Memo to Files from R G Humphries, Subject: Research Contract at-(40-1)-233 with Tulane University

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TAL MIREDCENT, entered into this m day-of menta), represented herein by the UNITED STAm ATOMIC WWOY COMMISSION sm3e ff ect ive as of February 6 , 1953, by and m,t h e bovernment and the Contractor entered into Contract lo. AT-(L0-1)-233, dated February 6, 1950, for the performance by the Contractor of a research project involviag a study of the turnover rote of chlorine under controlled dietary therapeutic cocdition8 in patients rrith congestive heart failure and in control subjects; and UH-, the contract has been amended heretofore by Modifim,t he parties desire to extend the tew of the contract in ‘order t o continue the study as herein irldicated; and WHEREAS, t h i s Supplemental Agreement is authorized by and executed under the Atomic Energy kt of 19b6; NOW, THEREFORE, the parties hereto do mutually agree that Contract No. AT-(LO-1’)-233, as heretofore modiPled, is further modified i n the following particulars, but i n no others: 1. Add the following new subsection d. t o Section 2 of ARTXCLE I - PURPOSE AND SCOPE: md. The work in the fourth period, i n addition to further study of data heretofore accumulated, rill consist of continued study of the turnover r a t e s of chlorine, potassium, sodium, rubidium and cesium under controlled dietary and therapeutic conditions In patient8 with congestive heart failure and i n control subjects a8 described in Title IV of Appendix * AI. ”

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2. Add the follouing new Section 3 t o ARTXCLE I1 - TWY OF "The fourth period of performance will commence on Febhary 6, 1953, and ell end on February 5 , 199.' 3. Add the following new subsection d. t o Section 1 of Rd. I n consideration of the performance of the work described In Title TV of Appendix 'A', the Government rill pay tothe Contractor the sum of Six Thousand Nine Hundred Fifty Dollars (16,950.00) for the fourth period of performance.' RECORDS AND INSPECTIOR: @&. Examination of Records. a. The Contractor agrees that the Comptroller & nerd of the United States o r &y of h i s duly authorized represent tlves shall,until the expiration of three years after final payment under this contract, have access t o and the right to examine any directly pertinent books, documenb, papen and recorda of the Contractor involving transactions related to b. ' h e Contractor further agrees t o include i n all his subcontracts hereunder a provision to the effect that the sut contractor agrees .that the ' Comptroller General of the United States o r any of his duly authorized representatives 6hall, until the expiration of three years after final payment undei this contract (Irith the Government, have access t o and the right to examine aqy directly pertinent books, documents, papers, and records of such subcontractor involving transactions related to the subcontract. used herein does n o t include (i) purchase orders not exceedir. $500, or(ii)contracts or purchase orders for public utility aervlces at rates established for uniform applicability to the general public. an audit by t h e General Accounting Office of any transaction Tne term subcontract as C. Nothing in this contract shall be deemed t o preclude

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5. Add the following new TITLE I V t o Appendix "An: with chronic congestive heart failure and i n control subjects are continuing. life and the rapid dlsappe erythrocytes have been determined. has been shown t h a t Cis, RbB6 and Ha2! exchange among several compartments in the body, t h e rates of exchange varying from time t o time, To date t h e biologic halfance rates of the isotope from t h e plasma and of Rbtt; from whole blood and rates have been calculated. From the xperlmemts it 'Studies on the transfer of these isotopes into and out of erythrocytes i n Vitro have progressed satisfactorily. Some of the data have been submitted f o r publication and others are being prepared for publication. Grperimenta are i n progress In do swith the use of alone and i n t o the heart muscle of the dog as well BS other 0 l . g ~ and also to determine further the adequacy of Rba6 a8 simultaneously with KE2 t o learn the transfer rates "b. Scope and Plan of Approach "It is planned to continue the observations of t h e including a study of blister surfaces produced on the forearm with cantharides plaster and isolated by plaster thus produced will permit observation of these compartmental exchange phenomena across a membrane i n man which is readily acceibible, will be employed i n normal and abnormal etates. The small, fairly unifoxm isolated compartments 2he Contractor will furnish as its contribution t o

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(1) Salaries of staff members, including the Project Leader, and other personnel engaged i n the work in excesE of t h e Governsentls contribution under b. below. ( 2 ) Use of laboratory work space; and equipment, materials, and supplies needed for the pro3ect In excess of the Government's payment under b. below. ( 3) All clerical, administ rat ive and overhead costs 9b. The Government will pay t o the Contractor the sum of Sir Thousand Nine Hundred Fifty Dollars ($6,950.00) which will cover the Contractor Is other expenses, os timated aa followa, i n the performance of the contract during the (1) Salaries and Wages Remaining from third period , 50.00 "c. Items of property procured or manufactured by the Contractor, title to which ell vest i n the Goverwent 6. Delete the faurth sentence of paragraph a., Section 3 - OF INFO W TION of Appendh RB", and substitute therefor the

