Harvard University: Timeline of key events

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JA Doudna, BP Cormack, JW Szostak, 'RNA Structure, Not Sequence, Determines the 5? Splice-Site Specificity of a Group I Intron', PNAS, 86/19 (1989), 7402-06.1989-10-01T00:00:00+0000Wald was an American biologist renowned for his research on how the eye passes images to the brain. He first made his mark in the early 1930s when he discovered that vitamin A was an important component in rhodopsin, a light-sensitive biological pigment found in the rods of the retina. Over the next 30 years he conducted a series of experiments which showed when exposed to light rhodopsin changes its form which triggers signals in a complicated network of optic nerve cells which eventually convert into visual impressions in the brain. In 1967 he was jointly awarded the Nobel Prize for Medicine for 'discoveries concerning the primary physiological and chemical visual processes in the eye.'1997-04-12T00:00:00+0000Porter was a Canadian biologist. He is renowned for having developed many of the techniques and experimental approaches that underpinned the founding of cellular biology as a new discipline in biomedical research. Critically he developed the first electron microscope techniques to get high resolution images of cells and tissues. In 1945 he published the first electron microgragh of a complete animal cell. His other major contributions to the field was his development a roller-flask for culturing cells and helping to invent an instrument for getting ultra-thin slices of tissue for microscopy. 1997-05-02T00:00:00+0000Bloch was a German-American biochemist who shared the 1964 Nobel Prize for Physiology or Medicine for helping to uncover the mechanism and regulation of cholesterol and fatty acid metabolism. This work laid the foundation for understanding the relationship between blood cholesterol levels and atherosclerosis, a disease in which plaque builds up inside the body's arteries. 2000-10-15T00:00:00+0000A team at Harvard Stem Cell Institute reported fusing adult skin cells with embryonic stem cells to reset the culture so that the cells behave like embryonic stem cells. The researchers did the work using pelvic bone cells as the somatic cells and a different human embryonic cell line. Chad A Cowan, Jocelyn Alenza, Douglas A Melton, Kevin Eggan, 'Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells', Science, 309/5739 (2005), 1369-73. 2005-08-25T00:00:00+0000A Ventura, et al, 'Restoration of p53 function leads to tumour regression in vivo', Nature, 445 (2007), 661-5; W Xue, et al, 'Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas', Nature, 445 (2007), 656–60.2007-01-01T00:00:00+0000A team of scientists led by George Q Daley at the Harvard Stem Cell Institute reported the creation of stem cells for 10 genetic disorders that will enable researchers to watch diseases develop in a lab dish. The researchers used ordinary skin cells and bone marrow from people with a variety of diseases, including Parkinson's, Huntington's and Down syndrome to produce the stem cells. They published their results in I H Park, et al, 'Disease-specific induced pluripotent stem cells', Cell, 134/5 (2008), 877-86.2008-09-05T00:00:00+0000Zhang, F, Cong, L, Lodato, Kosuri, S, Church, G, Arlotta, P, 'Efficient construction of sequence-specific TAL effectors for modulating mammalian transcription', Nature Biotechnology, 29 (2011), 149–53. 2011-01-19T00:00:00+0000Benacerraf was an immunologist who, based on experiments with guinea pigs in the 1960s, provided the pathway to understand how T lymphocytes recognise structures on the cell surface of foreign substances that invade the body. He showed that immune responses are controlled by genes that exist in a certain area on a certain chromosome. He was awarded the Nobel Prize for Medicine in 1980 for his discoveries of genes that regulate immune responses and the role some of these genes play in autoimmune disorders. Born in Venezuaela and brought up in Paris, Bernaceraf and his parents were forced to move to United States in 1940 because of their Jewish heritage. 2011-08-02T00:00:00+0000Osborn, M J, Starker, C G, McElroy, A N, 'TALEN-based gene correction for epidermyolysis bullosa', Molecular Therapy, 21/6 (2013), 1151-9.2013-06-01T00:00:00+0000The aim was to to inactivate 62 endogenous retroviruses in the pig embryos. All pigs have these viruses embedded in their genomes. The presence of such viruses, which can transmit diseases like cancer, is a major hurdle to the transplant of pig organs into humans. The gene editing work was carried out by the geneticist George Church of Harvard Medical School. He and his team presented the results to the US National Academy of Sciences. 2015-10-05T00:00:00+0000The technique involved splitting the Cas9 based gene drive system into two physically separate parts. It was published in J E DiCarlo, A Chavez, S L Dietz, K M Esvelt, G M Church, 'Safeguarding CRISPR-Cas9 gene drives in yeast', Nature Biotechnology, doi:10.1038/nbt.3412.2015-11-16T00:00:00+0000The work laid a pathway for using CRISPR to correct genetic mutatiuons in affected tissues of sick patients. It was published in CE Nelson, CH Hakim, DG Ousterout, PI Thakore et al, 'In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy', Science, DOI: 10.1126/science.aad51432015-12-31T00:00:00+0000Kleinstiver, B P, Pattanayak, V, Prew, M S, Tsai, S Q, Nguyen, N T, Zheng, Z, Joung, K, 'High-fidelity CRISPR–Cas9 nucleases with no detectable genome-wide off-target effects', Nature, doi:10.1038.2016-01-06T00:00:00+0000Based on the analysis of data from hundreds of patients, scientists found markers on tumour cells flagging up very early mutations of the disease. The advantage is these appear on all tumour cells, thereby providing a good target for treatment. N. McGranahan, et al, 'Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade', Science, 351/6280 (2016), 1463-69. 2016-03-25T00:00:00+0000A.C. Komor, Y.B. Kim, M.S. Packer, J.A. Zuris, D.R. Liu, 'Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage', Nature, 533/7603 (2016), 420–24.2016-05-16T00:00:00+0000LD Landegger et al, 'A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear', Nature Biotechnology, 6 Feb 2017, doi:10.1038/nbt.37812017-02-06T00:00:00+0000J. S. Gootenberg, O.O. Abudayyeh, J. W. Lee, et al, 'Nucleic acid detection with CRISPR-Cas13a/C2c2', Science, 13 April 2017, eaam9321, DOI: 10.1126/science.aam9321 2017-04-13T00:00:00+0000L. Xu, et al, 'Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques', Science, 20 September 2017, Science, 20 Sep 2017, eaan8630, DOI: 0.1126/science.aan86302017-09-20T00:00:00+0000Total of 17 boys treated in clinical trial, of which 15 showed marked improvement. Treatment used a modified form of HIV as the vector for infusing corrective genes to generate glial cells. F. Eichler, C. Duncan etl al, 'Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy', NEJM, DOI: 10.1056/NEJMoa17005542017-10-04T00:00:00+0000
