Modern Biology: A S. E. LURIA Mr. Luria ir Se&wick P,nfrsror (~,f Biology at .Zf.f.T. He is the arrthor of General Virology (John Wiley di: Sam). In the past twenty years, one has heard much talk of a biological revolu.tion and `of its consequences for man- kind--no't only in medical and economic achievement but in the nature of man itself. Man may soon be able b influence his own heredity directly, rather than only by the indirect process of eugenics. Scientists and soience writers discuss suoh prospects with ;~n uneasy mixture of optimistic predictions of benefits to come and dire warn- ings of possilble catastrophes-as in Desmond Taylor's The Biological Time Bomb. Here I shall attempt to exam- %e briefly the scientific basis of the expeoted devdop- men&, tiheir probable nature. and the responsibility they present to both soientists and the public. What has happened in biology in the last two decades is not a revolution but a scientific fulfillment, Modem biol- ogy started &oust 100 years ago with the foundation of Darwin's t,heory of evolution. which ties togatlher all liv- ing organisms. past, present and future. into a single his- torical process of parenthood, The achievement of the last decades is the understanding of the nature. function and changes of the organic substrate of evolution, !/le genetic material, which is the stuff that carries from one generation to the next the set of instructions that dictate what an organism is. how it responds, and what kind of descendants it will in turn produce. By 1952 the material of the genes was identified chemi- cally as consisting of nucleic acid-generally (except in some viruses) desoxyribonucleic acid or DNA. In 1953 Watson and Crick proposed for the structure of DNA a model,the famous double helix-whioh not only proved to bc correct but opened up entire new approaches to the `study of the chemistry of heredity. Within the la$t sixteen years biologists have come up with the following satis- factory picture of what genes are and how they function. A gene is a certain stretch in a long DNA fiber con- 406 tained in the chromosomes of the cell n,ucletis. It carries in chemi,oal imprint the detailed instruotions for making hoth new copies of i&elf at each cell division and dispos- able "subcopies" or messages, which are used as in%ruc- ,tions for synthesizing all the machinery of the cell. The messages are mole&&s of anot,her kind of nucleic acid called RNA. Gene structure and gene function are not immutable- if they were, evolution and development could not take place. On the one hand, the struoture of genes can ahange by mutation. a relatively rare a&dental change in uhemi- oal composiltion. Na,tural selection then brings about evo- lution by selecting for reproductive success those individ- uals endowed with particular genetic constitutions. On the other hand. bhe funobion of the genes in a 41 is regulated by the environment, including tie action of other genes in the same cell. the chemical merges from other cells. and also the external environmen,t such as food and temperature. Thus wh.ile all cells of a complex organism have identical sets of genes (barring rare muta- tions), rhey function differently because some of their penes (which may number from a few thousand to several million. depending on the organism) receive different en- vironmental signals. The relevant point for this article is tha't all the essen- tial features of the genetic process. insofar as they have been clarified. h.ave turned out to be interpretable in strictly biochemioal terms. No new prinoiple or phenom- enon has emerged to justify tie assumption that some unique "vitalist" principle is at work in biological proc- esses. This point is essential to a grasp of tihe present status and future course of biological technology. What molecular biologists have done is to make the genetic mechanism directly available to ohemioal experimentation. Arthur Kornberg and other biochem,ists have purified DNA from baoneria. viruses and from animal celb, in- cluding human cells. They have then caused it to produce more copies of itself in the test tube. under the influence of enzymes extraoted eit,her from the same organism or THE tumoWOctober 20, 1969 from o:her organisms. At the time of this writ.ing. Gho- bind Khorana is perfecting the chemiad synthesis of a gene in the test tube. The ohemioal mecban~isms of gene mubation hate been clarified. The prmess of mlakin:g gene messages. and .?e USC of these messages to produce the individual pieces (>I' cell machinery. have hccn duplic;r:terl and analq-icd in the :x: tuhc. The nature of the chemical signals-ihc rcgul;itor\' s~lhst;~ncex that turn on and off specific ~cncs--is now `h ?