Timeline of key events in biotechnology

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The test analyses a group of 21 genes found in breast cancer and works out what the risk is of cancer recurring. A trial supported by the National Cancer Institute with 10,273 patients with the most common forms of breast cancer, showed that the test was highly accurate in determining which women would benefit most from chemotherapy after an operation to remove the cancer and who could be safely spared such treatment. The trial was led by Joseph A Sparano at the Albert Einstein Cancer Center, New York. Results from the trial, presented to the American Society of Clinical Oncology in California in Chicago, were described by doctors as 'practice changing'. The test, called Oncotype DX, was developed by Genomic Health, a Californian diagnostics company. The trial's results were published in JA Sparano, et al, 'Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer', New England Journal of Medicine, 379 (July 12 2018), 111-21. 2018-07-12T00:00:00+0000The drug, patisiran, was approved for the treatment of a rare, progressive polyneuropathy caused by hereditary transthyretin-mediated, which affects approximately 50,000 people worldwide. Developed by Alynylam Pharmaceuticals, patisiran targets mRNAs for mutated transthyretin, which causes peripheral amyloidosis. The drugs works by delivering small interfering RNAs to the liver where they bind and degrade transthyretin messenger RNA. 2018-08-14T00:00:00+0000The phase 1/2 trial is designed to test the genome-editing technique in patients with transfusion-dependent beta-thalassemia, an inherited blood disorder. Sponsored by Vertex Pharmaceuticals and CRISPR Therapeutics the trial is being conducted at a single hospital in Regensburg Germany and will recruit 12 adults. It is testing CTX001, a gene-editing therapy that targets a region of DNA that acts like a brake on production of fetal haemoglobin, a type of haemoglobin that the body usually stops producing after the first months of life. Treatment involves taking blood from the patient and genetically altering them in the laboratory so that they when reintroduced into the patient are able to produce red blood cells that contain fetal haemoglobulin. 2018-08-27T00:00:00+0000Allison helped to demonstrate the importance of blocking CTLA-4, a protein found on T-cells, for cancer treatment, which laid the foundation for the development of ipilimumab. Honjo discovered, PD-1, another type of protein found on T-cells which cancer cells were subsequently discovered to hijack to evade attack by the immune system. 2018-10-01T00:00:00+0000Shimomura was a Japanese organic chemist and marine biologist who shared the Nobel Prize for Chemistry in 2008 for discovering a green fluorescent protein (GFP) in a small-mouse-sized jellyfish. The fact that the protein emits a green light in the presence UV lights makes it very useful for many different applications. Organisms, for example, can be genetically engineered with the gene for the protein. This makes it possible to study the inside of a living cell on an unprecedented scale. 2018-10-19T00:00:00+0000The researchers inserted genetic instructions into a virus called enadenotuvirev to produce a protein, called a bispecific T-cell engager. Already being clinically tested for treating carcinomas the virus has been bred to infect only cancer cells and leave healthy ones alone. The objective is to hijack the virus's machinery so that the T-cell engager is only produced in infected cancer cells and nowhere else in the body. Such an approach aims to kill both carcinoma cells and adjacent cells that are tricked into shielding the cancer from destruction from the immune system. Funded by the MRC and Cancer Research UK, the scientists successfully tested the innovative viral delivery system on fresh human cancer samples collected from consenting patients, including solid prostate cancedr tumours. The results were published in JD Freedman et al, 'An Oncolytic Virus Expressing a T-cell Engager Simultaneously Targets Cancer and Immunosuppressive Stromal Cells', Cancer Research (2018), 1-14. 2018-11-16T00:00:00+0000A chemist and biophysicist, Klug won the 1982 Nobel Prize in Chemistry for the development of crystallographic electron microscopy. He used the technique to investigate nucleic acid-protein complexes and the structure of viruses. He developed an interest in viruses after meeting Rosalind Franklin in late 1953. Klug also discovered zinc-finger proteins, a class of proteins that bind specific DNA sequences. Scientists now use the modular nature of these proteins to design synthetic proteins for targeted therapies. Klug left Lithuania for South Africa with his Jewish parents when he was two. He went to England after completing his master's degree. Klug was the director of the Laboratory of Molecular Biology (1986-1996) and President of the Royal Society (1995-2000).2018-11-20T00:00:00+0000He Jiankui, a genome-editing researcher at Southern University of Science and Technology of China, reported transplanting embryos into a woman that he had edited with CRISPR-Cas9 to disable a gene called CCR5, to disable the genetic pathway HIV uses to infect cells. More than 100 Chinese biomerical researchers condemned the experiment and called on Chinese authorities to investigate the case and introduce strict regulations. 2018-11-24T00:00:00+0000The project, led by Genomics England in partnership with the NHS, sequenced the DNA of both cancer patients and those with rare disorders. Overall 15,000 cancer patients had their DNA analysed, half of whom went on to take part in a clinical trial or receive targeted treatment. One in four participants with rare diseases who had their genomes sequenced received a diagnosis for the first time, thereby paving the way to getting effective treatment. All the sequencing was carried out by the Wellcome Sanger Institute, near Cambridge, in laboratories run by Illumina, a Californian biotechnology company. 