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"The Contractor agrees t h a t It rill not penrdt any individual to have access to restricted data until the designated investigating agency shall have made an investigation and report t o the Commission on t h e character, associations, and loyalty of such individual and the Commission shall have determined that permitt;ng such person t o have access to restricted data will not endanger t h e common defense or security. b used inthe paragraph the tern means the United States Civil Service Commission or the Federal Bureau of Investigation, or both, as detennined pursuant to the provision3 of t h e Atomic Energy Act of 1946, as amenhd by t h e Act of April5, 1952, Public Law 298, 82nd Congress, 66 Stat. &3.= I N WITNESS WEREOF, the parties hereto have executed this Supplemental Agreement the day and year first above written. 2222 mlirbon SI. TITLE: ---(Address) ACCEPTUCB BY PRNECT LEADER I have read the foregoing Supplemental Agreement and agree t o be bound by i t s terns.

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NHHWS, the Gove ~ a m ~ ba d the Zontrestor entered into ConIEBBEASO the contract k s bsen amecded' heretofore by bbctfficaticn ' l e Add the fcllcming new subzection 0. to section 2 of '%.The mrk in the third period, in addition t o oontinued Study Of data a co mls ted h th8 sec

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"The third period of performance n i l l cameme on 3. Add the f oll ming ueu oubsection C.to section1 of UTInc . In considerntion of the performanoe of the work desoribed in Title 111 of Appendix lAQ, the Oovernment rill pap tothe contractor the rwn o f &ne Thousand h e Hudrod Eighty Dollars ($9,180.00) for the t h i r d period of per4. Add thb toll m hg TITU 111 t o Appendix "A"; ne. Preaept Statu FGW human experiments have been conducted over a six-reek period of continuous observance, hriog whioh time the dietary intake of sodium, chlorine rad potassium u a s known. The urine and faoes were collected separately a8 passed, and blood samples were collected eaah nort o r determhations of 80dium, potasaiurn, chloride aad Rb86 i n the urine, whole blood and erythroc . The tions were conducted a8 tr0 separate experiments, one as a pilot study on a control subject, and another consisting of simultaneous observations on a control subject nnd two patients with chronic congestive heart failure. The data from these exprlmontr rill be examined critically not only to loam I A e turn mer rate of CdM and speoimens of feces were studied only for Rb@ a. The oboervpScope and Plan of Approach The data oollected from these experiments w i l l be studied and cdr experiment8 rill be conducted usi

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per dt ting a tracing of a11 three simultaneously. m d ab86 will be in j so ted rimultaneously i n order t o trace th9 elemnts had i at ely and for s9vera.l hourr t o one or tw:, days afternards OP the phjrsical decay of d2 upon the aocuracy of count iq X?2. It i s hoped tro these exprime sto determi- more depending upon the influence In addition experiment8 rill be contimed t o tram jhloride and sodium in red c e l l o aad in the therms1 meat of man. Studies will a160 be made of diffusion of libs6 md acroas blister surfaces of skin of man, blisters being mode are =de on ths Ma, g, and Cl concentrations i n the b li ater fluid e n d blood serum. (1) Salaries of staft members, includhg the Project Lsader, and other perronnel engaged in the work in ex ces ~ of the OoverllpLBnt'a oootrlbutian under b. below, (2) Use of laboratory work apace; and equipmmt, materiala, and rupplies needad i z r %he project in excesr of the (3)All clar i col,add do tra tire and overhead costa i n *b. T b Government rill pay t o the Contractor the sum of B i n s Thoueand 0118Hundred Eighty Dollars ()9,180.00) rrhloh will the performance of the oontract during the third period: (1) Salaries and Ruee already trained, to be anployed during the course of metabolio

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“a. Items of. property procured or manufactured by t h e ConBY: UHITZD STATES ATOMIC EWRGY CCUIS32(iN BY: s/ Clarence Scheps

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Nm, THEREFORE, the pmtIe8 hereto do mutually hgrer that - sad Contraot No, AT-(&011)-233 18 modiiied in the following per ti alarm, but in no othem: L Add the fol.&.rring new subscotion b to Section 2 of rrtudy of the turnover rata6 of chlorine and mbidium under controlled dietary and therapeutic conditio- in patients with chronic congestive heart failure and i n control subjects, an described in Ti* zf of Appendix ARTICLE 1 - PURPOSE AND SCOPE:

