%"ransctibed from fild lechure Hovembc3r 15, 1959 Lecmm - X%xhmnical Or&b of Terrestrial Life by J. Lederbeqj Expex3m8ntd wcrk in bbhemical geneUc8 haa casto~y ixmtlved the c3xami- lnation of the mimltest oI?ganisms and deals with processes of micros00pic, even mokcu- lar, &mensioxM. Likewise, the eve&3 with which it is cx3~& are measured on a scale of secorxis, or fractions of a second. The events with which I propose to deal now are of a somewhat differed magnfeudle. They 001~~3~ eons of time, and the wb& mass of the universe. And Pm referring to thus went8 related to #f3 ultimate origin of pif8 on this planet, and its pOBflibl8 distrib-utJon 8ls8wbsre in the unl.vers8. `lb obtab some perspective on the problem posed by the in3tia.l origin or origins of life, it fs neceesary to have a com0ptIon of the time scale of cosmic processes. We will adopt, somewhat arbitrarily, the figure of abo& 10 bil2Son years for the estimated age of the dWXt38, of &out half that wemd for the cdculatgd -8 of the earth, and of about 1 Mlion years as the interval over whkb there is a percx3ptible fossil record. How8ver, PBere ia wry little in the foe& record &at can tdl w of then early 6tagm of the origin and development of life. Cindy those organisms with relatively hard exteriors ami of sxhtidy apprmidde dimesaions have any hop8 of b8lng preserved, We tier@- fore mu& turn from an an&Tticd att8mpt to dff3cern the p&nary feaapres of kbg origins to a synth8ti~ one -- to attempt to recreate from plm.dbl8 argumab, ranging from cosn~3logy to geopbysi~s, what We staearS of the plan& was at the time of tie earth's onrgtn tmi to attempt to put tog&m th8 most likely f8atiw out of which living formsdevd~. perhaps the strongest evidence on which we may rely for the primary fetatm3s -2- of life's origin come8 not from paleox&ology but from oomparatkx3 biolw, in partI- darc0mparatjlvs~O~h8mi6trg. li%mts have been separat& from animals in the pbylogenetic scheme for a Parge part, if not moz-8 than, this interpa of a billion years OV8SY whbh there 9s 8 foseil record. Y8t a b,tockmica analysis of the fond- co~tltuenta of higher plants and of anbale, and iadeed of bac&ia and of many viruses, 8hows an almoat uniform gronnd plan. we find the same amino acids represented UIli- versally among the protc?ins of all oqganisms. Indeed, a hydrolysate cont&ing the amino acids present in the tobacco mosaic v&us could not r8adUy be distinguished by tie biochemist_from the bydrolysate of #e amino acid8 pres8nt in our own tissues and organs. LikerwiS8, we have atresdy comm8aIkd on the ubiqoie~ of deoxyribonucledc acid aa the oar&z of ge~8tic information. And we hav8 her8 the same -ti Structure in au organisms. In addition, we hisve the fact, that can b8 observed at a higher level of integrattort, of a remarkably uniform process of -mitotic ditieion of well-orgaxrized chromot3omes as a basis of the uniform tsansmie&oR of information &I the dwgbters, be it of plant or of animat O&B. We must coaclude fxlom these observ&ons, with at least reasonable certsinty, that tife haa hati a cmnmon plrm since tim sgpsiraton of th8 major lcb@cmm of organ- isms, namely over an interval of nearly a billWk years, which means that the nucleic ~~9ndthep~~~#~~mplerx~~ral~O~~,~tstheir~gply dJ7WXdC features, aX'0 pWbCQH3 ti Xl!Ost dU&43 @OCh8It3iCd features OXl this pkU.U?& Whatwonldbethe mitrimnm requirm for the first development of an or- ganiSrmfromwhfahwecan~planaiblyaulgaetheFestOfOrganic3 evolution? W8I(r;noW from tie point of view of -the development of life that l%irwin has given us, and we are of court3e celebrating m c0nw of his great sy&beais, *at it would be suffWent -3- to start with a self-repnniuoing tsyst0m capable of mutaUon, subject to some improve- ment by tirtUe of spontaraeous muMon, anal s&cted by n&xn%l forces tir the con- t3.nued elaboration of fitter and fitter forms. At the present time the bactetia am pm- hqss the eimplest of the free4iting organk~, aad we could not in the present e&r- OnmentOftheearfhi~~~Organi6m of &4d82?5tZ?LM3~8C~~8Of~V~ and t3&j8& t0 Iktrwin'S CoditiOn. 