Genetic modification caused by human activity has been occurring since around 12,000 BC, when humans first began to domesticate organisms. Genetic engineering as the direct transfer of DNA from one organism to another was first accomplished by Herbert Boyer and Stanley Cohen in 1972. The first genetically modified animal was a mouse created in 1974 by Rudolf Jaenisch. In 1983 an antibiotic resistant gene was inserted into tobacco, leading to the first genetically engineered plant. Advances followed that allowed scientists to manipulate and add genes to a variety of different organism and induce a range of different effects.

In 1976 the technology was commercialized, with the advent of genetically modified bacteria that produced somatostatin, followed by insulin in 1978. Plants were first commercialized with virus resistant tobacco released in China in 1992. The first genetically modified food was the Flavr Savr tomato marketed in 1994. By 2010, 29 countries had planted commercialized biotech crops. In 2000 a paper published in Science introduced golden rice, the first food developed with increased nutrient value.

Genetic engineering is the direct manipulation of an organism's genome using certain biotechnology techniques that have only existed since the 1970s.[2] Human directed genetic manipulation was occurring much earlier, beginning with the domestication of plants and animals through artificial selection. The dog is believed to be the first animal domesticated, possibly arising from a common ancestor of the grey wolf,[1] with archeological evidence dating to about 12,000 BC.[3] Other carnivores domesticated in prehistoric times include the cat, which cohabited with human 9,500 years ago.[4] Archeological evidence suggests sheep, cattle, pigs and goats were domesticated between 9 000 BC and 8 000 BC in the Fertile Crescent.[5]

The first evidence of plant domestication comes from emmer and einkorn wheat found in pre-Pottery Neolithic A villages in Southwest Asia dated about 10,500 to 10,100 BC. The Fertile Crescent of Western Asia, Egypt, and India were sites of the earliest planned sowing and harvesting of plants that had previously been gathered in the wild. Independent development of agriculture occurred in northern and southern China, Africa's Sahel, New Guinea and several regions of the Americas.[7] The eight Neolithic founder crops (emmer wheat, einkorn wheat, barley, peas, lentils, bitter vetch, chick peas and flax) had all appeared by about 7000 BC.[8]Horticulture first appears in the Levant during the Chalcolithic period about 6 800 to 6,300 BC. Due to the soft tissues, archeological evidence for early vegetables is scarce. The earliest vegetable remains have been found in Egyptian caves that date back to the 2nd millennium BC.

Selective breeding of domesticated plants was once the main way early farmers shaped organisms to suit their needs. Charles Darwin described three types of selection: methodical selection, wherein humans deliberately select for particular characteristics; unconscious selection, wherein a characteristic is selected simply because it is desirable; and natural selection, wherein a trait that helps an organism survive better is passed on.[11]:25 Early breeding relied on unconscious and natural selection. The introduction of methodical selection is unknown.[11]:25 Common characteristics that were bred into domesticated plants include grains that did not shatter to allow easier harvesting, uniform ripening, shorter lifespans that translate to faster growing, loss of toxic compounds, and productivity.[11]:2730 Some plants, like the Banana, were able to be propagated by vegetative cloning. Offspring often did not contain seeds, and therefore sterile. However, these offspring were usually juicier and larger. Propagation through cloning allows these mutant varieties to be cultivated despite their lack of seeds.[11]:31

Hybridization was another way that rapid changes in plant's makeup were introduced. It often increased vigor in plants, and combined desirable traits together. Hybridization most likely first occurred when humans first grew similar, yet slightly different plants in close proximity.[11]:32Triticum aestivum, wheat used in baking bread, is an allopolyploid. Its creation is the result of two separate hybridization events.[12]

Grafting can transfer chloroplasts (specialised DNA in plants that can conduct photosynthesis), mitichondrial DNA and the entire cell nucleus containing the genome to potentially make a new species making grafting a form of natural genetic engineering.[13]

X-rays were first used to deliberately mutate plants in 1927. Between 1927 and 2007, more than 2,540 genetically mutated plant varieties had been produced using x-rays.[14]

