SECTION I DEPARTMENT OF LEAVE BLANK (For PHS Office Use Only) HEALTH. EDUCATION, AND WELFARE Tet PROGRAM NOMBER pueliC HEALTH SERVICE 2 ROL BD 00045-03 : yas REVIEW GROUP FORMERLY ASD com se DC : APPLICATION FOR RESEARCH GRANT COUNCIL (Meath, Year) [DATE RECHVED | «June 66_. 1/3/66 APPLICANT CODE: "| @ COBE TO BE COMPLETED BY PRINCIPAL INVESTIGATOR (Usems £ through 9 and 17A) T ABBREVIATED TITLE OF RESEARCH PAOPOSAL (De wot exceed $3 typewriter «paces} Kindred Patterns (Mentally.Retarded; Control ) 2. TYPl OF APPUCATION (Check ona) : CD new morct 0 XEDORNEWaL oF pus Geant noHD=O0085 1D GEVISION OF PHS APPLICATION NO. (D) SUPPLEMENT TO PHS GRANT NO. 3. DATES OF ENTIRE PROPOSED PROJECT Peaioo 4. TOTAL AMOUNT REQUESTED 5. AMOUNT REQUESTED FOR HIRST : FOR PERIOD IN ITEM 3 12-MONTH PERIOD (This epplcation) : . FROM . THROUGH $ 256.014.- $ 83. 614.- June 1, 1966 May 31, 1969 ee 6A. NAME OF PRINCIPAL INVESTIGATOR {Last, Firet, Initial) n eA oed _— OF PRINCIPAL ENVESTIGATOR (Serees, Cay, Santa, . . Department of Genetics Lederberg, Joshua ae School of Medicine 9h 304 i DIG | © SOCIAL SCURITY.HO. D. TELEPHONE DATA Stanford University, Palo Alto,Cal ‘Ares Code | Telephone Number | 7A. IDENTITY ORGANIZATIONAL L LOMPONENT izspONGINE FOR CONDUCT OF SY Ph. 0. -| IS (3et-1200 504 ; © Title OF POSITION School of Medicine Ww - Professor and Executive Head . rg. DEPARTMENT ‘Department of Genetics Genetics Department et cheetah F. OEPARTMENT, SERVICE, LABORATORY O8 EQUIVALENT . 2. ADDRESS WHERE RESEARCH WILL BE CONDUCTED Gf same as izem aw {See -Insructions} chech bea} , Genetics Department G. MAJOR SUBDIVISION {See Instructions] ARE FEDERAL FACILITIES YO BE USED FOU THIS RESEARCH? : chool of Medi: School o ici ne. wo ves “oF run TO BE COMPLETED BY RESPONSIBLE ADMINISTRATIVE AUTHORITY firems 10 threugh 18 ead 173) 30. an Soar me [Name ond Addzess-Sireet, “ 2, TYPE o en {Check applicable sem) [_]} INDIVIDUAL Stanford University oe : FEDERAL STATE LOCAL om . Stanford, California 94304 a o [19s 0 . . PRIVATE INSTITUTION EG NONPROFTT, (J sont Ta. NAME AND TITLE OF OFFICIAL SIGNING FOR APPLICANT ORGANIZATION Earl G. L. Cilley 1. NAME TILE AND ADDRESS GF OFFICIAL TO WHOM CHECKS SHOUD Assistant Research Administrator BE JAAILED Mr. Kenneth D. Creighton, Controller TRIS ACCOUNT ROME TEL TSTADUSHED PHS INDIRECT COST BATE | Encina Hali, Stanford University _ (Bmser if (Emer known , Stanford, California 458210 20 « 1s. TERMS AND CONDITIONS. The undersigned accept, ss to any grant awarded, the obligation to comply with Public Health Ser-' vice Research Project Grant Regulations in effect at the time of the award (42 CFR, Part 52), the terms and conditions in the Grants for Research Projects Policy Statement, and the undersigned sgrce to comply with Title VI of the Civil Rights Act of 1964 (P.L. 88-352), and the Regulstion yssued pursuant thereto and state that our formally filed Assurance of Compliance with such Regulation (Form HEW-441) applies to this project. The undersigned also certify that they have no commitments or obligations, including those with respect to inventions, inconsistent with compliance with such Regulations, the Manval, and the Act. T. . A. SIGNSIQRE OF PERSON RAMMED IN i DATE . StanaTunes 0 SL ee ct (af2 of, Ss Wee ink. “Per” signatwres = or RG iw i, a 1 DATE - v WO. | (2/20 PHS-390 (REV. +65) - * (Ast 4 Form Approved © {All previews editions ebentete) Budget Bureau No. 68-2140 SECTION 1 OT FOR P' LEAVE BLANK - (Per office use only) NOT FOR PUBLICATION DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE baregoner samen OR PUBLICATION PUBLIC HEALTH SERVICE REFERENCE, RESEARCH OBJECTIVES ABBREVIATED TITLE OF PROJECT _ Kindred Patterns (Mentally Retarded; Control) eT Professor and Executive Head, Department of Genetics Assistant Professor, Department of Genetics no S.S. not yet) Res. Associate, Department of Genetics Joshua Lederberg Walter F, Bodmer Albert Jacquard NAME AND ADDRESS OF APPLICANT ORGANIZATION Stanford University Stanford California USE THIS SPACE TO MAKE A MOAD STATEMENT OF YOUS RESEARCH OBECTIVES . Census data will be acquired and tabulated that will allow the statistical analysis. of reproductive patterns - the temporal distribution of birth, marriage and birth of offspring (and number of offspring) - in relation to socio-economic variables. Similar data will be obtained on kindreds of