combination of gas chromatography, and molecular spectroscopy, they have identified and confirmed the presence of glycine, alanine, valine, proline, glutamic acid, 2-methylalanine, and sarcosine. "The presence of almost equal amounts of the D and L enantiomers of valine, proline, alanine, and glutamic acid minimizes the possibility of terrestrial contamination from biological sources in which only the L-form occurs," Dr. Ponnamperuma points out. Further bolstering this contention and pointing to an abiogenic mode of origin is the presence of 2-methylalanine and sarcosine, nonproteinaceous amino acids not generally found in biological systems but occurring among the products of lab experiments.
SICKLE CELL ANEMIA:
Successful Treatment Sickle cell anemia—a disease as common as such highly publicized maladies as cystic fibrosis, muscular dystrophy, and acute childhood leukemia, and typically just as fatal—can now be successfully diagnosed and treated as the result of research conducted under the leadership of Dr. Robert M. Nalbandian, associate pathologist at Blodgett Memorial Hospital, Grand Rapids, Mich. The disease is characterized by aching joints and swollen extremities. "All of our discoveries have a molec-
ular basis," Dr. Nalbandian emphasizes, and stem from the hypothesis for the molecular mechanism of sickling put forth by Dr. Makio Murayama, research biochemist at National Institutes of Health, Bethesda, Md. Sickle cell anemia occurs almost exclusively in Negroes and at a rate in the U.S. of about 0.25%. The disease is usually fatal with almost none of its victims living past his 40th birthday. Very few whites are struck by the disease, which is genetically based. Dr. Murayama's work, which opened the way for the treatment devised by Dr. Nalbandian and his associates at Wayne State University, Detroit, and the U.S. Army Medical Research Laboratory, Fort Knox, Ky., dealt directly with the molecular structure of hemoglobin S, the red blood cell molecule involved in sickle cell anemia. In hemoglobin S, the amino acid valine is substituted for glutamic acid in the beta chains. Dr. Murayama constructed a model of the hemoglobin molecule and showed that the number 1 and number 6 valines form a hydrophobic bond at the end of each beta chain. These combining sites, one on each beta chain, are attached to reciprocal combining sites on the alpha globins of adjacent hemoglobin tetramers. These tetramers then polymerize forming a microfilament, and six such microfilaments form microcables of sickled hemoglobin.
THE CHEMICAL WORLD THIS WEEK
The simple, specific, and inexpensive diagnostic test and the treatment devised by Dr. Nalbandian's group are based completely on this theory. Hydrophobic bonds, such as those at the beta-chain combining sites, can be destroyed by intrusion of linear hydrocarbons, pressure effects, or changes in temperature. Urea, Dr. Nalbandian knew, will denature such hydrophobic bonds, and thus the technique of intravenous injection of urea in an osmotically balanced solution of invert sugar was developed to treat sickle cell crisis—a period of excruciating pain brought on by periodic blockage of small vessels by the crescent-shaped sickled cells.
