRISPR/Cas9, which can precisely edit, insert or delete genes at specific locations, are being studied for their possible role in transforming perennials, but a few challenges remain. Chung-Jui Tsai at the University of Georgia, recently showed that CRISPR could be used to alter genes in existing perennials (like fruit and nut trees, for example), once some hurdles like frequent polymorphisms and other variations could be overcome.

Still others are not so optimistic about using genetic modification to enact the perennial-annual switch. First, the whole field would require much more research funding than currently exists, Glover warns. Then, as Paterson told Brooke Borel in her article in Popular Science, perennial traits are much more complicated than those currently addressed by genetic engineering. We dont really know all of the genes involved, not yet:

We dont actually have any of the genes in hand. We know where they are in the genome and we are working on their locations more and more finely, but there arent any of these genes that we can yet point to the specific gene among the 30,000 or so in sorghum. Even if they did know the exact genes, most GMOs that are currently available only insert a single new trait rather than information from multiple genes. The technology isnt yet able to handle something so complicated as perennialism.

Andrew Porterfieldis a writer, editor and communications consultant for academic institutions, companies and non-profits in the life sciences. He is based in Camarillo, California. Follow@AMPorterfieldon Twitter.

Related Stories

See original here:
Can genetic modification turn annual crops into perennials? - Genetic Literacy Project

What began as a broad-based and occasionally sympathetic conduit for anti-Trump activists has evolved into a platform for the maladjusted to receive unhealthy levels of public scrutiny. The cycle has become a depressingly familiar. A relatively obscure member of the political class achieves viral notoriety and becomes a figure of cult-like popularity with some uncompromising display of opposition toward the president only to humiliate themselves and their followers in short order.

Democratic Rep. Maxine Waters is not the first to be feted by liberals as the embodiment of noble opposition to authoritarianism. In May, the Center for American Progress blog dubbed her the patron saint of resistance politics. Left-leaning viral-politics websites now routinely praise Waters as a Trump-bashing resistance leader, the Democratic rock star of 2017, and an all-around badass for her unflagging commitment to trashing the president as a crooked and racist liar, the Daily Beast observed. Waters was even honored by an audience of tweens and entertainers at this years MTV Movie Awards. Even a modestly curious review of Waters record would have led more cautious political actors to keep their distance. Time bombs have a habit of going off.

Zero hour arrived late Friday evening when Waters broke the news of a forthcoming putsch. Mike Pence is somewhere planning an inauguration, the congresswoman from California wrote. Priebus and Spicer will lead the transition. That sounds crazy, but its a familiar kind of crazy.

Anyone who has followed the congresswomans career knows she has a history of making inflammatory assertions for the benefit of her audience. It only takes a cursory google search to discover that, in her decade in politics, Citizens for Responsibility and Ethics in Washington (CREW) has named her the most corrupt member of Congress four times and the misconduct of her chief of staff ensnared her in a House Ethics Committee probe. The Resistance is willing to overlook a plethora of flaws and misdeeds as long as their prior assumptions are validated.

This is not the first time its own heroes have undercut The Resistance.

National Reviews Charles C. W. Cooke recently demonstrated why Louise Mensch, formerly a prominent poster child for The Resistance, has a habit of seeing Russians behind every darkened corner. They are responsible for riots in Missouri, Democratic losses at the polls, and Anthony Weiners libido. In Menschs imagination, a secret Republican Guard is mere moments away from dispatching this administration amid some species of constitutional coup. Cooke also noted that Mensch was elevated to unearned status as a celebrity of the Resistance by the anti-Trump commentary class desperate for what she was selling.

Menschs star has faded, but not before she managed to embarrass those who invested confidence in her sources. Those who embraced her should have been more cautious in the process. Menschs British compatriots long ago caught onto her habit of lashing out at phantoms. A prudent political class would have given her a wide berth.

