5

f

 

 

Reprinted from Man and his Future, 1963, pp. 263-2 73.
(A Ciba Foundation volume edited by Gordon Wolstenholme.)
Published by J. & A. Churchill Ltd.. 104 Gloucester Place, London. Wor.

Biological Future of Man
JOSHUA LEDERBERG

Today, with a new biology we mirror his future. Poetry

may speak more bravely than Science. However, Policy
must rely on Science for an accurate vision of the bounds of
human evolution.

Dm= theory set off the historic debate on man’s past.

MOLECULAR BIOLOGY

Molecular biology has lately unravelled the mechanism of
heredity, and we can say that the main features of terrestrial
life are within the perceptible grasp of experimental chenustry.
Many of its puzzles have already worked out with astonishing
simplicity. The basic strategy of life is that of molecular struc-
ture. The linear, bi-helical structure of deoxyribonucleic acid
(DNA) (and who would have thought that genes would be
resolved before tendons?) tells us the mechanism of molecular
reproduction—the selection of nuclein molecules that have a
complementary fit to the available space on the existing DNA
chain. We have also a fair picture of how the nuclein sequence in
DNA is translated into the corresponding sequence of amino
acids in proteins. And the coiling of the amino acid chain,
determined by this sequence, generates the three-dimensional
shape by which the protein works. The protein molecules, by a
similar fit of shape, recognize one another to aggregate into
structural fibres and membranes, or enfold smaller molecules to
direct the metabolic flow chart of the cell.

Now we can define man. Genotypically at Icast, he is six feet
ofa particular molecular sequence of carbon, hydrogen, oxygen,
nitrogen and phosphorus atoms—the Iength of DNA tightly
coiled in the nucleus of his provenient egg and in the nucleus of

263
JOSHUA LEDERBERG

every adult cell, 5 thousand million paired nucleotide units long.
This store of “information” could specify 10 million kinds of
proteins. Almost certainly, most of this information controls
just when and where some few thousands of proteins will be
made—the tendons and enzymes, antibodies, hormones and the
like, of which the body is composed.

Evolution is the duplication and exploitation of structural
error. Simple organisms have as few as 100,000 units (the even
simpler viruses plagiarize the larger genctic “library” of their
host cells). Mistakes in molecular reproduction—mutations—
are inevitable: one of evolution’s marvels is that they are so rare.
The innovation rarcly serves better; when it does, the cell that
carrics the mutant DNA will be favourably selected, and the
new DNA thus preferentially propagated in future gencrations.

From principle to detail is still a big step. We do not in fact
yet know the actual nucleotide sequence of any gene. Only in
micro-organisms, whose DNA content is from a millionth to a
thousandth of man’s, can we momentarily substitute one DNA
molecule for another in the genctic composition of a cell, and
then inferentially judge the chemical differences between them.
But a little inspiration and reasonable effort will be rewarded
by detailed knowledge of genetic structure, very soon for mi-
crobes, no more than a decade or so away for parts of the
human genome.

EUGENICS AND EUPHENICS

Most gencticists, however they may be divided on their
specifications for policy, are deeply concerned over the status
and prospects of the human genotype.

Human talents are widely disparate; much of the disparity
(no one suggests all) has a genetic basis. The facts of human
reproduction are all gloomy—the stratification of fecundity by
economic status, the new environmental insults to our gencs,
the sheltering by humanitarian medicine of once-lethal defects.
Even if these evils were tolerable or neutralized or mus-stated,
do we not still sinfully waste a treasure of knowledge by ignoring
the creative possibilities of genetic improvement ? Surely the

264

Biological Future of Man

same culture that has uniquely acquired the power of global
annihilation must generate the largest quota of intellectual and
social insight to secure its own survival ?

The recent achievements of molecular biology strengthen our
eugenic means to achicve this purpose. But do they necessarily
support proposals to transfer animal husbandry to man? My
own first conclusion is that the technology of human genctics
is pitifully clumsy, even by the standards of practical agriculture,
Surely within a few generations we can expect to learn tricks
of immeasurable advantage. Why bother now with somatic
selection, so slow in its impact? Investing a fraction of the
effort, we should soon learn how to manipulate chromosome
ploidy, homozygosis, gametic selection, full diagnosis of hetcro-
zygotes, to accomplish in one or two gencrations of cugenic
practice what would now take ten or one hundred. What a
clumsy job we would have done on mongolism even just five
years ago, before we understood the chromosomal basis of this
discase! No one would undertake a costly programme of animal
improvement without a clear cut engineering design from which
we could compute the anticipated benefits in relation to the
costs.

