Recombinant DNA Technology (opens the original in a new tab)
National Human Genome Research Institute. Talking Glossary of Genomic and Genetic Terms. National Human Genome Research Institute, NIH.
Biotechnology uses living things and their molecules to make medicines, food and tools. See how it grew, one discovery at a time.
Trace how discoveries about DNA became tools such as PCR and CRISPR, and which uses are established practice versus still emerging.
Follow the path from molecular genetics to genome engineering, with primary sources for each milestone and a clear line between established methods and early-stage research.
How we label how settled something is
EstablishedWidely replicated, or in routine use in research or medicine.
Emerging researchNewer, with limited long-term evidence, or still mainly in research or early clinical use.
Pick a technology to see how it works, what it is used for, and the ethical questions it raises. Each one is labeled established or emerging.
Technologies
Scientists cut a gene out of one organism's DNA and paste it into another, so that organism makes something new.
Enzymes cut DNA at specific sequences, and the pieces are joined into a carrier such as a bacterial plasmid. Cells that take up the plasmid copy it and can produce the protein the gene encodes.
Restriction enzymes and ligases assemble recombinant molecules that replicate in a host. Expression systems produce proteins such as insulin; regulators assess the safety of the organisms and products.
At the 1975 Asilomar conference, scientists concluded that this research should proceed only under strict guidelines. Risk-based biosafety containment and oversight remain standard practice.
Sources
Key discoveries, tools, medicines and governance decisions, each dated by the publication or announcement it cites. Filter by kind of milestone or by how settled it is.
Showing 39 of 39 milestones
1929
Alexander Fleming reports that a Penicillium mold stops the growth of nearby bacteria, the observation behind penicillin.
1944
Avery, MacLeod and McCarty show that purified DNA can transform one type of bacterium into another.
1952
Experiments with viruses that infect bacteria show that DNA, not protein, enters the cell and directs new viruses.
1953
Watson and Crick propose the double-helix structure of DNA, supported by X-ray data from Franklin, Gosling, Wilkins and colleagues.
Cited: Watson & Crick, 1953: Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid (Primary research, opens in a new tab)Franklin & Gosling, 1953: Molecular configuration in sodium thymonucleate (Primary research, opens in a new tab)Wilkins et al., 1953: Molecular structure of deoxypentose nucleic acids (Primary research, opens in a new tab)
1958
Meselson and Stahl show that each new DNA molecule keeps one old strand and makes one new one.
1961
Nirenberg and Matthaei decode the first codon, and Crick and colleagues show the code is read in triplets.
Cited: Nirenberg & Matthaei, 1961: The dependence of cell-free protein synthesis in E. coli upon naturally occurring or synthetic polyribonucleotides (Primary research, opens in a new tab)Crick et al., 1961: General nature of the genetic code for proteins (Primary research, opens in a new tab)
1969
Thermus aquaticus is described from hot springs. Its heat-stable enzymes later make PCR practical.
1972
Researchers join DNA from different sources into a single molecule for the first time.
1973
Engineered plasmids are shown to work inside bacteria, the foundation of genetic engineering.
1975
Participants at the Asilomar conference conclude, though not unanimously, that recombinant DNA research should proceed, but under strict guidelines.
Cited: Berg et al., 1975: Summary statement of the Asilomar conference on recombinant DNA molecules (Perspective, opens in a new tab)U.S. National Library of Medicine: Recombinant DNA Technologies and Researchers' Responsibilities, 1973-1980 (Reference, opens in a new tab)
1975
Köhler and Milstein fuse antibody-making cells with tumor cells, creating continuous cultures that secrete a single antibody of predefined specificity.
1976
U.S. National Institutes of Health guidelines assign each kind of experiment a physical and a biological level of containment.
1977
Sanger and colleagues, and Maxam and Gilbert, publish methods to determine DNA sequences.
Cited: Sanger et al., 1977: DNA sequencing with chain-terminating inhibitors (Primary research, opens in a new tab)Maxam & Gilbert, 1977: A new method for sequencing DNA (Primary research, opens in a new tab)
1979
Chemically made genes for human insulin are expressed in E. coli, leading to recombinant insulin medicines.
Cited: Goeddel et al., 1979: Expression in Escherichia coli of chemically synthesized genes for human insulin (Primary research, opens in a new tab)Johnson, 1983: Human insulin from recombinant DNA technology (Review, opens in a new tab)
1985
PCR copies a chosen stretch of DNA millions of times; an early use detected the sickle cell variant.
