Biotechnology Timeline
1946: Radiation protection and effects
ORNL elevates research efforts to protect people from exposure to unsafe levels of radiation, focusing on radiation tolerance, radiation protection services and training, and the development of new methods to measure radiation exposure. At the same time, concerns about health effects of radiation from reactors, atomic weapons testing, and radioactive elements that enter the body spur the development of a broad biological research program..
Paul Galyon, left, holds a paper strip from which smear tabs are stamped and used to collect samples of radioactivity.
Eugene Wigner hands the first shipment of a reactor-produced radioisotope, carbon-14, to the director of the Barnard Free Skin and Cancer Hospital.
1946: First shipment of radioisotopes
The first official shipment of a radioisotope produced at a nuclear reactor, carbon-14, is produced at the Graphite Reactor and shipped to Barnard Free Skin and Cancer Hospital in St. Louis in August 1946. During the program’s first year, more than 1,000 shipments of 60 different radioisotopes are used for cancer treatment and as tracers for academic, industrial, and agricultural research. Thousands of radioisotope shipments from the Graphite Reactor will occur between 1946 and 1963.
1949: First analytical separation of DNA and RNA
Researchers develop analytical separation of the components of nucleic acids (DNA and RNA) based on principles developed during the Manhattan Project. This technology is basic to the subsequent explosive growth of DNA and RNA biochemistry and molecular genetics
DNA strands: diagram (left); under microscope (right).
Geneticists Liane and Bill Russell arrive at ORNL in 1947 and start a large-scale mouse genetics project to study radiation’s genetic effects.
1952: Universal prenatal guidelines
Based on results of studies with mice, Liane and Bill Russell—a husband-and-wife research team—inform the medical community that the prenatal stage at which radiation is introduced strongly influences the amount and type of damage to the human embryo and fetus. They make specific recommendations on avoiding risks to human pregnancies from diagnostic X-rays that are then adopted worldwide.
1956: Messenger RNA discovery
Elliot Volkin and Larry Astrachan discover messenger RNA, which “reads” DNA’s genetic code and becomes a template for mass-producing proteins.
Elliot Volkin
1956: Genetic effects of radiation
A National Academy of Sciences Committee uses ORNL-generated mouse data to formulate projections for the genetic effects of radiation in humans. National and international organizations rely on ORNL data for recommendations of human radiation exposure limits.
1959: Y chromosome discovery
Liane Russell and colleagues discover that maleness in a mouse depends on the presence of the Y chromosome and is unrelated to the number of X chromosomes. She reveals the next year that only one of the two X chromosomes of a mammalian female is active.
Liane Russell
Mock-up of bomb shelter arrangements.
1964: Civil defense
ORNL organizes assessment of national vulnerabilities to nuclear attack and explores ways to reduce the potential impact. ORNL hires demographers and social scientists to understand the number and age distribution of populations being protected by civil defense systems, such as underground shelters, and the reactions of people using them.
1972: Surrogate reproduction demonstrated
Researchers freeze, thaw, and implant mouse embryos in surrogate mothers that give birth to healthy mouse pups. The technique is featured on the cover of Science magazine and adopted by the cattle industry for multiplying the reproductive potential of prize cattle.
Mouse pups.
In the electron microscope, nucleosomes resemble the beads on a string of beads.
1974: Nucleosome discovery
University of Tennessee/ORNL researchers Ada and Donald Olins discover the nucleosome by electron microscopy and propose its structure. The nucleosome is fundamental to chromosome structure and function as the subunit for packaging DNA within chromosomes and the cell nucleus. The Olins propose that these particles have a dyad axis (like DNA) and pairs of the basic proteins (histones), which is later confirmed.
1992: Mouse agouti gene discovery
Researchers identify and clone the mouse agouti gene. The mutated gene is found to cause obesity, altered fur color, diabetes, and skin cancer in mice, and it has a human counterpart.
Ed Michaud watches the activity of normal and mutant mice in large beakers.
Russ Knapp, lead developer, with the rhenium-188 generator.
1993: Cancer and heart disease treatment
ORNL develops the rhenium-188 isotope generator to treat cancer-induced bone pain and arthritis and prevent the buildup of smooth muscle cells in coronary arteries after balloon angioplasty.
