Celebrating 25 Years of Tocris Cookson
Twenty five years ago, Tocris Neuramin and Cookson Chemicals merged to form Tocris Cookson, which remains our trading name to this day. Since then, Tocris has provided the life science community with the latest and most innovative research tools available, which has resulted in our unique catalog of >4,500 chemical tools on offer today, from industry standards to cutting edge technology, including our range of PROTACs, Janelia dyes, and GMP small molecules.
A whole quarter century of Tocris is a good reason to celebrate, so we've compiled 25 of our favorite scientific discoveries - from the Theory of Evolution in 1859, to the first Robotic Limb Controlled by the Brain in 2014. Download your free '25 of the Greatest Scientific Discoveries Poster' below!
25 Major Scientific Breakthroughs
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To celebrate our quarter century as Tocris Cookson we have put together a poster celebrating our 25 top scientific breakthroughs. How do they compare with yours?
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Greatest Moments in Science video
To celebrate our 25th anniversary we’re looking back at the greatest moments in science! We've narrowed down our list of 25 to 10 of the greatest scientific discoveries. Here's a video on our selection:
25 Major Scientific Breakthroughs
Find out more information on our favorite scientific breakthroughs from the last 25 years. Click on links to scientific papers and Ted Talks, as well as educational videos showing how these technologies work.
1859 Theory of Evolution
160 years ago, Darwin published his ideas on the theory of evolution by natural selection in the groundbreaking paper: “Origin of species by means of natural selection, or the preservation of favored races in the struggle for life” 1859. While less famous, Alfred Russel Wallace is also credited with this theory; this is because Darwin only published his work after discovering that Wallace had virtually the same theory. The theory states that organisms become more complex as they gain more beneficial adaptations, which increases chance of survival and reproduction.
1861 Germ Theory
Germ theory states that microorganisms known as pathogens or "germs" can lead to disease. Louis Pasteur was the first to prove this theory with his work on silkworms, where he identified two microorganisms that where devastating the silkworm population and silk production. He is thusly credited with saving Frances silk industry.
Pasteur also demonstrated that microorganisms caused fermentation and consequentially developed the process of pasteurization, whereby bacteria is destroyed by heating and then cooling. Pasteurization is now routinely used in the preparation of wine and milk. Pasteur is further credited with the first vaccines against fowl cholera, anthrax and rabies.
1869 Periodic Table
Dmitri Ivanovich Mendeleev created the periodic table by grouping the known elements together in order of increasing relative atomic mass. From this Mendeleev was able to arrange the elements into vertical columns and predicted the existence of undiscovered elements based on gaps in the columns. He was also able to predict the properties of these undiscovered elements based on the properties of the elements found around them. Mendeleev is one of only 15 scientists with an element named after them; Mendelevium (Md) found at position 101 in the periodic table.
1898 Discovery of Radium
In 1898 Marie and Pierre Curie discovered radium after studying a uranium-rich mineral ore known as uraninite (previously known as pitchblende). After the removal of uranium, two new radioactive elements remained, radium and polonium. The discovery of radium was especially important for the development of radiotherapy and nuclear medicine. Unfortunately, the dangerous effects of radiation were unknown at the time of discovery and eventually led to Maries death.
1927 Big Bang Theory
Georges Lemaître first proposed the big band theory in 1927, but it wasn’t until astronomer Arthur Eddington publicized it in 1931 that it gain traction in the scientific community. Lemaître reasoned that as the universe appeared to be expanding, it was logical that in the past the universe expanded from an initial point, called the "primeval atom" or "the Cosmic Egg”, exploding at the moment of the creation. Initially commentators such as Einstein were skeptical but this theory has remained the best explanation for the origins of the universe, winning over most scientists. Notably predictions of cosmic microwaves as well as hydrogen and helium levels by George Gamow, a theoretical physicist, provided important support to this theory.
1929 Discovery of Penicillin
During his time serving in World War I, Alexander Fleming observed many fellow soldiers perish, not only from battlefield wounds, but from the following infections. He postulated anaerobic bacteria deep in the wounds proliferated in spite of antiseptic treatment. As is the case with many paradigm shifting theories, his research was initially rejected. First, Fleming discovered the antibacterial enzyme lysozyme, but this enzyme was only effect against a few non-harmful bacteria.