25-year-old Teen Vogue columnist Lauren Duca became a sensation last December when her article accusing the president of gas lighting the nation went viral. She was festooned with praise for her work from forlorn Democratsculminating in a letter of praise from Hillary Clintonand soon found herself the subject of fawning New York Times profiles and delivering college commencement addresses without any apparent effort to vet her work.

Duca, too, became a source of bias-confirming misinformation for the left. Cute pic of Trump getting tired of winning, she tweeted with the image of an airplane going down in flames. The tweet was quickly deleted, but not before it provided a means by which the pro-Trump right could credibly undermine her integrity.

Attributable only to a plague mass hysteria, liberal Trump opponents collectively determined last December that a paranoid, 127-tweet rant was a work of unpatrolled genius. That diatribe was the work of Eric Garland, a self-described D.C. technocrat based in Missouri whos now infamous game theory polemic was an example of what he calls his spastic historical and political narratives.

Journalists and political activists who surveyed his work declared it not just compelling anti-Trump prose but near historic in its brilliance. It was anything but. Laced with profanity, exaggerated misspellings to caricature his political opponents, and an offensively indiscreet application of the caps lock, Garland threaded 9/11, Al Gore, Hurricane Katrina, Edward Snowden, and Fox News to tell the tale of how Americas sovereignty was repeatedly violated. The Resistance abandoned its better judgment.

It wasnt long before Garland had humiliated anyone who ever treated him as a credible political observer. Rupert Murdoch is a threat to Western Civilization and a Russian operative, he wrote. I WONT BE THE FIRST GARLAND OF MY LINE TO SPILL BLOOD FOR AMERICA AND THE RIGHT SIDE OF HISTORY AND NEVER THE LAST, YOU F***ERS. This kind of hyperventilating excess came as no surprise to anyone who didnt read his manic thread through tears as they struggled to come to terms with the age of Trump.

If Democrats hope to strike a favorable contrast with a lackadaisical White House, theyre not well served by surrounding themselves with reckless people. Too often, the faces of The Resistance wither in the spotlight. A serious movement attracts serious opposition. A frivolous, self-gratifying movement, well, doesnt.

Read the original:
We Need to Talk About Genetic Engineering - Commentary Magazine

Genetic engineering, the artificial manipulation, modification, and recombination of DNA or other nucleic acid molecules in order to modify an organism or population of organisms.

The term genetic engineering initially referred to various techniques used for the modification or manipulation of organisms through the processes of heredity and reproduction. As such, the term embraced both artificial selection and all the interventions of biomedical techniques, among them artificial insemination, in vitro fertilization (e.g., test-tube babies), cloning, and gene manipulation. In the latter part of the 20th century, however, the term came to refer more specifically to methods of recombinant DNA technology (or gene cloning), in which DNA molecules from two or more sources are combined either within cells or in vitro and are then inserted into host organisms in which they are able to propagate.

The possibility for recombinant DNA technology emerged with the discovery of restriction enzymes in 1968 by Swiss microbiologist Werner Arber. The following year American microbiologist Hamilton O. Smith purified so-called type II restriction enzymes, which were found to be essential to genetic engineering for their ability to cleave a specific site within the DNA (as opposed to type I restriction enzymes, which cleave DNA at random sites). Drawing on Smiths work, American molecular biologist Daniel Nathans helped advance the technique of DNA recombination in 197071 and demonstrated that type II enzymes could be useful in genetic studies. Genetic engineering based on recombination was pioneered in 1973 by American biochemists Stanley N. Cohen and Herbert W. Boyer, who were among the first to cut DNA into fragments, rejoin different fragments, and insert the new genes into E. coli bacteria, which then reproduced.