mentally retarded patients in State institutions. Computer studies wil) be made to establish the optimum means of retrieval and presentation of complex data. Relationships to fertility, maternal age effects on infant performance, seasona) variations in birth incidence, and the extent of endogamous stratification in the samples of the U.S. population are expected, LEAVE BLANK-DO NOT WRITE BELOW THIS LINE PHS-298 (REV. 1-65) PAGE 2 Continuation page Hy a) C 9 Q a 5 0 3 } Research Plan and Supporting Data, including Progress Report: The first phase of this project is coterminus with the current funding, expiring May 31, 1966. This has consisted predominantly of the processing of the 1960 Census 5% Population Sample for a detailed report on child spacing. This work is being ‘ carried out in close cooperation with the Bureau of the Census. Technical operations in programming the data processing are carried out here at Stanford under the super- vision of Mr. William Buell, seconded from the Bureau. This has been a very satis- factory arrangement, as it reconciles needs for (a) control of confidentiality of the files, (b) the Bureau's interests in the detail of the report, (c) access by our staff to the summary data, (d) supervision for later research requirements of data ; reduction and preparation of summary files, and Ce) efficient communication with the Bureau staff on technical details. The main results of the first phase will be the mentioned report, to be published by the Bureau as a volume in its regular report series. Perhaps equally important as a research resource will be a summary file of manageable size (10-20 tapes) for more ieisurely and independent reevaluation of the data used in the report. We have main- tained a purposely hostile and critical attitude about every aspect of these data. The ultimate limitations of Census data have been stressed by the Bureau itself, and its quality control is a subject of considerable effort and review on its part. Several considerationslimit the value of these data for health research. 1.) Relevance of the questionnaire The most important gaps are (a) linkage to mortality and morbidity data and (b) family versus household data 2.) Precision of the responses; completeness of enumeration 3.) Techniques used to compensate for missing data. We can do little more than (sympathetically) deplore the first two items, but our final reports will attempt to evaluate these for a quantitative perspective on the quality of the data base. Item 3 offers a more tangible operational challenge. Historically, the Bureau has interpreted missing data on a pragmatic basis, so that its reports would return consistent figures for totals. The credibility of this procedure will vary according to the sample; unfortunately, the usual form of publi- cation makes it impossible to recover the original data for reevaluation. Since childspacing is an analysis of the relationships of specific individuals to one another, it is, of course, especially sensitive to biases in imputation. The alloca- tion of a suitable birthdate is a particularly critical procedure, now done by extrapolation from a totally inadequate sample base. Without interfering with the production of the conventional tables, we are therefore paying special attention to the preservation of the actual recorded data in the sum mary files. A concrete model for estimation is .appended. . : As indicated earlier, our main interests in the analysis of the completed data files | ares - . . PHS-998 (REV. 6-64) Pose sonen eal wp C0045 O03. | Continuation page a 1.) Fitting smmmathematical models of family structure 2.) A critical examination of the variance of fertility “* ‘sf. 3.) Seasonality of birth in relation to socio-economic and to other seasonal parameters (marriage; birth of siblings) The studies are the main objectives of the continuation of this research. They represent. the main commitment to population study in this department, and in this way serve indirectly for advanced research training of participating students and |fellows, whether or not listed in the formal roster (e.g., Drs. Sved, Kessler, and Mr. Fischer).