Various genetic discoveries have been essential in the development of genetic engineering. Genetic inheritance was first discovered by Gregor Mendel in 1865 following experiments crossing peas. Although largely ignored for 34 years he provided the first evidence of hereditary segregation and independent assortment.[15] In 1889 Hugo de Vries came up with the name "(pan)gene" after postulating that particles are responsible for inheritance of characteristics[16] and the term "genetics" was coined by William Bateson in 1905.[17] In 1928 Frederick Griffith proved the existence of a "transforming principle" involved in inheritance, which Avery, MacLeod and McCarty later (1944) identified as DNA. Edward Lawrie Tatum and George Wells Beadle developed the central dogma that genes code for proteins in 1941. The double helix structure of DNA was identified by James Watson and Francis Crick in 1953.

As well as discovering how DNA works, tools had to be developed that allowed it to be manipulated. In 1970 Hamilton Smiths lab discovered restriction enzymes that allowed DNA to be cut at specific places and separated out on an electrophoresis gel. This enabled scientists to isolate genes from an organism's genome.[18]DNA ligases, that join broken DNA together, had been discovered earlier in 1967[19] and by combining the two enzymes it was possible to "cut and paste" DNA sequences to create recombinant DNA. Plasmids, discovered in 1952,[20] became important tools for transferring information between cells and replicating DNA sequences. Frederick Sanger developed a method for sequencing DNA in 1977, greatly increasing the genetic information available to researchers. Polymerase chain reaction (PCR), developed by Kary Mullis in 1983, allowed small sections of DNA to be amplified and aided identification and isolation of genetic material.

As well as manipulating the DNA, techniques had to be developed for its insertion (known as transformation) into an organism's genome. Griffiths experiment had already shown that some bacteria had the ability to naturally take up and express foreign DNA. Artificial competence was induced in Escherichia coli in 1970 when Morton Mandel and Akiko Higa showed that it could take up bacteriophage after treatment with calcium chloride solution (CaCl2).[21] Two years later, Stanley Cohen showed that CaCl2 treatment was also effective for uptake of plasmid DNA.[22] Transformation using electroporation was developed in the late 1980s, increasing the efficiency and bacterial range.[23] In 1907 a bacterium that caused plant tumors, Agrobacterium tumefaciens, was discovered and in the early 1970s the tumor inducing agent was found to be a DNA plasmid called the Ti plasmid.[24] By removing the genes in the plasmid that caused the tumor and adding in novel genes researchers were able to infect plants with A. tumefaciens and let the bacteria insert their chosen DNA into the genomes of the plants.[25]

In 1972 Paul Berg utilised restriction enzymes and DNA ligases to create the first recombinant DNA molecules. He combined DNA from the monkey virus SV40 with that of the lambda virus.[26] Herbert Boyer and Stanley Norman Cohen took Berg's work a step further and introduced recombinant DNA into a bacterial cell. Cohen was researching plasmids, while Boyers work involved restriction enzymes. They recognised the complementary nature of their work and teamed up in 1972. Together they found a restriction enzyme that cut the pSC101 plasmid at a single point and were able to insert and ligate a gene that conferred resistance to the kanamycin antibiotic into the gap. Cohen had previously devised a method where bacteria could be induced to take up a plasmid and using this they were able to create a bacteria that survived in the presence of the kanamycin. This represented the first genetically modified organism. They repeated experiments showing that other genes could be expressed in bacteria, including one from the toad Xenopus laevis, the first cross kingdom transformation.[27][28][29]

In 1974 Rudolf Jaenisch created a transgenic mouse by introducing foreign DNA into its embryo, making it the worlds first transgenic animal.[30][31] Jaenisch was studying mammalian cells infected with simian virus 40 (SV40) when he happened to read a paper from Beatrice Mintz describing the generation of chimera mice. He took his SV40 samples to Mintz's lab and injected them into early mouse embryos expecting tumours to develop. The mice appeared normal, but after using radioactive probes he discovered that the virus had integrated itself into the mice genome.[32] However the mice did not pass the transgene to their offspring. In 1981 the laboratories of Frank Ruddle, Frank Constantini and Elizabeth Lacy injected purified DNA into a single-cell mouse embryo and showed transmission of the genetic material to subsequent generations.[33][34]