~vn. at Ic;tsl in bactcriib. Bio- chemista have puriiicd s," `c of these rcgu txtory sub- stancrs mid tle~iw~islrated ti-.c:r actual ;iltachmcrl~t to the specific scncs that they block x unblock. Obviously such kno\vledgc. whsicll rcache,s to the most intimalte leve! of the hereditary mechanism, can gcnrr;ltc 3 ~kw :md pc~crful p,rnctic t~chnotagy. The Ir;~iiilion.rl tcclinology W;LS applied in ;rgricuIturr and bus- handry tn brcrding dcsirahlc varieties 01' crops and Toni- maI<. ;und in mcdicinc to under~randinp. tliilgnosillg and treating such gcnctic tli\ordcrx ;,s hemophilia. di;thctc> and phenylkctonuri;l. Elci;tl application of classic,;11 genelics in the form of hlJlll;tll eugcnicc has hccn advocated hut scl- dam carried 0111. The selcclive elimination of gcnctic dc- fects 1~~ restraining procreation on a voluntary basis has never found much favor. PoGtive "germinal ssleation"- thalt is;. the spreadin? of cxcepiinn'ally desirable sets of rcncs thrwgii 5pml banks and artificial insemiilalion- was advocated forcefullv by tile groat geneticist. H. J. Mnlier. but 1~1s encouniered mani objeotions, including the cthicul prohlenls of who ib to d&de what is dcsirahlc in human heredity. In any C:ISC, gcrniinal sclcotion gives x-m t+A-rlordOctober 20. 1969 at best improved odds for superior progeny: the lottery of gcnctics-the randvm distribution of chromosomes and gents of each parent into different sperm cells or eggs --makes this process slow and inefficient. In BK~LY I\~PIY World, his nightmarish utopia of a con- ditioncd humanity published in 1932. Aldous Huxley fore* saw for the year 600 "After Ford" a type of eugenics based on artificial fcrtilizatfion, twinning induced in the test tube, chemical conditioning of the growing embryos, and psychological conditioning of the growing children. Some of the embryologioal techniques imagined by Huxley, and others even more powerful, are rapidly approaching real- ity. For example, artificial fertilization of human eggs has been recently aahieved in the test tube by Edwards and his co-workers in England. The separation and reshuffling of the 031s of fcrtilizcd mouse eggs in course of divicion, followed by rcimplantdtion anti normal birth. has been accomplished by Beatrice MinLz. And more thorn twenty years ago, the ~luclcus of an unfertili& frog egg was re- placed with the nucleus of an adult cell---a process that could produce at will large numbers of truly identical twi'ns. It may soon become routinely feasible with mam- malts, including man. Thus, at least in principle, Huxley's made-to-order human being has become feasible much sooner than he anticipated. But thcsc eml~ryoIogicA methods rcprcscnt only :I rcla- lively clumsy. itnrel`incd Lcchnolo~y when coinpNcd to the one promised (or thrcatcncd) by true gcnctic surgery- the artificial corrrction. replacement, removal or addition of genes, based on the discoveries of molecular biology. A coupling of genetic intervention with embryological surgery would open the way to truly awesome possibili- ties. The actual applications are admittedly still very dis- tant; but I believe it is not too soon to become aware of the prospects. Here a,re some of rhe relevant facts. In bacteria. which are used most frequently for this kind of rcscnrch. it is already pnssihle to introduce penes or groups of sencs as purified picccs of DNA molecules. Under appropriate condit:ions. t.hesc genes enter the cells with a high chance of rcplacinp the corresponding resitlenl gcncs. Thus a bacterium that i 5 sensitive to streptomycin. for example, oan be "transformed" to being resistant to streptotnycin by replacement of the appropriate gene. The descendants of such a transformed bacterium arc all rcsibtant. When this process of gene replacomcnt is carrir.rl out with un- sorted DNA fragments it is vory ineffi,cient; hut there are methods, still being perfected. for sorting out DNA fmg- menIs to correspond with ind'ividual gents or groups of gents. I mentioned bcfnrc that the chemical synthesis and copying of genes in the lest tube is also becoming pos- sible. It is cic.ar, therefore, that the ability to manufacture large amounts of any specific gene may soon. like all purely teohnicnl achievements. become only a matter of investing sufficient money and pcrsonncl. The introd'uction of specific genes into human cells, especially in the cells of the germ line that give rise to sperm and egg. is still far from aotuality. But dcvclop- ments that may lead in that direction are already at hand. Thus. at least in bacteria, some mild viruses can