A Giant-Sized History of Biotechnology

Historically, biotech has been primarily associated with food (agtech), addressing such issues as malnutrition and famine. Today, biotechnology is most often associated with the development of drugs. But drugs are hardly the future of biotech. We’ve entered the Fourth Industrial Revolution (#4IR), and genetics are on a new level.

Biotech is paving a way for a future open to imagination, and that’s kind of scary. The next ten years will surely prove exciting as artificial intelligence and biotechnology merge man and machine…

The history of Biotech can be divided into three distinct phases:

1. Ancient Biotechnology

2. Classical Biotechnology

3. Modern Biotechnology

1. Ancient Biotechnology (Pre-1800)

Most of the biotech developments before the year 1800 can be termed as ‘discoveries’ or ‘developments’. If we study all these developments, we can conclude that these inventions were based on common observations about nature.

• Humans have used biotechnology since the dawn of civilization.
• After domestication of food crops (corn, wheat) and wild animals, man moved on to other new observations like cheese and curd.  Cheese can be considered as one of the first direct products (or by-product) of biotechnology because it was prepared by adding rennet (an enzyme found in the stomach of calves) to sour milk.
• Yeast is one of the oldest microbes that have been exploited by humans for their benefit. The oldest fermentation was used to make beer in Sumeria and Babylonia as early as 7,000BCE.
• By 4,000BCE, Egyptians used yeasts to bake leavened bread.
• Another ancient product of fermentation was wine, made in Assyria as early as 3,500BCE.
• The Chinese developed fermentation techniques for brewing and cheese making.
• 500 BCE: In China, the first antibiotic, moldy soybean curds, is put to use to treat boils.
• Hippocrates treated patients with vinegar in 400 BCE.
• In 100BCE, Rome had over 250 bakeries which were making leavened bread.
• A.D. 100: The first insecticide is produced in China from powdered chrysanthemums.
• The use of molds to saccharify rice in the koji process dates back to at least A.D. 700.
• 13th century: The Aztecs used Spirulina algae to make cakes.
• One of the oldest examples of crossbreeding for the benefit of humans is mule. Mule is an offspring of a male donkey and a female horse. People started using mules for transportation, carrying loads, and farming, when there were no tractors or trucks.
• By the 14th century AD, the distillation of alcoholic spirits was common in many parts of the world.
• Vinegar manufacture began in France at the end of the 14th century.
• 1663: Cells are first described by Hooke.
• 1673-1723: In the seventeenth century, Antonie van Leeuwenhoek discovered microorganisms by examining scrapings from his teeth under a microscope.
• 1675: Leeuwenhoek discovers protozoa and bacteria.
• 1761: English surgeon Edward Jenner pioneers vaccination, inoculating a child with a viral smallpox vaccine.

2. Classical Biotechnology (1800-1945)

• The Hungarian Károly Ereky coined the word “biotechnology” in Hungary during 1919 to describe a technology based on converting raw materials into a more useful product. In a book entitled Biotechnologie, Ereky further developed a theme that would be reiterated through the 20th century: biotechnology could provide solutions to societal crises, such as food and energy shortages.
• 1773-1858: Robert Brown discovered the nucleus in cells.
• 1802: The word “biology” first appears.
• 1822-1895: Vaccination against small pox and rabies developed by Edward Jenner and Louis Pasteur.
• In 1850, Casimir Davaine detected rod-shaped objects in the blood of anthrax-infected sheep and was able to produce the disease in healthy sheep by inoculation of such blood.
• 1855: The Escherichia coli bacterium is discovered. It later becomes a major research, development, and production tool for biotechnology.
• In 1868, Fredrich Miescher reported nuclein, a compound that consisted of nucleic acid that he extracted from white blood cells.
• 1870: Breeders crossbreed cotton, developing hundreds of varieties with superior qualities.
• 1870: The first experimental corn hybrid is produced in a laboratory.
• By 1875, Pasteur of France and John Tyndall of Britain finally demolished the concept of spontaneous generation and proved that existing microbial life came from preexisting life.
• 1876: Koch’s work led to the acceptance of the idea that specific diseases were caused by specific organisms, each of which had a specific form and function.
• In 1881, Robert Koch, a German physician, described bacterial colonies growing on potato slices (First ever solid medium).
• In 1888, Heinrich Wilhelm Gottfried Von Waldeyer-Hartz, a German scientist, coined the term ‘Chromosome.’
• In 1909, the term ‘Gene’ had already been coined by Wilhelm Johannsen (1857-1927), who described ‘gene’ as carrier of heredity. Johannsen also coined the terms ‘genotype’ and ‘phenotype.’
• 1909: Genes are linked with hereditary disorders.
• 1911: American pathologist Peyton Rous discovers the first cancer-causing virus.
• 1915: Phages, or bacterial viruses, are discovered.
• 1919: The word “biotechnology” is first used by a Hungarian agricultural engineer.
• Pfizer, which had made fortunes using fermenting processes to produce citric acid in the 1920s, turned its attention to penicillin. The massive production of penicillin was a major factor in the Allied victory in WWII.
• 1924: start of Eugenic Movement in the US.
• The principle of genetics in inheritance was redefined by T.H. Morgan, who showed inheritance and the role of chromosomes in inheritance by using fruit flies. This landmark work was named, ‘The theory of the Gene in 1926.”
• Alexander Fleming discovered ‘penicillin’ the antibacterial toxin from the mold Penicillium notatum, which could be used against many infectious diseases. Fleming wrote, “When I woke up just after dawn on September 28, 1928, I certainly didn’t plan to revolutionize all medicine by discovering the world’s first antibiotic, or bacteria killer.”
• 1933: Hybrid corn is commercialized.
• In 1940, a team of researchers at Oxford University found a way to purify penicillin and keep it stable.
• 1941: The term “genetic engineering” is first used by a Danish microbiologist.
• 1942: The electron microscope is used to identify and characterize a bacteriophage- a virus that infects bacteria.
• 1942: Penicillin is mass-produced in microbes for the first time.