The first genetically engineered plant was tobacco, reported in 1983.[35] It was developed by Michael W. Bevan, Richard B. Flavell and Mary-Dell Chilton by creating a chimeric gene that joined an antibiotic resistant gene to the T1 plasmid from Agrobacterium. The tobacco was infected with Agrobacterium transformed with this plasmid resulting in the chimeric gene being inserted into the plant. Through tissue culture techniques a single tobacco cell was selected that contained the gene and a new plant grown from it.[36]

The development of genetic engineering technology led to concerns in the scientific community about potential risks. The development of a regulatory framework concerning genetic engineering began in 1975, at Asilomar, California. The Asilomar meeting recommended a set of guidelines regarding the cautious use of recombinant technology and any products resulting from that technology.[37] The Asilomar recommendations were voluntary, but in 1976 the US National Institute of Health (NIH) formed a recombinant DNA advisory committee.[38] This was followed by other regulatory offices (the United States Department of Agriculture (USDA), Environmental Protection Agency (EPA) and Food and Drug Administration (FDA), effectively making all recombinant DNA research tightly regulated in the USA.[39]

In 1982 the Organization for Economic Co-operation and Development (OECD) released a report into the potential hazards of releasing genetically modified organisms into the environment as the first transgenic plants were being developed.[40] As the technology improved and genetically organisms moved from model organisms to potential commercial products the USA established a committee at the Office of Science and Technology (OSTP) to develop mechanisms to regulate the developing technology.[39] In 1986 the OSTP assigned regulatory approval of genetically modified plants in the US to the USDA, FDA and EPA.[41] In the late 1980s and early 1990s, guidance on assessing the safety of genetically engineered plants and food emerged from organizations including the FAO and WHO.[42][43][44][45]

The European Union first introduced laws requiring GMO's to be labelled in 1997.[46] In 2013 Connecticut became the first state to enact a labeling law in the USA, although it would not take effect until other states followed suit.[47]

The ability to insert, alter or remove genes in model organisms allowed scientists to study the genetic elements of human diseases.[48]Genetically modified mice were created in 1984 that carried cloned oncogenes that predisposed them to developing cancer.[49] The technology has also been used to generate mice with genes knocked out. The first recorded knockout mouse was created by Mario R. Capecchi, Martin Evans and Oliver Smithies in 1989. In 1992 oncomice with tumor suppressor genes knocked out were generated.[49] Creating Knockout rats is much harder and only became possible in 2003.[50][51]

After the discovery of microRNA in 1993,[52]RNA interference (RNAi) has been used to silence an organism's genes.[53] By modifying an organism to express microRNA targeted to its endogenous genes, researchers have been able to knockout or partially reduce gene function in a range of species. The ability to partially reduce gene function has allowed the study of genes that are lethal when completely knocked out. Other advantages of using RNAi include the availability of inducible and tissue specific knockout.[54] In 2007 microRNA targeted to insect and nematode genes was expressed in plants, leading to suppression when they fed on the transgenic plant, potentially creating a new way to control pests.[55] Targeting endogenous microRNA expression has allowed further fine tuning of gene expression, supplementing the more traditional gene knock out approach.[56]

Genetic engineering has been used to produce proteins derived from humans and other sources in organisms that normally cannot synthesize these proteins. Human insulin-synthesising bacteria were developed in 1979 and were first used as a treatment in 1982.[57] In 1988 the first human antibodies were produced in plants.[58] In 2000 Vitamin A-enriched golden rice, was the first food with increased nutrient value.[59]

As not all plant cells were susceptible to infection by A. tumefaciens other methods were developed, including electroporation, micro-injection[60] and particle bombardment with a gene gun (invented in 1987).[61][62] In the 1980s techniques were developed to introduce isolated chloroplasts back into a plant cell that had its cell wall removed. With the introduction of the gene gun in 1987 it became possible to integrate foreign genes into a chloroplast.[63]

Genetic transformation has become very efficient in some model organism. In 2008 genetically modified seeds were produced in Arabidopsis thaliana by simply dipping the flowers in an Agrobacterium solution.[64] The range of plants that can be transformed has increased as tissue culture techniques have been developed for different species.

