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36-583: Tricresyl phosphate (TCP) and other gasoline additives were developed at Emeryville. Tar sands extraction and other techniques to increase oil reserves were studied at bench scale and in pilot plants. Shell Development also pioneered de-sulfurization methods and standards for gasoline and motor oil, which were significant in reducing acid rain and other adverse environmental effects of auto exhaust gases. Shell Development scientist Thomas Schatzky also pioneered fingerprinting techniques to identify oil spills' origins. Shell Development Emeryville scientists created

72-681: A plasticizer in manufacturing for lacquers and varnishes and vinyl plastics and as an antiwear additive in lubricants. Pure tricresyl phosphate is a colourless, viscous liquid, although commercial samples are typically yellow. It is virtually insoluble in water, but easily soluble in organic solvents like toluene , hexane , and diethyl ether among others. It was synthesized by Alexander Williamson in 1854 upon reacting phosphorus pentachloride with cresol (a mixture of para-, ortho-, and meta- isomers of methylphenol), though today's manufacturers can prepare TCP by mixing cresol with phosphorus oxychloride or phosphoric acid as well. TCP, especially

108-521: A Nobel prize was awarded in 1963. Shell Development also pioneered a class of materials called block copolymers , useful for medical applications such as artificial heart valves . Shell Development had significant capital assets and technical resources, including a cyclotron , an early and long-running electron microscope facility, an elaborate radiation laboratory (whose facilities became Veedercrest Winery), and other then-advanced scientific tools. Shell Development Emeryville made many contributions to

144-401: A Shell Development scientist who contributed funding to their musical venture. Unionized, with a comfortable work pace, elaborate medical benefits for employees, a company-paid lifetime retirement plan and almost-ironclad job security, Shell Development for decades provided the comforts of a socialistic work environment within a corporate giant of capitalism. Because of competitive disadvantages

180-498: A considerable fraction of its investments to produce and test the drug. The company's CEO resigned six weeks later, and patent rights to the PCR process were sold to Hoffman-La Roche . Losses continued, and in 1991 the company was sold to Chiron Corporation . Chiron continued the development of IL-2, which was finally approved by the FDA in 1992. Chiron also collected the scattered rights for

216-518: A manufacturer of Ginger Jake added Lindol—a compound that consisted mainly of TOCP—to their product. The exact reason for why TOCP was found in Ginger Jake is disputed; one source claims it was to further extract the Jamaica root, another source claims it was to water the drink down, and yet another source claims it was a result of contamination from lubricating oils. Binges of Ginger Jake resulted in what

252-466: A marina restaurant nearby. Citing uninterrupted recordkeeping among the surviving employees, a spokesperson reported that somewhat less than half of the known employees from Shell Development were still alive in late 2006. Meetings were finally suspended in 2007. Shell Development's facilities languished briefly following its 1972 departure from its Emeryville campus. The properties then became an early home of biotechnology pioneers Cetus and Chiron . In

288-560: A principal component of most tires since World War II. After natural rubber from rubber trees was made unavailable by the Japanese conquest of Southeast Asia, SBR provided a new material for tires for the Allies' military vehicles. Shell's Charles Wilcoxen later demonstrated the kinetics of the polymerization process, amending the assumptions of the Ziegler-Natta polymerization equations for which

324-416: Is mainly excreted through urine and feces, it is partially metabolized by the hepatic cytochrome P450 system. Pathways include hydroxylation at one or more methyl groups, dearylation (removal of a o-cresyl group) and conversion of the hydroxymethyl groups to an aldehyde or a carboxylic acid . The first step results in a saligenin cyclic o-tolyl phosphate ( SCOTP ) intermediate , a neurotoxin . To

360-407: Is not irritating to the gastric mucous membranes. When creosote is combined with phosphoric acid the metabolic action produced is much more marked, and Phosote can be tolerated in larger doses and for a longer continuance than Creosote or Guaiacol. Dose of the preparation, one to two grammes three times a day. The greatest mass poisoning by TOCP occurred in 1930 when it was added as an adulterant to

396-482: Is not possible to establish a safe level of exposure" and "TOCP are therefore considered major hazards to human health." Therefore, strenuous efforts have been made to reduce the content of the ortho isomers in commercial TCP if there is a risk of human exposure. However, researchers at the University of Washington found that non- ortho TCP isomers present in synthetic jet engine oils do inhibit certain enzymes. TCP

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432-537: Is the name given to the alleged ill effects (with symptoms including memory loss , depression and schizophrenia ) caused by exposure to engine chemicals. However, industry-funded studies in the UK discussed in 1999–2000 did not find a link between TCP and long-term health problems. In studies on slow lorises ( Nyticebus coucang coucang ), numerous chronic effects observed from topical applications. Mammalian placental development were also negatively affected. Although TOCP

468-428: Is uncommon in acute exposure cases, the result of paralysis can last for months or years due to differences in gender, age, and route of exposure. The cardinal treatment is physical therapy to restore the use of the hands and feet, though it can take up to 4 years to only regain a fraction of motor control. Exposure to TOCP has been characterized by a list of observations: Cetus Corporation Cetus Corporation