3. Modern Biotechnology (1945-present)

The Second World War became a major impediment in scientific discoveries. After the end of the second world war some, very crucial discoveries were reported, which paved the path for modern biotechnology.

The origins of biotechnology culminate with the birth of genetic engineering. There were two key events that have come to be seen as scientific breakthroughs beginning the era that would unite genetics with biotechnology: One was the 1953 discovery of the structure of DNA, by Watson and Crick, and the other was the 1973 discovery by Cohen and Boyer of a recombinant DNA technique by which a section of DNA was cut from the plasmid of an E. coli bacterium and transferred into the DNA of another. Popularly referred to as “genetic engineering,” it came to be defined as the basis of new biotechnology.

• In Britain, Chaim Weizemann (1874–1952) developed bacterial fermentation processes for producing organic chemicals such as acetone and cordite propellants. During WWII, he worked on synthetic rubber and high-octane gas.
• 1950s: The first synthetic antibiotic is created.
• 1951: Artificial insemination of livestock is accomplished using frozen semen.
• In 1953, JD Watson and FHC Crick for the first time cleared the mysteries around the DNA as a genetic material, by giving a structural model of DNA, popularly known as, ‘Double Helix Model of DNA.’
• 1954: Dr. Joseph Murray performs the first kidney transplant between identical twins.
• 1955: An enzyme, DNA polymerase, involved in the synthesis of a nucleic acid, is isolated for the first time.
• 1955: Dr. Jonas Salk develops the first polio vaccine. The development marks the first use of mammalian cells (monkey kidney cells) and the first application of cell culture technology to generate a vaccine.
• 1957: Scientists prove that sickle-cell anemia occurs due to a change in a single amino acid in hemoglobin cells
• 1958: Dr. Arthur Kornberg of Washington University in St. Louis makes DNA in a test tube for the first time.
• Edward Tatum (1909–1975) and Joshua Lederberg (1925–2008) shared the 1958 Nobel Prize for showing that genes regulate the metabolism by producing specific enzymes.
• 1960: French scientists discover messenger RNA (mRNA).
• 1961: Scientists understand genetic code for the first time.
• 1962: Dr. Osamu Shimomura discovers the green fluorescent protein in the jellyfish Aequorea victoria. He later develops it into a tool for observing previously invisible cellular processes.
• 1963: Dr. Samuel Katz and Dr. John F. Enders develop the first vaccine for measles.
• 1964: The existence of reverse transcriptase is predicted.
• At a conference in 1964, Tatum laid out his vision of “new” biotechnology: “Biological engineering seems to fall naturally into three primary categories of means to modify organisms. These are: 1. The recombination of existing genes, or eugenics. 2. The production of new genes by a process of directed mutation, or genetic engineering. 3. Modification or control of gene expression, or to adopt Lederberg’s suggested terminology, euphenic engineering.”
• 1967: The first automatic protein sequencer is perfected.
• 1967: Dr. Maurice Hilleman develops the first American vaccine for mumps.
• 1969: An enzyme is synthesized in vitro for the first time.
• 1969: The first vaccine for rubella is developed.
• 1970: Restriction enzymes are discovered.
• 1971: The measles/mumps/rubella combo-vaccine was formed.
• 1972: DNA ligase, which links DNA fragments together, is used for the first time.
• 1973: Cohen and Boyer perform the first successful recombinant DNA experiment, using bacterial genes.
• In 1974, Stanley Cohen and Herbert Boyer developed a technique for splicing together strands of DNA from more than one organism. The product of this transformation is called recombinant DNA (rDNA).
• Kohler and Milestein in 1975 came up with the concept of cytoplasmic hybridization and produced the first ever monoclonal antibodies, which has revolutionized diagnostics.
• Techniques for producing monoclonal antibodies were developed in 1975.
• 1975: Colony hybridization and Southern blotting are developed for detecting specific DNA sequences.
• 1976: Molecular hybridization is used for the prenatal diagnosis of alpha thalassemia.
• 1978: Recombinant human insulin is produced for the first time.
• 1978: with the development of synthetic human insulin the biotechnology industry grew rapidly.
• 1979: Human growth hormone is synthesized for the first time.
• In the 1970s-80s, the path of biotechnology became intertwined with that of genetics.
• By the 1980s, biotechnology grew into a promising real industry.
