Orthobiosis: The Perfection of Man

By Joshua Lederberg

Stanford University, Stanford, Calif. U.S.A.

My assigned task is to comment on the promise and the menace of futuristic
advances in biological research.

This is a hazardous course.

A great deal of recent discussion about “genetic engineering” should be
mentioned only to be deplored, for it gives a distorted view of the present
status and ultimate purposes of research on molecular biology. Nevertheless,
it would be obtuse to deny the ultimate revolutionary importance of develop-
ments that bear on the further course of human evolution. By replacing
blind fate with human reason, they may place a crushing burden of responsi-
bility for the assignment of goals for man. Many people react with dismay
that knowledge is coupled with such a responsibility. Failing to accept it
is also a decision, and one that has its own consequences.

This is an old story, one that links Prometheus to Adam. Once man
knows that he can know, and that he can judge good and evil, his acts
have a moral significance whether he chooses to learn or to deny.

There are other problems, for example of time-scale. Twenty years is
a long time in the growth of science, and the fifty years of an adulthood
are too long for reasonable extrapolation. In such an interval, anything
might be possible, even the most lurid titillations that the popular press
advertises about humanoids of either mechanical or biological provenience.
In refusing to dwell on such extreme speculations, I do not deny the tech-
nical possibility of their accomplishment. J merely point out that so much
else will have happened in every other sphere of human concern that it
would be foolish to concentrate on very specific forecasts. The forecasts
will be objectively faulty, and more important, the context in which future
events will be judged will have changed more than we can foresee, (In
1920, contraception was a dirty word, and who would have dared discuss
voluntary abortion, much less advocate it!)

The critic of “biological engineering” should also be careful to deal with
the contemporary aspects of his subject in context, for which reason I prefer
the phrase orthobiosis (the correction or perfection of life and of man).
Orthobiosis is already implemented on a very large scale—constructively,
30 J. Lederberg

in the practice of medicine and hygiene; negatively via a global system that
ensures that hundreds of millions of underprivileged children will be men-
tally retarded owing to malnutrition and virus infection. The drastic ex-
tension of the average human lifespan during the past century is itself a
major orthobiotic influence. Apart from all the changes in the human en-
vironment, the quality of a life is very different with the average prospect
of 60 as compared to 20 years after adolescence. The side-effects of infant-
death control, without the balance of birth control, hardly need to be elab-
orated. The prospect that death can be postponed, without the means to
retard senescence, may be an equally painful technological disharmony of
the next few decades.

Some examples of orthobiosis may be unduly traumatic to the layman who
has had insufficient experience of human pathology to appreciate the gravity
of some of the ills that cry out for help. No procedure could be more
intrusive than the surgical modification of sex, and it would hardly be
condoned anywhere without the knowledge of the suffering that results from
gender-confusion. An awareness of the chromosome abnormalities, chime-
ras, hermaphrodites and congenital abnormalities that are nature’s experi-
ments with man is prerequisite to understanding research in embryology
that may lead to interventions in human development. Man’s evolution from
and biological affinities to other primate species must also be perceived
as an objective fact, not a literary allusion. This is not a demand that these
matters be left to experts; to the contrary, it is a plea to broaden the base
of public understanding for intelligent participation.

The techniques of biology cannot be fairly judged without comparing
them to those of education and of the multitude of other ways by which
normative behavior is shaped by the cultural milien—by just such institu-
tions, for example, as the Nobel prizes and this very series of symposia.
The understanding by the reader that the very act of perception both ac-
tively alters and is modulated by his own neurobiological structure is another
sine qua non for an informed perspective on orthobiosis. (Professor Bruner
will speak to this in detail.) This term, then, describes the whole category
of influences on the quality of the human organism—an enterprise in which
religion, politics, education, medicine and mass advertising converge with
the evolutionary endowment of the individual human being.

Antithetical reactions to the concepts of orthobiosis can be expected
from various people, depending on their accustomed ways of coping with
difficult problems. The scientist asks for more fundamental facts and is
sceptical about mere speculaticns; the philosopher resonates with issues
bearing on the nature of man; the legalist may already have proposals for
regulation and control. The poet may understand best of all that many of
The perfection of man 31

our discussions of orthobiosis are a metaphor, even a parody of existing
institutions. The greatest merit of talking about “genetic engineering” may
be the light it throws on the de facto patterns of human evolution; about
euphenics for the exposure of the brutally dysphenic effects of our present
environment; about sex control to illuminate the disparate value our culture
puts on the sexes. It is also important that we understand social control
in much broader terms than the compulsions of criminal law. To install a
policeman in the bedroom is not a promising approach to questions of
population control, whether we think of mere numbers or more subtle
questions like “who shall decide who is to be born?”

Value judgments inevitably play an important part in the implementation
of any programs of orthobiosis. Applied genetics in particular is so laden
with religious implications about the nature of man that some question the
morality of even investigating the scientific bases of human nature, just as
others challenge the basic commitment of western culture to scientific en-
quiry. This was once called the work of the devil (as in the Faustian
legend); the counter-cultures today denounce science simultaneously as a
toy of the intellectuals and a tool of class oppression. Since Galileo (or
might we say, Prometheus) the Establishment has also feared the revolution-
ary impact of objective scientific inquiry on the mythologies which sustain
the status quo.

At this symposium we have been taxed to make an explicit formulation
of a pro-scientific ideology. In general, I have been very leery of such
enterprises, and particularly of any claims that a particular ethical system
can be validated by a direct application of scientific reasoning, i.e., that
morals can be proven by science. Attempts to base ethics on evolutionary
biology have been conclusively criticized by Simpson and Dobzhansky’ as
examples of circular reasoning: “How do you prove from what we know
of evolution that human individuality is more important than human society?
And yet we do feel that individuals should not be sacrificed for attainment
of social ends.”

Ideology, furthermore, tends to degenerate into a set of wooden formulas
susceptible to self-serving rationalizations of the ideologists’ established pat-
tern of conduct. It is beyond doubt that more human misery has been in-
flicted in the name of public ideals, myths, gods, and altruistic interventions,
than through the sum total of private venality. Furthermore, the individual
ego-ideal is often quite unconscious. The complexes that reconcile the ego-
ideal with professed ideology, on the one hand, and actual behavior, on the
other, are even more obscure and self-reports about them most unreliable.

Few of us here have digested the vast literature on ideology and on value
systems from the different standpoints of religion, economics, history, pol-
32 J. Lederberg

itics and psychology. It is delightful to contemplate the creation of the
perfect slogan which might mobilize the disorganized efforts of the rest of
the world and perhaps even provide a convincing personal cause. In prac-
tice, we know that any group of intellectuals needs little license to produce
a number of precepts which is some higher power of the size of the group.
The “end of ideology” then comes forth as one of the major ideologies
of the current era.—The sources of “moral character and moral ideology”
are, nevertheless, amenable to scientific investigation as illustrated by the
studies of Lawrence Kohlberg? on the stages of their development in chil-
dren. The capacity to defer gratification, which he emphasizes, can be
translated as a measure of the scope of the personality. This can, as most
religions teach us, be extended in space (empathy or vicarious gratification)
as well as in time (investment for larger, future goals).

Science relates to ethics in many ways more defensible than claims on
its behalf for ultimate verification.? Logical argument can expose incon-
sistencies within and between posture and behavior. It often brings unwel-
come news about the consequences of an action that we might prefer to
ignore. (Unfed children will starve to death even if they live in Biafra or
India.) Technology which creates many ethical dilemmas can also make
for evasions of others: the American ethos has taken pride that an overall
glut in total production might soften the inequities of the relative distribu-
tion of wealth. If kidney machines or artificial hearts can be made cheap
enough we can evade the problem of choosing “who shall live?” now thrust
upon us. We already face so many difficult moral decisions that we ought
to be glad of any we can defer and keep our strength for the others.

This cautionary preamble still does not deter me from casting a tentative
vote in the direction of evolutionary humanism. Julian Huxley was, I be-
lieve, an accurate reporter in suggesting that self-admiration was the most
pervasive of human ideologies, and that no serious scientist doubted that
evolution, in the large, was good progress. Even the cynic must respect
his own uniquely human capacity for cynicism; the physicist for physical
cerebration; the biologist can add an informed wonderment about the actual
process of evolution itself and its culmination in man.

