science: losing a friend

1
PHARMACOLOGY: Code Word of Memory Another chapter has been added to the story of memory with the an- nouncement from Dr. Georges Ungar of Baylor University medical school, Houston, Tex,, that he has determined the composition and sequence of amino acids of what may well be the first of many chemical code words that control memory and learning. The announcement came last week at the Western Pharmacology Society meet- ing in San Diego, Calif. Members of the Baylor research team include Dr. Ing-Kang, Dr. Dominic Desiderio, and Louis Galvan. The material, which comprises 14 amino acids, is probably the first mem- ber of a very important family of sub- stances which serve for the coding of acquired information in the central nervous system, according to Dr. Un- gar. He calls these materials chemi- cal code words of memory, which are analogous to the genetic code words that control heredity (C&EN, Nov. 3, 1969, page 43). Whether these memory code words act by labeling the neural pathways or achieve the registration of experi- ence in some other fashion, "the knowledge gotten will considerably enhance our understanding of the processing of information in the brain," says Dr. Ungar. From a phar- macological standpoint, the presence in the brain of substances such as this one points to the possibility of design- ing drugs with highly specific beha- vioral effects. Dr. Ungar proposes to call the tetra- decapeptide "scotophobin" (from the Greek skotos = dark, and phobos fear). It's isolated from brains of rats which have acquired a fear of the dark from being subjected to electric shock whenever they take refuge in the dark chamber of a three-compart- ment system. Activity of the material is confirmed by injecting untrained mice with brain extracts of trained rats. Brains of more than 3000 rats were used to get enough material. The Texas team homogenizes the brains and makes a crude RNA prep- aration from which the active material is dialyzed out at pH 3.7. The mix- ture obtained after these initial steps is submitted to gel filtration on Sepha- dex G 25 and is further fractionated using thin-layer chromatography. Using a microdansylation procedure (two-dimensional chromatography), the scientists find after acid hydrolysis the following amino acids: aspartic acid (ASP), asparagine (ASN), glu- tamic acid (GLU), glutamine (GLN), glycine (GLY), lysine (LYS), serine (SER), and tyrosine (TYR). The N- terminal group is serine. Dr. W. C. Starbuck performed a quantitative amino acid analysis which yielded the composition amounts of each amino acid. After incubation with trypsin, two fragments (T x and T 2 ) were obtained. T 1 contains GLY, GLU, GLN, ASN, ASP, SER, and LYS. T 2 contains GLY, GLN, SER, and TYR. The N-terminal group of both fragments is serine. Dr. Desiderio determined the se- quence of the amino acids by high- resolution mass spectrometry. The spectrum was taken on a CEC Model 21-110, which gives accurate masses of the fragments to ±0.003 mass unit. All possible sequential dipep- tides along the chain were found. Although this determination has only been performed once, Dr. Desiderio stresses that the "compositions are so unique that there is a good probabil- ity that the sequence we've proposed is correct." The structure of the peptide will be confirmed by separate synthesis and tested for its behavioral effect, says Dr. Ungar, to determine if the pep- tide is the correct one. $$of.§eui®. i : -comprises SER - 14-amirTO acids- I 2 ASP 5 4 3 GLU mm ASN ---1 ASN I 6 GLN I 7 8 9 GLY LYS "• SER 1 10 GLN 1 13 12 11 GLN mm GLY mm GLY ' l; 14 TYR i Connecticut's Daddario Response to home state SCIENCE: Losing a Friend Federally funded scientific research, already suffering from a general de- cline in popularity on Capitol Hill, could receive yet another heavy blow if Congressman Emilio Q. Daddario (D.-Conn.) responds to home state pressures and decides to run for governor or for a Senate seat in the 1970 elections. Speculation, active since the announcement shortly after the first of the year by Connecticut Gov. John Dempsey (D.) that he will not seek re-election, reached a peak last week as pressure mounted on the Congressman to make a decision by the middle of February. Rep. Daddario, currently serving his sixth term, is one of the scientific com- munity's most effective Congressional spokesmen. A charter member of the House Committee on Science and Astronautics, he has chaired the im- portant Science, Research, and Devel- opment Subcommittee since its estab- lishment in 1963. During his tenure, Rep. Daddario has championed vari- ous reforms to make scientific infor- mation and "state of the art" knowl- edge readily available to members of Congress who must vote on science and technology policy questions, as well as on research funding. He is concerned with scientific approaches to pollution control and the need for what he calls "technological assess- ment." The Connecticut Congressman is also being touted as the leading con- tender for the seat held by Sen. Thomas Dodd who has fallen into dis- favor with the state Democratic party. Rep. Daddario's departure would leave Rep. John Davis (D.-Ga.) as number one man on the subcommittee, but a final decision on his successor would be made by chairman George Miller of the full committee. FEB. 9, 1970 C&EN 11

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Page 1: SCIENCE: Losing a Friend

PHARMACOLOGY:

Code Word of Memory Another chapter has been added to the story of memory with the an­nouncement from Dr. Georges Ungar of Baylor University medical school, Houston, Tex,, that he has determined the composition and sequence of amino acids of what may well be the first of many chemical code words that control memory and learning. The announcement came last week at the Western Pharmacology Society meet­ing in San Diego, Calif. Members of the Baylor research team include Dr. Ing-Kang, Dr. Dominic Desiderio, and Louis Galvan.

