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~4000 BC: Egyptians use yeast to ferment beer and leaven bread

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~4000 BC: Egyptians use yeast to ferment beer and leaven bread

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While it’s possible that humans began making some form of bread as early as about 30,000 years ago, they didn’t begin using yeast to produce beer, wine and leavened bread until about 6,000 years ago. Since then, yeast used for producing food has undergone a lot of changes.

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2500 BC: Bacteria are used to treat sewage for the first time in England

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2500 BC: Bacteria are used to treat sewage for the first time in England

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Bacteria is used to treat sewage because bacteria is anaerobic, an important element to the wastewater treatment process. It removes most of the contaminants from wastewater before being released into the natural water stream.

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600 BC: Chinese use moldy soybeans to treat boils 

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600 BC: Chinese use moldy soybeans to treat boils 

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By about 600 BC the Chinese were using moldy soybean curds to treat boils. The molds released natural antibiotics that killed bacteria and prevented the spread of infection.

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Early examples of biotechnology include breeding animals and crops, and using microorganisms to make cheese, yoghurt, bread, beer and wine.

Biotechnology can be broadly defined as purposefully using or altering living systems, organisms, or parts of organisms to develop products or systems that benefit humankind.

Earliest examples of biotechnology

The earliest example of biotechnology is the domestication of plants and animals. Domestication began over 10,000 years ago when our ancestors started keeping plants as a reliable source of food. Rice, barley and wheat were among the first domesticated plants. Wild animals were tamed to provide milk or meat or help with ploughing or guarding the farm. The dog, sheep and goat are thought to be among the first animals that were domesticated.

Making new foods using biotechnology

Our early ancestors used microorganisms to make cheese, yoghurt and bread. They also made alcoholic drinks like beer and wine. All of these foods and drinks are made by fermentation. Fermentation is the process that many microorganisms (yeasts, moulds and bacteria) use to convert sugars into energy. The products generated from fermentation affect the nature of the food that the microorganism is in - carbon dioxide causes bread to rise, lactic acid makes yoghurt sour, and alcohol is produced in the formation of beer and wine.

Fermentation was probably discovered by accident, and our early ancestors didn't know how it worked. Some societies thought fermentation was a miracle or gift from their god.

Louis Pasteur first described the scientific basis for fermentation in the late 1800s. Pasteur's hypothesis, called the germ theory, showed the existence of microorganisms and their effect on fermentation. Pasteur's work gave birth to many branches of science.

Traditional medicines

Some traditional medicines also used organisms or parts of organisms. For example, the ancient Egyptians used honey for respiratory infections and as an ointment for wounds. Honey is a natural antibiotic, killing the germs in wounds.

By about 600 BC, the Chinese were using mouldy soybean curds to treat boils. Similarly, Ukrainian peasants were using mouldy cheese to treat infected wounds. The moulds released natural antibiotics that killed bacteria and prevented the spread of infection. Despite these natural treatments, it wasn't until 1928 that Alexander Fleming first extracted penicillin - the first antibiotic - from mould.

Examples of selective breeding

Early pioneers of selective breeding mated organisms with desirable traits to enhance these traits in their offspring. Selective breeding pioneers were manipulating the genetic makeup of organisms, without even realising it.

Corn is a dramatic example of a plant that has been enhanced by selective breeding to become a better source of food. Early teosinte plants (about 5000 BC) had small cobs with few kernels, but by 1500 AD, the corn cobs were more than 5 times the size and packed full of sweet, juicy kernels.

Dog breeds are another example of selective breeding. There are more than 100 breeds of dog, all resulting from selective breeding. Dogs were bred for specific jobs and to enhance traits such as size, shape, agility and colour, resulting in breeds from the tiny Chihuahua to the Great Dane.

The discovery of genes

A monk named Gregor Mendel identified genes as the unit of inheritance in 1865. It took another 90 years of research before the structure of DNA was described in 1953. This discovery was the beginning of modern biotechnology.

Related content

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Early examples of biotechnology include breeding animals and crops, and using microorganisms to make cheese, yoghurt, bread, beer and wine.