pick up one or more gcnc,s from the cells in which they have `Frown and transfer them to other cells. T,hcn these genes m 407 may ether replace the resident ones or become added, more or less permanently, to the gene set. In some cases t,he added genes upset the regulation of their new host, for example, by mhlbltmg the functmn of certam other genes. Besides vu-uses, there are other, even less destruotlve, agents oalled eplsomes or plasnuds, which m bacteria can msfer and add genes from one cell to another. It would not be surprlsmg ti smular phenomena were soon to be dlscovered in the cells of anm~& and of man, where they would provide a way to add or replace genes. In fact, some viruses that produce tumors m annnals (and possibly also in man) have certam properties of the gene- transferring vu-uses. A major barner to genetic interven- tion will be, of course, the dlffloulty of manipulating the gem cells It IS concavable, however, that gene-carrymg viruses could be made speofilc for the germ cells. Even ahe injection of DNA molecules into eggs m the course of art&&d fentdlzation may become possible. What kind of applications oan we foresee for the discoveries that 1 have just outhned? By and large, they f;llli into four groups: medical, blo-industrial, social and military. In ,medicine, we may envisage replraoing the present treatments of genetic defects-for example, msufflclent production of a hormone such as insulm-by supplying the proper gene to certam cells from the outslde, or by implantmg funmonal cells, or by causing the correspond- ing gene to become activated in other cells of the body which normally do not produce the hormone because of regulatory repression. Mampulations of this kind could also, for example, alter the immunological reaotions fiti cause the body to reject foreign tissue, an aohievement ahat wousld make organ transplants much more successful. In the blo-industrial field, it might be possible to use direct genetic manipulahion Instead of selective breedmg to manufacture more desirable or healthier strains of a vanety of organisms, from yeasts to cereals to cadtle, by implanting or removing specific genes or chromosomes. With socla1 apphcations, we enter the truly controver- sial field. If it becomes possible to mampul'ate the genes of the human germ hne or to achieve arttiicial femhza- tion and nuclear transplantratron with human eggs. we would be faced wsth the terrIfylag responslbdlty of decld- ing wh,at we-the human race-intend to become. At the start, we may simply remove defective genes or replace them with their normal counterparts. Then we may start to fool around by mtroducing supposedly "desirable" genes. We may even be tempted to manufacture many identical copies of a supposedly "superior" mdlvidual; for example, by mtroducmg identical nuclei from its cells into series of enucleated eggs, which may then be im- planted in the wombs of foster mothers. At this poinlt, ethlcal and legal problems of a com- pletely new nature and magmtude arise Who is to decide what is desirable or undesirable, supenor or Inferior. in a man? The doctor? The state? And beyond that, what ethical and legal criteria would apply to human beings who are not born by a natural process but are the product of dehberate gene& mampulatlon? When does a "re- paired" or "manufaomred" man stop being a man (what- 408 ever thait means) `and become a robot, an object, Nan in- dustrial product? I shall refmm here from speculating on possible genetic weapons. Whereas the obstacles in the way of supposedly oonstrmotlve genatlc surgery are very great (but not m- surmountable), the obstacles to destrudtive uses may be smaller, d only because any one of many possible noxious results may be "desnrable" in the military sense. Thus, for example, we may witness efforts to invent ti- ruses that can spread m an enemy popdation genes that produce senslttvlty to pouons, or wsceptlbihty to tumors, or even transmissible gmebic defeats-in other words, genetic genocide. The d,evelopment of pathogemc germs reslstant to certain antiblotlcs has been gomg on for years in the biological arsenals of "civilized" countries. Fmally, we should not ignore the posslbtitity tihat genetic means of controllmg human heredity will be put to mas- slve uses of human degradation even outslde the mil.P.ary context. Huxley's mghtmazlsh #society might be achieved by genetic surgery rather than by conditioning, and m an even more terdymg way smce t,he process would be hereditary and nreversible. The situation that I have tried to project, based on biological developments whioh are either current (M reason- ably predictable, 