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2. Add t h e fouorrlng Section 2 to ARTICLE U - TERY OF “2. The second period of performance for the progee covered by this contract rill cammencd on Fsb ru q 6, 1951, and rill and on February 5 , 1952.m 3. Add the folloring subsection b to Section 1 of mb, In consideratian of tho perforrmnco of tbs work described h nt’L. If of Appendix ‘ A ’ the Oovarnumnt rill pay to the Contractor the pun of Hino Thclurpad One Hundred Ligtrty D0ll.n ($9,180.00) for theseeond

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problems related to tropical and subtropical environment aa well m to nornal end abnormal water and tltctrPlytc metabolbm and to the pie sent pnparotiom for atomic warfare is %e influence of chloride intake in the dirt upon these biologic decay rates of chloride w a s measured. The influence af Na, K, watm, bicarbonate, broddo, cortiaons, m d other oganb upon the biologic decay rater of chloridm was a h o dotennineti. Senam rzld urine 3oc!lum, potasslu, and ohlorlde u well aa radioahloride m m llsvund r ~ ~ ly. VariatloM in the chrorida oorrpuctrocrrt o f .ID and the* influence OD the aforramttbned factor8 m d variables were reo0rd.d. Tho d q t h o relative accuraq of tho roriow nethods of seaswing chloride oomputiprata wen Now that infunnation fa avallabla on the biologic dsocy rater of 80diu~. nyroury and chloride for =mal m a and for patients dth chronic congestive heart frihm, thr project will approach the Mologlo bay periods of potamfun Q mans of rrdiombidfwn and ulll reek to thrw light upan the kccuracy dth which this isotope traces pofaaulrup. Penalsalon ha3 already been obtained f m m the Suboormpittee on Human App li cat lo ~to stody n m with radiorubidium for the first -. It is tho opinion of mst phyaiologlata and cheapista that ~ Mdlum tenda to follow potassium in I t a nstabollc behavior, although recently it haa been mggtrttd that it nay follow calcium. Ihe proJect rill bo interested in studying tb turnover of potassium in the bo* of normal nun rrd o patients dth half - life that It l a not suitable for mch dim& obsematlon, kdiombidium night be qued for such patienta d t h congestive heart fallure and observe them thmugb vpFI~\wstage8 of the syndrom a l e slmltaneausly observing control rrubjcck without failure or edema. During the course of these observotiona under conditlom for rpskbolfc study, the intake of ordinary Na, C1, K ud water RIUbe congestive heart fail-, but K&2 haa ruch a rhort

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influence of agacta known t o vary I[ metabolism md txcmtion rate will oe cbscrved, for exanplc, the intltieiice of administering large diuretics will be ix lude d among the agents. *ch a study uil3 be conducted continuously until the injecteta aateriil. reaches levtb in the bow too low to be counted accurately, Initially, when injeeticm is made, the rapid transfer of radiombidium out of the blood will be observed in order to obtain the pattern of the concentration-the course curyea. Subjeck will b mkuned to t h e mstaboUc beds for the proconcepts devdopcd iroa the 8tudiw riwl radiounderatanding of rabidium ln stab ok and rate41 of tumover but, when correlated rith the r5mult.neous nrsurements of ordinmy poturiun, will d.80 indica tha IccuTQq with rhieh radiorubidium traces potassiua in tho body of aimo Thero rhdio rhould be of v a u o la mderutanding potassium metabolitm in diseased and n o d OM Applications o f various theoretie b applied, T h e m 8eUdios all aid not only In tho a. The Contractor dll furnish aa I t a contributioa (I) S alu iea of atdf mtmbem, including the Project krdrr, engaged in the work, except ( 2 ) h a of all necessary laboratory ro& space ead equipment on hand. other general and administrative typo coats, in excess of the overhead rUmw pmvided " b o Tha Oovrment will pay to tht Contractor the burp of Nina Thouand Uns Hundred Bghty Dollars other expenses esti ~ & ~ d95 follem, in tho perfomanca of the contract during the second

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otbt supplica, and ACCEPTANCE BY PROJECT IEADERa I have read the foregoing Supplomentol Agreement and agree bs bound

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- I . .a. On o r before the date of com..enceximt of work on t h e project described n Aioendix “ Aep the Government sLal’l ;uy to the Contra ot or, upcrn 6ubniseion by the Contractor of a …