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1857: Louis Pasteur proposes that microbes cause fermentation

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1857: Louis Pasteur proposes that microbes cause fermentation

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in 1857, Pasteur proved that a microscopic plant caused the souring of milk (lactic acid fermentation). Pasteur was able to prove that living cells, the yeast, were responsible for forming alcohol from sugar, and that contaminating microorganisms found in ordinary air could turn the fermentations sour.

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Photos.com/Thinkstock

Many people know Louis Pasteur for the process that bears his name- pasteurization. However, Pasteur made several other very important contributions to science that you should know about.

Vaccines
Using his germ theory of disease, Pasteur also made important strides in the field of vaccination. He developed vaccines for chicken cholera and anthrax. Arguably his most important work with vaccines was his development of a rabies vaccine, a new "inactivated" type of vaccine, consisting of a neutralized agent rather than attenuated microorganisms. In 1885 he vaccinated a nine-year-old boy who had been bitten by a rabid dog and helped usher in the practice of preventive medicine.

Virulence
Pasteur was the first scientist to recognize that virulence could be increased as well as decreased. This has become extremely important in the study of infectious diseases and their spread, especially epidemics of bovine spongiform encephalopathy ("mad cow" disease) and acquired immunodeficiency syndrome (AIDS), for example.

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Louis Pasteur's Contributions to Science

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Many people know Louis Pasteur for the process that bears his name- pasteurization. However, Pasteur made several other very important contributions to science that you should know about. Vaccines Using his germ theory of disease, Pasteur also made important strides in the field of vaccination. He developed vaccines for chicken cholera and anthrax.

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1890: Robert Koch publishes his postulates to determine causal relationships between microbes and disease

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1890: Robert Koch publishes his postulates to determine causal relationships between microbes and disease

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Koch’s postulates were devised as general guidelines to identify infectious microbes that could be detected with the available methods and that were demonstrably alive (i.e., capable of independent metabolism, growth, and reproduction). In many instances, one or more of the rules could not be fulfilled, such as when a pathogen could not be cultured, when a usually innocuous microbe becomes pathogenic, or when a valid animal model of the disease was unavailable for experimental transmission

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1928: Alexander Fleming discovers the antibiotic penicillin

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1928: Alexander Fleming discovers the antibiotic penicillin

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Alexander Fleming determined penicillin had an antibacterial effect that produced a self-defence chemical in order to kill bacteria. He discovered it by isolating the mold that belonged to the penicilium genus then proceeded to present it to the Medical Research Club.

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1953: James Watson and Francis Crick elucidate the structure of DNA

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1953: James Watson and Francis Crick elucidate the structure of DNA

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James Watson and Francis Crick discover the double helix, which is the twisted-ladder structure of deoxyribonucleic acid with the help of the first X-ray picture of DNA taken in 1952. Their historical discovery rose modern molecular biology

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(1960's) Osamu Shimamura isolated GFP from the jellyfish Aequorea victoria

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(1960's) Osamu Shimamura isolated GFP from the jellyfish Aequorea victoria

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Osamu Shimamura, who isolated GFP from the jellyfish Aequorea victoria in the 1960s and found that the protein glowed green when illuminated with ultraviolet light.

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As visual creatures, humans believe what they see. We rely on our vision for macroscopic observations. Vast advances in microscopy now also enable visualization of cellular and sub-cellular structures. However, even the best microscopes cannot directly view molecular-level processes such as gene expression or protein interaction in vivo. In 1962, scientists found a solution in the most unlikely place - the green fluorescent protein (GFP) isolated from the bioluminescent jellyfish Aequorea victoria, native to the northern Pacific Ocean.

The 2008 Nobel Prize in Chemistry was awarded
in three equal parts for the discovery and development of GFP. Osamu Shimomura was recognized for discovering and characterizing GFP in 1962. Martin Chalfie first demonstrated that GFP could be expressed in other organisms without the aid of auxiliary proteins thirty years later. Finally, Roger Tsien developed a diverse palette of GFP-related fluorescence proteins, with improved brightness, photo-stability, and other useful properties.

Discovery
Osamu Shimomura was initially interested in the protein aequorin, obtained from A. victoria, which emits blue light in response to calcium. However, the jellyfish appears bright green, not blue. The puzzle was solved in 1962 by Shimomura's discovery of GFP, which has a peak excitation wavelength (460 nm) closely matching the peak emission wavelength of aequorin (470 nm).

