Timeline of biotechnology

The historical application of biotechnology throughout time is provided below in order. These discoveries, inventions and modifications are evidence of the evolution of biotechnology since before the common era.

Before Common Era

• 7000 BCE – Chinese discover fermentation through beer making.
• 6000 BCE – Yogurt and cheese made with lactic acid-producing bacteria by various people.
• 4000 BCE – Egyptians bake leavened bread using yeast.[1]
• 500 BCE – Moldy soybean curds used as an antibiotic.
• 250 BCE – The Greeks practice crop rotation for maximum soil fertility.[2]
• 100 CE – Chinese use chrysanthemum as a natural insecticide.[1][3]

Pre-20th Century

• 1663 – First recorded description of living cells by Robert Hooke.
• 1677 – Antonie van Leeuwenhoek discovers and describes bacteria and protozoa.
• 1798 – Edward Jenner uses first viral vaccine to inoculate a child from smallpox.
• 1802 – The first recorded use of the word biology.
• 1824 – Henri Dutrochet discovers that tissues are composed of living cells.
• 1838 – Protein discovered, named and recorded by Gerardus Johannes Mulder and Jöns Jacob Berzelius.
• 1862 – Louis Pasteur discovers the bacterial origin of fermentation.
• 1863 – Gregor Mendel discovers the laws of inheritance.
• 1864 – Antonin Prandtl invents first centrifuge to separate cream from milk.
• 1869 – Friedrich Miescher identifies DNA in the sperm of a trout.
• 1871 – Ernst Hoppe-Seyler discovers invertase, which is still used for making artificial sweeteners.
• 1877 – Robert Koch develops a technique for staining bacteria for identification.
• 1878 – Walther Flemming discovers chromatin leading to the discovery of chromosomes.
• 1881 – Louis Pasteur develops vaccines against bacteria that cause cholera and anthrax in chickens.
• 1885 – Louis Pasteur and Emile Roux develop the first rabies vaccine and use it on Joseph Meister.

20th century''

• 1919 – Károly Ereky, a Hungarian agricultural engineer, first uses the word biotechnology.
• 1928 – Alexander Fleming notices that a certain mould could stop the duplication of bacteria, leading to the first antibiotic: penicillin.
• 1933 – Hybrid corn is commercialized.
• 1942 – Penicillin is mass-produced in microbes for the first time.
• 1950 – The first synthetic antibiotic is created.
• 1951 – Artificial insemination of livestock is accomplished using frozen semen.
• 1952 – L.V. Radushkevich and V.M. Lukyanovich publish clear images of 50 nanometer diameter tubes made of carbon, in the Soviet Journal of Physical Chemistry.
• 1953 – James D. Watson and Francis Crick describe the structure of DNA.
• 1958 – The term bionics is coined by Jack E. Steele.
• 1964 – The first commercial myoelectric arm is developed by the Central Prosthetic Research Institute of the USSR, and distributed by the Hangar Limb Factory of the UK.
• 1972 – The DNA composition of chimpanzees and gorillas is discovered to be 99% similar to that of humans.
• 1973 – Stanley Norman Cohen and Herbert Boyer perform the first successful recombinant DNA experiment, using bacterial genes.[4]
• 1974 – Scientist invent the first biocement for industrial applications.
• 1975 – Method for producing monoclonal antibodies developed by Köhler and César Milstein.
• 1978 – North Carolina scientists Clyde Hutchison and Marshall Edgell show it is possible to introduce specific mutations at specific sites in a DNA molecule.[5]
• 1980 – The U.S. patent for gene cloning is awarded to Cohen and Boyer.
• 1982 – Humulin, Genentech's human insulin drug produced by genetically engineered bacteria for the treatment of diabetes, is the first biotech drug to be approved by the Food and Drug Administration.
• 1983 – The Polymerase Chain Reaction (PCR) technique is conceived.
• 1990 – First federally approved gene therapy treatment is performed successfully on a young girl who suffered from an immune disorder.
• 1994 – The United States Food and Drug Administration approves the first GM food: the "Flavr Savr" tomato.
• 1997 – British scientists, led by Ian Wilmut from the Roslin Institute, report cloning Dolly the sheep using DNA from two adult sheep cells.
• 1999 – Discovery of the gene responsible for developing cystic fibrosis.
• 2000 – Completion of a "rough draft" of the human genome in the Human Genome Project.