At one time I may have scoffed at the efforts to dignify evolutionary
humanism as a religion—but the very convening of this session persuades
me that Huxley was quite right in his perception of the depth of the religious
instinct. If we distill the convergent essence of the beliefs of scientists,
we probably will not go far from the doctrines he suggested in his manifesto
upon the founding of UNESCO,‘ the working hypothesis of a scientific,
evolutionary humanism in which man is dignified as “the sole trustee of
further evolutionary progress”.
The perfection of man 33

My main complaint about humanism is the quibble that we do not quite
know how to define a man (i.e., to identify which bodies are inhabited by
souls). No other religion has solved this problem much better. The biologists
at least face a more manageable debate on where to divide a concensual
line, knowing that life and death, human and animal, are regions on a
continuum. My quibble is then a sectarian dissent, not basic schism.

In recent years, man-baiting has become a fashionable literary sport—all
our troubles come, we are told, from man’s implacably hostile and aggres-
sive character, inherited from his animal ancestors. I know too many good
men to accept such a generalization about man. If the trouble were merely
in man’s genes, we would have a relatively easy task assigned to us, and a
full license for the practise of eugenics. We must not overlook the vastness
of his task, the perfection of a culture to colonize the whole planet, with
no tools other than his wits.

One failing still stands out. Our imperfect solutions aggravate every prob-
lem. In contrast, the computer memory can be totally erased; its task is
hardly altered by successive iterations, and programs can then be gradually
perfected. We must always build on the sins, mistakes and hatreds of every
step on the way.

I may, then, summarize my conception of evolutionary humanism with
the conclusion that it depicts man as the historical animal. Our evolution
has reached the point that progress is far more a function of our tradi-
tions and our social forms than our biological functions. As part of the
world-mind,® with a unique consciousness of past and future, each individual
should be less jealous of the life of his own body, and more protective of
every other one, than a purely zoological ideology would encourage.

Molecular biologists are often slapped with a red herring, the imputation
that they degrade man into a mere machine. We do in the main insist on
“mechanism”, mainly as a reaction to the pessimists who have disparaged
and who discouraged research on the frontiers of biochemistry. (The recent
elucidation of the mechanism of DNA replication counts for more than all
the verbiage that has ever been expended on this debate.)

To insist on the inherent inaccessibility of other processes, like the brain
or feeling, to analyses of mechanism remains as much a mistake as to boast
of accomplishments whose realization is still remote and may never be
complete at the hands of finite human intelligence.

The attribution that man is merely anything is merely an idiosyncratic
misanthropism.

In the rapture of self-exaltation, many humanists may nevertheless forget
that evolution is a continuing process.

The perfectibility of man and the corollary of his present imperfection,

3~- 709705 Nobel Symposium 14
34 J. Lederberg

should stand out as one of the most precise implications of the evolutionary
outlook.7 We should be optimistic (and humble) that our posterity will pro-
gress beyond our capabilities, even for moral judgment, to the same degree
as our own proudly proclaimed emergence from apedom. We have then
one precept about values—that we ought to guarantee that there will be a
posterity, and that we take care not to foreclose the options available to
it. The ravaging of the earth, of primitive peoples, of our wild life, of one
another, and even our carelessness about the planets, are our cosmic sins.

This humility supports the policy of pluralism—that the state must not
intrude in the intimate lives of citizens except for the most inescapable
needs of public order. This principle must be renewed and reinforced to stem
the temptations of totalitarian exploitation of techniques of biological en-
gineering, just as the constitutional protection of free speech is the only
defense against mind control by the techniques of communication engineer-
ing.

“Orthobiosis” has the etymologically obvious meaning “right living”. Be-
fore discussing orthobiotic innovations—the possibilities of human improve-
ment from new knowledge of molecular biology and genetics—we ought
reflectively to ask “what are man’s real problems in biological perspective?”
We do better to look for solutions to real problems, if we can, than invent
problems for our new tricks and techniques.

Uppermost is the avoidance of war, or rather the positive promotion of
world harmony and economic development and integration. These are mani-
festly not problems of biology, at least not human biology; for the political
reaction would engulf any effort at biological change. (What could be more
hostile than to attack a neighbor with a pacificatory virus? For the tanks
would surely follow!)

Economic productivity, especially in tropical and semi-arid habitats,
clearly does have a biological basis about which we know very little. The
potential for biological innovation in tropical agriculture is now hinted at
by the “green revolution” of recent years. These improvements in wheat and
rice strains were brought about rather traditional methods; modern mo-
lecular genetics is just now being discovered by plant breeding specia-
lists.

The escape of world population growth rates, a byproduct of modern
medicine, is a well documented threat to the survival of the species, It is
primarily a problem of self-aggravating poverty, ie., failure of economic
development, rather than of the technical potential for food production.
Proposals for biological solutions, e.g., by the use of environmental sterilants
(antidotes by prescription requiring a license to bear a child) are, fortunately,
pure fantasy. Quite apart from the political problems of obtaining public
The perfection of man 35

acquiescence to such schemes, they could never be guaranteed to be safely
reversible so as to avoid sterilizing the species.

On the other hand, the present patterns of growth and urban concentra-
tion and poverty, are ideal for fulminating epidemics of virus diseases®
that may spontaneously solve the population problem in the harshest way
imaginable.

Poverty, hunger, pestilence, pollution are beyond doubt the further prob-
lems that this generation must face, or there will be no posterity. No one
of us here would hesitate to abandon every other commitment if he knew
any effective route to answer their challenges—and I offer my deepest re-
spect to men here who have had the wit and the power to make important
contributions in these spheres. But the paths are tortuous, and the main
problems are unabated.

Certainly it would be short-sighted to redirect all our resources into the
panaceas for instant relief of global problems. We need to maintain con-
stant vigilance that our remedies do not have side-effects as portentous as
the original disease—consider the history of DDT as a rather stark example.

Basic scientists who have worked in the genetics of bacteria and viruses
believe that these discoveries have ever growing importance for the preven- -
tion and healing of serious human diseases. We live, in the present era, in
an incompletely justified optimism about having “conquered infectious bac-
terial disease” as the fruit of the development of the antibiotics. However,
viruses are in general still beyond the reach of antibiotic therapy. Even bac-
teria, believed to be under firm control with antibiotics, are continuing
their own evolution and continue their assaults upon human health with
renewed vigor. In the long run, only our continued vigilance over bacterial
evolution can justify our hope of maintaining a decisive lead in this life and
death race.

However, whatever pride I might wish to take in the eventual human
benefits that may arise from my own research is turned into ashes by the
application of this kind of scientific insight for the engineering of biological
warfare agents. In this respect we are in somewhat the same position as the
nuclear physicists who foresaw the development of atomic weapons.

There is, however, a crucial difference. Nuclear weaponry depends on the
most advanced industrial technology. It has then been monopolized by the
great powers long enough to sustain a de facto balance of deterrence and
to build a security system based on non-proliferation. Nuclear power has
thus, ironically, become a stabilizing factor tending to reinforce the status
quo in parallel with established levels of economic and industrial develop-
ment. Germ power will work just the other way.

The United Nations Study Report on chemical and biological weaponry
36 J. Lederberg

has summarized some infectious agents that have served as points of depar-
ture for the development of biological weapons. Any knowledgeable viro-
logist could suggest many more. I will not repeat these technical details, nor
will I bludgeon you with the horrible diseases that some of these agents
provoke. I will also leave to your own conscience the burden of moral
judgements about using these kinds of weapons. Most civilized people would
be repelled by the thought, but perhaps no less by exposure to the human
realities of any other form of warfare. Overriding such comparisons should
be the grave moral issue in a policy that risks the lives of a world of
innocent bystanders. Fortunately, these concerns actually converge with our
self-interest in calling for a halt to BW before it becomes established in
the arms-traffic of the world. (This discussion of BW was written from the
standpoint of a U.S. citizen just prior to President Nixon’s announcement
(Nov. 25, 1969) of the U.S. renunciation of BW.)

My main fears about BW are to do with the side-effects of its prolifera-
tion 1. as a technique of aggression by smaller nations and insurgent groups
and 2. by the inadvertent spread of disease.

If the great powers could actually protect the secrecy of their BW work
I would be much less alarmed. The chance of BW ever being used in a
major strategic attack is essentially negligible in the face of the nuclear
deterrent. The suggestion that we need BW or CW weapons for specific re-
taliatory purposes in order to deter their use aims at a ridiculous kind of
precision. Will our deterrent missiles have to follow the same trajectories
as those that might potentially attack us? Will they have to be launched
at the same time of day? Will they have to have the same mix of explosive
energy and radioactive fallout? If we are attacked with anthrax strain B27
must we reply with anthrax B27?

On the other hand, if I were a Machiavellian adviser to a would-be Hitler
I might indeed advocate a considerable investment in biological weaponry
as a desperate approach to the cheap aquisition of great power even if at
a very great risk. And, of course, the first thing I would do would be to
plant my intelligence agents in the existing BW establishments of the high-
budget powers in order to get the necessary scientific information at the
lowest possible cost.