Others concluded that GFP (the acceptor) absorbs the energy emitted by aequorin (the donor) in a process now known as Fluorescence Resonance Energy Transfer (FRET). Shimomura also identified the central chromophore, the specific chemical group responsible for GFP's fluorescent properties (1).

At the time of Shimomura's discovery, experts believed that auxiliary enzymes were required to form this central chromophore. This would mean that if GFP were expressed in any organism other than A. victoria, it would likely be non-functional.

Martin Chalfie settled the issue by obtaining the gene for GFP from Douglas Prasher who had originally cloned it, and successfully expressed the flourescent protein in E. coli in 1992. He then expressed GFP in the nematode C. elegans, driven by a promotor for β-tubulin which is strongly expressed in six touch receptor neurons (1). This demonstrated the usefulness of GFP as a genetic marker, without the need for additional genetic manipulation. It was later expressed in yeast and, more importantly, mammals (1).

At this point, the mechanisms of GFP chromophore formation and fluorescence were still not understood, despite the obvious utility of the protein. Roger Tsien found that oxygen was all that was needed to activate the GFP, and since aerobic cells constitute the vast majority of biological research, the protein could be broadly expressed in these cells without additional enzymes. In addition, by inducing point mutations in the GFP gene, Tsien improved brightness and photo-stability, and created a colorful spectrum of variants which have proved invaluable in simultaneous labeling of multiple proteins. Tsien also engineered fluorescence proteins such as tdTomato and mCherry, which fluoresce in the orange-red part of the spectrum, based on the protein DsRed from the coral Discosoma. With the help of other collaborators, he also solved the crystal structure of GFP (1).

Properties
The original green florescent protein (GFP) found in Aequorea consists of 238 amino acids, of which residues 65-66-67 form a fluorescent chromophore in the presence of oxygen. The tertiary structure comprises a cylindrical eleven strand β-barrel threaded by an α-helix containing the fluorescent chromophore (1).

GFP is maximally excited by UV light at 400 nm, with another smaller peak at 470 nm (blue light). It emits photons with a sharp peak at 505 nm (green light) (1). It is non-toxic when expressed at reasonable levels. Additionally, it can typically be fused to other proteins without changing either its fluorescence properties or the functional properties of the protein. These qualities make GFP extremely conducive to diverse biological applications.

Research Applications
Since its discovery, GFP has revolutionized biological research. Over 20,000 publications involving GFP have appeared since 1992, permeating essentially every area of biology (1). Along with the discoveries being recognized this year with the Nobel Prize, concurrent advances in imaging techniques and data analysis have combined to maximize the utility of this versatile tool.

In the laboratory, scientists commonly fuse GFP to a protein of interest, in order to track the trafficking of the protein within a cell (1). For example, the oscillating movement of proteins during cell division in bacteria was observed by fusing MinC to GFP (5).

Expressing the GFP gene alone with a specific promoter is often used to label classes of cells in which that promoter is active. This is commonly used in neurobiology to label subsets of neurons, as first achieved by Chalfie in C. elegans. Currently, a modified form of GFP is being used to build a complete wiring diagram of the Drosophila brain (2). By concurrently expressing three or four fluorescent proteins, numerous individual cells can be viewed simultaneously, using a technique known as "Brainbow" (3). Another exciting application is specific expression of fluorescent proteins in tumor cells (4).

Fluorescence technology is also used to monitor the distance between two proteins that have been tagged using GFP-family proteins. In the technique known as FRET, the emission spectrum of one fluorophore (the donor) matches the excitation spectrum of the other (the acceptor). When the two tagged molecules are in close proximity (less than about ten nanometers) and the donor is excited by incident light at its excitation wavelength, the emitted energy is transferred to the acceptor and is then emitted at the acceptor's characteristic emission wavelength. FRET can not only reveal if two molecules are close together and therefore interacting in some way, but can also provide an estimate of the exact distance between them, based on the decay rate of the signal (1).

Other techniques include monitoring the interaction of two proteins by tagging each protein with half of the GFP molecule, so that when they bind, GFP is completed and becomes functional. GFP has also been strategically fused with other molecules to construct pH or calcium sensors, enabling concentrations to be imaged at high spatial and temporal resolutions across populations of cells (1).