Cited: Saiki et al., 1985: Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia (Primary research, opens in a new tab)Mullis & Faloona, 1987: Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction (Primary research, opens in a new tab)
1988
Using Taq polymerase lets PCR run through repeated heating cycles without adding fresh enzyme.
Cited: Saiki et al., 1988: Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase (Primary research, opens in a new tab)Chien et al., 1976: Deoxyribonucleic acid polymerase from the extreme thermophile Thermus aquaticus (Primary research, opens in a new tab)
1990
A fast heuristic algorithm makes it practical to search large sequence databases for sequences similar to a new one.
Cited: Altschul et al., 1990: Basic local alignment search tool (Primary research, opens in a new tab)
1996
The complete genome of baker's yeast is published, with about 6,000 genes.
Cited: Goffeau et al., 1996: Life with 6000 genes (Primary research, opens in a new tab)
1997
A sheep is cloned from an adult cell, showing that the nucleus of a specialized cell can still direct the development of a whole animal.
1998
Double-stranded RNA is found to silence matching genes, opening a new way to switch genes off.
2000
A genetic toggle switch and an oscillating circuit are built in bacteria, launching synthetic biology.
Cited: Gardner et al., 2000: Construction of a genetic toggle switch in Escherichia coli (Primary research, opens in a new tab)Elowitz & Leibler, 2000: A synthetic oscillatory network of transcriptional regulators (Primary research, opens in a new tab)
2001
Two teams publish draft sequences of the human genome.
Cited: Lander et al., 2001: Initial sequencing and analysis of the human genome (Primary research, opens in a new tab)Venter et al., 2001: The sequence of the human genome (Primary research, opens in a new tab)
2005
Modified nucleosides reduce the immune response to synthetic mRNA, a key step toward mRNA medicines.
2006
Four factors turn adult mouse cells into induced pluripotent stem cells.
2007
Bacteria are shown to use CRISPR sequences to resist viruses.
Cited: Barrangou et al., 2007: CRISPR provides acquired resistance against viruses in prokaryotes (Primary research, opens in a new tab)Mojica et al., 2005: Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements (Primary research, opens in a new tab)
2010
A bacterial cell is controlled by a genome that was chemically synthesized.
2012
Cas9 guided by an RNA can be programmed to cut a chosen DNA sequence.
2013
Two groups show CRISPR genome editing in human and mouse cells.
Cited: Cong et al., 2013: Multiplex genome engineering using CRISPR/Cas systems (Primary research, opens in a new tab)Mali et al., 2013: RNA-guided human genome engineering via Cas9 (Primary research, opens in a new tab)
2013
Engineered yeast produces a precursor that is converted chemically into artemisinin.
2016
Single DNA letters are changed without cutting both strands of the double helix.
2016
A synthetic cell with only 473 genes, fewer than any free-living cell found in nature, still grows. The functions of 149 of those genes were unknown.
2017
Phase 3 and early trials report benefits from gene therapies for an inherited blindness and spinal muscular atrophy.
Cited: Russell et al., 2017: Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial (Clinical trial, opens in a new tab)Mendell et al., 2017: Single-dose gene-replacement therapy for spinal muscular atrophy (Clinical trial, opens in a new tab)
2018
Engineered immune cells produce remissions in children and young adults with a form of leukemia.
Cited: Maude et al., 2018: Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia (Clinical trial, opens in a new tab)June & Sadelain, 2018: Chimeric antigen receptor therapy (Review, opens in a new tab)
2019
A search-and-replace editor rewrites DNA without double-strand breaks or donor DNA. Clinical use is still being studied.
2020
Randomized trials report high efficacy for mRNA COVID-19 vaccines; full FDA approval of the first follows in 2021.
Cited: Polack et al., 2020: Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine (Clinical trial, opens in a new tab)Baden et al., 2021: Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine (Clinical trial, opens in a new tab)FDA, 2021: FDA Approves First COVID-19 Vaccine (Regulatory notice, opens in a new tab)
2021
AlphaFold predicts many protein structures with high accuracy from sequence alone.
Cited: Jumper et al., 2021: Highly accurate protein structure prediction with AlphaFold (Primary research, opens in a new tab)Varadi et al., 2022: AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models (Primary research, opens in a new tab)
2021
The World Health Organization publishes recommendations for overseeing human genome editing.
Cited: WHO, 2021: Human genome editing: a framework for governance (Guidance, opens in a new tab)National Academies, 2017: Human Genome Editing: Science, Ethics, and Governance (Consensus report, opens in a new tab)
2022
The Telomere-to-Telomere consortium closes the remaining gaps in the human genome sequence.