However, if I were patient I would not bother to do even that. No
security system, no counter-intelligence system in the world expects more
than a delay of 5 to 10 years in the leakage of vital information. We do
not have, and I presume do not contemplate, security reservations like
war-time Los Alamos for the containment of BW research. If a high level
activity is to be maintained there will be frequent turnover of personnel.
It is unreasonable to expect a tighter security barrier here than has pre-
The perfection of man 37

vailed in any other area, given the problems of reconciling security with a
free society. Besides these channels for diffusion of information, there are
also bound to be Pueblo-like incidents, and finally calculated leaks in the
budget competition of the services. The American people might be the last
to know. But we can hardly rely on more than a ten year delay between
many important discoveries in BW research laboratories and their availa-
bility to hostile and irresponsible forces outside.

As a matter of prudent self-protection, BW research laboratories in the
USS. and the U.K. have pioneered in the technology of containing dangerous
microbes. I have great respect for the technical capabilities of the senior
civilian management of these laboratories. They should be credited with
the outmost diligence in protecting both their personnel and the surrounding
community. They have also published a great deal of their work in the
engineering of such protective facilities and this experience is unquestionably
of great value in public health work. For example, the British laboratories
at Porton were acclaimed for the safe handling of the very dangerous
Marburg virus upon its first outbreak in Europe two years ago.

In spite of these precautions, disease organisms have nevertheless escaped
from time to time and inevitably will do so in the future. Such escapes
already constitute a breach of security. They also compromise public health,
which is further complicated by keeping civilian physicians in ignorance
of potential agents that might fulminate into large scale epidemics. The
intentional development of virulent strains resistant to conventional anti-
biotics obviously worsens the problem. We simply have no way of assuring
ourselves that a BW development activity will not eventually seed a cata-
strophic world wide epidemic that ignores national boundaries.

On the immediate horizon are modern developments in molecular genet-
ics. These undoubtedly point to the development of agents against which
no reasonable defense can be mounted. Because of the uncertain danger
of retro-action, such agents are hardly likely to be used in consequence of
any rational military decision, but would obviously play into the hands of
aggressive insurgence and blackmail.

Finally, even the publication, albeit as a positive contribution to human-
ity, of the technology of safe containment insidiously helps solve a problem
that might have hindered a potential insurgent from dabbling in BW.

The problem of containing infectious agents being manufactured and
stockpiled in large quantities, or tested in the open air, is a much more
difficult technological challenge; and it is encumbered with even more of-
ficial secrecy than the laboratory work. The main effect of security has not
been to deny information to an enemy but to protect an establishment from
both destructive and constructive criticism at home. In this case, more
38 J. Lederberg

open constructive criticism would be crucial for assurance that procedures
for containing microbes are well conceived and correctly implemented.

BW agents for use against man can be expected to be far more capricious
than any other form of weapon. For any strategic purpose they are es-
sentially untestable since large populations would have to be held to an un-
certain risk. With nuclear weapons we can at least be confident of the laws
of scaling. The destruction of targets can be calculated from simple physical
measures like the energy released. Nothing comparable to this can possibly
apply to BW agents. For this reason again the United States and other nu-
clear powers have absolutely nothing to lose in disavowing their use in
war. Our continued participation in BW development is akin to our arrang-
ing to make hydrogen bombs available at the supermarket.

Microbiological research must be expanded in programs of public health
research for defense against our natural enemies. In fact, the public health
bureaucracy has refused to give prudent thought to the recurrence of major
pandemics of human disease, be they of spontaneous or human-intelligent
origin. Perhaps this is simply a consequence of their sense of futility about
mobilizing the necessary measures of global health needed to protect the
species. If we add to already urgent concerns the spread of dangerous dis-
eases from large foci of infection established by BW attack, the prospects
become even gloomier,.

Our self-interest as human beings urgently calls for the institution of
improved measures of world public health and of international controls on
the development and use of BW agents. Research related to BW perhaps
should continue; but it is of the first importance that this be fear-reducing
rather than fear-generating, for the latter can only lead to mutual escala-
tion of anti-human developments.

It is difficult at this stage to detail the texture of new agreements sub-
sequent to our ratifications of the Geneva protocol. We cannot suddenly
impose unilateral decisions on the international community; but no other
issue can evoke such a unanimity of world opinion. New agreements pro-
bably should include (1) public legal commitments against secret BW re-
search; (2) the establishment of central, international laboratories to monitor
the occurrence of threatening organisms and to help develop generally avail-
able means of protection against them; (3) a legal system to protect the
freedom of information and communication of data on disease organisms to
such central authorities; (4) a general acceleration of research and health
services to minimize the incidence of infectious disease, particularly in un-
derdeveloped countries. No situation could be better designed for the evolu-
tion of serious new viruses than the existence of crowded, underfed human
populations in which foci could develop and spread with a minimum of
The perfection of man 39

medical control; (5) treaty commitments on BW analogous to the nuclear
non-proliferation treaty; (6) pre-agreed sanctions by the civilized world
against the release or development of BW agents, clearly invoking inter-
national law against such “offenses against mankind” as akin to war crimes.

If political wisdom can dispel the threat that molecular biology will be
harnessed to the task of global suicide, the most important challenges to
applied biology are (1) monitoring and managing the threats of world-wide
epidemics from the spread of old viruses and the evolution of new ones even
worse; (2) world nutrition; (3) the understanding of the human consequences
of environmental degradation; and (4) efficient ways of assessing side effects
of drugs, food additives and substitutes and other consumer products of
vital importance in a crowded world.

The progress of science would in fact be paralyzed if its practitioners took
an all-or-nothing approach in the selection of problems for attack, and the
patient exploration of the possible must be weighted at least as dearly as
the pursuit of iconoclasms.

In this light, there remains some justification for saving some of our
energies to deal with some longer range problems like those pertaining to
man’s evolutionary future. These are also very immediate in the context
of family life, which counts for an important part of human concerns, even
while the storms of geopolitics rage.

The doctrine of pluralistic choice dominates my own prescriptions for
ethical policies in the general field of human reproduction. This is in part
an attempt to evade the external imposition of moral principles on others;
but it is also a constructive attempt to preserve the fluidity of human
options in facing rapid change in the physical and socio-technical environ-
ment. For example, the time is not far off, we hope, when soldiering will
be an obsolete profession and commitments by martial states to combat-
adapted genotypes would be grossly malfunctional. Almost every other as-
pect of human value, except the elusive one of intellectual breadth and
flexibility, is subject to the same reservation, which undermines the utility
of any comprehensive long-term eugenic schemes beyond the minimization
of undoubted defects. Even here we may expect ironic discoveries, for
example, that some “defectives” are the most amenable to specific treat-
ments with drugs or hormones that will more than restore “normal” capa-
bilities. Certainly we must be quite cautious about plans to “eradicate”
genes which make defective homozygotes (like cystic fibrosis) before we
understand the biological advantages of the heterozygotes that supposedly
maintain the gene in the population. The target of such programs should
be the disease itself, the immediate cause of human distress.°
40 J. Lederberg

“Individual choice” faces an inevitable paradox in this field: whose
choice, and when? For the child does not make himself—in many different
ways he is the creature of his parents and of his culture. The newborn
cannot have decided by and in whom he was conceived, and carried, and
to rely upon his choice about his early care would stand as criminal neglect.
The parents must undertake the systematic manipulation of their child’s
development—presumably in his own interests, and certainly constrained by
many realities of their particular culture. We call this, without irony, the
humanization of the child, for his acculturation is as indispensable to his
human functioning as is the biological substratum that makes it possible.

There are many compromises here, in different styles, between the vary-
ing interests of the community and of individual families; which change
from one polity and time to another. I propose that parents assume the same
kinds of responsibility in their wider orthobiotic choices as they now do
in the education and family discipline of the child. Indeed, they cannot
rationally be separated from one another. The traditions of political freedom
that minimize the intrusion of political and religious sectarianism in the
schools are precisely those that can protect the autonomy of the family at
home.

This approach is not free of patent ethical hazards—we must condemn
excesses of paternal authority, but within broad limits the children them-
selves will find more effective remedies than we would have the sophistica-
tion to apply by legal sanctions.

This discussion can only begin to open the issue of the meaning of
manipulation, The generation gap shows how urgently we must work on
our confusions, even before we face new problems of conscious orthobiosis.