Most recombinant DNA technology involves the insertion of foreign genes into the plasmids of common laboratory strains of bacteria. Plasmids are small rings of DNA; they are not part of the bacteriums chromosome (the main repository of the organisms genetic information). Nonetheless, they are capable of directing protein synthesis, and, like chromosomal DNA, they are reproduced and passed on to the bacteriums progeny. Thus, by incorporating foreign DNA (for example, a mammalian gene) into a bacterium, researchers can obtain an almost limitless number of copies of the inserted gene. Furthermore, if the inserted gene is operative (i.e., if it directs protein synthesis), the modified bacterium will produce the protein specified by the foreign DNA.

A subsequent generation of genetic engineering techniques that emerged in the early 21st century centred on gene editing. Gene editing, based on a technology known as CRISPR-Cas9, allows researchers to customize a living organisms genetic sequence by making very specific changes to its DNA. Gene editing has a wide array of applications, being used for the genetic modification of crop plants and livestock and of laboratory model organisms (e.g., mice). The correction of genetic errors associated with disease in animals suggests that gene editing has potential applications in gene therapy for humans.

Genetic engineering has advanced the understanding of many theoretical and practical aspects of gene function and organization. Through recombinant DNA techniques, bacteria have been created that are capable of synthesizing human insulin, human growth hormone, alpha interferon, a hepatitis B vaccine, and other medically useful substances. Plants may be genetically adjusted to enable them to fix nitrogen, and genetic diseases can possibly be corrected by replacing dysfunctional genes with normally functioning genes. Nevertheless, special concern has been focused on such achievements for fear that they might result in the introduction of unfavourable and possibly dangerous traits into microorganisms that were previously free of theme.g., resistance to antibiotics, production of toxins, or a tendency to cause disease. Likewise, the application of gene editing in humans has raised ethical concerns, particularly regarding its potential use to alter traits such as intelligence and beauty.

In 1980 the new microorganisms created by recombinant DNA research were deemed patentable, and in 1986 the U.S. Department of Agriculture approved the sale of the first living genetically altered organisma virus, used as a pseudorabies vaccine, from which a single gene had been cut. Since then several hundred patents have been awarded for genetically altered bacteria and plants. Patents on genetically engineered and genetically modified organisms, particularly crops and other foods, however, were a contentious issue, and they remained so into the first part of the 21st century.

ethics: Bioethics

Read This Article

origins of agriculture: Genetic engineering

Read This Article

history of science: The 20th-century revolution

Read This Article

in genetics

ReadThisArticle

in DNA sequencing

ReadThisArticle

in recombinant DNA technology

ReadThisArticle

in George Ledyard Stebbins, Jr.

ReadThisArticle

in Sir Ian Wilmut

ReadThisArticle

in genetically modified organism (GMO)

ReadThisArticle

See the original post:
genetic engineering | Definition, Process, & Uses ...

[+]Enlarge

Credit: Will Ludwig/C&EN/Shutterstock

Synthetic biologists have been creating the genomes of organisms such as viruses and bacteria for the past 15 years. They aim to use these designer genetic codes to make cells capable of producing novel therapeutics and fuels. Now, some of these scientists have set their sights on synthesizing the human genomea vastly more complex genetic blueprint. Read on to learn about this initiative, called Genome Project-write, and the challenges researchers will faceboth technical and ethicalto achieve success.

Nineteenth-century novels are typically fodder for literature conferences, not scientific gatherings. Still, at a high-profile meeting of about 200 synthetic biologists in May, one presenter highlighted Mary Shelleys gothic masterpiece Frankenstein, which turns 200 next year.

Frankensteins monster, after all, is what many people think of when the possibility of human genetic engineering is raised, said University of Pennsylvania ethicist and historian Jonathan Moreno. The initiative being discussed at the New York City meetingGenome Project-write (GP-write)has been dogged by worries over creating unnatural beings. True, part of GP-write aims to synthesize from scratch all 23 chromosomes of the human genome and insert them into cells in the lab. But proponents of the project say theyre focused on decreasing the cost of synthesizing and assembling large amounts of DNA rather than on creating designer babies.