2018-12-05T00:00:00+0000A team of managed to reprogramme the skin cells into dendritic cells. These immune cells search the body's tissues for foreign particles, such as bacteria, viruses or cancer cells, and devour them. The team identified three essential proteins (PU.1, IRF8 and BATF3) that are required to transform the the skin cells into dendritic cells. The process takes only 9 days and opens the possibility of developing novel dendritic cell-based immunotherapies against cancer. The research was published in FF Rosa et al, 'Direct reprogramming of fibroblasts into antigen-presenting dendritic cells', Science Immunology, 3/30 (2018) eaau4292, DOI: 10.1126/sciimmunol.aau42922018-12-07T00:00:00+0000The efficacy of the technique was tested in mice genetically modified to have only one working copy of genes known to regulate satiety (Sim1) and hunger (MC4R). CRISPRa was shown to increase the expression of the genes in the mice. Mice that had missing one copy of the Sim1 gene that received CRISPRa injections were found to maintain a healthy body weight like normal mice, whereas those that did not get the injections could not stop eating and developed severe obesity on a normal diet. The research was published in N Matharu et al, 'CRISPR-mediated activation of a promoter or enhancer rescues obesity caused by haploinsufficiency', Science 362/6420 (2018) eaau0629, DOI: 10.1126/science.aau06292018-12-14T00:00:00+0000Scientists found that it was possible to stop tumour growth in both tissue culture and in a mouse by disabling the tumour gene, NRF2, that helps the tumours develop resistance to drugs. They achieved this by using the CRISPR-Cas9 gene editing system. The work was led by Eric Kmiec at the Gene Editing Institute of the Helen F Graham Cancer Center and Research Institute, USA. It was published in P Bialk, Y Wang, K Banas, E B Kmiec, ' Functional Gene Knockout of NRF2 Increases Chemosensitivity of Human Lung Cancer A549 Cells In Vitro and in a Xenograft Mouse Model', Molecular Therapy Oncolytics', 11 (Dec 21 2018), DOI:https://doi.org/10.1016/j.omto.2018.10.0022018-12-21T00:00:00+0000A team of scientists managed to engineer mice to express Cas9 and a DNA sequence needed for the gene drive, called a cassette, which encoded a guide RNA that targets a sequence in the TYR gene which affects the mouse coat colour. This provided a means of tracking the frequency of the genetic modification over several generations of mice. The work was published in HA Grunwald et al. 'Super-Mendelian inheritance mediated by CRISPR–Cas9 in the female mouse germline', Nature, January 23, 2019.2019-01-23T00:00:00+0000The patient received a stem-cell transplant that replaced their white blood cells with HIV-resistant versions. The cells were taken from a donor who had two copies of a mutation in the CCR5 gene that confers resistance to HIV infection. The CCR5 gene codes for a receptor on white blood cells involved in the body's immune response. HIV normally binds to these receptors and attacks the cell. By removing the gene the receptors stop working normally. The patient was given the treatment as part of therapy for blood cancer. He was able to stop taking antiretroviral drugs after 16 months, and 18 months later had no sign of the virus. The research was published in RK Gupta, et al, Nature (2019), DOI 10.1038/s41586-019-1027-42019-03-05T00:00:00+0000Born in South Africa, Brenner was a geneticist and biologist who shared the 2002 Nobel Prize for Medicine for helping to discover how genes regulate tissue and organ development. Using the roundworm Caenorhabditis elegans as a model organism, Brenner demonstrated that triplets of nucleotides within RNA encode the individual amino acids of a protein, and signals when protein manufacture should stop. 2019-04-05T00:00:00+0000The recommendation was based on advice from WHO's 18 member expert advisory committee on human genome editing. 2019-07-30T00:00:00+0000The advantage of the technique is it enables scientists to disable specific genes and correct harmful mutations by providing cells with fresh DNA strands with to repair the cut. Unlike Crispr-Cas9, which chops target DNA in half, prime editing nicks it and then writes a new section of DNA into the specified region. The new procedure was published in AW Anzalone et al, 'Search-and-replace genome editing without double-strand breaks or donor DNA', Nature (2019), https://doi.org/10.1038/s41586-019-1711-42019-10-21T00:00:00+0000Developed by Biogen, the drug, aducanumab, targets a protein called amyloid that forms abnormal deposits in the brains of people with Alzheimer's. The company originally discontinued work on the drug in March 2019 after disappointing trial results. 2019-10-22T00:00:00+0000
Date Event People Places Sciences
12 Jul 2018Genetic test shown to accurately predict which women benefit from chemotherapySparanoGenomic HealthDNA sequencing, Genomics, Oncology
14 Aug 2018FDA approved first-ever drug based on RNAi Alynylam PharmaceuticalsRNA interference
27 Aug 2018First CRISPR-Cas9 clinical trial launched Vertex Pharmaceuticals, CRSIPR TherapeuticsCRISPR-Cas9, Gene therapy
1 Oct 2018James Allison and Tasuku Honjo were awarded the Nobel Prize in Physiology or Medicine for their discovery of immune checkpoint inhibitors for cancer therapyAllison, HonjoUniversity of Texas MD Anderson Cancer Center, Kyoto UniversityCancer immunotherapy, Immune checkpoint inhibitors, Oncology
19 Oct 2018Osamu Shimomura diedShimomura Princeton University 
16 Nov 2018Virus genetically engineered to kill cancer cells opening new immunotherapy avenueFreedman, Duffy, Lei-Rossman, Muntzer, Scott, Hagel, Campo, Bryant, Verrill, Lambert, Miller, Champion, Seymour, Fisher, RichardsonOxford UniversityCancer immunotherapy
20 Nov 2018Aaron Klug diedKlugBirkbeck College, Laboratory of Molecular BiologyX ray crystallography, RNA, Zinc fingers, Virology
24 Nov 2018First gene-edited babies announced by Chinese scientistJiankuiSouthern University of Science and Technology of ChinaCRISPR-Cas9, Reproduction
5 Dec 2018Genomics England completed sequencing 100,000 whole genomesCaulfieldSanger Institute, IlluminaDNA sequencing, Genomics
7 Dec 2018Mouse and human skin cells reprogrammed into immune cells to fight cancerRosa, Pires, Kurtochkin, Ferreira, Gomes, Palma, Shaiv, Solanas, Azenha, Papatsenko, Schulz, Reis e Sousa, Carlos-Filipe Lund University, Skolkovo Institute of Science and Technology, Francis Crick InstituteCancer immunotherapy, Stem cells
14 Dec 2018New gene modification technique (CRISPRa) makes it possible to increase expression of its target geneMatharu, Rattanasopha, Tamura, Maliskova, Wang, Bernard, Hardin, Eckalbar, Vaisse, AhituvUniversity of California San FranciscoCRISPR-Cas9
21 Dec 2018CRISPR-Cas9 editing helped restore effectiveness of first-line chemotherapies for lung cancerKmiec, Bialk, Wang, Hanas Helen F Graham Cancer Center and Research InstituteCRISPR-Cas9, Oncology
23 Jan 2019CRISPR-Cas9 used to control genetic inheritance in miceGrunwald, Gntz, Poplawski, Xu, Bier, CooperUniversity of California San DiegoCRISPR-Cas9, Genetics, Transgenic animals
5 Mar 2019Second patient reported free of HIV after receiving stem-cell therapyGuptaUniversity of CambridgeStem cells, Gene therapy
5 Apr 2019Sydney Brenner diedBrennerLaboratory of Molecular BiologyGenetics
30 Jul 2019World Health Organisation called on countries to ban experiments that would lead to more gene-edited babies  CRISPR-Cas 9, Genetic editing, Reproduction
21 Oct 2019New DNA editing technique called 'prime editing' publishedAnzalone, Randolph, Davis, Sousa, Koblan, Levy, Chen, Wilson, Newby, Ranguram, LiuMassachusetts Institute of Technology, Harvard UniversityCrispr-Cas9, Gene editing,
22 Oct 2019Monoclonal drug originally dismissed for treating Alzheimers got new green light from FDA for testing for the disease BiogenMonoclonal antibodies