Conclusion
Shimomura's initial discovery of GFP, followed by its expression in other organisms by Chalfie, and finally the development of a chromatically and functionally diverse spectrum of related florescent proteins by Tsien, have dramatically impacted biological research. Aside from increasing the visual appeal of otherwise dull figures, GFP-family proteins have already shed light on numerous important findings. The future looks even brighter.

References
1. The Royal Swedish Academy of Sciences, Scientific Background on the Nobel Prize in Chemistry (2008).
2. A. Chiang, "Building a wiring diagram of the Drosophila brain" (2008). Lecture delivered at the Marine Biological Laboratory, 30 June (2008).
3. J. Livet et al., Nature 450, 56 (2007).
4. M. Yang et al., Proc. Natl. Acad. Sci. U. S. A. 100, 14259 (2003).
5. D. M. Raskin, P. A. J. de Boer, Proc. Natl. Acad. Sci. U. S. A. 96, 4971 (1999).

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Nobel Prize in Chemistry: Green Fluorescent Protein

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As visual creatures, humans believe what they see. We rely on our vision for macroscopic observations. Vast advances in microscopy now also enable visualization of cellular and sub-cellular structures. However, even the best microscopes cannot directly view molecular-level processes such as gene expression or protein interaction in vivo.

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1973: Stanley Cohen and Herbert Boyer use restriction enzymes and ligases to express a foreign gene in bacteria

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1973: Stanley Cohen and Herbert Boyer use restriction enzymes and ligases to express a foreign gene in bacteria

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Both biotechnology experts invented a method of cloning genetically engineered molecules in foreign cells. In it, they used DNA segments made by digestion with restriction enzymes and enabled the start of the biotechnology industry with their what is now a multibillion-dollar industry.

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1980: The US Supreme Court approves the principal of patenting an organism, allowing oil company Exxon to patent an oil-eating bacterium

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1980: The US Supreme Court approves the principal of patenting an organism, allowing oil company Exxon to patent an oil-eating bacterium

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in Diamond v. Chakrabarty, a five-to-four Court ratified the patent eligibility of both transgenic microorganisms and DNA. This decision settled expectations that at least some biotechnological inventions were patent-eligible, and encouraged investment in such inventions

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1982: The first biotechnology drug, recombinant human insulin, is approved by the Food and Drug Administration (FDA) and marketed under the brand name Humulin

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1982: The first biotechnology drug, recombinant human insulin, is approved by the Food and Drug Administration (FDA) and marketed under the brand name Humulin

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October 28, 1982, after only 5 months of review, the FDA approved Humulin, the first biosynthetic human insulin product created using gene recombination in bacteria, and the first approved medical product of any kind that derived from this technology

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In October 1982, the U.S. Food and Drug Administration (FDA) approved Eli Lilly and Company's Humulin, the first human insulin for diabetes treatment created using recombinant DNA technology. The story is not just a landmark event for technology, but instructive about problems with the FDA's regulatory system.

Henry Miller, currently a Senior Fellow at the California Pacific Medical Center Research Institute, was the founding director of the FDA's Office of Biotechnology. He was directly involved in the Humulin approval and writes about the subject for the Genetic Literacy Project.

Prior to the approval of Humulin, insulin was manufactured out of pig or cow pancreases. The non-human insulin has a slightly different chemical composition than human insulin. Miller points out that, "During the early 1970s, as the supply of animal pancreases declined and the prevalence of insulin-requiring diabetes grew, there were widespread fears of possible future shortages of insulin."

It was around the same time, luckily, that recombinant DNA technology or genetic engineering, became available.

At that time Eli Lilly was one of the biggest companies handling insulin. They were quick to see the potential of recombinant DNA. They acquired recombinant E. coli that had the coding for synthesized human insulin from a small biotech startup called Lilly then developed techniques for large-scale cultivation of the recombinant E. coli as well as for the purification and formulation of the insulin.

Lilly began clinical trials of the recombinant insulin in July 1980. As Miller says, "The product performed superbly. There were nonsystematic problems with treating 'naïve' patients (who had never before received injections of insulin) or those switched from animal to human insulin."

In going back over the records, Miller finds several remarkable things-remarkable for the time, undoubtedly, but even more so now.