013 t?h8 other hand, we oan My coI1ceiVe of any spontaneous process by which an object as complex a~ a bracterium mwld conceivably have ax'i6eIk.z Andt W8 mxlst the&h8 pB8, QII i3iIy VbW Of th8 Oti@n of liti= m&Xtetid on earth, a period, a very rsubstantiti period, of evolution of mm@ezdty of which the simple ba&erium is draztdy a ftrassl result. Togoback perhapsonestag8ftn%h8r, webave,intheiUvitror8@itzatrion~f DNA in an eneymatic q&em, one of the cknplest agstem~ wbi@h would be subject fn princi@e to f3ome 8ort of evolMor2. However, in eu& ey~tem8 we must admit the role bf abiod38miSt, to fUrI.&h extraots mm tie nucleo~de trlpho~s and the en- -4- the release of oxygen into the atmosphere in consequence of photosynthesis. We may therefore wonder what tie early stages of the earth were like prior to the development of life, life whiuh in Certain respects is destructive. Any krge ac~ation of or- ganic materials which were to form, or were to be placed, on the earth% surface would at the present time be vary rapidly destroyed, by higher organisms or by sim- pler microorganisms whioh are universal in their distribution. Bowever, if we are concerning ourselves with the primeval conditions of the earth~s surface9 of course there would not yet have been such organized systems to destroy organies compounds. W8 may therefore inquire whether the general aspect of the earth%3 surface may not have be8n far mor8 compl8x in terms of the distrikation of organic compounds than it is at the present time. And to do this we should pay some att8ntson to processes which may conceivably have been responsible for the synth8sis and accumulation of 1-8 amounta of organic material. This stay perhaps b8ghs over a hundr8d years ago with the demomtration by Wmer that, what were then called, organtc compounds, that is to say compounds cow carbon, that had b8en isolated from living organisms, are really not udque to aem. Aad it was W&ler who had demonstrated in the test tub8 the easy possibility of synthef3i 4 f what was aaIled an organic compound, urea, which is isolated of course f'rom urine, by the heating of an inorgank? salt of ammonium, namely amsnotium cya- nate. We have really not evolved very far in our terminology since we still adhere to th8 CO~~ ldbZIk& of an area of chemistry that we call. organic ohemistry, a'& we sometimes have to correct ourselves wh8n we refer to a compound as being organh with regad to the ambagility of its vital biolog&il or&In or whether we simply mean that it is a compound of carbon. Since WBlhler'a time we know that compmxif3 of oarbon ar8 not unique to organic life. I've indicated on the board a series of reactions that the lhtssian biochemist, oparln, about 1928, had proposed as some of the fundamental steps for the natural production of organic compouixk prior to the development of life on the earth. He had proposed principally the formation of carbides by reductive reactfons involving carbon or methane with the metals, and then the hydrolysis of these carbideS by ansloga~ with th8 V8I'y wdi known hydrolysis of caMum carbide to yield aoetylene. As we know, from the important uSe of acetylene in organic synthesis in industry, this can be used as a precursor for the formation of large nixmbers of other more complex, interesting, compounds, for 8xample, its direct hydrolysis to ykld ac8tel- d8hyde. Likewise, nitrogen iS capable of reacting: either directly titb hydrogen, or through the bxkwmediate format&m of nitrides, followed by hydrolysis, to give am- monia, and the further reaction of ammonia with aldehydes is known to be capable of yielding polymers of high molecular weight which might be of great interest as precursors for biological development, A more direct approach to fh8 p of the o@#n of organic constituenti wa8 furnished by the expetim8nts more r8centiy of Miller and Urey, who subjected a 7.nixhre of gasis, of a composition which has tpeen predicated on other grot&s to b8 charaCteriS& Of the prirmitiV8 earth'8 atmOSpher8, to ukWiol9t light aadl, in par- citula.r, to spark dieohargea. The one point I would like to ma%ce about UIeir work is that they have empirically demonstrated, in a very 8aUsSying way, the production of a large amount ami large variety of amino acids from ties8 reactions. 