Date Event People Places Sciences
Oct 1989RNA demonstrated to help catalyse the process for synthesising proteinDoudna, Cormack, SzostakHarvard UniversityRNA
12 Apr 1997George Wald diedWaldHarvard University, Occular physiology
2 May 1997Keith Roberts Porter diedPorterHarvard University, University of ColoradoCell
15 Oct 2000Konrad Bloch diedBlochHarvard UniversityBiochemistry
25 Aug 2005Harvard scientists reported reprogramming adult skin cells into embryonic stem cells Cowan, Eggan, Melton, AlienzaHarvard Stem Cell InstituteStem cells
2007p53-induced senescence shown to prevent cancerVentura, Kirsch, McLaughlin, Tuveson, Grimm, Lintault, Newman, Reczek, Weissleder, Jacks, Xue, Zender, Miething, Dickins, Hernando, Krizhanovsky, Cordon-Cardo, LoweMassachusetts Institute of Technology, Massachusetts General Hospital, Harvard University, Howard Hughes Medical Institute, Cold Spring Harbor LaboratoryOncology, p53
5 Sep 2008Scientists created stem cells for 10 disordersDaley, Park, Arora, Huo, Maherall, Ahfedt, Shimamura, Lensch, Cowan, HochedlingerHarvard Stem Cell InstituteStem cells
19 Jan 2011US scientists publish a technique for genetically engineering transcription activator-like effectors customised to recognise specific DNA-binding sites which they show is an effective tool for editing mammalian genomesZhang, Cong, Lodato, Kosuri, Church, ArlottaHarvard University, Massachusetts Institute of Technology Gene editing, TALENs
2 Aug 2011Baruj Benacerraf diedBenacerrafHarvard Medical SchoolImmunology
1 Jun 2013Basic studies conducted with TALENs to see if can correct mutant genes associated with Epidermolysis Bullosa, a rare inherited skin disorderOsborn, Starker, Colby, McElroyUniversity of Minnesota, National Centre for Tumor Diseases Heidelberg, German Cancer Research Centre, Harvard UniversityGene Therapy, Gene editing, TALENs
5 Oct 2015CRISPR/Cas9 modified 60 genes in pig embryos in first step to create organs suitable for human transplantsChurchHarvard UniversityCRISPR-Cas9, Gene editing, Transgenic animals
16 Nov 2015US scientists published a technique for overwriting changes made by CRISPR/Cas 9DiCarlo, Chavez, Dietz, Esvelt, ChurchHarvard University, Swiss Federal Institute of Technology in Zurich CRISPR-Cas9, Gene editing
31 Dec 2015Gene editiing tool, CRISPR, successfully used to improve muscle function in mouse model of Duchenne muscular dystrophyNelson, Gersbach, Hakim, Ousterout, ThakoreDuke University, University of Missouri, University of North Carolina, Massachusetts Institute of Technology, Harvard UniversityCRISPR-Cas9, Gene editing, Gene therapy
6 Jan 2016US scientists published improved version of CRISPR/Cas 9 with less risk of off-target DNA breaksKleinstiver, Pattanayak, Prew, Tsai, Nguyen, Zheng, JoungHarvard UniversityCRISPR-Cas9, Gene editing
25 Mar 2016Common tags discovered on the surface of cancer cells opening up new avenues for immunotherapyMcGranahan, Furness, Rosenthal, Ramskov, Lyngaa, Saini, Jamal-Hanjani, Wilson, Birkbak, Hiley, Watkins, Shafi, Murugaesu, Mitter, Akarca, Linares, Marafioti, Henry, Van Allen, Miao, Schilling, Schadendorf, Garraway, Makarov, Rizvi,m Snyder, Hellman, MerghUniversity College London, Cancer Research UK, Francis Crick Insitute, Dana-Farber Cancer Institute, Broad Institute, University Duisburg-Essen, Memorial Sloan Kettering Cancer Center, Columbia Univertsity, Weill Cornell Medical College, Harvard Medical SImmunology, Cancer immunotherapy, Oncology, Immune checkpoint inhibitors
16 May 2016US scientists publish new base editing technique offering means to alter genome without needing to cleave double-stranded DNA or for a donor DNA templateKomor, Kim, Packer, Zuris, LiuHarvard UniversityCRISPR-Cas9, Gene editing
6 Feb 2017Gene therapy shown to restore hearing in deaf miceLandegger, Pan, Askew, Wassmer, Gluck, Galvin, Taylor, Forge, Sankovic, Holt, VandenbergheEaton Peabody Laboratories, Harvard Medical School, Medical University of Vienna, UCL, Boston's Children's Hospital, Harvard Stem Cell Institute, University of North Carolina, Grousbeck Gene Therapy CenterGene therapy
13 Apr 2017CRISPR shown to be sensitive diagnostic tool for detecting single target of DNA or RNA moleculeAbudayyeh, Bhattacharyya, Collins, Daringe, Donghia, Dy, Essletzbichler, Freije, Hung, Joung, Koonin, Lee, Livny, Myhrvold, Regev, Sabeti, Gootenberg, Verdine, ZhangBroad Institute, Massachusetts Institute of Technology, Harvard University, Howard Hughes Medical Institute CRISPR-Cas9, Gene editing
20 Sep 2017Combination of three monoclonal antibodies reported to protect monkeys from HIV Xu, Pegu, Rao, Doria-Rose, Beninga, McKee, Lord, Wei, Deng, Louder, Schmidt, Mankoff, Wu, Asokan, Beil, Lange, Leuschner, Kruip, Sendak, Kwon, Zhou, Chen, Bailer, Wang, Choe, Tartaglia, Barouch, O’Dell, Todd, Burton, Roederer, Connors, Koup, Kwong, YangSanhofi, National Institute of Allergy and Infectious Disease, Harvard University, Massachusetts Institute of Technology, Scripps Research Institute, Monoclonal antibodies, Infectious diseases
4 Oct 2017Gene therapy shown in clinical trials to halt progression of adrenoleukodystrophy, a fatal brain disease inherited by boys Eichler, Duncan, WilliamsHarvard University, Bluebird Bio, Boston Children’s Hospital Stem cells, Gene therapy