The first transgenic livestock were produced in 1985,[65] by micro-injecting foreign DNA into rabbit, sheep and pig eggs.[66] The first animal to synthesise transgenic proteins in their milk were mice,[67] engineered to produce human tissue plasminogen activator.[68] This technology was applied to sheep, pigs, cows and other livestock.[67]

In 2010 scientists at the J. Craig Venter Institute announced that they had created the first synthetic bacterial genome. The researchers added the new genome to bacterial cells and selected for cells that contained the new genome. To do this the cells undergoes a process called resolution, where during bacterial cell division one new cell receives the original DNA genome of the bacteria, whilst the other receives the new synthetic genome. When this cell replicates it uses the synthetic genome as its template. The resulting bacterium the researchers developed, named Synthia, was the world's first synthetic life form.[69][70]

In 2014 a bacteria was developed that replicated a plasmid containing an unnatural base pair. This required altering the bacterium so it could import the unnatural nucleotides and then efficiently replicate them. The plasmid retained the unnatural base pairs when it doubled an estimated 99.4% of the time.[71] This is the first organism engineered to use an expanded genetic alphabet.[72]

In 2015 CRISPR and TALENs was used to modify plant genomes. Chinese labs used it to create a fungus-resistant wheat and boost rice yields, while a U.K. group used it to tweak a barley gene that could help produce drought-resistant varieties. When used to precisely remove material from DNA without adding genes from other species, the result is not subject the lengthy and expensive regulatory process associated with GMOs. While CRISPR may use foreign DNA to aid the editing process, the second generation of edited plants contain none of that DNA. Researchers celebrated the acceleration because it may allow them to "keep up" with rapidly evolving pathogens. The U.S. Department of Agriculture stated that some examples of gene-edited corn, potatoes and soybeans are not subject to existing regulations. As of 2016 other review bodies had yet to make statements.[73]

In 1976 Genentech, the first genetic engineering company was founded by Herbert Boyer and Robert Swanson and a year later and the company produced a human protein (somatostatin) in E.coli. Genentech announced the production of genetically engineered human insulin in 1978.[74] In 1980 the U.S. Supreme Court in the Diamond v. Chakrabarty case ruled that genetically altered life could be patented.[75] The insulin produced by bacteria, branded humulin, was approved for release by the Food and Drug Administration in 1982.[76]

In 1983 a biotech company, Advanced Genetic Sciences (AGS) applied for U.S. government authorization to perform field tests with the ice-minus strain of P. syringae to protect crops from frost, but environmental groups and protestors delayed the field tests for four years with legal challenges.[77] In 1987 the ice-minus strain of P. syringae became the first genetically modified organism (GMO) to be released into the environment[78] when a strawberry field and a potato field in California were sprayed with it.[79] Both test fields were attacked by activist groups the night before the tests occurred: "The world's first trial site attracted the world's first field trasher".[78]

The first genetically modified crop plant was produced in 1982, an antibiotic-resistant tobacco plant.[80] The first field trials of genetically engineered plants occurred in France and the USA in 1986, tobacco plants were engineered to be resistant to herbicides.[81] In 1987 Plant Genetic Systems, founded by Marc Van Montagu and Jeff Schell, was the first company to genetically engineer insect-resistant plants by incorporating genes that produced insecticidal proteins from Bacillus thuringiensis (Bt) into tobacco.[82]

Genetically modified microbial enzymes were the first application of genetically modified organisms in food production and were approved in 1988 by the US Food and Drug Administration.[83] In the early 1990s, recombinant chymosin was approved for use in several countries.[83][84] Cheese had typically been made using the enzyme complex rennet that had been extracted from cows' stomach lining. Scientists modified bacteria to produce chymosin, which was also able to clot milk, resulting in cheese curds.[85] The Peoples Republic of China was the first country to commercialize transgenic plants, introducing a virus-resistant tobacco in 1992.[86] In 1994 Calgene attained approval to commercially release the Flavr Savr tomato, a tomato engineered to have a longer shelf life.[87] Also in 1994, the European Union approved tobacco engineered to be resistant to the herbicide bromoxynil, making it the first genetically engineered crop commercialized in Europe.[88] In 1995 Bt Potato was approved safe by the Environmental Protection Agency, after having been approved by the FDA, making it the first pesticide producing crop to be approved in the USA.[89] In 1996 a total of 35 approvals had been granted to commercially grow 8 transgenic crops and one flower crop (carnation), with 8 different traits in 6 countries plus the EU.[81]