1%~ indic&ed here the Synth8SiS Of @y&e, but this is Only one Of a 1EU'&J8 nUmbW Of OOnoponents that could be produc8ci this way. 338 detailed &8miCd Steps in th0sS 8n4&'iC~ r.eaC- -6- &fact, however, wecan~~aich~epro%Plesmfrornrun8v~b~8~8r~~~~Ve, ifwetake accountofthepresentcons~derat3ouofthegenerd ~omp~s~tio~OfthewhoPe universe. Wehowfrom ourown8xistenceonearththatit%s notanunUkelypk3ce for thedeve~Opm8ntofOrganic m&X'i& that& fOrth8ori@nof~i~~forms and th8ir further development. And yet, if we look at acom~arativetiew ofthe atomic compositionofehee~comparedwlth~e~vers3e~l~, wecsmetowhatmay be a rather startlingresult. This tablehasbeenoonstructed so as tiputhydrogen andhelium, which areby far the mostabundantcomponents ofth8universes in asepa- rate catsgOry. These aregaseous cOmp0n8nts, andhydrogen, of course, constitutes byfarthelargest partofthefzotal mamii oftheunkerse, uotonlydnth8fnterstella.r gasbutalso inthe stars --forexam@e, thesun. However9 ifw8sum~r8mafningatomS, th8condensab~8atoms,whichare ctap6lhteoffo~compaFueds~ataaf~tbeof~mein~~st, andgivethatsuma Valuel, ~8se8thattheuniv8rsalc0mpositfonplac8sgreatweightonthe abundance of0xyg8n,nitr0gmandcadxm, ~~thatthese~o~st~ge~ernaake upalm~st four-fifths Ofth8 total CQtiWabl8 IflBB8 Ofth43univers8. The68 ar8, Of Course, the elem~~chareOf~0uniqasi~rtaw?8in~8o~C~~~~atWeare -7- r8pr8sented in the oxides and carbonates and SilicateS, hydrogen is very much less zaixnbmt proportiQnately, much of the hydrogen of the earth havfng escaped from the atmosphere, and We find o&y tracee, rektively speak@, of carkn, while-silioon and Other el8nM3&3 aS8 p3I'Opo~Onateiy more zdiBX&Rt, We &Quid not I&~'w ihe ll&mrse fX.OJB th8 perSpeC93v8 Of the I?OCky 8artb. %rJe ShOdd r&her ITieW these figtIreS as in- dicative of the very h&h prevalence indeed of precisely those lighter elements which4 ED?0 iRQOI"bRt iR biQiO&.MliigT iRt43XWSti~ COmpOURdS. We must further view the primitive act of cQad8nSation of the free atoms in the interstellar or the pres4~3Uar gas as correSpon&ng ti Borne meaSure tx3 the formatiQn of mol8cukS which wiu u&imately be of some biolo@c~ intereSt -- Whether there 1s a direct transition from the aggregation of atoms to form such objects 88 the comets, which can be viewed spectros@spicdly, and which we know, from inch evidence, TV contain groags like th8 CB and CN and cc and co radiC& Which WOmd be part Qf Qr- ganic exmqmnh. But we do not know whether they can be part of the direct historical transition from the pre-sggregation stage throu@k $0 the final development of the planet. Hut we certainly have3 here, in addition, anQth8r model for the f~rmakion of cQmplex OXJ$UkiC pIwi8CUiBS WithOUt th8 inttXT8lltiOn Qf anJp Sp@fiC biQiO@Cd pFOC=S88. lllhe gusetion, of wh8ther the original aggregation of the interstellar dements TV form the earth is of any importance in its later develQpm8nt, is primtiy related to tpae qaes- tion of the maximum temperature through which the earth may have gone in the 00urse of its history. If this was never &x3 high then of course its original c~mpqsition will have persisted to some extent, snd on that basis ~QIDR of the organic material from which life started may have had ita origin &I the origiti formation of the very stark3 themaelvef3. -8- We can view ihen that in the early stages of the 8arl&Q3- history there were many processes which could lead to the formation of quite complex organic materials, and there were no specific processes for their d.egradation, 0f course, the snbjection of these organic compounds to ultraviolet light and to other chemical sea&ions m&M tend to reverm the syntheUc reacttion~ we have ju& disouesed, But there surely wo& have be8n many places on the earth% surface for the posmib3Uty of the 2%LeaAmulauon of large amounts of these materMs. Horowitz has pointed out that one can tisuabze the dW3iOpm8Rt of more nutri- tionally competent organisms in the following way. I.& us axppcw that the abotimal earth contained large amounts of materials required as building blocks for the produc- tion of a primitive protoplasm. As each of these compounds was utilized by the exist- ing primitive forms of l&f8 its concentration would be depleted, a& there would tha be a selG&iV0 adVantag8 for th8 development Of any loautaX&3, among that life, Which would be capable of r8synthesizing these compounds from simplffr components, And in this way one oould visualize the gradud accretion of synthetic capabilities as individual meta- bolites, as individud buih&@ blocks, for the development of liting structure, and which were ultimately of ina0rga.m~ origin as these became depleted owing to the& meta- bolism by exMent f'orms. HOWev8r, this probBem does not entirely bridge the gap, which must be btidged, between Ihe spontaneous development of perhaps of some relatively ompk3x pdym8rS and the final emergcenee of 8 specif%c polymer which has coded inf~rmaUon of the hind that we see in DNA. At the present time one of the most urgent protiems in recreating the early steps of the evolution of life is in brMging this gap, and this is perhaps in the direction of finding pdymerlc sy&enw whkh have some degree9 bowever fnefffeient, of self-r8pMcation, -9- Nbw, we have I think enough of an insight into the fundamental meohanisms of biological replication to anticipate with some conf%dence &at the primad &.ing mob cuie will be a linear polymer. And it ti8 be a j@yme~ which will have a reason&ly mOROtORc?u8 basic s&Ucture, blat with t?ae paaaibiifliiy of sySten323tic dEartion of its UrnttS, in much the same fashion sta we visuallee for DNA, And we, therefore, in oon- 6truoUng such polymers, must tisualize a meohaz&m for the h8bQiwkl attraction of monomeric units to the corresponding sites in the exbthg polymer and then &naPly some mechanism for putting the right units together. Thie, in effect, is a generdized version of DNA synthesis. Now on pager it is go&tie to w&8 a number of reactions whioh might possibly go this way, but none of them so far has3 Sucoeeded in the I&oratory, perhaps for la& of very urgent effort in those directions. NQW that the plymer industry has exhauSted some of the Simpler possibilities of the constnaction of interesting cornpoundS for in- duetrial purposek3, there it3 little question that more a& more emphasis will be given to the arfiificial prodnction of ordered strnctures, and I think it is a reaSonable anti- cipation that a by-product of this work will be the dedgn of linear po3iymers which Wl have at least some of the dem8ntary attributes that we would have visra~lized 8~3 part of the original living mole&e. Now we ha,ve, if we look juSt a very few years into the future, 01~3 Other possibi- lity for active r868srCh in this area, aside from attempts to rSt?onStrtaCt the OonditionS aa they may have ori- and develom On our own pkknet. I'm referring her8 to the InvestJgSlion of possible living forms on other bodies within the ~01ar syStenn, This possibility beoumes a reality by virtue of the very rapid stridaa in rocket technology which haV8 been Inad0 fn this COURtx"y Z&Rd in the mvi8t `6lalon Over the la& Very few y0arS. -lO- The objectsinwhichwe are most interest& are the planets Mars and Venus, ~e~8seasre~8a;woclQ~Stts42aee~, aSIdtheQEL8SwiXX30h;aPaitatS, iIISQfarE@ we now know them, are the most nearly compatible with forms of life which we can anticipate, Infact, anexcU&ga~~I ~St~~~b~~gPa~~~o~~~caaixwes~ga- djloa has been made by Dr. William Six&ton, as reported very recently in vTMeHLcefv. Dr, !%nton'B report which concerns further edd8me of vegetation dn %&US is an ac- COURt Of hia StUdie8 on the hfra-red Bpmtra Of t%iS pian8t obtained with th8 help Of the- 200 inch telescope at Palomar. Whenhis telescQpewas focussedon someofthedarker regionsofthisplanet, hewas abletopiek up&stinctband~ofabaorptionat 3.43, 3.56, and 3,67 p, a~11 are displayed on the accompanying projection. These bands are akkastcharactetistkofavariety oforganicmQleculee, particsular~ythoseinwhich thereissQmeassymmetry, e3athat~~rnlliacreo~ge~le'$o~~~aad=H~e. This ~~ischar~~rls~@ofamamberQforPganic compoI3nch3 0fMd0@catintar8& in- cludingcarb~hydratesandlipids. Ptistoosoon~sta~~atthioIsdefflai~~de~eof biologicalaotivityonaplanets~metensornearlyhundredlsofmillionsofmilesaway. Thele~t~atweo~sayisthstftc~~ti~~s atleastplausibl88vid8nce fortheoccur- renceof~~~la~~~~esoforg~c materialsonthesurfaceofthis planet. One r0asOnabl8~~eOftbese~~~SWO~d~bi0lO#~~S~~eS~, andthki0eS~f~ly ~~~Iln~~Qf~ev~aeionsinthe~~~~or~t~r8ofthepZanettPsys~- face that astronomers have reported for many years. However, this cannot be considered to be absolutely conclwive &dence of biologlcall activNy sinoe tie very processes of inorganio synthtie, so to speak, of organic twrpmds, to which we have alluded be- tire, sadwhich~tpreoedetpIed~~op~tofIlfsona~~~, couldinprincipledso giveusimag8softhisl&td. There seemstQbeV8ry1ittl8dQubtthatfQr afinsl eluoida- -ll- t-ion of MS problem, it will be necessary to conduct missions directiy TV, or at least to the vicinity of, theS8 planets. Phebry research has max&y motivations. 