It was Fleming’s work on staphylococcal bacteria that eventually lead to the breakthrough that would save millions of lives - Penicillin. Fleming observed that one of the petri dishes in which he was growing staphylococcal bacteria, had become contaminated with mold spores, and that the bacteria colonies in close proximity to the mold had died. He isolated this mold and identified at as a member of the Penicillium genus, although it was the “secreted mold juice” penicillin , not the mold itself, which was the effective antibacterial component against all Gram-positive pathogens. Fleming received many accolades for his work including being made a Knight Bachelor by King George VI in 1944.
Alexander Fleming “I did not invent penicillin. Nature did that. I only discovered it by accident.”
1933+ X Ray Crystallography of Biological Molecules Advances
Dorothy Hodgkin was instrumental in advancing X-ray crystallography of biological molecules, spurring on structural biology. Among her many achievements, she resolved the structure of penicillin, an act that went on to save millions of lives. This data allowed penicillin to be synthetically synthesized in large quantities and given to war time soldiers suffering from bacterial infections.
Hodgkin started her career as part of John Desmond Bernal’s group at Cambridge, here she was part of the group who recorded the first x-ray diffraction pattern from a protein crystal- the digestive enzyme pepsin. After this Hodgkin went on to continue her own work further developing and refining the technique of X-ray crystallography. She was involved in determining the crystal structure of hundreds of biological molecules including cholesterol, penicillin, vitamin B-12, and insulin. Quite a feat in the days where complicated math’s had to be done by hand. Hodgkin went on to receive the Royal Medal, a Nobel Prize in Chemistry (1964) and she was named by Queen Elizabeth II as a member of the Order of Merit in 1965.
1951 Protein Amino Acid Sequence
Fred Sanger determined the first complete amino acid sequence of a protein, the B chain of insulin, winning a Nobel prize in chemistry for his work in 1958. His pioneering method used :2:4 fluorodinitrobenzene (FDNB) to label N-terminus of amino acids. Acid treatment was used to break up proteins into small labelled fragments, which were then separated using electrophoresis and chromatography. He was then able to identify the amino acids that made up the sequences.
Sanger went on to sequence RNA and DNA, by developing a method using dideoxynucleotides, which when inserted in to DNA stop the elongation of that chain, thus producing multiple different length fragments of DNA. These fragments were than separated via electrophoresis allowing the nucleotides in the sequence to be identified.
1952 Polio Vaccine
Jonas Salk created the first inactivated polio vaccine (formalin-inactivated Salk polio vaccine (IPV)), which targeted all three virulent types. Using formaldehyde, Salk inactivated the polio virus but kept it intact enough to stimulate the body’s immune response. Salk was so confident with his vaccine he inoculated himself and his family. The vaccine was a tremendous success dramatically reducing incidences of polio.
Later, Albert Sabin created an oral vaccine (OPV), which was produced with a weakened virus rather than Salk’s inactivated virus. While the oral vaccine became the vaccine of choice, due to it being cheaper to make and easier to take than Salk’s vaccine, in rare cases the oral vaccine caused polio to take hold in some individuals (Vaccine-Associated Paralytic Poliomyelitis (VAPP)) and is consequently being phased out in favor of the IVP vaccine. The WHO has proposed the goal of worldwide poliomyelitis eradication, which it hope to achieve in the in the first half of their 21st century.
1953 DNA Structure Resolved
Maurice Wilkins first had the idea to study DNA using X-ray crystallographic techniques, while working at Kings College London. Here he was joined by the talented Rosalind Franklin who produced high quality diffraction patterns of DNA using this technique. In 1951 James Watson heard a talk by Wilkins presenting his research on DNA structure, and observed his recent X-ray crystallographic images of DNA. Watson then went on to recruit Francis Crick and using Franklin’s DNA X-ray photographs, developed the double helix DNA model. This model was a landmark discovery, which gave rise to modern molecular biology. In 1962 Watson, Crick and Wilkins were awarded the Nobel Prize in Physiology or Medicine.
1954 First Kidney Transplant
On December 23, 1954, Joseph Edward Murray, an American surgeon performed the first successful human kidney transplant on identical twins Richard and Ronald Herrick. Murray developed methodology that circumvented all the major obstacles of organ transplantation, including how to connect nerve, lymph and blood vessels from the recipient to the new organ. The biggest problem of all was how to prevent the rejection of the transplanted organ by the recipients own immune system. Using identical twins Richard and Ronald, Murray demonstrated that compatible tissues, from a closely related family member, would not evoke rejection by the hosts immune system. Murray’s pioneering work in the field of organ transplantation was honored with the 1990 Nobel Prize in Medicine.