‘ . ce, . . : One of the important uses of an ‘analysis of the variance of fertility is the estima- tion of the limits of the rate of natural selection in man. This was pointed out by Professor Crow some years ago, and has been the subject of considerable discussion since that time. The variance of fertility, however, includes a term of unknown magnitude for environmental effects which would play no part in the dynamics of gene frequencies in evolution. It is, however, very difficult to point to any attribute which is even reasonably free from genotypic influence. However, rank of birth within a family may be such an attribute, since the children within a kindred have, to a first approximation, the same expectation of genotype. A current population survey Wam covering some 39,000 families has provided some information for this pur- pose; a special study is obviously required covering at least two generations in order to assess any significant performance of individuals in relation to their birth rank. We were not able to find any gross effects of birth rank on fertility, or on general socio-economic performance. However, the effect of birth rank should not be considered only by itself, but also for its impact on the correlation between parent and offspring. As folklore would have predicted, and as the present data clearly show, at least in certain occupational categories, the firstborn tends to follow the parents' occupation, significantly more frequently than other members of the kindred. At least this was undeniably apparent for farmers and for professional occupations. The expected effect of rank of birth should then be to increase the apparent herit- ability for a number of traits without necessarily influencing the mean level of performance over all individuals of a given rank. In addition we have made some incursions into other data, such as the file from Pacific State Hospital. These patient files have now been completely coded and the last few data bugs are being weeded out. Some preliminary runs have been made, €.e, on kindreds of admissions for Down's syndrome. As Penrose had anticipated long ago, maternal age and not parity is a decisive etiological factor. We have found no support for the contention that impaired fertility and spontaneous abortion are pre- monitions of a trisomic birth. However, the control set has not been matched to the extent we intend before insisting on this conclusion. Further analysis of day~of-week effect on total births supports elective induction as the main culprit. The missing births (after holidays) appear on following days; we are waiting momentarily for some additional information in which the management of the delivery has been detailed to nail this down once and for all. Non-whites do not show this deficiency in weekend births. Perhaps surprisingly, however, there is no evidence, at least from mortality statistics, of any disadvantage to babies who insist on being born on inconvenient days from the standpoint of hospital routine. An earlier thought that this weekly birth cycle might be related to a conception _PHS-398 (REV. 6-64) Pope 4 Continuation page = TF | iH 5 Q 4 5 0 3 | ‘| eycle was a fantasy: the variance of gestation time would ‘have to be 2 - 3 days, rather than 15 to fit the distribution; also holidays are comparable to weekends. However, there is no factual information on conception statistics. Howbeit, no model can be quite complete without bate - A study of twin data has shown a surprising clustering in time of these statistics. They may well be artifacts, but we are in any event trying to sort out the time series of mono- and dizygotic types. Even as artifacts, these series may afford controls or cautions for the statistical treatment of current reports on clustering of chromosome abnormalities. The operational budget is intended to cover the statis-— tical analysis of the summary tapes. Our access to these and related background data will be facilitated by the renewal of our agreement with the Bureau of the Census for stationing a representative here and for furnishing various data files on a cost- reimbursement basis. We solicit the interest of other investigators in the summary tapes and will endeavor to assist their access to them, subject only to the recovery of added costs and Census Bureau policies on confidentiality. oo, In previous reports we have mentioned our expectations for real-time access to the data so that we could analyze these files on a conversational basis. We have so far implemented this only to a very limited extent, namely, a