By 2010, 29 countries had planted commercialized biotech crops and a further 31 countries had granted regulatory approval for transgenic crops to be imported.[90] In 2013 Robert Fraley (Monsantos executive vice president and chief technology officer), Marc Van Montagu and Mary-Dell Chilton were awarded the World Food Prize for improving the "quality, quantity or availability" of food in the world.[91]

The first genetically modified animal to be commercialised was the GloFish, a Zebra fish with a fluorescent gene added that allows it to glow in the dark under ultraviolet light.[92] The first genetically modified animal to be approved for food use was AquAdvantage salmon in 2015.[93] The salmon were transformed with a growth hormone-regulating gene from a Pacific Chinook salmon and a promoter from an ocean pout enabling it to grow year-round instead of only during spring and summer.[94]

Opposition and support for the use of genetic engineering has existed since the technology was developed.[78] After Arpad Pusztai went public with research he was conducting in 1998 the public opposition to genetically modified food increased.[95] Opposition continued following controversial and publicly debated papers published in 1999 and 2013 that claimed negative environmental and health impacts from genetically modified crops.[96][97]

Read more:
History of genetic engineering - Wikipedia

The idea of transplanting organs from pigs into humans has been around for a long time. And for a long time, xenotransplantsor putting organs from one species into anotherhas come up against two seemingly insurmountable problems.

The first problem is fairly intuitive: Pig organs provoke a massive and destructive immune response in humansfar more so than an organ from another person. The second problem is less obvious: Pig genomes are rife with DNA sequences of viruses that can infect human cells. In the 1990s, the pharmaceutical giant Novartis planned to throw as much $1 billion at animal-to-human transplant research, only to shutter its research unit after several years of failed experiments.

Quite suddenly, however, solving these two problems has become much easier and much faster thanks to the gene-editing technology CRISPR. With CRISPR, scientists can knock out the pig genes that trigger the human immune response. And they can inactivate the virusescalled porcine endogenous retroviruses, or PERVsthat lurk in the pig genome.

On Thursday, scientists working for a startup called eGenesis reported the birth of 37 PERV-free baby pigs in China, 15 of them still surviving. The black-and-white piglets are now several months old, and they belong to a breed of miniature pigs that will grow no bigger than 150 poundswith organs just the right size for transplant into adult humans.

eGenesis spun out of the lab of the Harvard geneticist George Church, who previously reported inactivating 62 copies of PERV from pig cells in 2015. But the jump from specialized pig cells that grow well in labs to living PERV-free piglets wasnt easy.

We didnt even know we could have viable pigs, says Luhan Yang, a former graduate student in Churchs lab and co-founder of eGenesis. When her team first tried to edit all 62 copies in pig cells that they wanted to turn into embryos, the cells died. They were more sensitive than the specialized cell lines. Eventually Yang and her team figured out a chemical cocktail that could keep these cells alive through the gene-editing process. This technique could be useful in large-scale gene-editing projects unrelated to xenotransplants, too.

When Yang and her team first inactivated PERV from cells in a lab, my colleague Ed Yong suggested that the work was an example of CRISPRs power rather than a huge breakthrough in pig-to-human transplants, given the challenges of immune compatibility. And true, Yang and Church come at this research as CRISPR pioneers, but not experts in transplantation. At a gathering of organ-transplantation researchers last Friday, Church said that his team had identified about 45 genes to make pig organs more compatible with humans, though he was open to more suggestions. I would bet we are not as sophisticated as we should be because weve only been recently invited [to meetings like this], he said. Its an active area of research for eGenesis, though Yang declined to disclose what the company has accomplished so far.

