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t . VNIb'ERSIZY OF CALIFORNIA, SAN FRANCISCO eeRooc or urn+tr+s ass~r~u.i or aaarcars Section of 8ar.atolo=y a.nd Is®vnolop July'20, 1972 Mr. tdYin Jacob Lauteretain i Lauteratain One Rockefeller ?lasa Hev York, liert York 10020 Da1r Mr. Jacobi i , As per your request, enclosed Is an outlina of the rationale rat studr for linka5e of cartain.Cti 6enotypes to cbronic obstructive diseasa, especially, emphysema. I did sona of this rationale praviou.IVi however, with the appearance of the data that the alphal-antitrypsin =enotypas are linked to the Ca =anotypa locus makas even mota seasa. . To start these studies, I think it would be beneficial to have Dr. John Vivian Wells ae the ?rincipal Investigator, since he was tAa first to denonsttate that a given Cs genotype was linked to height of i.=una •response to any antijen in man. ( We Sava you a reprint on thiv; hovever in the event you have misplaced it, thg reference is: J. V. Wells, 8. A. Fudenberg acd I. R. lfackay: Relat..on to the hunan antibody response to flajellin to Cm Canotypas. J. Iaunol., 107:1S0S-1S11, 1971.) As you know, sotealphol-antitrypsin genotypes vhich are rare are not sssociated vith reduction o! activity of the slphai-antitrypsin. Thus, the occurrence of emphlsema in these patients ni=ht meraly reflect the fact that liaka4e of this locus to th:s locus to the Ca locus rather than the fact that the ?is toflo:ytotas are prone to empayssaa. Another reason for have Dr. Vella participate in this study is that he has just discovered tsa first human genetic marker for Is.M,(J.V. Wells, J.I. Eleumers and Y. 8. ?udexibert: Humsn Mti-I=?S Iso-Antibodiu ia Subjects with Selective I&A Deficiency. Clin. e.~cp. Imunol., in Dress), and it Is conceivable that if C0?D or emphysama aloaa is due to an initial insult by a virus or other orjanism to which the antibodY rasponsa Is 1pY, the aama data aitAt hold true th.ra, i.e. the linkita i.s dua to 26M genotype rat=ar than 1tC. PLAINTIFF'S EXNIBIT O ..,~.~,....~..,.~ I continued /28 eax nutrasta, utJroun. 1.taa Directi (;1S) 666-1711 . CQRP!IDEWTJAL CTR HN ~~~~3b

'. Mr. Lduia Jacob taga - 2 - July 20, 1972 10 COYfIOfUTIRL Due to the fact that Dr. Walls i• an N.D., Ph.D., and startin= salary for Assistant Professot of ?tediciaa at the Uaiversity of Californii (including frinje benefits) is approxisstaly $25,000 per year, and since we hava found it is such easier for a trai.aed physician (aspecial.ly a faculty eember) to obtain cooperation fror the various pulaonary specialists here, Tiiaar Eospital and other institutioas.in the aay Area, I think•it would be such sore effective to provide funds for Dr. Walla t:a n sisply for a postdoe. I Turthar, we would test for sany sors Cs factors than orii(nally presented, i.s. not only the major five or six, but perhaps 10. Dr. ttalls would also require about $3,000 for supplies. ?Aarafors,ths total amount vould be $30,000 for ona yur. If va =at results during this tiaa, we could put in fos a l1IB grant for pursue this further and parhaps shift o•ot allocations from the AHA-ERP grant in part for this purpose, since alphal- antitrJpsin genotype charactari:atioa by the Taterhol mathod would be part of the project. wa are equipped to do this. Thank you. As you are aware, Dr. Wells has been offered an Associate Professo,r position alsevhers, and must maks a dccisioa by Saptea.ber 1; therefore, an early reply vould be greatly appreciated. Pleasa let us kaov if you are intarested.. Dr. Wells vould prefer stayinj here if funds can be arranged. Very sincerely, fl. Hu=h Fudenbert, N. D. " Professor of Medicine, VC, San Trancisco Professor of Eacteriolojy and Iz.:.unolojy, UC, Eerkelay kU/rv Encl. Outline of R.ationals 129 ~~~ 0~'~~~~ CTR