facility to permit scope display of the data tapes themselves on a local, readily available LINC computer. We had originally intended to program some routine statistical operations on the LINC, but have decided to postpone this in favor of work on a very much more powerful time- shared computer facility that is now planned for installation in the Medical School starting approximately June 1966. This facility, which will center on an IBM 360~—50 computer operated under a general time-sharing system, will be so mich more powerful than. the LINC that it would be a waste of effort to attempt to program the latter for the sake of the few months lead time. It will be necessary, however, to put together 4 rather sophisticated terminal to take full advantage of these capabilities. The financial arrangements for the Medical School computer are not yet fully erystal- lized. For that reason, the budget item of $15,000 computer time may be represented. in charges on exactly that basis, or may be reallocated to the lease or purchase of terminal equipment dedicated to the project. Our plans for this type of interroga- tion of statistical data have beén of some interest to the Bureau, and we remain in close contact about this. Until the new facilities are working smoothly, we will continue our data processing on the campus Computation Center's IBM 7090, and this will in any event require at least a portion of the budget for computer time. To anticipate a question that previous experience suggests will always be brought up, the computing services on this campus to which time charges are attached are already the subject of detailed audit by government agencies. The charges already include provision for overhead and are therefore excluded from the base for indirect cost allowances. PHS-398 (REV. 6-64) _ Pose 5 Ld CD “p> G1 Continuation page rl 3 t . ; APPENDIX Estimation of birth interval distributions for families with children absent from the home at the time of the census A major possible source of bias for family studies with census data arises from the fact that they are collected by the household rather than the family. Information on children who have left the household is missed, though the total number of chil ever born to each female is, of course, recorded. There are many socio-economic and cultural factors (including, for example, mental retardation) which are correlated with the age at which children leave the parental household. The average character- istics of families with all children present may, therefore, differ markedly from those with one or more children absent. It will, in practice, be impossible to con=_ trol (or perhaps even determine) all the variables which may influence such a bias. There may also be inherent ascertainment biases in the birth interval distributions obtained from such household data, which are not due to socio-economic and other stratifications. Thus if, for example, the age of the child were the main factor determining wher it leaves. a household, families from recently married couples with all children ever born present would be biased toward longer birth intervals. A preliminary attempt to determine the possible magnitude of such biases has been based on the construction of model populations having birth interval distributions corres- ponding to those observed in the August 1959 CPS, and incorporating various rules for when children leave the household. The indications, so far, are that these ascertains ment biases do not present a serious problem. There is, generally, from Census data, & conflict between obtaining information on the complete family and obtaining infor- mation from women whose fertility history is completed. There is an obvious need to try to obtain some information on the characteristics of the birth interval distributions for families with children missing from the house- hold. Following previous practice in analogous situations, the Census Bureau has suggested procedures for "allocating" information on missing children based on tables constructed from sample surveys (August 1959 CPS) which specifically provide informa- tion on the distribution of birth intervals for children absent from home. These are considered unsatisfactory for the following three main reasons: 1. The allocation distributions are based mostly on sub-classification only by race and marital status. A bias may thus be introduced when these allocations distribu- tions are used for more complex cross classifications such as will be required in the analysis of the 5% sample of the 1960 population census. 