Its great genetic-engineering work. Its an accomplishment to inactivate that many genes, says Joseph Tector, a xenotransplant researcher at the University of Alabama at Birmingham.

Researchers like Tector, who is also a transplant surgeon, have been chipping away at the problem of immune incompatibility for years, though. CRISPR has sped up that research, too. The first pig gene implicated in the human immune response as one involved in making a molecule called alpha-gal. Making a pig that lacked alpha-gal via older genetic-engineering methods took three years. Now from concept to pig on the ground, its probably six months, says Tector.

Using CRISPR, his team has created a triple-knockout pig that lacks alpha-gal as well as two other genes involved in molecules that that provoke the human immune systems immediate hyperacute rejection of pig organs. For about 30 percent of people, the organs from these triple-knockout pigs should not cause hyperacute rejection. Tector thinks the patients who receive these pig organs could then be treated with the same immunosuppressant drugs that recipients take after an ordinary human-to-human transplant.

Tector and David Cooper, another transplant pioneer, were both recently recruited to the University of Alabama at Birmingham for a xenotransplant program funded by United Therapeutics, a Maryland biotech company that wants to manufacture transplantable organs.

Cooper has transplanted kidneys from pigs engineered by United Therapeutics to have six mutations, which lasted over 200 days in baboons. The result is promising enough that he says human trials could begin soon. These pigs were not created using CRISPR and they are not PERV-free, though recent research has suggested that PERV may not be that harmful to humans. It will be up to the FDA to decide whether pig organs with PERV are safe enough to transplant into people.

If it happens, routine pig-to-human transplants could truly transform healthcare beyond simply increasing the supply. Organs would go from a product of chancesomeone young and healthy dying, unexpectedlyto the product of a standardized manufacturing process. Its going to make such a huge difference that I dont think its possible to conceive of it, says Cooper. Organ transplants would no longer have to be emergency surgeries, requiring planes to deliver organs and surgical teams to scramble at any hour. Organs from pigs can be harvested on a schedule, and surgeries planned for exact times during the day. A patient that comes in with kidney failure could get a kidney the next dayeliminating the need for large dialysis centers. Hospital ICU beds will no longer be taken up by patients waiting for a heart transplant.

With the ability to engineer a donor pig, pig organs can go beyond simply matching a human organ. For example, Cooper says, you could engineer organs to protect themselves from the immune system in the long term, perhaps by making their own localized dose of immunosuppressant drugs.

'Big Pork' Wants to Get In on Organ Transplants

At last Fridays summit, Church speculated about making organs resistant to tumors or viruses. When an audience member asked about the possibility of genetically enhancing pig organs to work as well as Michael Phelpss lungs or Usain Bolts heart, he responded, We not only can but should enhance pig organs, even if were opposed to enhancing human beings ... They will go through safety and efficacy testing, but part of efficacy is making sure theyre robust and maybe they have to be as robust as Michael Phelps in order to do the job.

Xenotransplantation will raise ethical questions, of course, and genetically enhancing pigs might come uncomfortably close to the plot of Okja. These enhancements are hard to fathom for now because scientist dont yet know what genes to alter if they wanted to make, for example, super lungs. Its taken decades of research to pinpoint the handful of genes that could make pig organs simply compatible with humans. But the technical ability to make any editsor even dozens of edits at oncewith CRISPR is already here.

See the rest here:
Genetically Engineering Pigs to Grow Organs for People - The Atlantic

This article originally ran on Ensia.

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.

It often surprises people to learn that GE commonly causes less disruption to plants than conventional techniques of breeding.

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.

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.

A substantial body of research shows proof-of-concept that a knockout of a susceptibility gene can increase resistance in plants to a 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.

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.

Mutations occur naturally every time a plant makes a seed; in fact, they are the very foundation of evolution.

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:

Microorganisms often can 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.

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.