The overall project is still under development, and the projects members have not yet agreed on a specific road map for moving forward. Its also unclear where funding will come from.

What the members of GP-write do agree on is that creating a human genome from scratch is a tremendous scientific and engineering challenge that will hinge on developing new methods for synthesizing and delivering DNA. They will also need to get better at designing large groups of genes that work together in a predictable way, not to mention making sure that even larger assembliesgenomescan function.

GP-write consortium members argue that these challenges are the very thing that should move scientists to pick up the DNA pen and turn from sequence readers to writers. They believe writing the entire human genome is the only way to truly understand how it works. Many researchers quoted Richard Feynman during the meeting in May. The statement What I cannot create, I do not understand was found on the famed physicists California Institute of Technology blackboard after his death. I want to know the rules that make a genome tick, said Jef Boeke, one of GP-writes four coleaders, at the meeting.

To that end, Boeke and other GP-write supporters say the initiative will spur the development of new technologies for designing genomes with software and for synthesizing DNA. In turn, being better at designing and assembling genomes will yield synthetic cells capable of producing valuable fuels and drugs more efficiently. And turning to human genome synthesis will enable new cell therapies and other medical advances.

In 2010, researchers at the Venter Institute, including Gibson, demonstrated that a bacterial cell controlled by a synthetic genome was able to reproduce. Colonies formed by it and its sibling resembled a pair of blue eyes.

Credit: Science

Genome writers have already synthesized a few complete genomes, all of them much less complex than the human genome. For instance, in 2002, researchers chemically synthesized a DNA-based equivalent of the poliovirus RNA genome, which is only about 7,500 bases long. They then showed that this DNA copy could be transcribed by RNA polymerase to recapitulate the viral genome, which replicated itselfa demonstration of synthesizing what the authors called a chemical [C332,652H492,388N98,245O131,196P7,501S2,340] with a life cycle (Science 2002, DOI: 10.1126/science.1072266).

After tinkering with a handful of other viral genomes, in 2010, researchers advanced to bacteria, painstakingly assembling a Mycoplasma genome just over about a million bases in length and then transplanting it into a host cell.

Last year, researchers upped the ante further, publishing the design for an aggressively edited Escherichia coli genome measuring 3.97 million bases long (Science, DOI: 10.1126/science.aaf3639). GP-write coleader George Church and coworkers at Harvard used DNA-editing softwarea kind of Google Docs for writing genomesto make radical systematic changes. The so-called rE.coli-57 sequence, which the team is currently synthesizing, lacks seven codons (the three-base DNA words that code for particular amino acids) compared with the normal E. coli genome. The researchers replaced all 62,214 instances of those codons with DNA base synonyms to eliminate redundancy in the code.

Status report International teams of researchers have already synthesized six of yeast's 16 chromosomes, redesigning the organism's genome as part of the Sc2.0 project.

Bacterial genomes are no-frills compared with those of creatures in our domain, the eukaryotes. Bacterial genomes typically take the form of a single circular piece of DNA that floats freely around the cell. Eukaryotic cells, from yeast to plants to insects to people, confine their larger genomes within a cells nucleus and organize them in multiple bundles called chromosomes. An ongoing collaboration is now bringing genome synthesis to the eukaryote realm: Researchers are building a fully synthetic yeast genome, containing 17 chromosomes that range from about 1,800 to about 1.5 million bases long. Overall, the genome will contain more than 11 million bases.

The synthetic genomes and chromosomes already constructed by scientists are by no means simple, but to synthesize the human genome, scientists will have to address a whole other level of complexity. Our genome is made up of more than 3 billion bases across 23 paired chromosomes. The smallest human chromosome is number 21, at 46.7 million baseslarger than the smallest yeast chromosome. The largest, number 1, has nearly 249 million. Making a human genome will mean making much more DNA and solving a larger puzzle in terms of assembly and transfer into cells.