The technology of orthobiosis differs from medicine only in its greater
breadth. Medicine is usually thought of as a reparative rather than con-
structive art, but this simply reflects an arbitrary definition of abnormal
and diseased. Thus, in the field of mental health, we see an unlimited range
of sources of distress that the therapist will aim to relieve; nor can we
find any sharp boundary between mental health and education. Medicine
is also abutted by nutrition and physical exercise, the traditional arenas of
domestic orthobiosis, whose importance to health is being rediscovered by
contemporary medicine.

In fact, biological engineering is merely speculative medicine—as theoreti-
cal promises are realized, they will and should be assimilated into the frame-
work of medical practice. This is important to insure not only technical
competence but also the ethical tradition of commitment to the needs of
the individual patient.

For the sake of orderly classification, orthobiosis can be classified into
The perfection of man 41

eugenics, euphenics or euthenics, depending on whether the target for im-
provement is the DNA of the germ cell(s), the somatic characteristics of the
individual, or the environmental scene. Eugenics implies an influence on
the genetic endowment of future generations; euphenics does not. As far as
euthenics is concerned, this paper will concentrate on those aspects of the
environment that most directly influence the characteristics of the individual.
Plainly, genes, soma and environment are intimately connected through
channels like natural selection, environmental hygiene and economic op-
portunity.

Especially with respect to psychotropic influences, euthenics is the input,
euphenics the output of the same process. I can speak with less authority
on these most important forms of human manipulation (education, mass
communication, language, the popular arts, explicit psychotherapy, and all
the subtleties of group behavior). For that reason only, an undue weight
of my remarks will be a technical exposition of processes which may
have only ancillary importance. These are, however, compressed in tables I
and IT, with a few additional notes.

My purpose in this exposition is to share my expertise with a wider com-
munity, so that the issues of orthobiosis may be ventilated, understood and
rationally decided. I hope this caveat is unnecessary, but it comes from
weary dismay at having advocacy for wide and intrusive applications thrust
at me for the sake of a critic’s rhetorical shorthand. I do however advocate
responsible, carefully thought out, and humane experimentation.

Euphenics. This term was coined! as a counter-slogan to eugenics, to paral-
lel the antinomy of phenotype and genotype. It was intended to suggest
that new knowledge of molecular genetics would be as powerful for medicine
as for direct genetic intervention. In fact, euphenics is simply medicine,
stressing the outlook on this as the modulation of developmental processes
towards the restoration of health, or some other optimum.

As indicated in table I, euphenics is widely practiced already, but with
few exceptions, its purpose is the restoration of normal health. Those who
would seek super-normal nutrition are likely to be labelled food-faddists,
insofar as an “optimum” nutrition has already been assimilated into our
norms for health. Nearly the same applies to education, although a wider
variety of styles is practised in the privacy of the home nursery than in
the public schools.

We know less than most people think about the norms for fetal and new-
born nutrition. The former are a matter of current controversy. The pre-
valent style of emphasizing control of the pregnant mother’s weight and
fluid accumulation has been sharply attacked by Brewer!® as neglecting the
42 J. Lederberg

Table I. Euphenic (and dysphenic) influences on human nature by period of life.

The entires in the table refer to important (LJ) or incidental (@) influences having parti-
cular impact on the stage indicated.

The table emphasizes effects that are likely to persist for long periods after the evoking
stimulus is removed. The “euphenic”’ effect is, in many cases, figurative, and may be implied
mainly by the remedial measures taken to prevent or repair injury.

 

Form
Fetus
Prem.
New Born
Youth
Adult

Age

 

Growth of brain
Dysnutrition
Specific regulation (hormones)*
Induced tolerance to grafts
Teratogenic drugs, radiation
& infections/prophylaxis
Induced abortion/therapy for threatened
abortion
General contro! of organ differentiation
with inducers and repressors**
Surgical repair of congenital
and other defect
Transfusion; organ transplant
Critical dietary (MSG) & hormonal
(estrogen, steroid) triggers
Hypoxia; oxygen poisoning
Sensory stimulation
Virogenic therapies** oO
Vaccination
Dietary & hygienic habits established
Psychotropic & other drugs, including
addiction & other side-effects
Hormonal, surgical mod’n of sex
Artificial organs
Environmental pollution Oo Oo oO ao
Sonic habituation; deafness
Psychodynamics & psychotherapy ?
Popular culture; music ?
Education; letters; arts
Propaganda

e O00
oO

oo

Oo

Oo Og O 00
Oo e OF OOO
@

OO e

e OOH 00 e
ee
e

eeXDl ef e@

OHOoooeO ee
e

eDDeDHhelt elleoe
enoonvetett

DOeO OO
OeOe OO e

 

* Known from animal experiments, but not observation on man.
** Speculative possibilities under laboratory investigation in animals.

fetus’ need for protein. Nor do we have the faintest idea as to the level of
early nutrition that would sustain the best vigor of the fully developed
youngster, in mind or in body. Now ancient experiments have shown that
rats lived longest when somewhat “undernourished” with respect to calories;
experiments like these are rare in man, for the political system tends to
produce kwashiorkor (protein malnutrition) instead.

Recently, Olney!! has shown that newborn mammals can be altered by
large doses of MSG (monosodium glutamate) with lifelong effects. The
furor that these findings have raised with respect to formulas for baby
foods may obscure the deeper interest of the finding. Evidently the neonatal
The perfection of man 43

hypothalamus can be injured by otherwise non-toxic doses of a normal
nutrient, with subsequent failure of appetite regulation. This suggests that
a wide range of nutrients can influence the setting of chemosensors that
signal important homeostats. Few other compounds have been studied so
far. There is little doubt, however, that our styles of baby-feeding have
amounted to considerable, if unconscious, developmental manipulation.*7

Hormones. The most potent regulators of organ development and function
are the “hormones”. We now have substantial information about the na-
tural systems involving such organs as the gonads, secondary sex apparatus,
thyroid and adrenal, and have some insight into the regulators of the muscle
and red cell mass, skeleton, kidney and liver. This knowledge now has
definite application mainly in replacement therapy to remedy obvious fail-
ures of the natural endocrines, or to inhibit the unwanted growth of tumors
derived from some of these tissues. With farm animals, the use of sex
hormones for fattening or improving food yield is a well-established euphe-
nic practice. One also hears that masculinizing hormones have been used
to promote muscular prowess in women competing in athletics—a rather
pointed illustration of the extrapolation of restorative medicine, which has
raised perplexing questions of criteria for, and means to enforce, social
controls. Is there much logic in prohibiting the use of a hormone to help
achieve the same ends that we encourage by physical exercise? It is, of
course, the possibility of insidious and irreversible side effects that elicits
the deepest concerns, though specific evidence for such side-effects may
bear no relationship to the social revulsion against the drugs.

We know the least about the regulation of the most important organ,
the brain. The extent to which its growth is regulated in part by external
hormones is beginning to become a popular research area.’? We have long
known that the thyroid hormone is indispensible for maturation.

Zamenhof!* has demonstrated that the pituitary growth hormone can in-
fluence the size and cell number of the brain of the newborn rat when
administered to the pregnant mother. This effect may, however, be an in-
direct one, mediated through dietary behavior, since prenatal insufficiency
of amino acids limits brain size. A hormone has already been described that
regulates the growth of nerve cells of the sympathetic ganglia. Since anti-
bodies to this hormone will inactivate the sympathetic nervous system of
the intact animal, the hormone is important in the normal functioning of
these neurones.

One can visualize that similar hormones operate on the central nervous
system, and even that some forms of mental retardation may be attributed
to auto-antibody formation. The elucidation of such a hormone may be the
44 J. Lederberg

Table II. Methods of eugenics, existing and prospective.

 

1

Genetic hygiene—controlling the environment to minimize germinal exposure to

mutagenic chemicals, radiation, and virus infections.

Effects of temperature are theoretically suspect but have not been satisfactorily

assessed.

II. Selective mating

1.

By phenotype of parents (assisted by biochemical and cytological assay)
{a) negative—distracting, discouraging or Sterilizing the “unfit”.
(b) positive—
i, encouraging select pairs.
ii. with artificial insemination, donor (“rational germinal choice”),
iii. with oval or ovarian transplant.*
iv. both, or fertilization in vitro, followed by implantation.*
v. extracorporeal gestation (est tube baby)—see also euphenics.**
(i-v are not very different in their genetic consequences).

. By genotype of parents—as above, with deeper analysis of parental constitution.

Except for specific aberrations very little can be said at present about genetics of
desirable traits.

. By relationship of parents.

(a) inbreeding. The main impact is to expose recessive, usually deleterious genes:
increase phenotypic variability of F.; decrease the genotypic variability of later
generations.