Oct 1989

RNA demonstrated to help catalyse the process for synthesising protein

12 Apr 1997

George Wald died

2 May 1997

Keith Roberts Porter died

15 Oct 2000

Konrad Bloch died

25 Aug 2005

Harvard scientists reported reprogramming adult skin cells into embryonic stem cells

2007

p53-induced senescence shown to prevent cancer

5 Sep 2008

Scientists created stem cells for 10 disorders

19 Jan 2011

US scientists publish a technique for genetically engineering transcription activator-like effectors customised to recognise specific DNA-binding sites which they show is an effective tool for editing mammalian genomes

2 Aug 2011

Baruj Benacerraf died

1 Jun 2013

Basic studies conducted with TALENs to see if can correct mutant genes associated with Epidermolysis Bullosa, a rare inherited skin disorder

5 Oct 2015

CRISPR/Cas9 modified 60 genes in pig embryos in first step to create organs suitable for human transplants

16 Nov 2015

US scientists published a technique for overwriting changes made by CRISPR/Cas 9

31 Dec 2015

Gene editiing tool, CRISPR, successfully used to improve muscle function in mouse model of Duchenne muscular dystrophy

6 Jan 2016

US scientists published improved version of CRISPR/Cas 9 with less risk of off-target DNA breaks

25 Mar 2016

Common tags discovered on the surface of cancer cells opening up new avenues for immunotherapy

16 May 2016

US scientists publish new base editing technique offering means to alter genome without needing to cleave double-stranded DNA or for a donor DNA template

6 Feb 2017

Gene therapy shown to restore hearing in deaf mice

13 Apr 2017

CRISPR shown to be sensitive diagnostic tool for detecting single target of DNA or RNA molecule

20 Sep 2017

Combination of three monoclonal antibodies reported to protect monkeys from HIV

4 Oct 2017

Gene therapy shown in clinical trials to halt progression of adrenoleukodystrophy, a fatal brain disease inherited by boys