Genetically modified organism

• 1. Introduction

  ›

  In 1973, Herbert Boyer and Stanley Cohen built the first genetically modified organism: a bacterium that could survive the antibiotic kanamycin. They had taken a gene that conferred that resistance, slipped it into a plasmid, and coaxed other bacteria into taking the plasmid up. The bacteria that did could now live where they should have died. A genetically modified organism is any organism whose genetic material has been altered using genetic engineering techniques. But the moment that bacterium survived, a far harder set of questions opened up. What counts as genetic engineering, and what does not? Is a tomato that ripens slowly the same kind of thing as a salmon that grows year-round, or a human embryo with an edited gene? Who decides whether these organisms are safe to eat, to release, to patent, to ban? And why is the most controversial creation in this whole story not an animal at all, but a crop?

• 2. A Category That Resists Definition

  ›

  The most common definition of a GMO is an organism altered in a way that "does not occur naturally by mating and/or natural recombination." That phrasing comes from the Food and Agriculture Organization, the World Health Organization, and the European Commission. It sounds precise. It is not. At its broadest, the definition could include anything whose genes have been altered, even by nature itself. In 1993, the Encyclopedia Britannica defined genetic engineering loosely enough to cover artificial insemination, in vitro fertilization, sperm banks, and cloning. The European Union's early reviews stretched as far as "selective breeding and other means of artificial selection." Pressure from scientists and farmers forced quick revisions, and exceptions piled up. The EU later excluded traditional breeding, in vitro fertilization, mutation breeding, and cell fusion that uses no recombinant nucleic acids. Then science complicated things further. The discovery that horizontal gene transfer is a fairly common natural event muddied what "occurs naturally" even means. There are crops that fit the GMO definition yet nobody treats as GMOs. The grain triticale was fully developed in a laboratory in 1930 using techniques that altered its genome. The Cartagena Protocol on Biosafety sidestepped the term in 2000, preferring "living modified organism" for anything with "a novel combination of genetic material obtained through the use of modern biotechnology." Because these definitions focus on the process rather than the product, two organisms with nearly identical genotypes can land on opposite sides of the line. Some scientists call the category scientifically meaningless. The confusion reaches absurd ends in marketing, where water and salt, which contain no genetic material at all and cannot be modified by definition, get labeled as non-GMO to seem more healthy.

• 3. Building An Organism

  ›

  Isolating a single gene is where the work begins. Genetic engineers pull out the gene they want, either from a cell or by synthesizing it, and if the donor genome is well studied, the gene may already sit in a genetic library. They then join it to a promoter, a terminator region, and usually a selectable marker. Getting that gene inside a host depends on the host. Bacteria can be pushed to take up foreign DNA through heat shock or electroporation. Animal cells often receive DNA by microinjection straight into the nucleus, or through viral vectors. In plants, the work is done with Agrobacterium-mediated recombination, biolistics, or electroporation. Only one cell takes up the new material, so the whole organism must be regenerated from it; in plants this happens through tissue culture, and in animals the inserted DNA must reach the embryonic stem cells. Confirmation comes from PCR, Southern hybridization, and DNA sequencing. For decades the new material landed randomly in the host genome. That changed with engineered nucleases that cut DNA at chosen points. There are four families: meganucleases, zinc finger nucleases, TALENs, and the Cas9-guideRNA system adapted from CRISPR. TALEN and CRISPR dominate, with TALEN offering greater target specificity and CRISPR proving easier to design and more efficient. CRISPR is the reason making GMOs has become so much simpler.

• 4. The Workhorse Microbes

  ›

  Bacteria were the first organisms modified in a laboratory, and they remain the easiest. They are cheap, clonal, multiply quickly, and can sit at minus 80 degrees Celsius almost indefinitely. Most of early molecular biology came from studying Escherichia coli. Once a gene is isolated, it can be stored inside bacteria as an endless supply. That convenience turned them into tools for building other GMOs. Genentech, founded in 1976 by Herbert Boyer and Robert Swanson, showed what bacterial production could mean for medicine. A year after founding, the company made the human protein somatostatin in E. coli. In 1978 it announced genetically engineered human insulin, branded Humulin, which the Food and Drug Administration approved in 1982. That was the first medicinal use of GM bacteria, made to treat diabetes. Others followed: clotting factors for hemophilia, human growth hormone for forms of dwarfism, interferon for some cancers, erythropoietin for anemia, and tissue plasminogen activator to dissolve clots. Food production drew on bacteria too, mostly lactic acid bacteria. Modified strains yield alpha-amylase to convert starch into sugars, chymosin to clot milk for cheese, and pectinesterase to clarify fruit juice. Most are produced in the US, and as of 2015 no bacteria-derived food products were available in Europe. Bacteria even entered art. In the 1980s, artist Jon Davis and geneticist Dana Boyd turned the Germanic symbol for femininity into binary code, then into a DNA sequence expressed in E. coli, and by 2012 a whole book had been encoded onto DNA.