REACTION MECHANISMS:
Molecular Narcissism New terms continue to pop up as theoretical chemists delve further into complexities of organic reaction mechanisms. Spatial symmetry turned up in studies of geometrical isomerization of cyclopropane that are under way by Dr. Lionel Salem and his associates at the Laboratorie de Chimie Theorique in Orsay, France. The studies led to his identification of "narcissistic" reactions. In another area of reaction mechanism research, favoritism in compet-
Great Salt Lake Starts $30 Million Pond-Plant Complex After eight years of research, testing, engineering, construction, political problems, and capital investment of about $30 million, Great Salt Lake Minerals & Chemicals Corp. (GSL) officially started up its 14,000-acre evaporation pond and plant complex for extraction of minerals last week on the east shore of the Great Salt Lake near Ogden, Utah. The giant solar evaporation installation—largest of its kind in the world, according to GSL—will have initial annual capacities of 240,000 tons of potassium sulfate, 150,000 tons of sodium sulfate, and 100,000 tons of anhydrous
magnesium chloride. Magnesium chloride, recovered from bitterns (liquids remaining after feed salts for potassium and sodium sulfate are produced from the lake's brines), will be produced as a high-quality hexahydrate crystal called Bischofite in a separate GSL multimillion-dollar facility slated to come on stream at the end of 1971. Sufficient bitterns are available to produce between 400,000 and 600,000 tons of anhydrous magnesium chloride annually, GSL says. Refined magnesium chloride may eventually be shipped to a $20 million plant being built by Dow in Dallesport, Wash. DEC. 7, 1970 C&EN 17
ing cycloadditions produces significantly more of one of the many possible thermally allowed pericyclic products, finds Dr. K. N. Houk of Louisiana State University, Baton Rouge. This selectivity in the reaction has caused him to coin the term "periselective" for these cycloadditions. Narcissistic reactions are those in which reactants and products are mirror images with respect to a fixed plane, Dr. Salem told the Symposium on New Developments in Concerted Reaction Processes held at the Quinquennial Southeast-Southwest Regional Meeting of ACS in New Orleans, La. A restriction exists in that at least one coordinate involved in the reaction be antisymmetric with respect to the mirror plane. The narcissistic definition covers all reactions which are equivalent to reflection, while excluding those reactions which are equivalent to reflection plus rotation, Dr. Salem says. The important question which must be answered concerning those reactions—many of which, such as racemization, are familiar to organic chemists—is whether or not the halfway point along the reaction path has a mirror-plane of symmetry. Knowing the physical difference between pathways which go "through" the mirror and those which go "around" it can have various uses. In Dr. Salem's work, the main application is in calculating the structure of the reaction midpoint, which can be expected to be quite close to that of the transition state. Such calculations have led to his elucidation of the structure of two trimethylene diradical entities resulting from the stretching of one carbon-carbon bond in cyclopropane and the twisting of methylene groups. More recently his group has discovered a third diradical structure whose striking feature is the collapse of the face-to-face terminal methylene groups toward each other. In periselective cycloadditions, three factors determine the relative energies of the transition states and, in turn, the predominating products of competing reactions, Dr. Houk says. Most important is orbital symmetry. Only if a total of (4n -+- 2) ?r electrons are present in the closed loop of atoms undergoing cycloaddition will the reaction be thermally allowed. The work of Dr. Houk and his associates has led to potential development of general synthetic routes to new classes of compounds using concerted cycloadditions of the 6TT electron system of the fulvenes and ( 6 + 4 ) 1,3-dipolar cycloadditions. Among examples from the work, supported by the Petroleum Research Fund and Research Corp., are new azulene and azulene heteroanalog syntheses. 18
C & E N DEC. 7, 1970
LIFE SCIENCES:
$500 million (normalized to 1956 purchasing power), or diminished (see graph). The present pause in funding, the committee says, should be used to plan a complete system of support for the future, to replace the present haphazard patchwork with an orderly continuum. Special emphasis should be given to continued training of graduate students, "even, if necessary, at the expense of basic research," the report says. The main recommendations of the report include: • Establishment of a funding program for the Department of Agriculture similar to that of the National Institutes of Health, with particular emphasis given to nonagricultural departments and schools. • Greatly increased federal support for graduate and professional schools; bloc grants to supplement faculty salaries and a 50% increase in funds for postdoctorals within four years. • Increased availability of traineeships for graduate students—initially requiring a doubled appropriation within five years—and an eventual shift to full support of graduate students through stipends.
Federal Support Needed The Federal Government should support life sciences on a scale commensurate with national aspirations to understand more about the nature of man, of all life, of fatal diseases, and of our complex environment. That is the essence of "The Life Sciences," a comprehensive report on the status of academic research and education issued last week by the National Academy of Sciences. The exhaustive survey is the result of a four-year study by the committee on research in the life sciences of the committee on science and public policy, an affiliate of NAS. The conclusions are based primarily on responses to questionnaires distributed to nearly 26,000 life scientists (55% of whom responded). The report indicates that U.S. biomedical enterprise has been a unique and highly successful endeavor, and that basic research in the life sciences is a prime national purpose in itself. The report also notes, in contrast, that 1970 is the fourth consecutive fiscal year in which support for this research has either remained at a level of about
Most agencies have reduced research support in the life sciences bU r
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