As further extensions of experimental cytology, we inight
anticipate the in vitro culture of germ cells and such manipula-
lions as the interchange of chromosomes and segments, The
ultimate application of molecular biology would be the direct
control of nucleotide sequences in human chromosomes, coupled
with recognition, sclection and integration of the desired genes,
of which the existing population furnishes a considerable variety.

These notions of a future cugenics are, I think, the popular
view of the distant rélc of molecular biology in human evolution,
but I believe that they mis-state its real impact on human
biology in the near furure. What we have overlooked is
euphenics, the engineering of human development.

Development is the translation of the genctic instructions of the
egg, embodicd in its DNA, which direct the unfolding of its
substance to form the living, breathing organism. The crucial
problem of embryology is the regulation and execution of

265
JOSHUA LEDERBERG

protein synthesis which underlies the orderly differentiation
of cell types—how some DNA segments are made to call out
their instructions and others are suppressed. These issues are
now suddenly accessible to experimental analysis. Embryology
is vcry much in the situation of atomic physics in 1900; having
had an honourable and successful tradition it is about to begin!
But it will not take long to mature. Most predictions of research
progress have proved recently to be far too conservative.

Until now, the major problems of human development—not
only embryology, but also the phenomena of Icarning (in its
neurobiological aspects), immunity (with its bearing on trans-
plantation), neoplasia and senescence—could be approached
at only the most superficial level. They are about to be trans-
formed in the sense that genctics has been, as epiphenomena of
protein and nucleic acid synthesis. The present intensity of
cffort suggests a span of from five to no morc than twenty years
for an analogous systematization. The application of these
advances to human affairs is equally imminent.

On these premises it would be incredible if we did not soon
have the basis of developmental engineering technique to regu-
late, for example, the size of the human brain by prenatal or
early postnatal intervention. In fact, it is astonishing how little
experimental work has been done to test some elementary
questions on the hormonal regulation of brain size in laboratory
animals or the functional interconnexion of supernumerary
brains. Needless to say, “brain size”’ and “intelligence” should
be read as cuphemisms for whatever cach of us projects as the
ideal of human personality.

The basic concept of molecular biology is the chain of infor-
mation from DNA to ribonucleic acid (RNA) to protein. We
are just beginning to ask questions about mental mechanisms
from this standpoint. The simplest and one of the oldest
suggestions about memory is the modification of ncuronal inter-
connexion through control of synthesis and deposition of durable
proteins at the interfaces. The link between electrical impulses
and protein synthesis could easily be the accompanying shifts
of potassium and sodium ion concentrations, these ions being

266

Biological Future of Man

also important cofactors for several enzymes involved in protein
synthesis. More claborate coding, such as the modulations of
the actual conformation of the protcins can also be invoked, but
may not be necessary to account for the actual storage capacily
of the brain. Speculative models for this kind of coding can be
built on the basis of present knowledge of protcin synthesis,
without impairing the conservation of information in the nucleic
acids or invoking unsubstantiated principles of electrical control
of nucleic sequences. Unlike other cellular systems, the neu-
rones, which rarely if ever divide, need mo mechanism to
propagate their information to cell progeny. The burden of
data storage may therefore be confided entirely to protein.

The purpose of mentioning these speculations is to dramatize
the relationship of mental science to molecular biology. The
analysis of protein structure and metabolism throughout the
brain, the correlation of structural development with Icarning,
its genotypic control, and its alteration in disease are beginning
to be attacked in force, impelled in part by social concern for
the immensely important problem of mental retardation, as
such research must tell us even more about normal mental
development. .

In another field of devclopmental engineering Professor Meda-
war has already exhibited a tour de force, the abolition of
immunity to transplants introduced in early life, a work which
has clarified the biology of immunity and points to the solution
of the transplantation problem. At present human individuality
is the obstacle to spare-part medicine: the organism rejects
grafts from other individuals, even though the alien tissuc might
be a life-extending kidney or heart. Why the chemistry of our
cell membranes should be so individualized is not clear; it may
impede the contagious spread of cancer cells, or perhaps of
viruses which attack host cell surfaces.