Today, genome-writing technology is in what Boeke, also the director for the Institute of Systems Genetics at New York University School of Medicine, calls the Gutenberg phase. (Johannes Gutenberg introduced the printing press in Europe in the 1400s.) Its still early days.

DNA synthesis companies routinely create fragments that are 100 bases long and then use enzymes to stitch them together to make sequences up to a few thousand bases long, about the size of a gene. Customers can put in orders for small bits of DNA, longer strands called oligos, and whole geneswhatever they needand companies will fabricate and mail the genetic material.

Although the technology that makes this mail-order system possible is impressive, its not prolific enough to make a human genome in a reasonable amount of time. Estimates vary on how long it would take to stitch together a more than 3 billion-base human genome and how much it would cost with todays methods. But the ballpark answer is about a decade and hundreds of millions of dollars.

Synthesis companies could help bring those figures down by moving past their current 100-base limit and creating longer DNA fragments. Some researchers and companies are moving in that direction. For example, synthesis firm Molecular Assemblies is developing an enzymatic process to write long stretches of DNA with fewer errors.

Synthesis speeds and prices have been improving rapidly, and researchers expect they will continue to do so. From my point of view, building DNA is no longer the bottleneck, says Daniel G. Gibson, vice president of DNA technology at Synthetic Genomics and an associate professor at the J. Craig Venter Institute (JCVI). Some way or another, if we need to build larger pieces of DNA, well do that.

Gibson isnt involved with GP-write. But his research showcases what is possible with todays toolseven if they are equivalent to Gutenbergs movable type. He has been responsible for a few of synthetic biologys milestones, including the development of one of the most commonly used genome-assembly techniques.

The Gibson method uses chemical means to join DNA fragments, yielding pieces thousands of bases long. For two fragments to connect, one must end with a 20- to 40-base sequence thats identical to the start of the next fragment. These overlapping DNA fragments can be mixed with a solution of three enzymesan exonuclease, a DNA polymerase, and a DNA ligasethat trim the 5 end of each fragment, overlap the pieces, and seal them together.

To make the first synthetic bacterial genome in 2008, that of Mycoplasma genitalium, Gibson and his colleagues at JCVI, where he was a postdoc at the time, started with his eponymous in vitro method. They synthesized more than 100 fragments of synthetic DNA, each about 5,000 bases long, and then harnessed the prodigious DNA-processing properties of yeast, introducing these large DNA pieces to yeast three or four at a time. The yeast used its own cellular machinery to bring the pieces together into larger sequences, eventually producing the entire Mycoplasma genome.

Next, the team had to figure out how to transplant this synthetic genome into a bacterial cell to create what the researchers called the first synthetic cell. The process is involved and requires getting the bacterial genome out of the yeast, then storing the huge, fragile piece of circular DNA in a protective agarose gel before melting it and mixing it with another species of Mycoplasma. As the bacterial cells fuse, some of them take in the synthetic genomes floating in solution. Then they divide to create three daughter cells, two containing the native genomes, and one containing the synthetic genome: the synthetic cell.

When Gibsons group at JCVI started building the synthetic cell in 2004, we didnt know what the limitations were, he says. So the scientists were cautious about overwhelming the yeast with too many DNA fragments, or pieces that were too long. Today, Gibson says he can bring together about 25 overlapping DNA fragments that are about 25,000 bases long, rather than three or four 5,000-base segments at a time.

Gibson expects that existing DNA synthesis and assembly methods havent yet been pushed to their limits. Yeast might be able to assemble millions of bases, not just hundreds of thousands, he says. Still, Gibson believes it would be a stretch to make a human genome with this technique.

One of the most ambitious projects in genome writing so far centers on that master DNA assembler, yeast. As part of the project, called Sc2.0 (a riff on the funguss scientific name, Saccharomyces cerevisiae), an international group of scientists is redesigning and building yeast one synthetic chromosome at a time. The yeast genome is far simpler than ours. But like us, yeasts are eukaryotes and have multiple chromosomes within their nuclei.

