This electrotype of “Hu’petha” was prepared by the Government Printing Office in Washington, D.C.; the image was published as Plate 28 (p.163) in an article by Alice C. Fletcher (1838-1923) and Francis La Flesche (1857-1932) entitled “The Omaha Tribe” in the Twenty-Seventh Annual Report of the Bureau of American Ethnology to the Secretary of the Smithsonian, 1905-1906.
Agracetus’s ACCELL gene gun, featured on this mug, delivers foreign genes into plant cells in order to create transgenic plants. To learn more about the ACCELL gene gun, please see object number 1993.0345.01, the Agracetus gene gun.
This machine is an automated DNA/RNA synthesizer, Model 394 from Applied Biosystems, Inc. It was on the market from 1991 to 2007. DNA/RNA synthesizers can produce short single strands of nucleotides known as oligonucleotides. These “oligos” can be linked together to create longer strands of DNA or RNA. Synthetic DNA or RNA is used by researchers both to study how genes work and for the purposes of genetic engineering and PCR (see object 1993.0166.01). Often it is easier to make a stretch of DNA or RNA with a synthesizer than it is to isolate that same stretch of DNA or RNA from a natural source. Synthetic oligos can also be created with slight changes from the naturally occurring forms, allowing researchers to study the impact of modifying the molecule.
The ability to synthesize oligos has been around since the late 1950s, when Har Gobind Khorana (1922-2011) discovered a method to make them in the lab using solution phase chemistry. In the 1960s, Robert Letsinger (1921-2014) devised a method for assembling oligos using solid phase chemistry, which constructs the oligo by linking its chemical building blocks onto a polymer bead scaffolding. This advance, along with slight adjustments to Khorana’s original protocol, simplified the reaction to the point where the first automated machines to perform oligo synthesis could be built in the late 1970s. At the time, however the reaction relied on very unstable chemicals that had to be prepared by a highly trained chemist just before the machine could be run.
By the 1980s further adjustments to the reaction and reagents made it possible for someone without a great deal of experience in chemical preparation to operate the machines, opening up their use to a wider audience and increasing their commercial viability. This work was accomplished by Marvin H. Caruthers (born 1940) and his research team at the University of Colorado. Caruthers, along with Leroy Hood of Caltech, founded Applied Biosystems, Inc. (ABI), to market these simpler-to-use DNA synthesizers. The first ABI synthesizer, Model 380A, shipped in 1983. This object, Model 394 introduced in 1991, was the second wave of Applied Biosystems’s DNA/RNA synthesizers. It consumed chemicals more efficiently than the previous model and could synthesize up to four oligos at one time.
Sources:
“Gene Synthesis Demystified.” Czar, Michael J., J. Christopher Anderson, Joel S. Bader, Jean, Peccoud. Trends in Biotechnology. 27 February 2009 (2):63–72.
Manual for DNA Synthesizer Models 392 and 394, Applied Biosystems, Inc.
“A Short History of Oligonucleotide Synthesis.” Hogrefe, Richard. TriLink BioTechnologies. http://www.trilinkbiotech.com/tech/oligo_history.pdf
Caruthers, Marvin H. “The chemical synthesis of DNA/RNA: our gift to science.” The Journal of biological chemistry vol. 288,2 (2013): 1420-7.
This capacitance extender is part of the Gene Pulser, one of the first commercial electroporators. Manufactured by Bio-Rad, the Gene Pulser was on the market from 1986 to 1995.
Electroporation is a technique used to get drugs, proteins, DNA, and other molecules into cells. The method works by delivering a controlled electric pulse to cells in a solution. The pulse causes cells to briefly open pores in their cell membrane and take in molecules around them. The process is particularly useful in the creation of transgenic organisms.
This unit increases the capacitance of the pulse generator (object number 1998.0018.01) alone. Together, the two are recommended for electroporation of most eukaryotic cells, including mammalian and plant cells.
Sources:
Accession File
Gene Pulser Product Manuals
“Electroporation Makes Impact on DNA Delivery in Laboratory and Clinic.” Glaser, Vicki. Genetic Engineering News, September 15, 1996. pp. 14–15.