(b) outbreeding—antithesis of (a). Most cultures strongly encourage outbreeding.

. By age of parents—to forfend accumulation of deleterious mutations and chromo-

some anomalies which increase with parental age.

- By phenotype or genotype of the zygote or of fetus (antenatal diagnosis and

voluntary abortion). Earlier selections would avoid the trauma of aborting an
established fetus.

. By genotype of the gametes, e.g. separation of X from Y, or normal from defect-

bearing sperm.**

- With sperm of other species (compare 1. (A)iv). Nothing is known of the conse-

quences among primate species. All contemporary races of man appear to be freely
interfertile.*

Ill. Innovations in zygote biology

Vegetative (asexual) propagation. Cloning.

1.

Parthenogenesis—development of an unfertilized egg. (This might be genetically
identical to the mother, or might be a product of meiosis, which would be an
intense form of inbreeding.)*

. Regeneration—development of whole individual from somatic tissues (as in some

plants and lower animals like earthworms).**

. Differentiation of gametes from somatic tissues previously subject to extensive

genetic manipulation.**

. Somatic reduction in gamete-forming cells in culture (somatic inbreeding)—would

allow predictable outcome of further matings from a given parent which is not
now assured.**

- Nuclear transplantation—renucleation of a fertilized, enucleated egg. Genetically

equivalent to cloning from the source of the nucleus.*

. Embryo—splitting to produce twins or multiplets, not to be confused with multiple

ovulation (occasionally induced by fertility-promoting drugs.) About 1/3 of spon-
The perfection of man 45

taneous twins are monozygotic, i.e. arise from the splitting of one embryo.*
Note also the opposite phenomenon.

7. Embryo fusion (chimerism) so that one individual comprises 2 or more genotypes.
This grades into tissue transplantation at later stages. It should allow different
genotypes a new latitude for mutual complementation, e.g. mens sana in corpore
sano. Somewhat less than 1/1000 live births are spontaneous chimeras, but some
of these arise by other mechanisms.*

IV. Adjuncts from somatic cell biology

For eugenic applications these would be coupled with procedures like III 5. For
euphenic effects, altered cells can be grafted back to a host or some manipulations
done directly on his tissues.

1. Algeny—directed alterations of genes
(a) Controversial claims of effects of DNA uptake in mammalian cells following a

long tradition of genetic work with DNA in bacteria.
(b) Incorporation of viruses.
i. Experimental tumor viruses.*
ii. Use of specially modified viruses
1) Vaccination to induce immunity to viruses.
2) Virogenic therapy to replace missing genes.**
3) Virogenic enhancement for superior performance—if we but knew the
biochemistry thereof.**
(c) Specifically induced mutations. No plausible approaches are now apparent.”*

2, Random mutation and specific selection of cells with altered properties—has full
precedent in strain selection in microbes. Many uncertainties relating to possible
cancer potential of such implants.*

3. Cell fusion to form somatic hybrids. These cells may then lose various chromo-
somes to give many new forms. Extends scope of 2. Can be readily applied to fuse
cells from “distant” species, ¢.g., fish and human.*

4. Development of symbiotic strains of lower species, with habitats that grade from
the external world (e.g. crops) to internal to intracellular. Parasitic worms in man
have evolved in this direction with the help of adaptations to thwart immunological
rejection. In principle they might be domesticated. So also might algae be trained
to an intracellular habitat in man where they might photosynthesize essential
nutrients, if not bulk calories, as they already do in primitive animals.**

 

* Known from animal experiments, but not observation on man.

** Speculative possibilities under laboratory investigation in animals.

next major turning point in the progress of human mental capacity. We
might find, for example, that it bridges the main gap between man and the
other apes. It may also pose dilemmas on the social regulation of its use,
analogous to those concerning the use of masculinizing hormones. If the
“norm” for cerebral capacity were suddenly open to a substantial jump,
what place would be left for vestigial imbeciles like ourselves? Or will we
therefore take every means to be sure this never happens?

It is not clear whether or how purified repressor proteins could be in-
troduced into target cells from outside, but when this step is also achieved,
we will have the tools for the most comprehensive regulation of gene func-
46 J. Lederberg

tions. This would be tantamount to instructing undifferentiated cells to co-
operate, say, to reform a liver or heart to replace a failing organ, or to
produce totally new kinds of tissues and organs.

Needless to say, we spend enormous effort at “manipulating” the develop-
ment of the child’s brain through mental exercise, i.e., education, though
the principles of action in wide use are too numerous for them all to be
well-founded.

The concept of hormonal regulation has also been expanded by studies on
gene action in bacteria, which have culminated in the isolation so far of
two specific “repressor” proteins, a prelude, without doubt, to many more.
The repressor interferes with the initial transcription of a specific segment
of DNA, in the formation of the RNA messenger, thereby regulating the
function of that gene. The role of repressors in mammalian systems is a
subject of hot controversy, and there is indeed good evidence that regula-
tion can (also?) occur at the level of the differential translation of existing
RNA messengers.

To summarize, it is enough to predict that the obstetrics-pediatrics (the
hyphenation, i.e., the gulf between the specialties, hints at part of the prob-
lem) of the new future will include respectful attention to hormones and
other growth regulators, as it now does in principle to nutrition and vaccina-
tions.

Vaccination and virogenic therapy. Since 1798, vaccination has exemplified
the use of viro-genic information in medicine, though its practitioners to
this day are often oblivious to it. Jenner found that inoculation with cow-
pox (vaccinia) caused a mild disease immunity which also protected against
the dangerous smallpox.

Many aspects of vaccination are still scientifically obscure; but we can
now describe the process in terms of molecular genetics. The DNA of the
cowpox virus is purposely introduced into certain cells which adopt the
genetic information contained therein. These cells thereupon produce new
gene products, encoded by the viral DNA, which stimulate other body cells
to produce antibodies against them. The cross-immunity is then a byproduct
of the virogenic alteration of some cells of the host.

Live viruses are now widely used for vaccination against many other
diseases, including polio, measles, and in special cases or in the near future,
rubella, mumps, rabies, and so on.

Vaccination can be regarded as if it were a therapy to replace the func-
tions of hypothetical genes not normally present in the human organism,
those that would endogenously stimulate the formation of antibodies. This
idea can be extended, in principle, to other gene products, for example en-
The perfection of man 47

zymes that may be missing in certain gene-defect diseases like phenylketo-
nuria and perhaps diabetes. Laboratory models for this kind of virogenic
therapy are well established; there is good reason to expect trials for human
disease in the near future.’* Although basic genetic principles underlie this
technique, and the genetic apparatus of somatic cells is altered, it is classi-
fied as euphenic because the germ cells are left unchanged and there should
be no effects in future generations. This is matter of empirical observa-
tion, rather than necessary principle in biology, and it is quite conceivable
that some inoculated virogenes might also be inherited, as has already been
postulated for certain tumor viruses in rodents. This reservation applies
with equal force to vaccination against infectious diseases, about which we
have little information in proportion to the enormous numbers of children
involved,

As applies to euphenics generally, the main limitation to broader applica-
tions is not in the detail of the technique. It is in the biochemistry of trait
whose modification is in question. When we know enough about the bio-
chemistry of brain development to make sensible statements about which
genes might be involved and how, a variety of approaches will be open to
reparative or constructive changes in that biochemistry. The poverty of
present knowledge is illustrated by our helplessness (late 1969) about dis-
eases like Huntingdon’s chorea, despite rather precise knowledge about its
mode of inheritance.

The practical application of virogenic therapy might lie in enzyme re-
placement. For example, a gene for phenylalanine hydroxylase (missing in
PKU) might be isolated from human DNA by an extension of techniques
successfully applied to bacteria. It would then have to be grafted on to
the DNA of some carrier virus already well authenticated for use in a
vaccine. After inoculation, some infected cells would be expected to have
restored the necessary function. Plainly, many further refinements, especially
in the cell-specificity and the regulation of enzyme levels, are also called
for—not to mention the most careful tests for the harmlessness of the
carrier virus.

The same criteria, may it be repeated, deserve to be applied to con-
temporary vaccines designed for immunization against virus infection.

Transplantation. The potentials for transplantation as a means of replacing
worn-out organs have already been too well advertised to warrant much
more comment. There remain serious problems of supply and allocation
of vital organs, like hearts, but a socially acceptable market has been organ-
ized after some early tribulations. Nevertheless, there will probably never
be enough suitable hearts to meet the demand, especially as the procedure
48 J. Lederberg

is technically perfected. The heart transplants may, however, serve an im-
portant way station in the development of artificial hearts, and for example
as an ethically acceptable backstop to their early trials, as well as a source
of important physiological information.