Lilly submitted the recombinant insulin to the FDA in May 1982. Miller was at that time a medical reviewer at the FDA and head of the evaluation team. "Over many years the FDA had had prodigious experience with insulins and also with drugs derived from various microorganisms, so it was decided that no fundamentally new regulatory paradigms were necessary to evaluate the recombinant human insulin."

In other words, the agency decided that the recombinant DNA techniques were an extension and refinement of existing techniques.

Receiving the application in May 1982, the agency approved it in October 1982. It took only five months to approve.

At the time, the agency's average approval time for new drugs was 30.5 months.

Even more remarkable is that Miller says he and his team were ready to approve after four months. "But when I took the packet to my supervisor, he said, 'Four months? No way! If anything goes wrong with the product down the road, people will say we rushed it, and we'll be toast.'"

A month later, the supervisor went on vacation and Miller submitted it to the division director, who signed off on it.

Miller feels this is representative of the bureaucratic mindset seen at the FDA (and probably everywhere), in which "self-interest" is an underlying theme. In other words, for the FDA, it's in its self-interest to not approve too fast in case the drug or products experience unanticipated problems in the future.

At the time, Miller thought it was a sign of things to come that would lead to faster approvals and streamlined regulatory processes. He laments that, of course, that didn't happen. He cites that, "Even with a toolbox of improved technologies available to both the FDA and industry, bringing a new drug to market on average now takes 10-12 years and costs, on average, over $2.5 billion."

He also points out that other FDA-regulated sectors are an even bigger mess. Genetically engineered animals, for example, which the FDA regulates as "'new animal drugs,' including a grotesquely prolonged, 20-plus year review of a faster-growing Atlantic salmon, and genetically engineered mosquitoes to control mosquitoes that carry viral diseases." The FDA announced changes here just this week.

Miller concludes, "It's too bad that government regulation hasn't aged as gracefully as genetic engineering technology itself."

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first recombinant insulin marks 36th year of dna technology

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First Recombinant Insulin Marks 36th Year of DNA Technology | BioSpace

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In October 1982, the U.S. Food and Drug Administration (FDA) approved Eli Lilly and Company 's Humulin, the first human insulin for diabetes treatment created using recombinant DNA technology. The story is not just a landmark event for technology, but instructive about problems with the FDA's regulatory system.

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1983: Kary Mullis invents the polymerase chain reaction (PCR)

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1983: Kary Mullis invents the polymerase chain reaction (PCR)

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The polymerase chain reaction (PCR) is a technique in the lab used to produce multiple copies of segments of DNA. It involves using DNA fragments as primers to make another segment of DNA amplified, then rounds of DNA synthesis to amplify the segment. PCR is the fundamental of biology and biomedical research. For example, PCR can diagnose certain diseases and genetic changes.

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1984: Georges Kohler and Cesar Milstein produce the first monoclonal antibodies

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1984: Georges Kohler and Cesar Milstein produce the first monoclonal antibodies

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George Kohler and Cesar Milstein produced the first monoclonal antibodies through the hybridoma technique. This immortalized antibody produced cells by fusing them with tumor which allowed unlimited production with predetermined specificity.

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1986: DNA fingerprinting evidence is used for the first time in court

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1986: DNA fingerprinting evidence is used for the first time in court

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DNA fingerprinting was first used when police in the UK requested Dr. Alec J. Jefferys to verify a suspect's confession that he was responsible for two rape-murders. Ever since then, DNA profiling has played a significant role in the court of law.

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1986: First field trials of genetically modified crop (herbicide-resistant tobacco) in the U.S. and France

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1986: First field trials of genetically modified crop (herbicide-resistant tobacco) in the U.S. and France

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Although genetically modified plants were tobacco and first made in 1983, they tested herbicide-resistance in 1986 throughout France and the U.S. Thus herbicide resistant tobacco increased yields and reduced costs though it also minimized moisture loss and soil erosion.