504-491: The epoxy resins and expanded their applications. In an early dramatization of the new material, Shell Development's team recorded and pressed a musical performance on epoxy resin rather than on vinyl. A classical harpsichordist who was the wife of a scientist performed. Epoxy / carbon fiber and other advanced composites were also pioneered there. Shell polymer scientists revised the scientific community's understanding of polymerization physics for styrene-butadiene rubber (SBR),

540-498: The immune system . In the early 1980s, an intense competition to clone the gene for IL-2 was underway among Cetus, Genentech , Immunex , and the Japanese researcher, Tadatsugu Taniguchi , and in 1982 Taniguchi was the first to succeed. By 1983 Cetus created a proprietary recombinant version of IL2 and collaborated with Steven Rosenberg to begin clinical trials . The drug showed promising effects in treating renal cancer , but also had significant side effects on patients. In 1990

576-427: The 21st century, many of the buildings of the former Shell Development campus are occupied by pharmaceutical giant Novartis . 37°50′03″N 122°17′19″W  /  37.8341°N 122.2886°W  / 37.8341; -122.2886 Tricresyl phosphate Tricresyl phosphate ( TCP ), is a mixture of three isomeric organophosphate compounds most notably used as a flame retardant . Other uses include as

612-482: The U.S. Food and Drug Administration (FDA) refused to approve the drug for clinical use, asking for additional information. It wasn't until two years later, after Cetus had been sold, that IL-2 was approved. It is now distributed under the name Proleukin . The company also had a broad effort to research and develop techniques for DNA diagnostics. Collaborations were made with Perkin-Elmer for diagnostic instruments, and with Kodak for commercial diagnostic kits. It

648-504: The U.S. space program, including development of rocket fuels, and handling techniques and storage methods for these highly explosive compounds. Shell Development's labs also contributed significant support to California-based land speed record holder Craig Breedlove and the Spirit of America vehicles. The American Chemical Society 's archives refer to Shell Development as one of a small number of large, pre-eminent private research facilities on

684-632: The West Coast. Shell scientists served as presidents and other officers of ACS during the decades when the facility was in operation. Though self-identified as a conservative employer, many Shell scientists were politically progressive, championing causes such as the Sierra Club and no-growth economic strategies. Country Joe and the Fish, a '60's anti-war counterculture rock band, dedicated an early album to Martin Dimbat,

720-425: The abortion-inducing (abortifacient) drug apiol . This drug, formed by the phenylpropanoid compound extracted from parsley leaves, was exploited throughout history—and even known to Hippocrates —as an agent to terminate pregnancies. The contamination of the modern drug in 1932 was not accidental, but rather included as an "additional stimulus." Those who took the pill experienced comas, convulsions, paralysis of

756-590: The all-ortho isomer, is the causative agent in a number of acute poisonings. Its chronic toxicity is also of concern. The ortho-isomer is rarely used on its own outside of laboratory studies that require isomeric purity, due to its extremely toxic nature, and is generally excluded from commercial products where TCP is involved. The most dangerous isomers are considered to be those containing ortho isomers, such as tri- ortho -cresyl phosphate, TOCP. The World Health Organization stated in 1990 that "Because of considerable variation among individuals in sensitivity to TOCP, it

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792-416: The company would experience if employees could publish freely, Shell Development scientists often experienced the minimal professional recognition compared to scientists in academia. Shell Development's senior scientific ranks included scientists who had been graduate students of Glenn Seaborg, a Berkeley scientist who pioneered techniques to create and verify transuranium elements. Shell Development also bore

828-423: The enzyme in nerve synapses can be lethal. The enzyme plays a tantamount role in terminating nerve impulse transmission "by hydrolyzing the neurotransmitter acetylcholine." Upon inactivation, acetylcholine can no longer be broken down in the body and results in uncontrollable muscle spasms, paralyzed breathing ( bradycardia ), convulsions, and/or death. Luckily, TOCP is considered a weak AChE inhibitor. In humans,

864-584: The first symptoms are weakness/paralysis of the hands and feet on both sides of the body due to damage to the peripheral nervous system ( polyneuropathy ) and a sensation of pins-and-needles ( paresthesia ). Onset typically occurs between 3–28 days from initial exposure. If ingested, this can be preceded by gastrointestinal symptoms that include nausea, vomiting, and diarrhea. Rates of metabolism vary by species and by individual; some people developed severe polyneuropathy after ingesting 0.15g of TOCP, whereas others have been reported asymptomatic after 1-2g. Though death

900-573: The formation of SCOTP, the interactions between TOCP and two different human cytochrome P450 complexes (1A2 and 3A4) can further produce 2-( ortho -cresyl)-4 H -1,2,3-benzodioxaphosphoran-2-one ( CBDP ). This metabolite can bind to butyrylcholinesterase (BuChE) and/or acetylcholinesterase (AChE). Binding to BuChE results in no adverse effects, for its typical role is to covalently bind to organophosphate poisons and detoxify them by inactivation. The dangers in metabolizing TOCP to CBDP occur when its potential to bind to AChE become imminent, for inactivation of