There is little evidence of forethought about the social impact
of the solution to the homograft problem, although this solution
seems very near and may prove a prototype for the exercise of
responsible power in biological engineering. Nor has the full
impact of tissue replacement on the practice of medicine been

267
JOSHUA LEDERBERG

widely appreciated. For example, many therapeutic measures
are at present barred or restricted by the possibility of damage
to some organs in the course of therapy.

The medical revolution should begin to arouse anxieties over
its orderly progress. We must recall that the homograft
“barrier”’ has preserved the personality of the body. We have
not hitherto had to think deeply about the technology and ethics
of allocating precious organs for lifesaving transplantations.
The potential dehumanizing abuscs of a market in human flesh
are fully anticipated in imaginative literature and modest
proposals have been wryly recorded for the furtherance of
international trade. Ultimately we must also reserve some con-
cern for the identification of the person: what is the moral,
legal, or psychiatric identity of an artificial chimera?

This is an alarmist and ungracious reaction to a gift of life.
But we cannot overlook what medical progress has already
done for the specics in the name of humanity—for example,
the catastrophic leap in world population through the uncom-
pensated control of early mortality. We must try to anticipate
the worst anomalies of biological powers. To anticipate them
in good time is the first clement of hope in developing institu-
tional and technological antidotes. Only preliminary sugges-
tions arc possible, but even imperfect ones may help to illuminate
the possibilities:

(1) Accelerated engineering development of artificial organs,
e.g. hearts, which may relieve intolerable economic pressures
on transplant sources.

(2) Development of industrial methodology for synthesis of
specific proteins: hormones, enzymes, antigens, structural pro-
teins. For example, large amounts of tissue antigens would
furnish the most likely present answer to the homotransplanta-
tion problem and its possible extension to hetcrotransplantation
from other species. Structural proteins may also play an impor-
tant réle in prosthetic organs.

(3) A vigorous cugenic programme, not on man, but on
some non-human species, to produce genctically homogeneous
material as sources for spare parts. The technical problem of

268

Biological Future of Man

overcoming the immune barricr would be immensely simplified
if the heterografts came from a genctically constant source, the
more so if the animal supplying the grafts could be purposely
bred for this utility. At present the only adequately inbred
mammals are small rodents.

(4) The formal registration of all organ transplants (with
some stated exceptions such as blood, patches of skin and simi-
larly dispensable parts that can pose no problems of availability).
This would furnish more precise statistics on present efforts at
transplantation and help assure an orderly evolution of the
technique.

The first three of these proposals illustrate an important gap
between academic science and its economic application which
too often private enterprise is discouraged or inapt to fill, and
which, unlike basic science, calls for detailed social planning.

Man’s control of his own development, “ cuphenics”’, changes
the means and also the ends of cugenics, as have all the pre-
ceding cultural revolutions that have shaped the species: lan-
guage, agriculture, political organization, the physical technolo-
gics. Eugenics is aimed at the design of a reaction system (a
DNA sequence) that, in a given context, will devclop to a
defined goal. But will culture stand still merely to validate the
cugenic criteria of a past generation? And for a given end, the
means will have shifted: the best inborn pattern for normal
development will not always react best to euphenic control.

Should biologists give first priority to long-range cugenic
concerns of human genotype, or to the gravely imminent issucs
of human numbers and phenotype: the allocation of intelli-
gence, motivation and longevity?

When cuphenics has worked itsclf out we should have a
catalogue of biochemically well-defined parameters for res-
ponses now describable only in vague functional terms. Then
we shall more confidently design genotypically programined
reactions, in place of evolutionary pressures, and search for
further innovations.

Eugenics and cuphenics are the biological counterparts of
education, a panacea that has a longer but cqually contentious

269
JOSHUA LEDERBERG

tradition. The troubled history of Utopian education warns us
to take care in rebuilding human personality on infirm philo-
sophy.

In our enquiry on man’s future, the aims of human existence
are inseparable from the power and responsibility for human
nature. As biological technology dissolves the barriers around
individual man and intrudes on his secret, germinal continuity,
we must face the issue of a definition of man, taking full account
of his psychosocial progeny. We now recognize genetic con-
tinuity in mechanistic terms as a nucleotide sequence—in due
course this will itself be subordinate to the psychosocial machi-
nery. (Our global experiments on human mutagenesis by
chemicals and by artificial radioactivity are the crude, random
initiatives.) What will then qualify “man”? for the aspirations
of humanistic fulfilment, apart from the other robots born of
human thought?