“Electroporation applications: Special needs and special systems.” Ostresh, Mitra. American Biotechnology Laboratory. January 1995. p. 18.
A spherometer is used primarily to measure the curvature of objects such as lenses and curved mirrors. This rather large example belonged to Bowdoin College. It has no markings but most likely was purchased from an educational instrument maker in the 19th century. It is accompanied by an optical flat used to zero the device. It has both a vertical scale and horizontal scale on the disc. To improve accuracy, a magnifying lever is mounted on the top of the micrometer disc. The two small arms would have pointed to a secondary scale that arched over the top of the device but is now missing.
From the 1920s through the 1950s biologists and medical researchers made a concerted effort to solve the problem of tissue culture—how to raise and maintain cells for scientific research. Part of the challenge was to create a home outside the body in which cells could survive. At the National Cancer Institute, a team led by Wilton Earle (1902–1964) used tissue culture to study the process by which normal cells become cancerous. Earle, along with researchers Katherine Sanford, Virginia Evans, and Gwendolyn Likely, worked to develop proper nutrition—through a specially formulated broth—for cells grown in culture.
This object was used in Dr. Wilton Earle’s laboratory at the National Cancer Institute. Earle joined NCI in 1937 and served as head of its Tissue Culture Section from 1946 to 1964. He and his researchers were pioneers in the use of tissue culture for cancer research.
Sources:
National Museum of American History Accession Files 1991.0071 & 1997.0139
The blockbuster cancer drug Taxol first became available in 1992 and has since been used in the treatment for ovarian, breast, and lung cancer, and for Kaposi’s sarcoma. Its active ingredient was discovered through a joint research project between the National Cancer Institute and the U.S. Department of Agriculture, which screened plant materials for their possible use as cancer drugs. In 1962 project researchers found that the bark of the Pacific yew, Taxus brevifolia, contains an anti-cancer chemical. The process to isolate the chemical, however, required trees to be stripped of their bark and consequently die, a fact that concerned both environmentalists and drug manufacturers.
Environmentalists worried that large-scale harvesting of the trees would damage the trees’ natural habitat through clear-cutting and massive harvest of the slow-growing Pacific yews. The drug’s manufacturers realized that the current supply of natural Pacific yew was far from large enough to provide a sustainable source of bark for the continued production of Taxol over time. Slow growth and maturation rates of the yew made replacing natural sources through cultivation an untenable solution.
For these reasons, alternate sources of Taxol were investigated. Some scientists worked in the lab, trying to make the drug from scratch. Others, like microbiologist Gary Strobel, turned to the field, hoping to find a new natural source of the drug. Strobel wore this shirt on trips to the Himalayas when studying Taxus wallachiana, the Himalayan yew. Strobel did succeed in finding several natural alternate sources, all of them fungi which grew within yew and produced their own Taxol. He suggested growing these fungi in the lab and harvesting the Taxol they produced.
In the end, however, a sustainable source of Taxol came from a substance found in the needles of the European yew, Taxus baccata, which could be transformed into Taxol using a chemical reaction. Because needles could be harvested without killing the tree, this semi-synthetic way of making Taxol replaced bark as the commercial source of the drug. Later this process was replaced by simply growing the plant’s cells in the lab in large quantities and harvesting the Taxol they produced.
Sources:
Accession File
“Success Story: Taxol (NSC125973).” National Cancer Institute. Accessed online. http://dtp.nci.nih.gov/timeline/flash/success_stories/S2_Taxol.htm
“Biologist Gets Under the Skin of Plants—And Peers.” Richard Stone. Science. Vol. 296 No. 5573. 31 May 2002. p.1597.
Taxol Product Insert.