1994: Lab on a chip
The “lab on a chip” is invented and used to help diagnose diseases and provide a quick and cheap method for DNA sequencing.
Mike Ramsey leads development of the technology
1997: Actinium-225
ORNL sends its first shipment of actinium-225, a promising medical isotope used in targeted alpha therapy for treating cancers, to the National Institutes of Health. ORNL remains a major supplier of Ac-225.
1998: MicroCAT scanner
ORNL researchers develop the MicroCAT scanner, an X-ray computed tomography system for mapping internal defects and organ changes in experimental mice.
Michael Paulus and Shaun Gleason develop the MicroCAT scanner.
Richard Mural, left, Ed Uberbacher, and Reinhold Mann (not pictured) develop the GRAIL gene-finding tool.
2001: Human gene-finding tool
The GRAIL gene-finding tool is used in Science and Nature’s landmark papers on the human genome in 2001. Frank Larimer, Jay Snoddy, and Ed Uberbacher are listed as coauthors on the lead paper. The GRAIL tool, developed by Uberbacher and Richard Mural, is used for the work and is mentioned on Science’s human genome program timeline.
2004: Nanoscale access to living cells
Researchers develop a nanoscale technology for investigating biomolecular processes in single living cells. The new technology enables researchers to monitor and study cellular signaling networks, including the first observation of programmed cell death in a single living cell.
ORNL’s biosensor technology enables researchers to visualize and track RNA activity in living plants.
Richard Mural, left, Ed Uberbacher, and Reinhold Mann (not pictured) develop the GRAIL gene-finding tool.
2004: Sequencing of the Populus genome
ORNL researchers and collaborators at the Joint Genome Institute and academic institutions around the world complete sequencing of the Populus genome in 2004. Completion of the sequencing and assembly of the poplar genome, is significant because it will allow scientists to lay out a molecular roadmap that shows how trees grow.
2005: Billion-Ton Report
In April 2005, ORNL and DOE publish the Billion-Ton Report, confirming that America has the potential to produce at least 1 billion dry tons of nonfood biomass resources annually by 2040. Updates are published in 2011, 2016, 2023.
ORNL’s biosensor technology enables researchers to visualize and track RNA activity in living plants.
Richard Mural, left, Ed Uberbacher, and Reinhold Mann (not pictured) develop the GRAIL gene-finding tool.
2009: Tracking neurons to predict and prevent disease
Researchers at ORNL and St. Jude Children’s Research Hospital study how developing nerve cells may hold a key to predicting and preventing cancer, Alzheimer’s, Parkinson’s disease, etc.
2011: Understanding Huntington’s disease
Researchers at ORNL and the University of Tennessee Medical Center use neutrons to successfully characterize, for the first time, the earliest structural formation of the disease type of the protein that causes Huntington’s disease, the incurable, hereditary neurological disorder that affects one in 10,000 Americans. Watch a video about ORNL research into the molecular roots of Huntington’s disease.
Radiochemical technicians DavidResearchers combine human settlement mapping (left) and high-resolution, spatially explicit population distribution data (right) from ORNL’s LandScan.
2014: Polio and the Gates Foundation ORNL’s Urban Dynamic
ORNL’s Urban Dynamics Institute works with the Bill & Melinda Gates Foundation to aid polio vaccination efforts in developing countries. Teams at the institute apply big data analysis to population dynamics in Nigeria to help polio vaccination crews better estimate the amount of vaccine needed and to target areas of priority, saving time and money in eradicating the disease.
2014: Vertimass licenses ORNL catalyst technology
Vertimass LLC, a California-based start-up company, licenses an ORNL-developed zeolite catalyst that directly converts ethanol into a hydrocarbon blendstock for use with jet, diesel, or gasoline fuels. Vertimass scales the technology with assistance from ORNL and collaborators, and the EPA approves its use in blends of up to 20% with conventional gasoline for the US market in 2024.
Inventors Chaitanya Narula, Brian Davison, and Martin Keller stand with Vertimass LLC’s Charles Wyman at the licensing ceremony.