• 5. Viruses As Delivery And Cure

  ›

  Viruses earn their place in this story as vectors, machines for inserting genetic information into other organisms through a process called transduction. Dangerous sequences must be stripped out while the delivery machinery stays. Their value is sharpest in treating human disease. Gene therapy has replaced defective genes with real success, most clearly in patients with severe combined immunodeficiency arising from adenosine deaminase deficiency, known as ADA-SCID. The path was not smooth. Some ADA-SCID patients developed leukemia, and the death of Jesse Gelsinger in a 1999 trial set the field back for years. In 2009, an eight-year-old boy with Leber's congenital amaurosis regained normal eyesight, and in 2016 GlaxoSmithKline gained approval to commercialize a gene therapy for ADA-SCID. Different viruses carry different payloads. Adenoviruses hold up to 7.5 kilobases of foreign DNA and infect many cell types, but provoke immune responses and offer only short expression. Adeno-associated viruses carry about 4 kilobases with less toxicity. Herpes simplex viruses manage over 30 kilobases. Retroviruses integrate best for the long term but insert randomly, while lentiviruses can infect both dividing and non-dividing cells. Viruses can also become the treatment itself. In 2004, researchers reported that a modified virus exploiting the selfish behavior of cancer cells might kill tumors. In 2017, a virus engineered to express spinach defensin proteins was injected into orange trees to fight citrus greening disease, which had cut orange production by 70 percent since 2005. The same myxoma virus has even been modified for opposite ends: to immunize wild rabbits in the Iberian peninsula and to lower fertility in Australia's rabbits. Outside biology, engineered M13 bacteriophages have been coaxed into coating themselves in iron phosphate and assembling along a carbon nanotube to build a lithium-ion battery.

• 6. Fungi, Flowers, And A Mushroom That Broke The Rules

  ›

  Yeast bridges two worlds, combining the easy handling of a single-celled organism with the advanced protein modifications of a eukaryote. As of 2016, two genetically modified wine yeasts were commercialized in the United States and Canada: one improved malolactic fermentation efficiency, the other prevented dangerous ethyl carbamate compounds during fermentation. Fungi are also the most common pathogens of insects, which makes them attractive biopesticides able to infect by contact alone. Engineers have modified Metarhizium anisopliae and Beauveria bassiana to delay when mosquitoes become infectious, reducing the selection pressure that would otherwise breed resistance. Plants tell a parallel story of research and ornament. Tobacco was the first plant altered by genetic engineering and is a model organism well beyond that field. Arabidopsis thaliana, with its small genome and short life cycle, was the first plant sequenced and can be transformed by dipping a flower into an Agrobacterium solution. Not all modified plants are practical; some exist purely for beauty. Carnations released in 1997 were the first commercialized genetically modified ornamentals, altered for color. A blue rose, actually lavender or mauve, was created in 2004 and sold in Japan, the United States, and Canada. The sharpest regulatory jolt came from a mushroom. Agaricus bisporus, the common white button mushroom, was gene edited with CRISPR to knock out a gene encoding polyphenol oxidase, leaving it resistant to browning with a longer shelf life. Because no foreign DNA was introduced, it fell outside existing GMO frameworks and became the first CRISPR-edited organism approved for release. That decision sharpened a debate still unsettled: whether gene-edited organisms should count as GMOs at all.