Read the original:
When genetic engineering is the environmentally friendly choice - GreenBiz

On August 2nd, scientists achieved a milestone on the path to human genetic engineering. For the first time in the United States, scientists successfully edited the genes of a human embryo. A transpacific team of researchers used CRISPR-Cas9 to correct a mutation that leads to an often devastating heart condition. Responses to this feat followed well-trodden trails. Hype over designer babies. Hope over new tools to cure and curb disease. Some spin, some substance and a good dose of science-speak. But for me, this breakthrough is not just about science or medicine or the future of humankind. Its about faith and family, love and loss. Most of all, its about the life and memory of my brother.

Jason was born with muscle-eye-brain disease. In his case, this included muscular dystrophy, cerebral palsy, severe nearsightedness, hydrocephalus and intellectual disability. He lived past his first year thanks to marvels of modern medicine. A shunt surgery to drain excess cerebrospinal fluid building up around his brain took six attempts, but the seventh succeeded. Aside from those surgeries complications and intermittent illnesses due to a less-than-robust immune system, Jason was healthy. Healthy and happy very happy. His smile could light up a room. Yet, that didnt stop people from thinking that his disability made him worse off. My family and those in our religious community prayed for Jason. Strangers regularly came up to test their fervor. Prayer circles frequently had his name on their lists. We wanted him to be healed. But I now wonder: What, precisely, were we praying for?

Jasons disabilities fundamentally shaped his experience of the world. If praying for his healing meant praying for him to be normal, we were praying for Jason to become someone else entirely. We were praying for a paradox. If I could travel back in time, Id walk up to young, devout Joel and ask: How will Jason still be Jason if God flips a switch and makes him walk and talk and think like you? The answer to that question is hard. Yes, some just prayed for his seizures to stop. Some for his continued well-being. But is that true of most? Is that what I was praying for?

The ableist conflation of disability with disease and suffering is age-old. Just peruse the history of medicine. Decades of eugenic practices. Sanctioned torture of people with intellectual disability. The mutilation of otherwise healthy bodies in the name of functional or aesthetic normality. These stories demonstrate over and over again how easily biomedical research and practice can mask atrocity with benevolence and injustice with progress. Which leads me to ask: What, precisely, are we editing for?

Although muscle-eye-brain disease does not result from a single genetic variant, researchers agree that a single gene, named POMGNT1, plays a large role. Perhaps scientists will soon find a way to correct mutations in that and related genes. Perhaps people will no longer be born with it. But that means there would never be someone like Jason. Those prayers I mentioned above? Science will have retroactively answered them. That thought brings me to tears.

I wish we could cure cancer, relieve undue pain and heal each break and bruise. But I also wish for a world with Jason and people like him in it. I want a world accessible and habitable for people full stop not just the people we design. I worry that in our haste to make people healthy, we are in fact making people we want. We, who say we pray for healing, but in fact pray for others to be like us. We, who say were for reducing disease and promoting health, but support policies and practices aimed instead at being normal. We, who are often still unable to distinguish between positive, world-creating forms of disability and negative, world-destroying forms between Deafness, short stature or certain types of neurodiversity and chronic pain, Tay-Sachs or Alzheimers. It is with great responsibility that we as a society balance along the tightrope of biomedical progress. I long for us to find that balance. Ive certainly not found it for myself. Lest I forget how often weve lost it and how easy it is to fall, I hold dearly onto the living memory of Jason. I no longer pray for paradoxes, but for parity for the promise of a world engineered not for normality, but equality.

But that world will never come if we edit it away.

Read more:
Gene Editing Might Mean My Brother Would've Never Existed - TIME

The DNA of early human embryos carrying a sequence leading to hypertrophic cardiomyopathya potentially deadly heart defecthas been edited to ensure they would carry a healthy DNA sequence if brought to term. The Nature paper announcing this has reenergized a terrific national and international debate over whether permanent changes in DNA that can be passed from one generation to another should be made. Bioethicists are asking, Should we genetically engineer children? while some potential parents are almost certainly asking, When will this technique be available?

The Should questions bioethicists are asking are probably not relevant. The only question whose answer ultimately matters is: Can techniques like CRISP-R be used to genetically engineer children safely? Because a variety of forces guarantee that if they can be, they will be.