Synthetic biologists arent interested in rebuilding existing genomes by rote; they want to make changes so they can probe how genomes work and make them easier to build and reengineer for practical use. The main lesson learned from Sc2.0 so far, project scientists say, is how much the yeast chromosomes can be altered in the writing, with no apparent ill effects. Indeed, the Sc2.0 sequence is not a direct copy of the original. The synthetic genome has been reduced by about 8%. Overall, the research group will make 1.1 million bases worth of insertions, deletions, and changes to the yeast genome (Science 2017, DOI: 10.1126/science.aaf4557).

So far, says Boeke, whos also coleader of Sc2.0, teams have finished or almost finished the first draft of the organisms 16 chromosomes. Theyre also working on a neochromosome, one not found in normal yeast. In this chromosome, the designers have relocated all DNA coding for transfer RNA, which plays a critical role in protein assembly. The Sc2.0 group isolated these sequences because scientists predicted they would cause structural instability in the synthetic chromosomes, says Joel Bader, a computational biologist at Johns Hopkins University who leads the projects software and design efforts.

The team is making yeast cells with a new chromosome one at a time. The ultimate goal is to create a yeast cell that contains no native chromosomes and all 17 synthetic ones. To get there, the scientists are taking a relatively old-fashioned approach: breeding. So far, theyve made a yeast cell with three synthetic chromosomes and are continuing to breed it with strains containing the remaining ones. Once a new chromosome is in place, it requires some patching up because of recombination with the native chromosomes. Its a process, but it doesnt look like there are any significant barriers, Bader says. He estimates it will take another two to three years to produce cells with the entire Sc2.0 genome.

So far, even with these significant changes to the chromosomes, the yeast lives at no apparent disadvantage compared with yeast that has its original chromosomes. Its surprising how much you can torture the genome with no effect, Boeke says.

Boeke and Bader have founded a start-up company called Neochromosome that will eventually use Sc2.0 strains to produce large protein drugs, chemical precursors, and other biomolecules that are currently impossible to make in yeast or E. coli because the genetic pathways used to create them are too complex. With synthetic chromosomes well be able to make these large supportive pathways in yeast, Bader predicts.

Whether existing genome-engineering methods like those used in Sc2.0 will translate to humans is an open question.

Bader believes that yeast, so willing to take up and assemble large amounts of DNA, might serve as future human-chromosome producers, assembling genetic material that could then be transferred to other organisms, perhaps human cells. Transplanting large human chromosomes would be tricky, Synthetic Genomics Gibson says. First, the recipient cell must be prepped by somehow removing its native chromosome. Gibson expects physically moving the synthetic chromosome would also be difficult: Stretches of DNA larger than about 50,000 bases are fragile. You have to be very gentle so the chromosome doesnt breakonce its broken, its not going to be useful, he says. Some researchers are working on more direct methods for cell-to-cell DNA transfer, such as getting cells to fuse with one another.

Once the scientists solve the delivery challenge, the next question is whether the transplanted chromosome will function. Our genomes are patterned with methyl groups that silence regions of the genome and are wrapped around histone proteins that pack the long strands into a three-dimensional order in cells nuclei. If the synthetic chromosome doesnt have the appropriate methylation patterns, the right structure, it might not be recognized by the cell, Gibson says.

Biologists might sidestep these epigenetic and other issues by doing large-scale DNA assembly in human cells from the get-go. Ron Weiss, a synthetic biologist at Massachusetts Institute of Technology, is pushing the upper limits on this sort of approach. He has designed methods for inserting large amounts of DNA directly into human cells. Weiss endows human cells with large circuits, which are packages of engineered DNA containing groups of genes and regulatory machinery that will change a cells behavior.