21st century

Further information: CRISPR gene editing § Recent events, Bioethics § Issues, Timeline of biology and organic chemistry § 1990–present, Timeline of medicine and medical technology § 2000–present, and Timeline of senescence research

• 2001 – Celera Genomics and the Human Genome Project create a draft of the human genome sequence. It is published by Science and Nature Magazine.
• 2002 – Rice becomes the first crop to have its genome decoded.
• 2003 – The Human Genome Project is completed, providing information on the locations and sequence of human genes on all 46 chromosomes.
• 2008 – Japanese astronomers launch the first Medical Experiment Module called "Kibo", to be used on the International Space Station.
• 2009 – Cedars-Sinai Heart Institute uses modified SAN heart genes to create the first viral pacemaker in guinea pigs, now known as iSANs.
• 2012 – Thirty-one-year-old Zac Vawter successfully uses a nervous system-controlled bionic leg to climb the Chicago Willis Tower.
• 16 April 2019 – Scientists report, for the first time, the use of the CRISPR technology to edit human genes to treat cancer patients with whom standard treatments were not successful.[6][7]
• 21 October 2019 – In a study researchers describe a new method of genetic engineering superior to previous methods like CRISPR they call "prime editing".[8][9][10]

2020

• 27 January – Scientists demonstrate a "Trojan horse" designer-nanoparticle that makes blood cells eat away – from the inside out – portions of atherosclerotic plaque that cause heart attacks[11][12][13] and are the current most common cause of death globally.[14][15]

• 5 February – Scientists develop a CRISPR-Cas12a-based gene editing system that can probe and control several genes at once and can implement logic gating to e.g. detect cancer cells and execute therapeutic immunomodulatory responses.[16][17]

• 6 February – Scientists report that preliminary results from a phase I trial using CRISPR-Cas9 gene editing of T cells in patients with refractory cancer demonstrates that, according to their study, such CRISPR-based therapies can be safe and feasible.[18][19][20][21]

• 4 March – Scientists report that they have developed a way to 3D bioprint graphene oxide with a protein. They demonstrate that this novel bioink can be used to recreate vascular-like structures. This may be used in the development of safer and more efficient drugs.[22][23]

• 4 March – Scientists report to have used CRISPR-Cas9 gene editing inside a human's body for the first time. They aim to restore vision for a patient with inherited Leber congenital amaurosis and state that it may take up to a month to see whether the procedure was successful. In an hour-long surgery study approved by government regulators doctors inject three drops of fluid containing viruses under the patient's retina. In earlier tests in human tissue, mice and monkeys scientists were able to correct half of the cells with the disease-causing mutation, which was more than what is needed to restore vision. Unlike germline editing these DNA modifications aren't inheritable.[24][25][26][27]

• 9 March – Scientists show that CRISPR-Cas12b is a third promising CRISPR editing tool, next to Cas9 and Cas12a, for plant genome engineering.[28][29]

• 14 March – Scientists report in a preprint to have developed a CRISPR-based strategy, called PAC-MAN (Prophylactic Antiviral Crispr in huMAN cells), that can find and destroy viruses in vitro. However, they weren't able to test PAC-MAN on the actual SARS-CoV-2, use a targeting-mechanism that uses only a very limited RNA-region, haven't developed a system to deliver it into human cells and would need a lot of time until another version of it or a potential successor system might pass clinical trials. In the study published as a preprint they write that the CRISPR-Cas13d-based system could be used prophylactically as well as therapeutically and that it could be implemented rapidly to manage new pandemic coronavirus strains – and potentially any virus – as it could be tailored to other RNA-targets quickly, only requiring a small change.[30][31][32][33] The paper was published on 29 April 2020.[34][35]