1971 Discovery of Place Cells
John O’Keefe, May-Britt Moser and Edvard I. Moser received the 2014 Nobel Prize in Physiology or Medicine for the discovery of the brains “inner GPS”. John O’Keefe discovered a type of nerve cell, which he named “place cells” in the hippocampus, which are active when rats were at certain point in the room- effectively producing a map. In 2005, a new piece of the puzzle was resolved when the Moser’s identified another type of nerve cell located in the entorhinal cortex, “the grid cell”, which recorded the precise position of the rat. Together these two cells types allow the brain to establish a map of its surroundings and navigate through them.
This is especially relevant to Alzheimer’s disease research, because the hippocampus and entorhinal cortex are significantly affected in early stage Alzheimer’s disease, with patients reporting initial symptoms of becoming lost and disorientated, as well as loss of memory.
1977 MRI Used on First Live Person
Raymond Damadian first postulated the concept of using magnetic resonance imaging (MRI) to diagnose diseases in the human body in 1971. In 1977 Damadian and his team produced the first MRI images, although the system they used was too slow and inefficient for routine clinical use. Paul Lauterbur and Peter Mansfield were also working (in parallel) on similar ideas and went on to produce better scanners, which subsequently earned them the 2003 Nobel Prizes for Medicine, a prize that was controversially not shared with Damadian. The ability of MRI to image internal organs and investigate bodily functions without invasive and damaging techniques has revolutionized medical diagnosis.
1985 PCR Invented
Kary Mullis invented polymerase chain reaction (PCR) - a technique that allows short segments of DNA to be amplified quickly and in large quantities. There are three main stages in PCR, denaturing, annealing and elongation. Step one: DNA is heated to separate the two strands; step 2: specifically designed primers bind to the DNA; and step three: extension of the DNA strands as nucleotides bind and a new double strand is formed. This process is then repeated until the desired amount of DNA is produced. PCR revolutionized genetic engineering, detecting genetic diseases and forensic science.
1985 DNA Profiling
DNA profiling or genetic fingerprinting was the brainchild of geneticist Alec Jeffreys, a professor working at the University of Leicester. Having previously worked on detecting individual genes with Dick Flavell in Amsterdam, he began thinking about practical uses for studying the variations in DNA profiles among the population. Initially he thought about applications regarding inherited diseases and resolving paternity, and then one day he had his eureka moment. To quote his grandson "One day my granddad was messing around in the lab and he accidentally invented DNA fingerprinting." Jefferys' was in a dark room, developing a bit of film with DNA on, with the intention of looking at inherited diseases passing through families. He quickly realized that the variation patterns in segments of DNA, differed so greatly between individuals, that you could identify a person based purely on the pattern of bars on the film. He predicted that this would be a powerful tool in identifying criminals. DNA profiling has indeed revolutionized criminal identification and paternity testing. Jeffreys' was knighted for his services in genetics in 1994.
1990 Cryo-Electron Microscopy
Jacques Dubochet, Joachim Frank, and Richard Henderson were awarded the 2017 Nobel prize in chemistry for inventing cryo-electron microscopy. This technique allows atomic structural resolution of proteins and other biomolecules. In 1990, Henderson produced the first high-resolution model of the protein bacteriorhodopsin, using cryo-electron-microscopy (cryo-EM). He was able to do this by cooling the protein with liquid nitrogen, which protected it from the electron beam and the vacuum required to do EM. However for this technique to have wider applications, the sample preparation had to be refined, to prevent image distorting crystal formation during the cooling process. Dubochet solved this problem, when he refined the cooling process by developing vitrified water. Using vitrified water prevented ordered crystal structures from forming. The last remaining problem was processing power; Frank developed algorithms that were capable of processing the data to produce the sharp atomic-level resolution images we associate with cryo-EM. This technology has advanced drug development and structural biology in addition to and beyond the capabilities of X-ray crystallography and NMR.
1993 The Directed Evolution of Enzymes
Pioneered by Frances Arnold, directed evolution of enzymes is now a widely used strategy for optimizing chemical reactions throughout the scientific disciplines. Directed evolution is an iterative technique that involves introducing random mutations into genes and inserting those genes into bacteria. The bacteria will then produce randomly mutated enzymes, which can be screened to find the enzyme with the desired characteristic. Arnold was awarded the 2018 Nobel prize in chemistry for her work.