• 1980: Smallpox is globally eradicated following 20-year mass vaccination effort.
• In 1980, The U.S. Supreme Court (SCOTUS), in Diamond v. Chakrabarty, approved the principle of patenting genetically engineered life forms.
• 1981: Scientists at Ohio University produce the first transgenic animals by transferring genes from other animals into mice.
• 1981: The first gene-synthesizing machines are developed.
• 1981: The first genetically engineered plant is reported.
• 1982: The first recombinant DNA vaccine for livestock is developed.
• 1982: The first biotech drug, human insulin produced in genetically modified bacteria, is approved by FDA. Genentech and Eli Lilly developed the product. This is followed by many new drugs based on biotechnologies.
• 1983: The discovery of HIV/AIDS as a deadly disease has helped tremendously to improve various tools employed by life-scientist for discoveries and applications in various aspects of day-to-day life.
• In 1983, Kary Mullis developed polymerase chain reaction (PCR), which allows a piece of DNA to be replicated over and over again. PCR, which uses heat and enzymes to make unlimited copies of genes and gene fragments, later becomes a major tool in biotech research and product development worldwide.
• 1983: The first artificial chromosome is synthesized.
• In 1983, the first genetic markers for specific inherited diseases were found.
• 1983: The first genetic transformation of plant cells by TI plasmids is performed.
• In 1984, the DNA fingerprinting technique was developed.
• 1985: Genetic markers are found for kidney disease and cystic fibrosis.
• 1986: The first recombinant vaccine for humans, a vaccine for hepatitis B, is approved.
• 1986: Interferon becomes the first anticancer drug produced through biotech.
• 1986: University of California, Berkeley, chemist Dr. Peter Schultz describes how to combine antibodies and enzymes (abzymes) to create therapeutics.
• 1988: The first pest-resistant corn, Bt corn, is produced.
• 1988: Congress funds the Human Genome Project, a massive effort to map and sequence the human genetic code as well as the genomes of other species.
• In 1988, chymosin (known as Rennin) was the first enzyme produced from a genetically modified source-yeast-to be approved for use in food.
• In 1988, only five proteins from genetically engineered cells had been approved as drugs by the United States Food and Drug Administration (FDA), but this number would skyrocket to over 125 by the end of the 1990s.
• In 1989, microorganisms were used to clean up the Exxon Valdez oil spill.
• 1990: The first successful gene therapy is performed on a 4-year-old girl suffering from an immune disorder.
• In 1993, The U.S. Food and Drug Administration (FDA) declared that genetically modified (GM) foods are “not inherently dangerous” and do not require special regulation.
• 1993: Chiron’s Betaseron is approved as the first treatment for multiple sclerosis in 20 years.
• 1994: The first breast cancer gene is discovered.
• 1995: Gene therapy, immune-system modulation and recombinantly produced antibodies enter the clinic in the war against cancer.
• 1995: The first baboon-to-human bone marrow transplant is performed on an AIDS patient.
• 1995: The first vaccine for Hepatitis A is developed.
• 1996: A gene associated with Parkinson’s disease is discovered.
• 1996: The first genetically engineered crop is commercialized.
• 1997: Ian Wilmut, an Irish scientist, was successful in cloning an adult animal, using sheep as model and naming the cloned sheep ‘Dolly.’
• 1997: The first human artificial chromosome is created.
• 1998: A rough draft of the human genome map is produced, showing the locations of more than 30,000 genes.
• 1998: Human skin is produced for the first time in the lab.
• 1999: A diagnostic test allows quick identification of Bovine Spongicorm Encephalopathy (BSE, also known as “mad cow” disease) and Creutzfeldt-Jakob Disease (CJD).
• 1999: The complete genetic code of the human chromosome is deciphered.
• 2000: Kenya field-tests its first biotech crop, virus-resistant sweet potato.
• Craig Venter, in 2000, was able to sequence the human genome.
• 2001: The sequence of the human genome is published in Science and Nature, making it possible for researchers all over the world to begin developing treatments.
• 2001: FDA approves Gleevec® (imatinib), a gene-targeted drug for patients with chronic myeloid leukemia. Gleevec is the first gene-targeted drug to receive FDA approval.
• 2002: EPA approves the first transgenic rootworm-resistant corn.
• 2002: The banteng, an endangered species, is cloned for the first time.
