The historical application of biotechnology throughout time is provided below in chronological order.

These discoveries, inventions and modifications are evidence of the application of biotechnology since before the common era and describe notable events in the research, development and regulation of biotechnology.

Before Common Era

7000 BCE – Beermaking is discovered in the land-circle of Kulmbach 6000 BCE – Yogurt and cheese made with lactic acid-producing bacteria by various people. 5000 BCE – Chinese discover fermentation through beer making. 4500 BCE – Egyptians bake leavened bread using yeast. 500 BCE – Moldy soybean curds used as an antibiotic. 300 BCE – The Greeks practice crop rotation for maximum soil fertility. 100 AD – Chinese use chrysanthemum as a natural insecticide.

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 – invents first centrifuge to separate cream from milk. 1869 – Friedrich Miescher identifies DNA in the sperm of a trout. 1871 – Felix 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. In 1919, a pivotal milestone was reached with the production of citric acid by Aspergillus niger, marking the inception of the first aerobic fermentation process. This breakthrough spurred the development of technologies to ensure the supply of sterile air at a large scale, paving the way for future advancements in industrial fermentation processes. 1928 – Alexander Fleming notices that a certain mold 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. 1974 – Scientists invent the first biocement for industrial applications. 1975 – Method for producing monoclonal antibodies developed by Köhler and César Milstein. 1977 – Frederick Sanger publishes the first method for sequencing DNA allowing for the analysis of specific nucleotide sequences. 1978 – North Carolina scientists Clyde Hutchison and Marshall Edgell show it is possible to introduce specific mutations at specific sites in a DNA molecule. 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

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. 2004 – Addgene launches. 2008 – Japanese astronomers launch the first Medical Experiment Module called "Kibō", to be used on the International Space Station. 2010-Over the past two decades, a considerable focus has been directed toward creating sustainable alternatives for petroleum-based fuels, chemicals, and materials. Major players in the chemical industry, such as BASF, DSM, BP, and Total, have initiated significant projects and collaborations in metabolic engineering. Additionally, various startups have emerged with the goal of pioneering new bio-based processes for sustainable chemicals. Despite advancements in establishing large-scale processes, the overall impact on transitioning the chemical industry from petroleum-based to bio-based has been limited. For instance, efforts to engineer microbial production of succinic acid have faced challenges, leading to the termination or minimal-scale production of related research and commercial activities. Out of the chemicals listed by the US Department of Energy, only lactic acid and itaconic acid have achieved industrial-scale production. Lactic acid, added to the list in 2010 after large-scale production was established, currently holds a market value exceeding US$2.5 billion, primarily used in the production of polylactate. 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. 2018-The Joint Centre of Excellence by Imperial College and the UK National Physical Laboratory focuses on advancing industry collaboration to transform high-value manufacturing into high-value products. Noteworthy progress includes the adoption of SBOL by ACS Synthetic Biology in 2016 and ongoing efforts, such as engagement with the BioRoboost project, aiming for international standards with partners from the US, China, Japan, and Singapore. 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. The progression of commercial applications in synthetic biology is notably swift, propelled predominantly by investments directed towards start-up enterprises and small to medium-sized enterprises (SMEs) engaged in the dissemination of tools, services, and products to the market. This is exemplified by the informational resource titled 'Synthetic Biology UK — A Decade of Rapid Progress,' disseminated online in July 2019, which furnishes a demonstrative compilation of instances rooted in the United Kingdom. 2019 – In a study researchers describe a new method of genetic engineering superior to previous methods like CRISPR they call "prime editing".

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 and are the current most common cause of death globally. 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. 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. 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. 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. 9 March – Scientists show that CRISPR-Cas12b is a third promising CRISPR editing tool, next to Cas9 and Cas12a, for plant genome engineering. 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. The paper was published on 29 April 2020. 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 has 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. 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.