1996 Dolly the Sheep Cloned
In 1996 Campbell et al. developed the methodology that produced the first live mammalian offspring following nuclear transfer from an established adult somatic cell line. They cloned a sheep from an adult cell taken from the mammary gland of another sheep and famously called her Dolly. There were three sheep involved in Dolly’s creation, one provided the egg, another the DNA, and a third carried and birthed Dolly. She died shortly before her 7th birthday but this is not thought to be due to the cloning processes, but a natural underlying health condition. Since Dolly’s creation, many more mammals have been cloned including horses, pigs and bulls. Among its potential applications, it is hoped that cloning may be a useful tool in preventing animal extinctions, by preserving DNA of endangered species. If an extinction event occurs there is now the capability to reintroduce them.
1998 RNA Interference
Andrew Fire and Craig Mello, discovered the process of RNA interference (RNAi) in 1998 and were award the Nobel prize in 2006. RNAi occurs naturally in the cell, where it regulates gene expression by silencing genes. RNAi is an important line of defense against viral infection and genetic replication errors. RNAi is now widely used in the lab for silencing target genes and is a promising candidate for future therapies for myriad diseases with aberrant gene expression.
2003 Human Genome Project Completed
The mammoth international project that is the Human Genome Project was started in 1990 and completed in 2003. The project aimed to resolve the sequence of nucleotide base pairs that make up human DNA, as well as mapping all the genes in the human genome. The finished sequence records over 99% of the genome and is considered to be 99.99% accurate. Scientists are now focusing on mining this information for useful applications in medicine and biotechnology.
2006 Adult Human Cells are Reprogrammed into PSCs
In 2006, Takahashi and Yamanaka were able to induce pluripotent stem cells (induced pluripotent stem cells; iPSCs) from mouse embryonic and adult fibroblast cultures by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4. These cells displayed all the cell marker genes and morphological properties of embryonic stem cells. This was particularly exciting because it demonstrated that adult somatic cells could be induced into a state that allowed for differentiation into any cell type in the body. The following year they demonstrated the reprogramming of adult human cells. This has opened up huge potential for therapies in nearly every area of medicine, replacing damaged or genetically corrupted tissue.
2012 Discovery of CRISPR
Jennifer Doudna, Emmanuelle Charpentier and their teams, pioneered a new tool for editing gene sequences - The CRISPR-Cas9 system. CRISPR (Clustered regularly interspaced short palindromic repeats) is a precise technique for studying and manipulating gene function. Originally discovered as a prokaryotic host defense system, Doudna and Charpentier realized that the same principals could be used to carry out targeted gene sequence editing in any cell type. Watch the video below for a detailed explanation of how CRISPR works.
2012 Immune Checkpoint Therapy
160 years ago Darwin had published his ideas on the theory of evolution by natural selection in the ground breaking paper: On the “Origin of species by means of natural selection, or the preservation of favoured races in the struggle for life” 1859. Alfred Russel Wallace is also credited with this theory as it was only one year after Darwin discovered that Wallace had virtually the same theory did he publish his work. The theory states that organisms become more complex as they gain more beneficial adaptations that increase its chance of survival and reproduction.
2012 Higgs Boson discovered
Peter Higgs and François Englert predicted the Higgs Boson existence in 1964 however, it was only in 2012 that the ATLAS and CMS collaboration finally detected, and confirmed the existence of the particle, using the large Hadron collider at CERN. The Higgs field and its corresponding Higgs Boson, give mass to elementary particles. In the beginning of the universe’s history, particles interacted with the Higgs field just 10-12 seconds after the Big Bang, giving them mass. Before this interaction, all particles were massless and traveled at the speed of light.
2014 Robotic Limb Controlled by the Brain
Ortiz-Catalan and his colleagues addressed three major problems with prosthetic limbs: mobility, discomfort and providing sensory feedback.
They pioneered a procedure called osseointegration, a ground breaking approach where a titanium implant carrying electrodes was inserted into the bone. Using this implant allowed for greater access to nerves and muscle, and crucially this prosthetic system was the first of its kind to provide sensory feedback allowing the user to grip and respond to touch. Furthermore, the bone cells grew around the insert, providing an anchor point for the limb to attach, which prevented the abrasions and discomfort associated with tradition artificial limbs. This resulted in a significant leap forward in the usability of robotic limbs, with improved motion capability and control.