1s not umque to biology. Whenever a science develops to tie point of gener,aQng new tech- nology, it presents soolety with a mixed bag of opportuni- ties and nsks. The question that faces society 1s not tiat of feasibility. Once the scientLflc principles are established, teohnoIogma1 application is almost certam to come. Thus, faced with the prospedt of a new genetic technology, we must ask ourselves as soon as possible whether and how it will be used and what can we do about it. Optimists and pessunists differ. Robert Smshenner, of the Cahfomia Institute of Teohnology, stresses "the chmce to ease the internal strains and heal the mtemal flaws dire&y." Rollin Hotchkiss, of Rockefeller University, warns that m putting the nzw genertic technologies to supposedly constructive uses, "the pathway wti, hke t,hat leading to all of men's enterpnise and m&&f, be built from a com- bmauon of altruism, private proht, and ignorance." But they both stress tie need "to prepare now for the new reality" and "to caution an nnpatlent altruism, curb an overenthusmstlc self-mtereut. or offset an unmformed m- terventiomsm." These concerns have to do, of course, with the construot,lve possibili,ties. The deutructlve ones, military or otherwise, would be wel'comed only by the most narrow-mmded, Neanderthal type of rabid national- ist or totahtarmn. What oan we do about it? The leaat rational and least effective approach would be to advocate a moratorium on science m order to prevent the nse of potenhally mis- applicable technologtes. The human cultural enterprise depends on freedom of mquu-y. Science, hke the arts, has become an inseparable part of the intellectual adventure of man. What is needed, rather, 1s a rational machmery, both national and international, to determine sensible policies and priorities in the applioation of soientiflc knowledge. The present absence of such machinery is sadly reflected m rhe way decisions are made on major pro- grams suoh as the man-on-tie-moon venture. Even more THE NATmN/ocfober 20, 1969 relevant and more frightening is the apparent mablllty of orgamzed sootdy to cope wth the menace of overpopula- tion, a threat greater than that of nuclear self-destructton. Whether or not a rattonal dectston-making maohmery can be achieved w&n society as it is now structured, et$her m the United States or in any other country, re- mains to be seen. A recently published report of a Panel on Technology of the National Academy of Sciences deals wrth some of the rssues m a coastmotwe way Its limited mnge of recommendations, however, provides little comfort to those who feel th'at the problems of tech- nology and human life require radical action by informed and responsible governmental bodms. Baacally, we need to create a society in which tech- nology 1s purposefully dweotcd toward socrally ohosen goals. Thts 1s a polmcal rather than a soientrftc task, and scientists can hardly be expected to provide the solution. W,bat they can and must do, however, 1s Eace the prob- lems wtthin their own sphere of aotivlty. On the negative ude, scientists can make a conscious effort not to promote or encourage technologloal develop- ment without havmg first faced and resolved in their own minds the social imphcations. On the positive skde, scren- nsta must assume the responstbihty to tell society, in a forceful and perststent manner, what science is discolor- rng and what the teahnologtcal consequences are likely to be. We ought not to be deterred by the widespread and mcreasmg Ignorance of the public, including governmenta, m acxeatlftc matters, but rather should strive to break th,rough that barrmr Long-term educational programs may be Inadequate because time is short. Faster ways must be found to convey the practical unplioations of the modern wo,rld of scrence to the scientifiaally untivilized pubhc consczousness. If these responstbllmes, however hmited, are to be met, most scientists must undergo a major ohange of atitude. I believe that such change aan be brou,ght about beoause ,the present and forthcoming real&es-whether those of an overpopulated world or of a humamty that can re- make Itself in whatever image it chooses-are stirring and dtsturbmg the unaginanon of more and more soientists. Still. active leaderslblp will be needed to develop and crystalhze within the scienlufic milieu an enhanced concern for the social consequences of science and for the rcspon- Isrbilmes of its p~aotitloners. Even more imeant, this leadership must find the way to awaken the public and bherr elected representatives from the complacency thlti lies bahmd the distorted priorkies of present-day society.