The augmentation of the brain has also been accomplished—in fish—by
the pooling of primordia from two embryos into a single hatchling. These
fish evidently were able to make good use of their enlarged cerebrums, at
least from a man’s-eye view of their behavior.1*

We should not, however, confuse any organ with personality, which is
a complex process that functions through a variety of tissues, and in a
larger sense, even of many extensions of the body in the form of machines
(clothing, automobiles, telephones and radio communication, computers,
etc.)

The problem of graft-rejection by the immunological defenses of the
host remains unsolved at a fundamental level. However, so much important
theoretical as well as empirical information is being accumulated that this
must also be surmountable. We will then find that the spectacular, life-
saving accomplishments of heart-and kidney-transplantation will be much
more mundane, but equally important life-enhancing procedures, involving
many other tissues. Even cosmetic transplants of skin and hair should not
be shrugged off as a humanly important application.

The prime hint to an answer to graft-rejection is the phenomenon of
induced tolerance, obtained by exposing the fetus to graft antigens before
the stage of immunological reactivity. The antigen-specificity is then treated
as part of the “self-identity” of the host, and later grafts of tissues from
related sources will be accepted. (The phenomenon also sheds indispensable
light on the diseases of “auto-immunity” and some on the prevention of
cancerous growths.) If other methods fail, we could envisage the precau-
tionary injection of pooled, purified human tissue antigens as a kind of
vaccination during fetal life.

The experiment has, in fact, been done with other intentions—namely
the transfusion of a fetus mortally afflicted by RH-disease with fresh blood
from another donor. Unfortunately, viable white cells in the donated blood,
now protected against rejection by the infant, survived to react instead
against him. The result nevertheless verified the theory of induced tolerance
as applied to man.1”

Eugenics. Selective breeding; selective abortion; algeny.

Having domesticated his food crops and animals, and his pets, man has
speculated at least as far as his knowledge of heredity permits about in-
fluencing his own progeny by the wise choice of genetic “stock”. Optimism
The perfection of man 49

may be the most responsive trait, for there is little else to support the
tenability of such experiments over any period of time: the recombination
of genes that accompanies sexual reproduction is an almost insuperable
barrier to eugenic progress by selection alone. The farmyard domesticators
have the additional advantage of inbreeding (incestuous matings) to stabi-
lize the genetic characteristics of a given breed. Wisely, even the most
enthusiastic eugenicists refrain from this breach of custom—for its short
term consequence to human viability would be disastrous. The corn breeder
is after all quite willing to sprout and discard millions of seeds in order to
select an advantageous genotype—a price no one could negotiate for human
improvement.

A specific approach to selective breeding, “germinal choice”, has how-
ever been strongly advocated by the late Herman J. Muller and by Julian
Huxley.1® Their scheme would provide for the banking of sperm from in-
dividual men in cold storage for later voluntary use in artificial insemina-
tion. They suggest that a considerable period of time elapse to allow a
calm retrospective judgment of which men carried the most useful set of
genes. The problems so far of promulgating such a scheme are all social,
not technical. So far there is little evidence that “rational germinal choice”
has become a household phrase. It is hard to see any fundamental objec-
tions to discreet small-scale experiments along these lines: legal recogni-
tion of artificial insemination is needed to prevent the hardships that arise
from confusion about proper procedures of parental consent and anonymity.
We have ample experience with adoption to use as a precedent.

Real problems arise, of course, in the identification of preferred males,
even some years posthumously, and the advertisement of the qualities of
potential sires probably should be confined to professional journals, pack-
age inserts, and a physicians’ desk reference.

More recently, a genetic engineering mania, algeny, has been advertised
as an aftermath of research on DNA as the chemical embodiment of gene-
tic information. “We have merely to specify the optimum sequence of some
5 billion nucleotides—the DNA information of the fertilized ege—and we
can define the ideal man.” This fantasy has elicited dark anxieties about
“genetic control”, in an absurd misunderstanding of the metaphor “specify
the sequence”. This of course already happens to some degree by the volun-
tary sexual coupling of two parents. They have thereby decided that a
child will be formed, specified as a Mendelian sample of each of their
chromosomes.

At the present time, we have no plausible approach to the use of “synthe-
sized” DNA that could begin to match fertilization as a way of “specifying”
the DNA of the zygote. And if we did, it could hardly differ from the act
4-709705 Nobel Symposium 14
50 J. Lederberg

of choosing a particular sperm and an egg from specified parents. Some
lay readers have unfortunately misread these fantasies to occasion a worry
that “their own genes” might be controlled from without. We should reas-
sure them that this is the least of their legitimate worries, if for no other
reason than the redundancy of their DNA in trillions of different cells.

What of the future? The main impact of the fruition of algeny would be
to reduce the relevance of the genetic constitution as the seat of destiny.
When the genes are so easily changed, this deep knowledge of genetics
cannot be developed without the means to divert the action of the genes
in specific developmental pathways—i.e., the full realization of euphenics.
Finally, algeny will hardly be possible before the materialization of other
manipulations of the germ cells, for example the renucleation of egg cells
with nuclei taken from somatic cells of an existing individual or in cell
culture.

This technique has already been worked out in frogs by Briggs and
King; Gurdon and others.}* Their experiments were intended to determine
whether tissue differentiation is invariably associated with a permanent loss
of developmental functions in the cell nucleus. Apparently this is not al-
ways true, for some nuclei of adult tissue cells are capable of supporting
the total development of a new frog from a re-nucleated egg. From a
genetic point of view, however, the new frog was vegetatively propagated
from the mature tissue since it carries exactly the same set of genetic in-
formation.

Groups of individuals derived by vegetative propagation and having iden-
tical genetic constitutions are called clones. The propagation of new plants
from cuttings is such a familiar experience in horticulture that the term
“vegetative propagation” is used generally for the by-passing of sexual re-
production. In lower animals like the earthworms, cloning is a common
occurrence with the spontaneous regeneration of “whole animal from cut-
tings” of the previous individual. (There is no theoretical argument against
this kind of regeneration in mammals, but no experimental evidence for it
either.) The most immediate implication of cloning is the production ge-
netically homogenous groups of individuals, and particularly of propagating
a genotype already tested in one generation for further trial in a second.

We already have a foretaste of the properties of a clone in the behavior
of identical twins. Twins are commonly recognized as having an unusual
psychological relationship to one another, and in that sense, differing al-
ready from non-twin individuals. There has, however, been relatively little
critical psychological study of twins, particularly from the point of view of
objectively testing their capacity to communicate with one another more
efficiently than obtains for randomly chosen individuals. These observa-
The perfection of man 51

tions would be very difficult to control for the usual reason that the here-
ditary similarity between twins will often be confounded with the empirical
fact of their having been reared together and treated nearly as identical in-
dividuals during their early development. One can argue on purely theoreti-
cal grounds, however, that at least some twins will have a great advantage
in mutual communication (and this, of course, also means education) just
by virtue of the similarity in their blueprints for their central nervous sys-
tems. Since the thread of culture is what binds the human experience, the
mere fact of their homogenity may make clones more efficient in intellectual
cooperation and educational advance. This hypothesis is independent of the
opportunity to select those genotypes for clones which already manifest
outstanding capabilities.

The chief human motivation for taking advantage of clonal reproduction
would, undoubtedly, be in the quest for some kind of immortality, which
plainly has a deep influence in the direction of human affairs. Quite apart
from this, clonal propagation would afford an otherwise unavailable op-
portunity for certain humanic “experiments”, in the same sense that efforts
to optimize a child’s education are an experiment. It is unlikely that we
will otherwise ever be able to know the extent which the performance of
acknowledged geniuses or athletic stars are manifestations of unusual gene-
tic endowment.—The technical limitation to cloning by renucleation, is
mainly the much smaller size of mammalian eggs by comparison with the
frog’s egg, but this is almost certainly not an insuperable difficulty. There
may be other obstacles based on differences in the biology of the frog egg
as compared to that of the human which are unknown to us at present.