12 Jul 2018

Genetic test shown to accurately predict which women benefit from chemotherapy

14 Aug 2018

FDA approved first-ever drug based on RNAi

27 Aug 2018

First CRISPR-Cas9 clinical trial launched

1 Oct 2018

James Allison and Tasuku Honjo were awarded the Nobel Prize in Physiology or Medicine for their discovery of immune checkpoint inhibitors for cancer therapy

19 Oct 2018

Osamu Shimomura died

16 Nov 2018

Virus genetically engineered to kill cancer cells opening new immunotherapy avenue

20 Nov 2018

Aaron Klug died

24 Nov 2018

First gene-edited babies announced by Chinese scientist

5 Dec 2018

Genomics England completed sequencing 100,000 whole genomes

7 Dec 2018

Mouse and human skin cells reprogrammed into immune cells to fight cancer

14 Dec 2018

New gene modification technique (CRISPRa) makes it possible to increase expression of its target gene

21 Dec 2018

CRISPR-Cas9 editing helped restore effectiveness of first-line chemotherapies for lung cancer

23 Jan 2019

CRISPR-Cas9 used to control genetic inheritance in mice

5 Mar 2019

Second patient reported free of HIV after receiving stem-cell therapy

5 Apr 2019

Sydney Brenner died

30 Jul 2019

World Health Organisation called on countries to ban experiments that would lead to more gene-edited babies

21 Oct 2019

New DNA editing technique called 'prime editing' published

22 Oct 2019

Monoclonal drug originally dismissed for treating Alzheimers got new green light from FDA for testing for the disease

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