• 16 March – Researchers report that they have developed a new kind of CRISPR-Cas13d screening platform for effective guide RNA design to target RNA. They used their model to predict optimized Cas13 guide RNAs for all protein-coding RNA-transcripts of the human genome's DNA. Their technology could be used in molecular biology and in medical applications such as for better targeting of virus RNA or human RNA. Targeting human RNA after it's been transcribed from DNA, rather than DNA, would allow for more temporary effects than permanent changes to human genomes. The technology is made available to researchers through an interactive website and free and open source software and is accompanied by a guide on how to create guide RNAs to target the SARS-CoV-2 RNA genome.[36][37]

• 16 March – Scientists present new multiplexed CRISPR technology, called CHyMErA (Cas Hybrid for Multiplexed Editing and Screening Applications), that can be used to analyse which or how genes act together by simultaneously removing multiple genes or gene-fragments using both Cas9 and Cas12a.[38][39]

• 10 April – Scientists report to have achieved wireless control of adrenal hormone secretion in genetically unmodified rats through the use of injectable, magnetic nanoparticles (MNPs) and remotely applied alternating magnetic fields heats them up. Their findings may aid research of physiological and psychological impacts of stress and related treatments and present an alternative strategy for modulating peripheral organ function than problematic implantable devices.[40][41]

• 14 April – Researchers report to have developed a predictive algorithm which can show in visualizations how combinations of genetic mutations can make proteins highly effective or ineffective in organisms – including for viral evolution for viruses like SARS-CoV-2.[42][43]

• 15 April – Scientists describe and visualize the atomical structure and mechanical action of the bacteria-killing bacteriocin R2 pyocin and construct engineered versions with different behaviours than the naturally occurring version. Their findings may aid the engineering of nanomachines such as for targeted antibiotics.[44][45]

• 20 April – Researchers demonstrate a diffusive memristor fabricated from protein nanowires of the bacterium Geobacter sulfurreducens which functions at substantially lower voltages than previously described ones and may allow the construction of artificial neurons which function at voltages of biological action potentials. The nanowires have a range of advantages over silicon nanowires and the memristors may be used to directly process biosensing signals, for neuromorphic computing and/or direct communication with biological neurons.[46][47][48]

• 27 April – Scientists report to have genetically engineered plants to glow much brighter than previously possible by inserting genes of the bioluminescent mushroom Neonothopanus nambi. The glow is self-sustained, works by converting plants' caffeic acid into luciferin and, unlike for bacterial bioluminescence genes used earlier, has a high light output that is visible to the naked eye.[49][50][51][52][53][54]

• 8 May – Researchers report to have developed artificial chloroplasts – the photosynthetic structures inside plant cells. They combined thylakoids, which are used for photosynthesis, from spinach with a bacterial enzyme and an artificial metabolic module of 16 enzymes, which can convert carbon dioxide more efficiently than plants can alone, into cell-sized droplets. According to the study this demonstrates how natural and synthetic biological modules can be matched for new functional systems.[55][56][57][58]

• 11 May – Researchers report the development of synthetic red blood cells that for the first time have all of the natural cells' known broad natural properties and abilities. Furthermore, methods to load functional cargos such as hemoglobin, drugs, magnetic nanoparticles, and ATP biosensors may enable additional non-native functionalities.[59][60]

• 12 June – Scientists announce preliminary results that demonstrate successful treatment during a small trial of the first to use of CRISPR gene editing (CRISPR-Cas9) to treat inherited genetic disorders – beta thalassaemia and sickle cell disease.[61][62][63][64]

• 8 July – Mitochondria are gene-edited for the first time, using a new kind of base editor, by a team of researchers.[65]

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