“2004 Greener Synthetic Pathways Award: Development of a Green Synthesis for Taxol Manufacture via Plant cell Fermentation and Extraction.” United States Environmental Protection Agency. http://www2.epa.gov/green-chemistry/2004-greener-synthetic-pathways-award
The bone marrow stem cell isolator, used to separate out bone marrow stem cells from blood samples, found its beginnings in 1981 when Dr. Curt Civin at the Johns Hopkins Oncology Center identified an antibody that binds to a protein on the surface of bone marrow stem cells. The antibody provided a unique way to identify bone marrow stem cells among mixtures of different kinds of cells. Bone marrow stem cells, also known as progenitor cells, have the capability to develop into any of the various blood cell types, including those which play a vital role in the immune response.
In 1988 Dr. Alan Hardwick, a bioengineer at Baxter Healthcare Corporation’s Biotech Group in Santa Ana, California, designed and built a prototype bone marrow stem cell isolator using Dr. Civin’s antibody. Hardwick bound the antibody to small beads, and then placed the beads in solution with a mixture of blood cells. The antibody coated beads bound only to the bone marrow stem cells, and could be separated from the rest of the blood cell solution with the use of a magnet. Once the stem cell-bound beads were separated out, an enzyme could be used to remove the cells from the antibody beads, providing a pure sample of bone marrow stem cells. This object is a second-round prototype of the machine, developed in 1989.
The machine, under the brand name “Isolex,” was on the market starting in 1992. Although it was specifically marketed as a way to build stem cell reserves to replace the blood and immune systems in cancer patients whose own systems were destroyed by chemotherapy, the machine was also popular in experimental research projects, such as gene therapy, that often use stem cells.
Source:
Accession File
“Companies Use Many Methods to Select Elusive Stem Cells.” Hugh McIntosh. Journal of the National Cancer Institute. Vol. 88. No. 9. 1 May 1996. p.573.
“Varmus to Rule in Fight Over Cell-Sorting Technology.” Eliot Marshall. Science. Vol. 276. 6 June 1997.
Isolex Magnetic Cell Selection System Instructions.
Small compound monocular microscope with square stage, sub-stage mirror, horseshoe base, and wooden box with extra lenses. The “C. VERICK / PARIS” inscription refers to Constant Verick, a microscope maker who described himself as a “special student” of Edmund Hartnack after Hartnack moved from Paris to Potsdam in 1870. Verick’s son-in-law, Maurice Stiassnie, took charge of Verick’s shop in 1882, and changed the name a few years later. The serial number “3227” appears in the small box holding extra objectives.
This may have been used in Louis Pasteur’s laboratory in Paris.
Ralph Burnham and Nick Djeu made this prototype excimer laser in mid-1975 while at the Naval Research Laboratory. A modified carbon-dioxide laser known as a TEA laser (Transversely Excited, Atmospheric pressure), this laser used a mixture of xenon and fluoride gasses to produce a pulse of ultraviolet laser light. Ultraviolet light has a shorter wavelength than visible light and thus a higher energy level.
The term "excimer" refers to a molecule of two identical atoms that remains stable when in an excited state. The first laser to use such molecules was made in Moscow in 1970 and used molecules consisting of two xenon atoms. Lasers using molecules of differing atoms (technically called an exciplex-laser) were made by several teams of researchers in the US early in 1975. Burnham and Djeu's breakthrough lay in using a commercially available TEA laser to generate the excimer laser pulse. Their apparatus was much smaller and used less energy than prior excimer lasers that were energized by electron-beams.
This sample of tobacco mosaic virus RNA was part of the National Institute of Health lab of Dr. Marshall Nirenberg, a scientist who won the 1968 Nobel Prize in Physiology or Medicine for his work in helping to “crack the genetic code,” or to understand the way DNA codes for the amino acids that are linked to build proteins. Prior to the availability of synthetic oligonucleotides (see object 2001.0023.02), Nirenberg used this sample of tobacco mosaic virus RNA as a source of mRNA for his experiments in optimizing the function of cell-free protein synthesis systems, an important precursor to his work of cracking the genetic code.
By the late 1950s, scientists understood that DNA was the molecule containing the instructions for life. The structure of DNA was also known-- a sort of twisted ladder shape known as double helix where the “side rails” consisted of a sugar phosphate backbone and the “rungs” were made of paired nucleic acid bases (represented by A, T, G, C). The structure suggested that the order of the bases formed a code representing the order in which amino acids should be joined to produce different kinds of proteins.