• 2003: China grants the world’s first regulatory approval of a gene therapy product, Gendicine (Shenzhen SiBiono GenTech), which delivers the p53 gene as a therapy for squamous cell head and neck cancer.
• In 2003, TK-1 (GloFish) went on sale in Taiwan, as the first genetically modified pet.
• 2003: The Human Genome Project completes sequencing of the human genome.
• 2004: UN Food and Agriculture Organization endorses biotech crops, stating biotechnology is a complementary tool to traditional farming methods that can help poor farmers and consumers in developing nations.
• 2004: FDA approves the first antiangiogenic drug for cancer, Avastin®.
• 2005: The Energy Policy Act is passed and signed into law, authorizing numerous incentives for bioethanol development.
• 2006: FDA approves the recombinant vaccine Gardasil®, the first vaccine developed against human papillomavirus (HPV), an infection implicated in cervical and throat cancers, and the first preventative cancer vaccine.
• 2006: USDA grantsDow AgroSciences the first regulatory approval for a plant-made vaccine.
• 2006: The National Institutes of Health begins a 10-year, 10,000-patient study using a genetic test that predicts breast-cancer recurrence and guides treatment.
• In 2006, the artist Stelarc had an ear grown in a vat and grafted onto his arm.
• 2007: FDA approves the H5N1 vaccine, the first vaccine approved for avian flu.
• 2007: Scientists discover how to use human skin cells to create embryonic stem cells.
• 2008: Chemists in Japan create the first DNA molecule made almost entirely of artificial parts.
• 2009: Global biotech crop acreage reaches 330 million acres.
• In 2009, Sasaki and Okana produced transgenic marmosets that glow green in ultraviolet light (and pass the trait to their offspring).
• 2009: FDA approves the first genetically engineered animal for production of a recombinant form of human antithrombin.
• In 2010, Craig Venter was successful in demonstrating that a synthetic genome could replicate autonomously.
• 2010: Dr.  J. Craig Venter announces completion of “synthetic life” by transplanting synthetic genome capable of self-replication into a recipient bacterial cell.
• 2010: Harvard researchers report building “lung on a chip” – technology.
• In 2010, scientists created malaria-resistant mosquitoes.
• 2011: Trachea derived from stem cells transplanted into human recipient.
• 2011: Advances in 3-D printing technology lead to “skin-printing.”
• 2012: For the last three billion years, life on Earth has relied on two information-storing molecules, DNA and RNA. Now there’s a third: XNA, a polymer synthesized by molecular biologists Vitor Pinheiro and Philipp Holliger of the Medical Research Council in the United Kingdom. Just like DNA, XNA is capable of storing genetic information and then evolving through natural selection. Unlike DNA, it can be carefully manipulated.
• 2012: Researchers at the University of Washington in Seattle announced the successful sequencing of a complete fetal genome using nothing more than snippets of DNA floating in its mother’s blood.
• 2013: Two research teams announced a fast and precise new method for editing snippets of the genetic code. The so-called CRISPR system takes advantage of a defense strategy used by bacteria.
• 2013: Researchers in Japan developed functional human liver tissue from reprogrammed skin cells.
• 2013:  Researchers published the results of the first successful human-to-human brain interface.
• 2013: Doctors announced that a baby born with HIV had been cured of the disease.
• 2014: Researchers showed that blood from a young mouse can rejuvenate an old mouse’s muscles and brain.
• 2014: Researchers figured out how to turn human stem cells into functional pancreatic β cells—the same cells that are destroyed by the body’s own immune system in type 1 diabetes patients.
• 2014: All life on Earth as we know it encodes genetic information using four DNA letters: A, T, G, and C. Not anymore! In 2014, researchers created new DNA bases in the lab, expanding life’s genetic code and opening the door to creating new kinds of microbes.
• 2014: For the first time ever, a woman gave birth to a baby after receiving a womb transplant.
• 2014: An international team of scientists reconstructed a synthetic and fully functional yeast chromosome. A breakthrough seven years in the making, the remarkable advance could eventually lead to custom-built organisms (human organisms included).
• 2014 & Ebola: Until this year, ebola was merely an interesting footnote for anyone studying tropical diseases. Now it’s a global health disaster. But the epidemic started at a single point with one human-animal interaction — an interaction which has now been pinpointed using genetic research. A total of 50 authors contributed to the paper announcing the discovery, including five who died of the disease before it could be published.