2. Many of the allocations are based on small numbers leading possibly to relatively large random errors when they are applied to a considerably larger body of data. , 3. There may be a bias in the source data for the allocation tables, for example, if these changed from the 1959 CPS to the 1960 population census. The allocation procedure actually combines data from complete families with the allo- cation distributions, which latter may be both biased and subject to relatively large random variation due to small numbers in the August 1959 CPS relative to the amount of information available from the 1960 census on the completed families. The con- founding of these two sources of information dilutes the value of the actual data from the completed families. , . We shall now outline formally a procedure for estimating birth intervals for families with children absent from home, using only the information contained in the 1960 population census. _ The estimation problem is considered for a given category, by which is meant a partic-— ular set of cross classifications (i.e., cells) for which child spacing distributions PHS-398 (REV. 6-64} - Page & 19 6G0045 03 11 Continuation page are desired. Thus, for example, we may be interested in these distributions for women classified by educational status, by age of marriage, and by epoch. To illus- trate the method we consider first the case of families with two children ever born. As indicated in Table I, there are four types of families according to which child is present or absent. Families of type 2 and 3 cannot be distinguished in the census data as collected. We thus observe directly only the quantitites pl], po.t P35 Pus the distribution of the interval from marriage to the first child and from the first child to the second child for completed families (type 1) and the distribution of the interval from marriage to the child which is present for families of types 2 and 3. Our concern in trying to obtain some estimate of the interval distributions for fam ilies of types 2 and 3 with one child missing is, of course, in case they differ sig- nificantly from those observed for the completed families. If this were the case, then these differences would have to be taken into account in describing the interval distributions for the particular category under consideration. It is clear that no information can be obtained on the interval distribution for families of type 4 where both childrén are missing. Possible biases introduced by using only data from the completed families will of course be minimized when the proportions po, P3> and ph are small. The observed distribution of the interval from marriage to the child present for families with one child missing will be a weighted combination of the distribution of the interval from marriage to the first child for families of type 2 and the dis- tribution of the interval from marriage to the birth of the second child for families of type 3. The latter is, in fact, the distribution of a “double” interval which, of course, would be expected to be appreciably longer than the corresponding distribu- | tion for a single interval. The observed distribution should therefore be bi-modal and its components resolvable by fitting a weighted mixture of two distributions describing in turn the expected distributions for the interval from marriage to the first child for families of type 2 and the interval from marriage to the second child for families of type 3. More specifically, if -fp,;(x) represents the expected dis- tribution of the interval from marriage to the first child for families of type 2 and F3(x) represents the probability density function for the distribution of the interval from marriage to a second child for families of type 3 then the expected probability density function for the interval from marriage to the child present for families with one child absent is given by : P2 fo, (x) + P3 F3(x) Po + P3 Po + p3 - Given a theoretical distributional form for birth intervals, i.e. for fo, (x) and F3(x), we can use standard statistical procedures, such as maximum likelihood, to fit this expected mixed