The key questions reliable practitioners must answer are: Can we prove it works? Then: Can it be used safely?. If yes on these questions, then we will see: Who is marketing this technique to potential parents? Finally, we will learn: Where was it done, who did it, and who paid for its use?

We are closer than ever before to using CRISP-R to replace dangerous DNA sequences with those that wont keep a baby from being healthy. Fortunately, this Nature paper leaves many questions Unanswered because the embryos were not allowed to come to term.

Most importantly, we still dont know Could the embryos have developed into viable babies? Just as in 2015 when researchers at Sun Yat-Sen University in China didnt implant engineered embryos into a womans womb, the scientists who published in Nature recently didnt feel ready (and didnt have permission) to try this potentially enormous step. As experiments proceed, this question will, at some point, be answered.

It will be answered because there is an enormous, proven market for techniques that can be used to ensure that a baby will be born without DNA sequences that can lead to genetically-mediated conditions; many of which are devastating as we have been tragically reminded of late.

Under the best circumstances, in-vitro fertilization leads to a live birth less than half of the time. As a result, whoever tries to see if an embryo that has had targeted DNA repaired using CRISP-R will doubtless prepare a lot of embryos for implanting in quite a few women. When those women are asked to carry these embryos to term we will not know about it. We will probably not find out if none of the embryos come to term successfully.

We *will* know about this procedure if even one baby comes to term and is born with the targeted genetic sequence corrected as intended. Until now, (and maybe even with our new knowledge), any baby brought to term after CRISP-R was used to edit and replace unhealthy DNA would have almost certainly had other DNA damaged in the editing process. This near-certainty and other concerns have held people back from trying to genetically engineer an embryo that they would then bring to term. They could not, until recently, have confidence that only the sequence being targeted has been affected. With this new Nature report, this, at least, is changing.

The results of these newly reported experiments are many steps closer to usability than the Chinese experiments reported in 2015. This is the nature of scientific experimentation, particularly when there is demand for the capability or knowledge being developed.

People try something. It either works or it doesnt. Sometimes when it doesnt work, we learn enough to adjust and try again. If it does work, it often doesnt function exactly the way we expected. Either way, people keep trying until either the technique is perfected or it ultimately proves to be unusable.

This Nature paper is an example of trying something and doing a better job than the first attempt. It does not represent a provably safe and reliable technique . Yet. If market driven research works as it often does, people will work hard to publish data (hopefully from reliable experimental work) suggesting they have a safe and effective technique. Doing so will let them tell some desperate set of wealthy prospective parents: We should be able to use this technique with an acceptable chance of giving you a healthy baby.

Princetons Lee Silver predicted parents desire for gene editing in his Remaking Eden, a book published in 1997. He argued this because people fear sickness or disability and feel strong personal, economic and social pressures to have healthy, beautiful children who should become healthy attractive adults.

People already spend a great deal on molecular techniques like pre-implantation genetic diagnosis (PGD). PGD is regularly used to reduce couples risk of having babies with known (or potential), chromosomal abnormalities and/or single gene mutations that can lead to thousands of DNA-mediated conditions.

As I showed in my Genetics dissertation published from Yale in 2004, different countries respond differently to controversial science like this. Similarly, different individuals responses are equally diverse. One poll indicates nearly half of Americans would use gene editing technology to prevent possible DNA-mediated conditions in their children. Policy makers who object to the technology therefore have a problem: if they succeed in blocking it somewhere, research and real world experience indicate other governments may well permit its use. If this happens, these techniques will be available to anyone wealthy and desperate enough to find providers with the marketingand hopefully scientificskill needed to sell people on trying them.

This gene editing controversy is a reminder that we are losing the capacity to effectively ask, Should we? As our knowledge of science grows, becomes more globalized, and is increasingly easy to acquire for people with different morals, needs and wants, we must soon be ready to ask, Can we? and ultimately, Will someone? Their answers will give us the best chance to ensure any babies that may come from any technique described as genetic engineering are born healthy, happy, and able to thrive.

The Morning Email

Wake up to the day's most important news.

Read this article:
It's Time to Stop Asking Whether Human Genetic Engineering Should Happen and Start Planning to Manage it Safely - HuffPost