• 2014: Doctors discovered a vaccine that totally blocks infection altogether in the monkey equivalent of the disease — a breakthrough that is now being studied to see if it works in humans.
• 2015: Scientists from Singapore’s Institute of Bioengineering and Nanotechnology designed short strings of peptides that self-assemble into a fibrous gel when water is added for use as a healing nanogel.
• 2015 & CRISPR: scientists hit a number of breakthroughs using the gene-editing technology CRISPR. Researchers in China reported modifying the DNA of a nonviable human embryo, a controversial move. Researchers at Harvard University inserted genes from a long-extinct woolly mammoth into the living cells — in a petri dish — of a modern elephant. Elsewhere, scientists reported using CRISPR to potentially modify pig organs for human transplant and modify mosquitoes to eradicate malaria.
• 2015: Researchers in Sweden developed a blood test that can detect cancer at an early stage from a single drop of blood.
• 2015: Scientists discovered a new antibiotic, the first in nearly 30 years, that may pave the way for a new generation of antibiotics and fight growing drug-resistance. The antibiotic, teixobactin, can treat many common bacterial infections, such as tuberculosis, septicaemia, and C. diff.
• 2015: A team of geneticists finished building the most comprehensive map of the human epigenome, a culmination of almost a decade of research. The team was able to map more than 100 types of human cells, which will help researchers better understand the complex links between DNA and diseases.
• 2015: Stanford University scientists revealed a method that may be able to force malicious leukemia cells to change into harmless immune cells, called macrophages.
• 2015: Using cells from human donors, doctors, for the first time, built a set of vocal cords from scratch. The cells were urged to form a tissue that mimics vocal fold mucosa – vibrating flaps in the larynx that create the sounds of the human voice.
• 2016: A little-known virus first identified in Uganda in 1947—Zika—exploded onto the international stage when the mosquito-borne illness began spreading rapidly throughout Latin America. Researchers successfully isolated a human antibody that “markedly reduces” infection from the Zika virus.
• 2016: CRISPR, the revolutionary gene-editing tool that promises to cure illnesses and solve environmental calamities, took a major step forward this year when a team of Chinese scientists used it to treat a human patient for the very first time.
• 2016: Researchers found that an ancient molecule, GK-PID, is the reason single-celled organisms started to evolve into multicellular organisms approximately 800 million years ago.
• 2016: Stem Cells Injected Into Stroke Patients Re-Enable Patient To Walk.
• 2016:  Cloning does not cause long-term health issues, study finds
• 2016: For the first time, bioengineers created a completely 3D-printed ‘heart on a chip.’
• 2017: Researchers at the National Institute of Health discovered a new molecular mechanism that might be the cause of severe premenstrual syndrome known as PMDD.
• 2017: Scientists at the Salk Institute in La Jolla, CA, said they’re one step closer to being able to grow human organs inside pigs. In their latest research they were able to grow human cells inside pig embryos, a small but promising step toward organ growth.
• 2017: First step taken toward epigenetically modified cotton.
• 2017: Research reveals different aspects of DNA demethylation involved in tomato ripening process.
• 2017: Sequencing of green alga genome provides blueprint to advance clean energy, bioproducts.
• 2017: Fine-tuning ‘dosage’ of mutant genes unleashes long-trapped yield potential in tomato plants.
• 2017: Scientists engineer disease-resistant rice without sacrificing yield.
• 2017: Blood stem cells grown in lab for the first time.
• 2017: Researchers at Sahlgrenska Academy – part of the University of Gothenburg, Sweden – generated cartilage tissue by printing stem cells using a 3D-bioprinter.
• 2017: Two-way communication in brain-machine interface achieved for the first time.
• Today, biotechnology is being used in countless areas including agriculture, bioremediation and forensics, where DNA fingerprinting is a common practice. Industry and medicine alike use the techniques of PCR, immunoassays and recombinant DNA.
• Genetic manipulation has been the primary reason that biology is now seen as the science of the future and biotechnology as one of the leading industries.

Thanks for reading!