936-623: The indirect imprint of Robert Oppenheimer, director of the Manhattan Project. Manhattan Project alumni worked at Shell / Emeryville, and Oppenheimer himself is asserted to have been an offstage force in unionizing parts of Shell Development's workforce. After Shell Oil dissolved the Shell Development / Emeryville organization and decommissioned its facilities, its employee culture proved robust. For over forty years after Shell Development ceased to exist, employees continued monthly meetings at

972-411: The late 1970s, however, three new revolutionary techniques had been developed: recombinant DNA , monoclonal antibodies , and gene expression , the foundations of the biotechnology industry. In order to enter these new fields, Cetus raised $ 108 million in an initial public offering (IPO) in 1981, the largest IPO to that date. Its first large development project, in conjunction with Triton Biosciences,

1008-441: The lower body (paraplegia) and often death. Apiol was subsequently criticized by doctors, journalists, and activists until it was discontinued, citing that the dangers were too great and the number of poisonings was likely higher than accounted for. Other mass poisonings include: TCP is used as an additive in turbine engine oil and can potentially contaminate an airliner cabin via a bleed air " fume event ". Aerotoxic syndrome

1044-578: The para- and meta- isomers of TCP due to the lack of neurotoxic potential within these isomers. The earliest known mass poisoning event by TOCP occurred in 1899 when six French hospital patients were given a phosphocresote cough mixture containing the organophosphate compound. Pharmacist Jules Brissonet had synthesized this compound in the hopes of treating tuberculosis , but soon after administration all six patients developed polyneuropathy . The original paper described this phosphocresote to be: A bland, limpid liquid, nearly tasteless and odourless, which

1080-657: The popular drink Jamaica ginger , also known as Ginger Jake, during the United States Prohibition era, when all alcoholic drinks had been outlawed by the Eighteenth Amendment to the United States Constitution . Jake was listed as a cure for "assorted ailments" in the U.S. Pharmocopoeia and thus easy to obtain; as it had a high alcohol content it was used as a way to obtain alcohol legally. Up to 100,000 people were poisoned and 5,000 paralyzed when

1116-428: The right, the first step of TOCP metabolism is depicted by means of chemical structures. This intermediate is able to inhibit neuropathy target esterase ( NTE ) and results in the classic organophosphate-induced delayed neuropathy ( OPIDN ). In tandem, TOCP exerts physical damage by causing axon al destruction and myelin disintegration within specialized cells that transmit nerve impulses ( neurons ). In addition to

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1152-537: Was here that the technique of polymerase chain reaction (PCR) DNA amplification was conceived by Kary Mullis . The technique has been widely used in DNA research , forensics , and genetic disease diagnostics. Its inventor received the Nobel Prize in 1993, the only one awarded for research performed at a biotechnology company. The delay in FDA approval for IL-2 created a major funding crisis at Cetus, which had been spending

1188-498: Was known to be a "Jake walk", in which patients experienced a highly irregular gait caused by numbness in the legs, followed by eventual paralysis of the wrists and feet. In medical journals it was described to have produced an organophosphate-induced delayed neuropathy (OPIDN) neurodegenerative syndrome, "characterized by distal axonal lesions, ataxia, and neuronal degeneration in the spinal cord and peripheral nervous systems." In 1932, 60 European women experienced TOCP poisoning due to

1224-683: Was one of the first biotechnology companies. It was established in Berkeley, California , in 1971, but conducted most of its operations in nearby Emeryville . Before merging with Chiron Corporation in 1991 (now a part of Novartis ), it developed several significant pharmaceutical drugs as well as a revolutionary DNA amplification technique. Cetus was founded in 1971 by Ronald E. Cape, Peter Farley, and Nobelist Donald A. Glaser . Its early efforts involved automated methods to select for industrial microorganisms that could produce greater amounts of chemical feedstocks, antibiotics, or vaccine components. By

1260-553: Was the source of a 1977 epidemic of acute polyneuropathy in Sri Lanka where 20 Tamil girls were poisoned by TCP-contaminated gingili oil . It is a toxic substance that causes neuropathy , paralysis in the hands and feet, and/or death for humans and animals alike. It can be ingested, inhaled, or even absorbed through the skin. Its ortho-isomer is notoriously known as a source of several delayed neurotoxic outbreaks across recent history. Contemporary commercial products typically contain only

1296-434: Was the successful cloning , expression, modification, and production of beta-interferon . Unfortunately, the resultant protein did not live up to its expectations as a broad-spectrum anti- cancer drug, and only much later was it approved for use to treat symptoms of multiple sclerosis . The product is now sold under the name Betaseron . The company's flagship product was Interleukin-2 (IL-2), an important modifier of

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