distribution to the observed distribution. This will give estimates of the proportions po and p3 and of the parameters defining the distribu- tions fo; (x) and F3(x). We can then ask the question as to whether these distribu- tions differ significantly from the corresponding distributions observed for com— ~ pleted families (type 1), and so assess biases introduced by ignoring incomplete families. It is anticipated that some general two parameter distribution, for example, the gamma distribution or if necessary a three parameter distribution, possibly a modified gamma distribution, may turn out to be a suitable analytical. form for fitting birth interval distributions. It will in any case be important to choose the most appropriate theoretical distribution for fitting the observed. birth. interval distributions (see below). The general approach outlined above can easily be ‘extended to larger families. The — eight types of families for three children ever born are given. in Table TI. We ob- ‘serve data for completed families of type 1; for families with one child missing, namely the combination of families of types 2, 3 and 4; for families with 2 children missing, corresponding to the combination of families of types os 6 and TH and fin- PHS-398 (REV. 6-64) Poge ¥ / 2 [=p 15 03 1. fF ‘ 9 C0 woe Continuation page ally the proportion pg of families with all three children missing. For families with one child missing there are two observed interval distributions, namely the interval from marriage to the first child present, and the interval from the first child present to the second child present. If we write £3;(x), fh ,(x) and Fo(x) for the probability density functions of the interval from marriage to the first child for families of type 3 and type h and from marriage to the second child for families of type 2, respectively, then the expected probability density function for the distribution of the interval from marriage to the first child | Present for families with one child missing will ‘be Pe Fo(x) + P3 £5)(x) + By £4) (x) oh. Pa ¥ 33° PE Parry Tr Pa * 3 * Ph oy This is a weighted sum of the distributions of two single intervals and one double interval. If we make the simplifying assumption that the expected distributim func- tions of the two single intervals are identical, this problem reduces to the one described above for families with two children ever born and one child missing. An exactly analogous procedure applies to the resolution of the distribution of the interval from the first child present to the second child present for families with onechild missing. For families with two children missing, there is a single interval observed, namely that from marriage to the child which is present. The expected distribution is now a composite of three distributions: one for a single interval, one for a double interval, and the third for a triple interval. These are respec- tively the distribution from marriege to the first child for families of type T, from marriage to the second child for families of type 6 and from marriage to the third child for families of type 5. Adequate resolution of this observed distribu- tion would then require the fitting of a mixture of three distributions, which is likely to be the limit for this statistical procedure. Families with four children ever born will provide the following observed distributions: Ll. 1D 00045 03 Continuation page Dr. Bodmer is co-investigator with Drs. Karlin and McGregor of the Stanford Mathe- matics Department on a research grant (GM 10452) entitled "Stochastic Models in Medicine and Biology” (renewal from May 1, 1966 pending under title "Mathematical Models in Genetics and Population Biology") which supports some of the theoretical and model building (as opposed to data analysis) aspects of the work described above. Dr. John Sved, who has been working with Dr. Bodmer on models for the ascertainment biases and birth interval distributions is supported under this grant. (CGM 10452). HD 00045 03. #47 Continuation page Publications: - Bodmer, W. F., 1965. A program for genetic demography based on data from large~ scale social surveys. Eugenics Quarterly 12:85-89. Bodmer, W. F. and L. L. Cavalli-Sforza, 1965. Perspectives in genetic demography. Proc. of the 1965 World Population Conference (in press). PHS-398 (REV. 6-64) Poge sf 3 iJ UNAS Q3 SECTION