What are the real hazards of cloning? The shock of such a large devia-
tion in the fundamental biological system may cloud clear thinking; it is of
the same magnitude as the institution of voluntary reproduction, which de-
pends on human knowledge of the relationship of sex to pregnancy. We
may not be able to ignore incidental aspects of the technique that may be
quite crucial to public acceptance. There are not many arguments for by-
passing sexual reproduction, but they might include (1) parental narcissism,
and instinctive attachment to some form of personal immortality; (2) some
social and familial interest in the perpetuation of unique genotypes, for their
own sake, and to improve our educational methods; (3) the wish of some
couples to have “their own” children when this is frustrated by some forms
of sterility or risk of genetic disease that would be unmasked by sexual re-
production, and (4) social need or other dynamic encouragement to produce
many similar individuals of a specific genotype, e.g., an elite guard, an
SS, or a suicide squad who could be relied upon to end the world in a
national interest.
52 J. Lederberg

The trap of over-specialization is indeed the main hazard that the evolu-
tionary biologist would warn about. World-enders are all too easy to pro-
duce without orthobiotic innovations, but a society might well trap itself
into staking its genetic resources to meet more legitimate short-term chal-
lenges, and find itself unable to adapt rapidly enough to change. This is
a general objection to any scheme for genetic commitment, and to in-
stitutional rigidity overall. Cloning has the advantage of retaining the latent
variability of heterozygotes, which can be re-expressed in future, sexual
generations.

A vegetative progeny suffers from another hazard, the accumulation of
new mutations without the constant filtering of natural selection against
homozygotes. A commitment to cloning will then require a new level of
vigilance about reducing the hazards from mutagenic pollutants of the en-
vironment (an important element of any eugenic program).

Biological theory offers no basis for opposing vegetative propagation on
a modest scale, as an option to isolated families, so long as the population
processes most of its genetic heritage through the sexual mechanism. We
have to fear the social hazard that cloning may become too attractive,?°
that no parent will again care to face the hazards of bearing a randomized
child. However, some of the more serious perils of that gamble can be
countered by prenatal diagnosis and abortion (discussed hereinbelow).

Cloning will surely reawaken the zeal of the eugenicists, which is now
dampened by the sheer inefficacy of their proposals.”! It is easy to see how
a totalitarian government might wish to add imposed clonal propagation to
the repertoire of its techniques for homogenizing its subjects and minimizing
dissidents. Legally enforced pregnancy of any kind is an abhorrent viola-
tion of human rights,

This is not to exclude the interest of the community in, say, discouraging
the birth of a repeated series of defective children who are burdens to
themselves as well as the group. However, these incidents are so rare that
we ought to exhaust non-compulsive solutions before inviting a massive in-
trusion of the authority of the state into reproductive decisions.

The deepest and most irrational fears about the abuse of scientific know-
ledge are fueled by anxieties that some external authority might succeed
in dominating our lives through control of the mechanisms of genetic con-
trol. Every advance, major or minor, in experimental molecular genetics
is followed by editorializing on this theme, rarely spelled out explicitly
enough to be answerable.** The main thrust is that the state might acquire
the means to turn reproduction from a family avocation into an assembly-
line for manufacturing loyal citizens, along the lines of The Republic, or
Brave New World.
The perfection of man 53

In all candor, this outcome cannot be dismissed but it must be viewed
as a political rather than a technological disaster. One should ask more
concretely, just which traits is the state likely to impose involuntarily? And
how could it enforce unpopular edicts without already having enslaved the
population? If there is to be a “correct” skin color or shape of nose,
does the totalitarian state—by historical evidence—not already have ample
technology to achieve these among its citizenry, at the point of a gun?

These anxieties are in fact promoted, or ought to be, by another move-
ment that holds it necessary to impose legal controls in order to confine
population growth. The bureaucracy that administers such controls plainly
would have a leverage on the life of the community that would be vulner-
able to the most flagrant abuses. (Fortunately, no such involuntary atmos-
pheric contraceptive can now be forecast; we have enough trouble authenti-
cating the safety and wide use of acceptable, voluntary ones. Besides the
obvious need for better techniques of contraception, we have the most
urgent need for social inventions that can press the needs of the community
for population limitations, without destroying personal freedoms.) A well
established totalitarian society might, indeed, try to assure its own perpetua-
tion by genetic technology, as further support to its existing apparatus of
thought control. The most obvious step would be to encourage the uni-
formity of outward appearance (which all more primitive cultures have done
spontaneously) as a way of bolstering Groupthink or distinguishing Ins from
Outs.

More realistic moral problems arise in the area of the proper social con-
trols over the use of new techniques, even as experiments, by individual
family units. Should the community have any concern about isolated trials
of cloning, artificial insemination, oval transplantation, or similar techni-
ques, if these are done with an obligation and intention of responsible care
for the human individuals born as a consequence? The community does,
however, insist that every child be a potential citizen, and therefore in-
vokes such laws as compulsory vaccination and schooling. Its requirement
that a child be taught English (in the U.S.) might be regarded as barbarous
by any objective onlooker, but we do not usually indict this as an un-
warranted intrusion.

It is certain then that the community will properly set bounds on the
characteristics of individuals produced by any kind of rational design. If
the technical power now existed, it would probably vent its wrath on any
person who, for example, intentionally and knowingly produced an idiot.
Laws for compulsory sterilization have wisely been held in abeyance mainly
out of scientific uncertainties and the difficulties of fair enforcement, not
a constitutionally protected privilege to make any kind of monster one
54 J. Lederberg

pleases. The same principles will undoubtedly evolve in our adjustment to
genetic innovations. In fact, the moral issues that attach to the problems
of new genetic technology are fully foreshadowed in our present customs
of public health and education.

An interesting variant arises, however, in the speculation that sub-human
races might be evolved, like Aldous Huxley’s “gammas”. This is plainly
a vicious parody on the institutions of race prejudice. Szilard has stated the
speculation in a possibly more confusing way: what if we were to discover
that the dolphins were (or could be altered to be) at least as intelligent as
humans? Would we not have to tax them, restrain their movements by
requiring visas, conscript them and offer other privileges of human dignity?

It has been answered that the world will continue on its dubious course
so long as the scientists and the politicians shuttle the responsibility to one
another about these central problems. The definition and nurturing of per-
sonal freedom is one of the most difficult and most important that we
face. In a non-ideal world, the responsibilities and the temptations of new
powers may be more than the system can bear.

The suppression of knowledge appears to me unthinkable, not only on
ideological, but on merely logical grounds. How can the ignorant know
what they should not know? We can, however, try to play the other game
better, to use our scientific skill and artistic intuition to forecast some
glimpses of the future, and in particular of the worst paths to be avoided.”8
That prevision may help to plan the compensatory institutions, the public
education, or the balancing research to regain the harmony that is the best
measure of human progress.?* 28

Appendix

Does modern science dehumanize man?

It is easy to find deeply ambivalent feelings about science among in-
tellectuals (even including some scientists), in Congress, among alienated
youths and among bewildered citizens. We live in a scientific age whose
glories and terrors are both credited to science. At this level, we can hardly
deny that our ever-growing scientific mastery over the forces of nature im-
poses an almost unbearable responsibility on political authority and on a
democratic electorate to learn about, think about, plan for, and use these
forces for real human benefit.

In this climate, many people have become highly sensitized to more
ethereal questions that are raised by the scientific study of man. One such
question is the doctrine of mechanism. Dr. D. E. Wooldridge, a well-known
The perfection of man 55

physicist and systems engineer and a successful industrialist—formerly presi-
dent of TRW (Thompson—Ramo-Wooldridge) Inc.—has written several ex-
cellent syntheses of present day thought in biology. His latest work, Me-
chanical Man—the Physical Basis of Intelligent Life, concludes “that a
single body of natural laws operating on a single set of material particles
completely accounts for the origin and properties of living organisms. Ac-
cordingly, man is essentially no more than ‘a complex machine.”

A few eccentrics aside, the whole community of contemporary science
shares the view that the same laws of nature apply to nonliving and living
matter alike. All of us who investigate the chemistry and physics of living
organisms pursue our work as if organisms were complex machines, and we
find man to exhibit no tissues or functions that would except him from
this way of analyzing human nature.

Nevertheless, we are or should be careful to state just what we mean
before we assert that “man is a machine,” and much more so before using
the phrase “merely a machine”. The statement that man is “a mere ma-
chine”, or a mere anything, is a needless irritant to precise communica-
tion between scientists and laymen. (We might better proclaim that “man
is merely the most complex product of organic evolution on earth, the only
organism whose intelligence has evolved to the point that his culture far
transcends his biological endowment.”)

The “mere machine” phrase is usually a retort to the claim that there
are mysteries of human nature that are, in principle, beyound the reach of
scientific investigation. Scientists would do better to save their breath quar-
reling about what they can analyze in principle; in their own work, they
are mercilessly pragmatic about confining their conclusions to what they
can examine in practice.

There are, in fact, theoretical limits to scientific analysis that may justify
men in repudiating Dr. Wooldridge’s assertion that “the concept of the ma-
chine-like nature of man is incompatible with a long-cherished belief in
human uniqueness”. There is nothing “mere” about a machine as complex
as a man; the word “machine” is just a manner of speaking about the
scientist’s faith in a universe ordered by natural law. That faith was ex-
pressed most eloquently by the French philosopher the Marquis de Laplace,
who averred that, given complete knowledge of the universe at one instant,
the scientist could in principle compute all of its future states in infinite
detail.