0f the138~ . it is difficult for me to assess one with higher scientific vahae than the sear& for de- flnithre evidence of life on anotber celestial body. We have 80 few precedents for the design of experfments on this scale and in this field that it is somewhat diffidt to lay down the critetia for a desid~e program of investigation. How8ver, tier8 can be very little doubt that high on a list of priori- tlesforbiologfcalreseaxchwouldb8adefimitteseaxxh forthe%mportantcQm~unds which are so prevaMt to terrestrial life and 830 common to aI3 Qf them. In partkular, the question of whether DNA $13 the unique replicting mah?id, wM& it3 tie basis of genetic transmission, is among the first that shQnld be wered. In ordar to do thiS it may be necessary to develop new forms of instrumentation which will be able TV con- dud anaiy#3es in situ and to trdt nec8Ssary inform&on by radio communieat3on back to th8 .%listh. Ev8n reSss of the existence of tiV0 forms of pife, whether or not they resemble terresttia% f&me, on Mars and on Venus, Qlher biological question13 which may be of great gen8tic tmp~rt have presented themeelves already. TheVeI3'f~&!tthat W8~w~ve~~-rad6~~~~cevid~ceof~eaccumu- lation of large sm0Mnts of OrgCuIiC material On th8 MartIan surface, j?CxM?e the question Ofwhat ~~dbappenif~erewe~k,Ibgdegosi~ontfneplanetaPgstnrface~~ a Si4@8 micrQorg&sm. In adiscussion of clones w0 cowti8d the rapidUy with which bacteria would be able to mu&iply given an environment favorable to their continued growth. And, in fact, one can cslexalate by a simple exponential t8rm that it would SeQuire not much mire than 48 haurs of continued xnwfti~ication of a baoterium like Eschetihia cerli tooccupyavolume ofmf&umwhich hadthesizeoftbeearth. ESs&ereforequite -12- possible that the genetic event of replication of terrestrial material, should a minute portion of tSs be tra.nspl2nti to another planet, wolrpcl have ex@sive consequences frcml a-geo&emicd point of v&m, Aad it is ah easy to see how disastrous the premature transplantation of ter- restrial genotypes would be for any hqe of ultimate investigation of the aboriginal, in- cli~nous, form8 of life that may exist there, and even if there should not exist zmy sc- tive forms of life, the destxwtion of the iiicmmdatecl orfgxnic material which may be the stuff from which life elsewhere has svoMd, and for wbicb thhere is the evidence from t3kdxmts paper, to which 1 have already alluded. Now, Venus is possibly a less at&active object for this type of investigation than Mars, but this agatn is more a tribute to our igwrance of the coriditions on its surface l&m It is to any cW3ct knowledge of the habitat. Estimates of the tempera- ture of V0nus varywidely. Some of #em are @te cmnpat?b.Ie with the axlstence of life, tdmrs are set very mu& too high, However, since we know mthing of t&e exact nature of tif3 surface of this planet which lies beneath the opaque and Mghly reflecting cloud layer, it would be premature to design any sq~roaehes Ice, this planet on the assump- tion that biological activity w0uk.i be impossible at. that site. There is one &her objeot whioh already has beep remhed by terrestrial investi- gation, arm3 which is fin&j& to further study. And that fs the li&30~ the satellite of the ear&b. It ia quite unlikely that the lukmn is a site of active living forms, slme the tf.M abseme of an atmosphere and the, therefore inferred, sbsence of my liquid water waulcl make terrestrld forms q&e out of the question. However, it hsa been suggested that the moon might aat aa a gravitational trap for fossil spores, so to speak, which by some hIyp&hes6s might have drifted between the planets, some of them to light on the -x3- moon, Although this is quite improbable, the possibility of an Wxwplmetmy gene flow woulcl have such weighty consmuemces for our gmera3 cosmic: biology that it &ould not be totally affsreg2rdd in mar plans for the 0xploitation and exploration of space. Wt3 see then that the compass of genetics of mkmolrgdsms mm prowed to a ceramic scale, and that we must take I;I@wmt of the emmmo~ powers of replication of DNA on experiments at every ievd of lnmwn activity.