Cited: Nurk et al., 2022: The complete sequence of a human genome (Primary research, opens in a new tab)
2023
The FDA approves Casgevy, a CRISPR-based gene therapy for sickle cell disease, for patients 12 and older.
Approved, but long-term outcomes are still being followed, so we label it emerging.
Cited: FDA, 2023: FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease (Regulatory notice, opens in a new tab)Frangoul et al., 2021: CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia (Clinical trial, opens in a new tab)
Simplified model
1Separate
Heat splits the double-stranded DNA into single strands.
2Bind primers
Cooling lets short primers attach on either side of the target.
3Copy
A heat-stable polymerase builds a new strand from each primer.
After 35 cycles: 4.3 × 10¹¹ copies
Without any limit: 5.7 × 10¹¹
Crosses the detection threshold at cycle 28.7.
Quantitative PCR uses this curve to measure how much DNA a sample started with. More starting DNA crosses the threshold sooner: at 90% efficiency, ten times more template reaches it about 3.6 cycles earlier. Try moving the starting copies slider and watch the threshold marker shift.
Decide how settled each use of biotechnology is, then check your answers. This is practice only; nothing is saved.
0 of 6 answered.
Biotechnology has developed alongside rules for using it safely. In 1975, participants at the Asilomar conference concluded, though not unanimously, that recombinant DNA research should proceed under strict guidelines. The U.S. National Institutes of Health guidelines that followed in 1976 assigned each kind of experiment physical and biological containment levels.Source: Berg et al., 1975Source: U.S. National Library of Medicine Today the World Health Organization's laboratory biosafety manual takes an evidence- and risk-based approach, balancing safety measures against the actual risk of the work on a case-by-case basis.Source: WHO, 2020
Human genome editing raises its own questions. Reports from the U.S. National Academies in 2017 and the World Health Organization in 2021 set out recommendations for oversight, distinguishing editing a patient's body cells from heritable editing that could pass changes to future generations.Source: National Academies, 2017Source: WHO, 2021Source: WHO, 2021
Safety note
The explanations on this page are our own summaries of these sources. Follow a link to read the original; if anything here disagrees with it, the original wins. How we choose and check sources.
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Recombinant plasmids that replicate in bacteria.
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Scientists' own guidelines for the safe conduct of recombinant DNA research.
U.S. National Library of Medicine. Paul Berg: Profiles in Science. U.S. National Library of Medicine, NIH.
Historical overview of the Asilomar conference and the 1976 NIH guidelines.
World Health Organization (2020). WHO publications. World Health Organization. Published 2020-12-21.
National Human Genome Research Institute. Talking Glossary of Genomic and Genetic Terms. National Human Genome Research Institute, NIH.
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PCR with heat-stable Taq polymerase.
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National Human Genome Research Institute. genome.gov. National Human Genome Research Institute, NIH.
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The Telomere-to-Telomere consortium's gapless human genome assembly.
National Human Genome Research Institute. Talking Glossary of Genomic and Genetic Terms. National Human Genome Research Institute, NIH.
Jinek M, Chylinski K, Fonfara I, et al. (2012). Science 337:816-821.
Showed Cas9 can be programmed with guide RNA to cut chosen DNA sequences.
U.S. Food and Drug Administration (2023). FDA News Release. U.S. Food and Drug Administration. Published 2023-12-08.
Approval of Casgevy (CRISPR-based) and Lyfgenia for patients 12 and older.
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Modified nucleosides reduce innate immune recognition of synthetic mRNA.
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Full approval of Comirnaty, an mRNA vaccine, for people 16 and older.
National Human Genome Research Institute. Talking Glossary of Genomic and Genetic Terms. National Human Genome Research Institute, NIH.
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BLAST, the fast heuristic search used to compare sequences against databases.
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Two mutually repressing genes form a switch with two stable states.
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The repressilator: three repressors wired in a loop produce oscillations.
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The original report of penicillin's antibacterial activity.
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Evidence that DNA is the transforming principle that carries hereditary information.
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Proposed the double-helix model of DNA.
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X-ray diffraction evidence for a helical DNA structure, published alongside Watson and Crick.
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Showed that DNA replication is semiconservative.
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First codon assignment: poly-U RNA directs synthesis of polyphenylalanine.
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Frameshift experiments indicating the code is read in non-overlapping triplets.
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Isolation of the hot-spring bacterium later used as the source of Taq polymerase.
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The hybridoma method for monoclonal antibodies.
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The first complete genome of a eukaryote, baker's yeast.
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Discovery of RNA interference.
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