The material, which comprises 14 amino acids, is probably the first mem­ber of a very important family of sub­stances which serve for the coding of acquired information in the central nervous system, according to Dr. Un­gar. He calls these materials chemi­cal code words of memory, which are analogous to the genetic code words that control heredity (C&EN, Nov. 3, 1969, page 43) .

Whether these memory code words act by labeling the neural pathways or achieve the registration of experi­ence in some other fashion, "the knowledge gotten will considerably enhance our understanding of the processing of information in the brain," says Dr. Ungar. From a phar­macological standpoint, the presence in the brain of substances such as this one points to the possibility of design­ing drugs with highly specific beha­vioral effects.

Dr. Ungar proposes to call the tetra-decapeptide "scotophobin" (from the Greek skotos = dark, and phobos — fear). It's isolated from brains of rats which have acquired a fear of the dark from being subjected to electric shock whenever they take refuge in the dark chamber of a three-compart­ment system. Activity of the material is confirmed by injecting untrained mice with brain extracts of trained rats. Brains of more than 3000 rats were used to get enough material.

The Texas team homogenizes the brains and makes a crude RNA prep­aration from which the active material is dialyzed out at pH 3.7. The mix­ture obtained after these initial steps is submitted to gel filtration on Sepha-dex G 25 and is further fractionated using thin-layer chromatography.

Using a microdansylation procedure (two-dimensional chromatography), the scientists find after acid hydrolysis the following amino acids: aspartic acid (ASP), asparagine (ASN), glu­tamic acid (GLU), glutamine (GLN), glycine (GLY), lysine (LYS), serine (SER), and tyrosine (TYR). The N-terminal group is serine.

Dr. W. C. Starbuck performed a quantitative amino acid analysis which yielded the composition amounts of each amino acid. After incubation with trypsin, two fragments (Tx and T2) were obtained. T1 contains GLY, GLU, GLN, ASN, ASP, SER, and LYS. T2 contains GLY, GLN, SER, and TYR. The N-terminal group of both fragments is serine.

Dr. Desiderio determined the se­quence of the amino acids by high-resolution mass spectrometry. The spectrum was taken on a CEC Model 21-110, which gives accurate masses of the fragments to ±0.003 mass unit. All possible sequential dipep-tides along the chain were found. Although this determination has only been performed once, Dr. Desiderio stresses that the "compositions are so unique that there is a good probabil­ity that the sequence we've proposed is correct."

The structure of the peptide will be confirmed by separate synthesis and tested for its behavioral effect, says Dr. Ungar, to determine if the pep­tide is the correct one.

$$of.§eui®. i : -comprises SER

- 14-amirTO acids- I 2 ASP

• 5 4 3

GLU mm ASN ---1 ASN

I 6 GLN

I 7 8 9

GLY — LYS "• SER

1 10 GLN

1 13 12 11 GLN mm GLY mm GLY

' l ;

14 TYR

i

Connecticut's Daddario

Response to home state

SCIENCE:

Losing a Friend Federally funded scientific research, already suffering from a general de­cline in popularity on Capitol Hill, could receive yet another heavy blow if Congressman Emilio Q. Daddario (D.-Conn.) responds to home state pressures and decides to run for governor or for a Senate seat in the 1970 elections. Speculation, active since the announcement shortly after the first of the year by Connecticut Gov. John Dempsey (D.) that he will not seek re-election, reached a peak last week as pressure mounted on the Congressman to make a decision by the middle of February.

Rep. Daddario, currently serving his sixth term, is one of the scientific com­munity's most effective Congressional spokesmen. A charter member of the House Committee on Science and Astronautics, he has chaired the im­portant Science, Research, and Devel­opment Subcommittee since its estab­lishment in 1963. During his tenure, Rep. Daddario has championed vari­ous reforms to make scientific infor­mation and "state of the art" knowl­edge readily available to members of Congress who must vote on science and technology policy questions, as well as on research funding. He is concerned with scientific approaches to pollution control and the need for what he calls "technological assess­ment."

The Connecticut Congressman is also being touted as the leading con­tender for the seat held by Sen. Thomas Dodd who has fallen into dis­favor with the state Democratic party.

Rep. Daddario's departure would leave Rep. John Davis (D.-Ga.) as number one man on the subcommittee, but a final decision on his successor would be made by chairman George Miller of the full committee.

FEB. 9, 1970 C&EN 11