In 2014, Weiss developed a landing pad method to insert about 64,000-base stretches of DNA into human and other mammalian cells. First, researchers use gene editing to create the landing pad, which is a set of markers at a designated spot on a particular chromosome where an enzyme called a recombinase will insert the synthetic genetic material. Then they string together the genes for a given pathway, along with their regulatory elements, add a matching recombinase site, and fashion this strand into a circular piece of DNA called a plasmid. The target cells are then incubated with the plasmid, take it up, and incorporate it at the landing site (Nucleic Acids Res. 2014, DOI: 10.1093/nar/gku1082).

This works, but its tedious. It takes about two weeks to generate these cell lines if youre doing well, and the payload only goes into a few of the cells, Weiss explains. Since his initial publication, he says, his team has been able to generate cells with three landing pads; that means they could incorporate a genetic circuit thats about 200,000 bases long.

Weiss doesnt see simple scale-up of the landing pad method as the way forward, though, even setting aside the tedium. He doesnt think the supersized circuits would even function in a human cell because he doesnt yet know how to design them.

The limiting factor in the size of the circuit is not the construction of DNA, but the design, Weiss says. Instead of working completely by trial and error, bioengineers use computer models to predict how synthetic circuits or genetic edits will work in living cells of any species. But the larger the synthetic element, the harder it is to know whether it will work in a real cell. And the more radical the deletion, the harder it is to foresee whether it will have unintended consequences and kill the cell. Researchers also have a hard time predicting the degree to which cells will express the genes in a complex synthetic circuita lot, a little, or not at all. Gene regulation in humans is not fully understood, and rewriting on the scale done in the yeast chromosome would have far less predictable outcomes.

Besides being willing to take up and incorporate DNA, yeast is relatively simple. Upstream from a yeast gene, biologists can easily find the promoter sequence that turns it on. In contrast, human genes are often regulated by elements found in distant regions of the genome. That means working out how to control large pathways is more difficult, and theres a greater risk that changing the genetic sequencesuch as deleting what looks like repetitive nonsensewill have unintended, currently unpredictable, consequences.

Gibson notes that even in the minimal cell, the organism with the simplest known genome on the planet, biologists dont know what one-third of the genes do. Moving from the simplest organism to humans is a leap into the unknown. One design flaw can change how the cell behaves or even whether the cells are viable, Gibson says. We dont have the design knowledge.

Many scientists believe this uncertainty about design is all the more reason to try writing human and other large genomes. People are entranced with the perfect, Harvards Church says. But engineering and medicine are about the pretty good. I learn much more by trying to make something than by observing it.

Others arent sure that the move from writing the yeast genome to writing the human genome is necessary, or ethical. When the project to write the human genome was made public in May 2016, the founders called it Human Genome Project-write. They held the first organizational meeting behind closed doors, with no journalists present. A backlash ensued.

In the magazine Cosmos, Stanford University bioengineer Drew Endy and Northwestern University ethicist Laurie Zoloth in May 2016 warned of unintended consequences of large-scale changes to the genome and of alienating the public, potentially putting at risk funding for the synthetic biology field at large. They wrote that the synthesis of less controversial and more immediately useful genomes along with greatly improved sub-genomic synthesis capacities should be pursued instead.

GP-write members seem to have taken such criticisms to heart, or come to a similar conclusion on their own. By this Mays conference, human was dropped from the projects name. Leaders emphasized that the human genome would be a subproject proceeding on a conservative timescale and that ethicists would be involved at every step along the way. We want to separate the overarching goal of technology development from the hot-button issue of human genome writing, Boeke explains.

Bringing the public on board with this kind of project can be difficult, says Alta Charo, a professor of law and bioethics at the University of Wisconsin, Madison, who is not involved with GP-write. Charo cochaired a National Academy of Sciences study on the ethics and governance of human gene editing, which was published in February.