Il - PRIVILEGED COMMUNICATION SO 3. BIOGRAPHICAL SKETCHES (Give the following information fer EACH key staff member, beginning with the Principal Javestigator. Use continuation pages and follow the same general format for each person.) BIRTHDATE (Mo., Day, Yr.) NAME : TITLE PLACE OF BIRTH (City, State, Country) PRESENT NATIONALITY {If non-U.S. citizen, indicate visa SEX - . status} oo . CD Mele [1 Female EDUCATION (Begin with b. L ini: and include postd: al) INSTITUTION AND LOCATION DEGREE MAJOR RESEARCH INTEREST RELATIONSHIP TO PROPOSED PROJECT RESEARCH AND/OR PROFESSIONAL EXPERIENCE (Start with present position; list ALL experience relevant to project. See attached material. PriS-398 (REY. be) - 77 wal me ip 4690045 03 a. JOSHUA LEOERSERG Department of Genetics Stanford University School of Nedicine Palo Alto, California Born; Hay 23,1925, Montclair, New Jersey Educations 1938-41 IGht-hb 19b-b6 19h6-47 Expertence: 19h45“h6 19)6-L7 1947-59 1959 1962 - Stuyvesant High School (New York City)- B.A. Columbia College Enrotled as medical student, Columbla University, College of Physicians and Surgeons Ph.D., Yalo University Research assistant in Zoology (with Professor F. J. Ryan), Columbia University Research Fellow of the Jane Coffin Childs Fund for. Hedical Research at Yale University (with Professor —E. L. Tatum) Professor of Genetics; 1957-59, Chairman, Department of Medical Genctics, University of Wisconsin Professor of Genctics (also Biology); Executive Head, ' Department of Genetics, Stanford University Director, \ennedy Laboratories for Molecular Medicine, Stanford University a . Visiting Appointments; 1950 1957 1g62 Special Field: Distinctions: 1957 1958 Visiting Professor of Bacteriology, University of California, Berkeley . Fulbright Visiting Professor of Bacteriology, Melbourne University (Australia) Lecturer, Japan Society fer the Promotion of Science Genetics, Chemistry and Evolution of Unicollular Organisms se a National Academy of Sciences | Nobel Prize (Hedicine or Physiology) “for studies on organization of the genetic material fa bacteria” HD 00045 O03 WALTER FRED BODMER Born: Frankfurt .am Main, Germany, January 16, 1936. Nationality and Citizenship: British _ . "Married Julia G. Pilkington (born July 31, 1934, Manchester, England) Children: Mark William, born June 23, 1957 Helen Clare, born March 28, 1959: Charles Walter, born June 12, 1961 Education: B.A. (1956), Clare College, Cambridge University. Mathematics. Ph.D. (1959), Department of Genetics, Cambridge University. Population Genetics. Appointments: . Research Fellow (1958-60), Official Fellow (1961), Clare College, Cambridge. Demonstrator (1960-61), Department of Genetics, Cambridge University Fellow, Visiting Assistant Professor (1961-62); Assistant Professor (July, 1962 - August, 1968) Department of Genetics, Stanford University School of Medicine, Palo Alto, California. —— Scholarships, Honors: Ceneral Certificate of Education (1952) in Mathematics and Theoretical Mechanics at Advanced and Scholarship levels; Physics at Advanced level; English, French, German and Latin at Ordinary level. , Awarded State Scholarship 1952. Major Scholarship in Mathematics to Clare College, Cambridge University, 1952. Undergraduate at Clare College, Cambridge, 1953-56. Wrangler (1st class honors) in Part IT of Mathematics Tripos, 1955. Obtained honors in Part III of Mathematics Tripos, 1956, having taken courses in Genetics, Statistics and Numerical Analysis. | Awarded Owst Prize by Clare College for performance in Part III, 1956. Agricultural Research Council doing research in genetics under Professor Sir Ronald Fisher, F.R.S., and Dr. A.R.G. Qwen at the Department of Genetics, University of Cambridge, 1956-58. : Elected to a Research Fellowship by competition at Clare College, 1958. Obtained Ph.D. 1959-(Short title of thesis: The Study of Population Genetics and Gene Effects). Sumer, 1959, worked. under Professor Pontecorvo in the Genetics Department, University of Glasgow, Scotland. Subsequently started microblological work on Neurospora and Aspergillus at Department of Genetics, Cambridge. Director of Studies for Clare College in Mathematics and Statistics for Scientists, 1959-61. July 1961-April 1962, Postdoctoral Research Fellow, Department of Genetics, Stanford University. Sb: 17 ome iD C0045 03 e : INSTITUT NATIONAL D'ETUDES DEMOGRAPHIQUES (Male) LeMemes TACQUARD Llbers, Marie, Joseph 2 = Curriculum vitae . = Born : Decexber 23 - 1625 at LYON (France) Present Nationality: French. - Education | Degrees : I948 : Ecole Polytechnique T950 : Institut de Statistiques ~ Université ca Paris I955 + Institut de Dénosrepmie -— Université de Paris = occupations : . IG5i-58 3 Cosanization Department of the Evate Tobacco Monopoly . . I95G-6I 3 Deputy general Seeretary of State Tobaces Monopoly I962—64 : DSaputy Director of the Equipgnent Deparcment, Ministry of Puwolic Health bay 1965 : Research workci, National Institute of Denographic ose rid LUUSGD US | SECTION It - PRIVILEGED COMMUNICATION . 4. DETAILED BUDGET FOR FIRST 12-MONTH PERIOD (DIRECT COSTS ONLY) DESCRIPTION Usemize} AMOUNT REQUESTED (Omit Cents} SALARY FRINGE BENEFITS TITLE OF POSITION Professor Asst. Professor es iate ramme at 9.000.+ CONSULTANT SERVICES EQUIPMENT r °o 1 for me-sharin ter rt of this amoun be requested instead for purchase or lease o 1 " " SUPPLIES DOMESTIC FOREIGN patients) TIENT OR COSTS (Ssudy patients) ATIONS _ COsTs _ : , Publication, photography, reproduction costs ~ tf OTHER EXPENSES er me *(See e e under "E ental office space ~ , — Reimbursement of costs to other data sources . a State o lif office o } Census Bureau ~ Contract reimbursement AL (Enter on Page 1, Item 5} s 83.614. “y PHS iOS {iy 1-65} SECTION II - PRIVILEGED COMMUNICATION (DIRECT COSTS ONLY - OMIT CENTS) 5. BUDGET ESTIMATES FOR ALL YEARS OF SUPPORT REQUESTED FROM PUBLIC HEALTH SERVICE TOTAL FOR ENTIRE PROPOSED PROJECT PERIOD. (Enter on Page 1, Item 4) ————————> IST PERIOD ADDITIONAL YEARS SUPPORT REQUESTED [This application only) DESCRIPTION (SAME AS DE- TAILED BUDGET) 2ND YEAR SRD YEAR 4TH YEAR STH YEAR 6TH YEAR 7TH YEAR : PERSONNEL ‘Salaries, fringe : * ev benefits, esc.) 33.918.- | 35.610.-] 37. 390.- CONSULTANT SERVICES Quclude fees, travel, etc.j EQUIPMENT 3 000. - 3. ed 3e = DOMESTIC TRAVEL FOREIGN HOSPITALIZATION Study patients} OUTPATIENT OR SUBSECT COSTS {Study patienzs) ALTERATIONS AND RENOVATIONS PUBLICATION COSTS 500. - 500. - 500. - ALL OTHER EXPENSES L6.200.- | 46,200.~| 46. 200. - 83.614.- | 85. 310.-| 87.090.- s 256. O14, - REMARKS (Justify continuing funds where the necd may not be apparent) *Same personnel as first year, but include .each year. s a 5% increase in salary PHS-398 (REV. 1-65) . Fe C9 SECTION Il - 1D 00045 93 | pAbae Ev ete members, PRIVILEGED COMMUNICATION 6. RESEARCH SUPPORT List all other research support of the principal Training Grants. Include support for this project investigator, including requests now being considered received from own organization. Amounts shown as well as any proposals which the principal - should reflect total funds awarded or pending investigator plans to submit to the Public Health over the entire grant periods indicated in the final Service or other granting agencies, regardless of column, relevance to this application. . . Use blank continuation pages, if necessary, and follow To be included also are current or pending contracts, the same format, Fellowship Awards, Research Career Awards, and A. PUBLIC HEALTH SERVICE SUPPORT GRANT NUMBER : PERCENT TOTAL TOTAL PERIOD OY deans me or monet smear, | two | of Sromt (1) ACTIVE OR APPROVED a 3460 .600 2 5TI GM 295 Training Program in Genetics KRERTRKRE 17/1/64 to. 6/30/69 AI-5160 Genetics of bacteria 253,348 19/1/63 to 8/31/68 NB-04270 Molecular Neurobiology — 453,183 |12/1/62 to , 11/30/67 12} APPLICATIONS PENDING DECISION O8 PLANNED FR 00311 Advanced Computer for Medical Research 2,763,407 4/1/66 to 3/31/T1 B. ALL OTHER RESEARCH SUPPORT SOURCE AND —-- PERCENT TOTAL TOTAL PEUOD PROJECT NO. TITLE OF PROJECT TIMEJEFFORT AMOUNT OF SUPPORT Uf designated) ON PROJECT WITH DATES (1) ACTIVE OR APPROVED $ NSF GB-4130 Program in Genetics & Molecular Biology 65,200 10/15/65 to 10/14/66 Kennedy Foundation. Molecular Neurobiology 100,000 1/31/63 to 1967 NASA NsG 81-60 |Cytochemical studies of planetary micro- 349,899 4/1/65 to | organisms; medical instrumentation 3/31/66 hie Force : 49(638)-1599| Molecular Biology Applications of Mass 75,564 {7/1/65 to Spectrometry 12/31/66 (2) APPLICATIONS ORG DECISION OR PLANNED NASA Computer Control of External Devices and 1,196,854 First year an Automated Biological Laboratory NOTE: Most of the projects listed are cooperative programs involving a number of ot O