2016: Demonstrating large-scale 3D-printed biomaterials
Researchers 3D print a large-scale pavilion for the DesignMiami exposition in Florida using biomaterials. They use polylactic acid (PLA), a biodegradable, thermoplastic polyester, combined with bamboo in a composite that is 20% bamboo and 80% PLA by weight. The result is a printed product that has the properties of wood—the same sound, smell, and touch. The pavilions, entitled “Flotsam and Jetsam,” are the largest structures ever commissioned by DesignMiami for its meeting.
DesignMiami attendees experiencing Flotsam and Jetsam.
2016: Developing drought-resistant crops
As part of an effort to develop hardier food and bioenergy crops, ORNL scientists uncover the genetic and metabolic mechanisms that allow certain plants to conserve water and thrive in semi-arid climates. The team pinpoints which genetic behavior signals desert plants like agave to open and close their stomata, the pores in leaves that allow gas exchange and water evaporation. The research opens pathways to introduce water-saving traits into bioenergy and food crops.
Kaitlin Palla studies agave plants at ORNL as part of research into a water efficient mode of photosynthesis called crassulacean acid metabolism.
2018: Actinium-227
ORNL starts producing actinium-227 to meet the high demand for Xofigo®, a highly effective drug used in the treatment of prostate cancer. The work is part of a 10-year agreement between the DOE Isotope Program and Bayer.
Radiochemical technicians David Denton and Karen Murphy use hot cell manipulators at ORNL during the production of actinium-227.
ORNL’s Dan Jacobson and Wayne Joubert lead the team that develops the award-winning algorithm.
2018: Speeding discovery with supercomputing
The Association for Computing Machinery awards the Gordon Bell Prize to ORNL researchers for developing an algorithm that rapidly reveals hidden gene networks underlying complex traits in plants and animals. Running on DOE supercomputers, the tool accelerates discovery—from improving bioenergy crops to understanding the genetics of opioid addiction.
2018: Printing with plants
ORNL develops a scalable processing technique that uses plant-based materials for 3D printing. Scientists create a new material with excellent printability and performance by combining a plant component called lignin with rubber, carbon fiber, and acrylonitrile butadiene styrene, or ABS, to 3D print structures with 100 percent improved weld strength between the layers over ABS alone.
Researchers develop a scalable processing technique to 3D print a plant-based composite material.
A new method uses E. coli to generate DNA with methylation patterns that target microbes recognize and accept as their own.
2019: Bypassing microbial defenses
Researchers demonstrate a method to insert genes into a variety of microorganisms that previously would not accept foreign DNA. The approach facilitates customization of microbes to produce valuable chemicals, fuels, and materials.
2021: Detecting CRISPR activity with the naked eye
Scientists develop and demonstrate biosensors for real-time detection of CRISPR gene editing in living organisms. The biosensors employ a green fluorescent protein that glows under an ultraviolet flashlight, allowing scientists to confirm CRISPR activity quickly and nondestructively. The sensors increase biosecurity and accelerate plant and microbial engineering for biotechnology.
ORNL biosensors allow scientists to detect the presence of CRISPR in live plants using an ultraviolet flashlight.
Scientists engineer a microbe, shown in light blue, to convert industrial waste gases into acetone.
2021: Automating plant science
Researchers demonstrate a proof-of-principle automation system that harnesses artificial intelligence and robotics to quickly manipulate and sample living plants, accelerating efforts to optimize traits in energy and agricultural crops.
2022: Producing valuable chemicals for industry
Scientists from LanzaTech, ORNL, and Northwestern University engineer a microbe, Clostridium autoethanogenum, to convert molecules of industrial waste gases into acetone and isopropanol. These widely used chemicals serve as the basis of thousands of products, from fuels and solvents to acrylic glass and fabrics.
Scientists engineer a microbe, shown in light blue, to convert industrial waste gases into acetone.
A 3D printed home sits on the campus of UMaine and is made from biomaterials developed in collaboration with ORNL.
2023: ORNL, UMaine 3D print home from biobased materials
On the grounds of the University of Maine’s Advanced Structures and Composites Center sits the nation’s first additively manufactured home made entirely from biobased materials. The 600-square-foot home, the result of a collaboration between ORNL and UMaine, serves as a testbed to see how well the materials perform over time in the Northeastern environment. If weatherization testing and energy data gathering are favorable, the home could lead to the printing of more like it, providing an energy efficient and economical housing alternative in the United States.