She says the likelihood of positive outcomes, such as new therapies or advances in basic science, must be weighed against potential unintended consequences or unforeseen uses of genome writing. People see their basic values at stake in human genetic engineering. If scientists achieve their goalsmaking larger scale genetic engineering routine and more useful, and bringing it to the human genomemajor changes are possible to what Charo calls the fabric of our culture and society. People will have to decide whether they feel optimistic about that or not. (Charo does.)

Given humans cautiousness, Charo imagines in early times we might have decided against creating fire, saying, Lets live without that; we dont need to create this thing that might destroy us. People often see genetic engineering in extreme terms, as a fire that might illuminate human biology and light the way to new technologies, or one that will destroy us.

Charo says the GP-write plan to keep ethicists involved going forward is the right approach and that its difficult to make an ethical or legal call on the project until its leaders put forward a road map.

The group will announce a specific road map sometime this year, but it doesnt want to be restrictive ahead of time. You know when youre done reading something, Boeke said at the meeting in May. But writing has an artistic side to it, he added. You never know when youre done.

Katherine Bourzac is a freelance science writer based in San Francisco.

Excerpt from:
Writing the human genome - The Biological SCENE

Diamondback moths may be a mere half-inch in length, but their voracious appetite for Brussels sprouts, kale and cauliflower make them a major pain for farmers. This week, the U.S. Department of Agriculture approved a potential solution: moths genetically engineered to contain a special gene that makes them gradually die off. A field trial slated to take place in a small area of upstate New York will become the first wild release of an insect modified using genetic engineering in the US.

The moths have been engineered by the British biotech firm Oxitec, the same company that last year caused a stir with its plans to release genetically modified, Zika-fighting mosquitoes in the Florida Keys. The diamond back moths take a similar approach to the mosquitoes, modifying male mosquitoes to limit the population over time by passing on a gene to offspring when it mates with wild females that causes female moths to die before they reach maturity.

The technique is a riff on an approach used to manage agricultural pests since the 1950s, known as sterile insect technique. Using radiation, scientists made insects like the screwworm unable to produce viable offspring. By 1982, screwworm was eradicated from the US using this alternative to pesticides. In Silent Spring Rachel Carson suggested this approach was the solution to the dangers of harmful pesticides agricultural producers required to protect their crops. The problem was that it did not work on every insectin many cases, it simply left irradiated insects too weak to compete for mates with their healthier kin.

Diamondback moths are a sizable problem for farmers, and a problem thats growing as the moths develop resistance to traditional pesticides. They do about $5 billion in damage to cruciferous crops worldwide every year. In the upcoming trial, a team at Cornell University will oversee the release of the genetically engineered moths in a 10-acre field owned by Cornell in Geneva, New York.

After a review found that the field trial is unlikely to impact either the environment or humans, the USDA issued a permit that allows for the release of up to 30,000 moths per week over several months. It is caterpillars that damage crops, so the plan to release adult males that produce unviable offspring should not cause any additional crop damage. And any surviving moths will likely be killed off by pesticides or upstate New Yorks frigid winter, according to the report submitted to the USDA.

The plan to release modified mosquitoes in the Keys attracted much local ireafter initially getting the greenlight from the FDA, the project was ultimately stalled by a local vote and forced to find a new location for a trial.

In upstate New York, too, the moths have stirred up a debate over GMOs for the past several years, though the plan has not been met with quite the same level of opposition. The approval process through the USDA rather than the FDA, too, was much swifter.

In laboratory and greenhouse trials, the modified mosquito was reportedly effective in decreasing the overall population. But tests still need to determine how it will fare in open air.

Oxitec has released its engineered mosquitoes Brazil, Grand Cayman, and Panama, and still plans to go ahead with a field trial in the Keys. In December, the company announced plans for field trials of a genetically modified Mediterranean fruit fly in Western Australia. It is also working on genetically engineering several other agricultural pests, including Drosophila suzukii and the Olive fly.

Read more:
America's First Free-Roaming Genetically Engineered Insects Are ... - Gizmodo