In practice, we must now remind ourselves, the scientist and his com-
puters are machines that occupy space and consume energy. Dr. Rolf Lan-
dauer of IBM has pointed out that the process of calculation itself soon
reaches fundamental limits. If the whole visible universe were one gigantic
56 J. Lederberg

computer, made of components at the theoretical lower limit of size and
energy consumption, it would still be insufficient for some problems that are
soluble “in principle”.

Far short of the complexity represented by a human being, some mere
machines called computers nevertheless have already reached the point
where their actual behavior is predictable only to a rough approximation,
and we must be careful to program internal checks to detect when these
highly individualized robots deviate from their intended instructions. (Wash-
ington Post, 28.12.68.)

Notes

1 Dobzhansky, T. Mankind Evolving. New Haven and London: Yale University
Press. 1962, page 342; Simpson, G. G. The Major Features of Evolution.
New York: Columbia University Press. 1953.

2 Kohlberg, L. “The development of moral character and ideology.” in M.
Hoffman (Ed.), Review of Child Psychology. Russell Sage Foundation. Vol. J
1964.

3 Haldane, J. B. S. The Inequality of Man and Other Essays. London: Chatto
and Windus. 1932. Chapter Three, “Science and Ethics”.

4 Huxley, J. UNESCO: Its Purpose and its Philosophy. Washington: Public
Affairs Press. 1948.

5 Muller, H. J. “Mankind in Biological Perspective.” in The Centennial Re-
view, Vol. X, No. 2, Spring 1966, pages 163-213; Thorpe, W. H. Science,
Man and Morals. Ithaca, N.Y.: Cornell University Press. 1965; Haldane, J. B. S.
The Inequality of Man and Other Essays. London: Chatto and Windus. 1932.
Chapter Three, “Science and Ethics”.

® Koestler, A. and Smythies, J. R. Beyond Reductionism. The Alpbach Sym-
posium 1968. London: Hutchinson of London. 1969. See Appendix to this
article for the view of the present author on the mechanistic theory of man.
7 Lederberg, J. “Experimental genetics and human evolution.” in Bulletin of
the Atomic Scientists. Vol. XXII, No. 8, October 1966.

8 Dorolle, P. “Old plagues in the jet age.” in WHO Chronicle, Vol. 23, No. 3,
pages 103-111.

® Fraser, G. R. and Motulsky, A. G. “Genetic effects of selective abortion
for inherited diseases.” in Program and Abstracts. American Society for Human
Genetics. Annual meeting, October 10-13, 1968. Austin, Texas.

10 Brewer, T. H. Metabolic Toxemia of Late Pregnancy: A Disease of Malnutri-
tion. Springfield, Hlinois: Charles C. Thomas. 1966.

11 Qiney, J. W. “Brain lesions, obesity and other disturbances in mice treated
with monosodium glutamate.” in Science, Vol. 164, pages 719-721, May 9, 1969.
12 Hamburgh, M. “The role of thyroid and growth hormones in neurogenesis.”
in Moscona, A. A. and Monroy, A. Current Topics in Developmental Biology.
New York: Academic Press. 1968. Vol. IV, Chapter Two.

18 Zamenhof, S., et al. “DNA (Cell Number) and protein in neonatal brain:
alteration by maternal dietary protein restriction.” in Science, Vol. 160, pages
322-323, April 19, 1968; Zamenhof, S., et al., “Stimulation of proliferation of
cortical neurons by prenatal treatment with growth hormone.” in Science, Vol.
152, page 1396, 1966.

14 Rogers, S. “Skills for genetic engineers.” in New Scientist. Vol. 45, No.
686, pages 194-196, January 29, 1970.
The perfection of man 57

15 Shapiro, J., et al. “Isolation of pure Jac operon DNA.” in Nature. Vol.
224, pages 768-774. November 22, 1969.

18 Bresler, D. E. and Bitterman, M. E. “Learning in fish with transplanted
brain tissue.” in Science. Vol. 163, pages 590-592. February 7, 1969.

17 Naiman, J. L., e¢ al. “Possible graft-versus-host reaction after intrauterine
transfusion for Rh erythroblastosis fetalis.” in The New England Journal of
Medicine. Vol. 281, No. 13, September 25, 1969, pages 697-701.

18 Muller, H. J. “Human evolution by voluntary choice of germ plasm,” in
Science, Vol. 134: page 643+, September 8, 1961. Reprinted in Young, Louise
B. (Ed.) Evolution of Man. New York: Oxford University Press. 1970, page
530.

19 Harris, M. Cell Culture and Somatic Variation. New York: Holt, Rinehart
and Winston. 1964.

20 Brunner, J. Stand on Zanzibar. New York: Ballantine Books. 1969 (Fiction).
21 Haller, M. H. Eugenics. New Brunswick, N. J.: Rutgers University Press.
1963; Osborn, F. The Future of Human Heredity. New York: Weybright and
Talley. 1968; Pickens, D. K. Eugenics and the Progressives. Vanderbilt Uni-
versity Press. 1968.

22 Taylor, G. R. The Biological Time-Bomb. New York and Cleveland: The
World Publishing Company, 1968; “The gene: iolated—for good or evil?” The
New York Times. November 30, 1969; “Genetic tampering.” Washington Post.
November 3, 1967; “Genetic warnings.” The Christian Science Monitor. Jan-
uary 8, 1970; “Voice fears on possible uses; Scientists isolate single gene.”
The Palo Alto Times. November 24, 1969.

28 Popper K. The Open Society and Its Enemies. Princeton, N. J.: Princeton
University Press. 1950.

*4 Tiselius, A. “Balance and unbalance in scientific progress.” Address to the
Athens Meeting 1964. The Royal National Foundation. Elsevier Publ. Comp.
1966.

*5 Lederberg, J. “Humanics and genetic engineering.” in 1970 Yearbook of
Science and the Future. Encyclopaedia Britannica. Metz, C. B. “Gamete surface
components and their role in fertilization.” in Metz, C. B. and Monroy, A.
(Eds.) Fertilization. Comparative Morphology, Biochemistry and Immunology.
New York: Academic Press. 1967. Vol. 1; Harris, H., et al “Suppression
of malignancy by cell fusion.” in Nature Vol. 223. No. 5204. Pages 363~
368. July 26, 1969; Gurdon, J. B. “Transplanted nuclei and cell differentia-
tion.” in Scientific American. Vol. 219. No. 6, pages 24—36. December, 1968.
26 Bichenwald, H. F. and Fry, P. C. “Nutrition and Learning.” in Science.
Vol. 163, page 645-648. February 14, 1969; Shooter, E. M. “Some aspects of
gene expression in the nervous system.” in Schmitt, F. O. (Ed.) The Neuro-
sciences: Second Study Program. New York: Rockefeller University Press. in
press; Scott, J. P. “Critical periods in behavioral development” in Science, Vol.
138, No. 3544. Pages 949-958. November 30, 1962; Levine, S. and Mullins,
R. F., Jr. “Hormonal influences on brain organization in infant rats.” in Sci-
ence. Vol. 152. Pages 1585-1592. June 17, 1966. Denenberg, V. H. and Rosen-
berg, K. M. “Nongenetic transmission of information.” in Nature. Vol. 216,
pages 549-550. November 11, 1967; Mintz, B. “Gene expression in allophenic
mice.” in “Symposia of the International Society for Cell Biology”. Symposium
on Control Mechanisms in Expression of Cellular Phenotypes. New York: Aca-
demic Press. in press; Altman, J., et al. “Behaviorally induced changes in
length of cerebrum in rats.” in Developmental Biology. Vol. I (No. 2), pages
112-117. March 1968.

27 A recent report suggests that rats reared on cyclamates suffer from an irrever-
58 J. Lederberg

sible induced hyperactivity. (The effect was initially interpreted as an augmenta-
tion of “intelligence”)—see Stone, D., E. Matalka, and J. Riordan “Hyperactivity
in rats bred and reared on relatively low amounts of cyclamates.” in Nature.
Vol. 224, page 1326. 1969.

28 The general subject of value questions in relation to science is the subject
of several comprehensive studies, including the Harvard University Program on
Technology and Society, and the Columbia University Institute for the Study
of Science in Human Affairs. At Indiana University, the Program in Public
Policy for Science and Technology of the Department of Government has

published an unusually extensive annotated bibliography, so far in two volumes,
1968-69.