But what was the code? What order of bases made up the “code words” or "codons” DNA used to represent each of the 20 amino acids? Researchers hypothesized that each codon for amino acid would be three bases long. If it was only two bases long, that would allow for only 16 different combinations of the four bases (4^2 = 16). If each codon was three bases however, that would result in 64 possible codons (4^3 =64), plenty of codons to represent each of the 20 amino acids separately.
With this knowledge, Dr. Nirenberg and his colleagues set about trying to figure out which three-base combinations represented each amino acid. It was known at the time that DNA is “transcribed” into a template RNA that interacts with ribosomes in the cell to produce proteins. Because RNA, not DNA, is what the cell reads directly to make proteins, Dr. Nirenberg reasoned that he could use a man-made stand-in for RNA that had a repeating known sequence (the same codon over and over) to produce proteins consisting of only one amino acid.
These stand-ins were known as “oligonucleotides” (see object 2001.0023.02). Using a cell-free system (one that has all the necessary parts for protein synthesis in a test tube rather than in a cell) Dr. Nirenberg introduced the oligonucleotides, consisting only of a single base, uracil, represented by U, over and over. This meant the only codon that could be read by the system was UUU or “poly-U.”
He then fed the system a supply of all 20 amino acids, one of which was radioactively labeled. Twenty different experiments were done, with only a single kind of amino acid radioactively labeled per experiment. Only when the cell was supplied with the radioactively labeled amino acid, phenylalanine, did the specially made poly-U oligonucleotide produce a radioactive protein. Nirenberg had demonstrated that the codon “UUU” is the code word for phenylalanine, and in doing so, he had cracked the first word in the genetic code.
Within five years, between the work of Nirenberg and that of several scientists using similar methods, the code for the remaining 63 codons would be understood.
The late 1960s were a time of rapid change in processes for cataloging and circulating books at the U.S. Library of Congress. Computers were introduced for preparing cataloging records for libraries across the nation and for tracking and distributing books sent out on interlibrary loan. This is one card used in the process. It relates to a volume entitled Apparatus and Experiment SD Int. by Weiss, which had call number QP461 W4 1916. It was checked out on 12-22-72 to Borrower OS500. A mark on the bottom edge of the card reads: HP/ECC-1294-0.
From the 1920s through the 1950s biologists and medical researchers made a concerted effort to solve the problem of tissue culture—how to raise and maintain cells for scientific research. Part of the challenge was to create a home outside the body in which cells could survive. At the National Cancer Institute, a team led by Wilton Earle (1902–1964) used tissue culture to study the process by which normal cells become cancerous. Earle, along with researchers Katherine Sanford, Virginia Evans, and Gwendolyn Likely, worked to develop proper nutrition—through a specially formulated broth—for cells grown in culture.
Cells required the broth to be changed regularly, necessitating the scientists to first remove the old broth. Researchers realized, however, that the floating cells were often removed along with the old broth. To address this problem, Earle developed a new kind of flask in which to grow the cells. The so called T-flask (named for the glass tubing from which it was blown), could be centrifuged prior to changing broth. Doing so trapped cells in the conical end, preventing them from being sucked out with the old broth.
This objects were used in Dr. Wilton Earle’s (1902–1964) laboratory at the National Cancer Institute. Earle joined NCI in 1937 and served as head of its Tissue Culture Section from 1946 to 1964. He and his researchers were pioneers in the use of tissue culture for cancer research.
Sources:
Lyons, Michele, and Jr. Museum of Medical Research DeWitt Stetten. Seventy Acres of Science the National Institutes of Health Moves to Bethesda. Bethesda: Office of NIH History, National Institutes of Health, 2006. http://history.nih.gov/research/downloads/70acresofscience2.pdf.
National Museum of American History Accession Files 1991.0071 & 1997.0139
Stetten, DeWitt, and W. T. Carrigan. NIH : An Account of Research in Its Laboratories and Clinics. Orlando: Academic Press, 1984. http://archive.org/details/nihaccountofrese00stet.