2023: Researcher Adam Guss leads the development of SAGE tools for microbial engineering
An ORNL-adapted DNA editing tool enables scientists to engineer nearly any microorganism, including wild strains that have historically been difficult to modify. The Serine Recombinase-Assisted Genome Engineering (SAGE) system can make precise genetic changes in just days instead of weeks or months, accelerating the development of new biotechnologies.
Researcher Adam Guss leads the development of SAGE tools for microbial engineering.
Neutron experiments help reveal the enzymatic mechanism that synthesizes vital food sources for cancer cells that depend on vitamin B6.
2023: Advancing understanding of cancer pathways
Scientists use neutrons and X-rays to draw a roadmap of every atom, chemical bond, and electrical charge inside a key enzyme that belongs to a metabolic pathway that cancer cells overuse to reproduce. The insight offers a pathway to developing drugs that block this metabolic pathway and target aggressive cancers, including lung, colon, breast, pancreatic, and prostate.
2024: Stacking genes for plant transformation
The ORNL-developed, R&D 100 award-winning split-marker for gene stacking system makes it easy to add and study multiple genes at once, doubling the speed and halving the cost of plant transformation. It also allows easy identification of which plants have the new genes – using the naked eye through visualization of two reporters: RUBY, which turns the leaf red under white light, and GFPuv, which causes the plant to glow green under UV light.
Plants modified using the split-marker for gene stacking technology glow bright green under a UV light.
The study analyzed 2,068 traits using data from the Million Veteran Program, with computing power from the Summit supercomputer at ORNL.
2024: Summit helps Veterans Affairs connect genetic dots
In one of the largest genome-wide association studies ever done, researchers use the Summit supercomputer to analyze the genetic architecture of 2,068 traits based on statistics collected by the Department of Veterans Affairs’ Million Veteran Program from 635,969 veterans of all ages, races, and backgrounds. The resulting insights bring scientists a step closer to the long-sought goal of precision medicine, which would use personalized cures tailored to an individual’s genetic makeup.
2024: Boosting plant height through genetics
A team of scientists from two Department of Energy Bioenergy Research Centers identifies a gene, dubbed Booster, that enhances photosynthesis and can increase poplar tree height by about 30% in the field and up to 200% in the greenhouse. When inserted in a different plant, Arabidopsis, the Booster gene results in a similar increase in biomass and a 50% increase in seed production. This finding indicates the wider applicability of Booster to potentially trigger higher yields in other plants.
Biruk Feyissa works with poplar trees that have a naturally occurring gene that enhances photosynthetic activity and boosts plant growth.
The study analyzed 2,068 traits using data from the Million Veteran Program, with computing power from the Summit supercomputer at ORNL.
2024: Summit helps Veterans Affairs connect genetic dots
In one of the largest genome-wide association studies ever done, researchers use the Summit supercomputer to analyze the genetic architecture of 2,068 traits based on statistics collected by the Department of Veterans Affairs’ Million Veteran Program from 635,969 veterans of all ages, races, and backgrounds. The resulting insights bring scientists a step closer to the long-sought goal of precision medicine, which would use personalized cures tailored to an individual’s genetic makeup.
2024: Illuminating RNA in real-time
ORNL develops a first-ever method of detecting ribonucleic acid, or RNA, inside plant cells using a technique that results in a visible fluorescent signal. The technology can help researchers detect and track changes in RNA and gene expression in real time, providing a powerful tool for the development of hardier energy and food crops and for detection of unwanted plant modifications, pathogens, and pests.
ORNL scientists created a biosensor technology that lets researchers visualize and track RNA activity in living plants, using a molecular splicing tec
Pennycress roots are imaged in an APPL facility chamber.
2026: Imaging delivers insights for plant engineering
ORNL adds new belowground imaging capabilities to the Advanced Plant Phenotyping Laboratory (APPL), an automated facility that already uses high-resolution cameras to quickly assess aboveground plant traits. With whole plant imaging, researchers gain faster, deeper insight into how root structure and function influence plant growth, productivity, and hardiness. The platform yields AI-ready data to accelerate the development of stress-tolerant crops for biomanufacturing.