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1996: Scottish scientist Ian Wilmut creates Dolly the sheep, the first cloned animal from an adult cell

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1996: Scottish scientist Ian Wilmut creates Dolly the sheep, the first cloned animal from an adult cell

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Ian Wilmut, a British developmental biologist who was the first to use nuclear transfer of differentiated adult cells to generate a mammalian clone, a Finn Dorset sheep named Dolly, born

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1998: FDA approves Herceptin, a breast cancer drug targeted to a particular cancer genotype, the first form of personalized medicine

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1998: FDA approves Herceptin, a breast cancer drug targeted to a particular cancer genotype, the first form of personalized medicine

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The discovery of the HER2 gene led to the development of herceptin in order to treat breast cancer patients. It was the first monoclonal antibody that blocks cancer-causing protein and was a breakthrough in the field to improve outcomes for those with advanced cases of breast cancer.

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2001: The Human Proteome Organization (HUPO) is formed and announces the Human Proteome Project, whose mission is to map the human proteome

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2001: The Human Proteome Organization (HUPO) is formed and announces the Human Proteome Project, whose mission is to map the human proteome

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The Human Proteome Organization (HUPO) promotes the development and application of proteomics technologies for enhancement of biological knowledge, global health, and wellness. Its goal is to experimentally observe all of the proteins produced by sequences translated from the human genome.

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2001: The first draft of the complete human genome (the Human Genome Project) is released

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2001: The first draft of the complete human genome (the Human Genome Project) is released

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The human genome project provided the genetic makeup of humans and provided evidence on genetic variations that can lead to disease or increase the risk of developing disease. Today, we can sequence the DNA in cancer cells and compare that to the sequence found by the Human Genome Project.

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1990: CHY-MAX, an enzyme used for making cheese, is the first product of recombinant DNA technology to be used in the U.S. food industry

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1990: CHY-MAX, an enzyme used for making cheese, is the first product of recombinant DNA technology to be used in the U.S. food industry

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The new kind of rennin is produced by bacteria, a species called Escherichia coli. The bacteria were altered by implanting in them the cow gene carrying the blueprints for rennin. Since all cells read the same genetic code, the bacteria, now carrying so-called recombinant DNA, make rennet identical to the rennin calves make.

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2003: GloFish, the first transgenic fish expressing green fluorescent protein, are launched as pets in the U.S

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2003: GloFish, the first transgenic fish expressing green fluorescent protein, are launched as pets in the U.S

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GloFish is a trademarked brand that genetically modifies fluorescent with the colors red, green, orange, orange, blue, pink, and purple. It is also known to be the first genetically modified pet to be publicly available, and the FDA finds no reason to regulate it.

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2007: First patients receive CRISPR-based treatment for genetic disorders (sickle cell disease and beta thalassemia)

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2007: First patients receive CRISPR-based treatment for genetic disorders (sickle cell disease and beta thalassemia)

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Victoria Gray was the sickle cell patient that had received CRISPR-based treatment. CRISPR now allows scientists to quickly create cells that rewrite genetic code in almost any organism which speeds up the process of plant tissue culture and plant genetic engineering.

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2007: Human adult skin cells are reprogrammed to have the same properties as embryonic stem cells, for the first time opening the door for personalized stem cell therapies

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2007: Human adult skin cells are reprogrammed to have the same properties as embryonic stem cells, for the first time opening the door for personalized stem cell therapies

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human embryonic stem cells have been successfully created by reprogramming skin cells (making them behave like embryonic stem cells) But although stem cell scientists share this enthusiasm, they go on to point out that the new technique, in its current form, is potentially hazardous. This issue will have to be dealt with before reprogramming can be applied in clinical medicine.

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2010: FDA approves Provenge, the first cancer vaccine for prostate cancer. Craig Venter and colleagues create the first synthetic cell.

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2010: FDA approves Provenge, the first cancer vaccine for prostate cancer. Craig Venter and colleagues create the first synthetic cell.

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Provenge is a personalized immunotherapy that activates the immune system to help fight advanced prostate cancer by removing some white blood cells then exposing them to a protein from prostate cancer cells. Although the manufacturer has faced marketing challenges and was forced to declare bankruptcy, about half the people who receive provenge still live after twenty one months of treatment.

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2017: FDA approves first CAR-T therapies for leukemia and lymphoma

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2017: FDA approves first CAR-T therapies for leukemia and lymphoma

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two chimeric antigen receptor-T (CAR-T) therapies were approved by the FDA for advanced/resistant lymphoma and acute lymphoblastic leukemia. However, despite the breakthrough efficacy results, the safety of CAR-T treatment is still a concern for treating physicians and their patients.