• 7. The Crops Everyone Argues About

  ›

  Soybeans accounted for half of all genetically modified crops planted in 2014, and that single fact captures how narrow this revolution has stayed. The commercialized crops are mostly cash crops, cotton, soybean, maize, and canola, and almost all the introduced traits provide either herbicide tolerance or insect resistance. In the USA, 93 percent of soybeans are glyphosate tolerant. Most insect-resistance genes come from Bacillus thuringiensis and code for delta endotoxins. The one commercial insect-protection gene not from that bacterium is the Cowpea trypsin inhibitor, first approved for cotton in 1999. Adoption moved fast. Between 1996 and 2013, the total land cultivated with GM crops grew by a factor of 100, though unevenly, strong in the Americas and parts of Asia, slight in Europe and Africa. By 2013, roughly 54 percent of GM crops worldwide grew in developing countries. Golden rice stands apart as the best-known crop aimed at nutrition rather than profit. Engineered with three genes that biosynthesize beta-carotene, a precursor of vitamin A, it targets a deficiency estimated to kill 670,000 children under the age of five each year and cause another 500,000 cases of irreversible childhood blindness. The original produced 1.6 micrograms per gram of carotenoids; later versions raised that 23 times. It gained its first approvals for food in 2018. Crops have also become factories. Plants and plant cells produce biopharmaceuticals in a process called pharming, including a drug treatment for Gaucher's disease grown in carrot and tobacco cells. Edible vaccines stored in plant tissue could be disseminated without cold storage. A 2021 study found that widespread adoption of gene-edited crops in the EU alone could cut greenhouse gas emissions by 33 million tons of equivalent, or 7.5 percent of farming-related emissions. Yet despite the most documented health and environmental benefits of any GMO, crops remain the most publicly controversial of all.

• 8. Animals, Humans, And The Lines Being Crossed

  ›

  ATryn, approved in 2009, was the first human biological drug produced from a genetically modified animal: an anticoagulant extracted from a goat's milk that lowers the chance of blood clots during surgery or childbirth. Animals are far harder to transform than plants, and most remain at the research stage. As of 2018, only three genetically modified animals had been approved, all in the USA: a goat and a chicken engineered to produce medicines, and a salmon engineered to grow faster. That salmon, the AquAdvantage salmon, became in 2015 the first genetically modified animal approved for food use and the first non-plant GMO food commercialized. It carries a growth-hormone-regulating gene from a Pacific Chinook salmon and a promoter from an ocean pout, letting it grow year-round. To keep it from breeding with wild salmon, all the food fish are female, triploid, 99 percent reproductively sterile, and raised where escapees could not survive. Mammals are the best models for human disease. Genetically modified mice came to dominate biomedical research, and in 2009 scientists transferred a gene into a primate, marmosets, for the first time, targeting Parkinson's disease. Pigs offer another frontier: organs modified so they no longer carry retroviruses or are less likely to be rejected. The first human transplant of a genetically modified pig heart occurred in 2023, and a kidney in 2024. Then there are the lines that alarm even the field's practitioners. Gene therapy in humans affects only somatic cells, so its changes cannot be inherited. Germline therapy changes that, and it has raised deep concern. In November 2018, He Jiankui announced he had edited the genomes of two human embryos to disable the CCR5 gene, which HIV uses to enter cells. He said twin girls, Lulu and Nana, had been born weeks earlier, carried a mix of functional and disabled CCR5, and were still vulnerable to HIV. The work was widely condemned as unethical, dangerous, and premature, a verdict that hangs over every conversation about how far this technology should go.

  The first regulatory framework for genetic engineering was drafted not in a parliament but at a meeting, at Asilomar, California, in 1975, where scientists recommended cautious use of recombinant technology. International law caught up with the Cartagena Protocol on Biosafety, adopted on the 29th of January 2000 and in force from the 11th of September 2003, with 157 member countries. The deepest divide runs between the United States and Europe. US policy looks at verifiable scientific risks and uses the concept of substantial equivalence, focusing less on the process. Europe treats any organism made with genetic engineering techniques as a GMO. The split widens over gene editing: US regulators see gene-edited organisms as separate and do not regulate them the same way, while in Europe they fall under the GMO definition. Bans are widespread. In 2016-38 countries officially banned or prohibited cultivating GMOs, and nine, Algeria, Bhutan, Kenya, Kyrgyzstan, Madagascar, Peru, Russia, Venezuela, and Zimbabwe, banned their importation, though most still permit research. Labeling is its own battleground. The European Commission argues mandatory labeling and traceability allow informed choice and product withdrawal. The American Medical Association and the American Association for the Advancement of Science counter that without evidence of harm, even voluntary labeling misleads and falsely alarms consumers. Labeling is required in 64 countries. In the US, the National Bioengineered Food Disclosure Standard set a mandatory compliance date of the 1st of January 2022. In Europe, any food or feed with more than 0.9 percent approved GMOs must be labeled. Underlying all of it is a scientific consensus that currently available food from GM crops poses no greater risk than conventional food, paired with a public far less convinced. That gap is why, in 2014, sales of products labeled non-GMO grew 30 percent to 1.1 billion dollars even as the science said the label promised nothing.