COMMUNICATION: OTHER WORLDS AND OUR OWN

In illuminating the chemical mechanism of terrestrial life,
molecular biology has completed Darwin’s effort at a gencral
theory. This coincides neatly with the technical realization of
space flight and of radio astronomy. The challenge of planctary
exploration has made us think more deeply about the general
principles of carthly life. The prime questions of exobiology,
life beyond the earth, concern molecular biology. Do the
Martian organisms use DNA and amino acids as we do, or are
there other solutions to the basic problem of the architecture of
evolution ?

How seriously the radio astronomers take the prospects of
interstellar communication is hard to fathom. Atany rate, there
is nothing in biology to discourage the hypothesis of multifocal
intelligence in the universe. We have not really thought very
much about the problem of finding the rapport needed to estab-
lish the first contact. It is many times morc costly to transmit
than to listen, which can lead to a perplexing stalemate in
these cosmic negotiations. Hopefully, this technological issuc
will ripen into a more sophisticated theory of communication

270

Bulogical Future of Man

without convention which may have wider interest, as it may
also motivate greater investment in the technology of mes-
sage transmission.

The content of the communication has been least thought
about. It might be the greatest help to understanding our own
philosophy. How should we epitomize ourselves in telling our
story to others? I do not doubt we should describe DNA and
proteins, possibly the most arbitrary and unpredictable con-
sequences of cosmic evolution. Technically, the periodic table
of the clements would be easy to encode, and would establish
chemistry as a context of discourse. But what then? As our
presence at this symposium witnesses, man is a communicative
animal and it may be some convort to offer this instinct an
infinite challenge.

One prospect may be alarming—that we receive messages
that betray our own scientific backwardness. What could erode
scientific creativity, so dependent on the delusion of something
new under the sun, more than the knowledge that everything
is already known but only our access to the oracle is imperfect
and costly?

The topic of our symposium warrants other insights, the
style and allegorical licenses of the artist; the verifiable statements
that any scientist might make in predicting man’s biological
future are probably vacuous. I have been alarmed about my
own credentials, which should include responsible appreciation
of the relevant science. I could reassure myself that it would be
the utmost of human capacity to assimilate a fraction of what
others have already said on the same issues, that I was sctting
myself an impossible task to achicve any novelty of concept or
statement. But in acquicscing to this fact do we not now sce
another image of man’s biological future, his future as a
scicntist ?

Today some scientists succeed in assuring themselves of
currency in thcir investigative work, partly Uhrough sclf-delu-
sion, partly through choice of narrowly delimited fields, partly
through arrogant but sometimes justifiable assumptions about
the incompetence of most of their colleagues, whose papers may

271
JOSHUA LEDERBERG

then lic unread. A typical weekly reminder list distributed in
our department may include upwards of a hundred titles. It
would be a more than full-time occupation to digest just this
sample of science, and it takes a constant act of judgment to
decide what to take time for. ‘The useful output of scientific
work has not yet been impaired by the density of “creativity
space’’. In any case, society’s rcturn for its investment in science
is so great that it cannot afford to hold back from an even
greater, though possibly less efficient, allocation of its resources
to science and technology. Whether the individual motivation
for a scientific carcer can sustain the pressure on creative oppor-
tunity is a perturbing question. ‘The situation is bound to be
aggravated by the general increase in population and in the
relative popularity of science, peghaps most of all by the sudden
accession of the once underdeveloped nations to the main
streams of world science.

The problem is compounded by the archaic clumsiness of our
basic mechanisms of communication. Man’s dilemma is the
discrepancy between the size of his population and complexity
of his institutions, on one hand, and his individual fecbleness,
measured as a data input rate ofno morc than 50 bits per second.
The linguistics of the future may improve the technique of
speech, or open other channels of communication for our daily
needs. Meanwhilc it is anomalous how inefficiently science has
applied existing tcchnology to tend to its own needs of com-
munication. Incredible to say, within the present system only
by chance could I in future discover comments that others
might publish in criticism of this very paper. The phenomenon
of science has only recently attracted the analytical interest that
can help to expose such anomalies. Until it has gone much
further we can only guess at their roots in personal and cultural
psychology. They do lend support to the hypothesis of uncon-
scious resistance to effective, and therefore perhaps disturbing,
communication.

The changes in the scope of research have changed its quality.
Research is the effort to add to Auman knowledge. The extent
of existing knowledge was hitherto more readily discoverable:

272

Biological Future of Man

contributions were less competitive, did not nced endless per-
suasion and repetition to be heard; the challenge was the struggle
with nature. The complication of science has made it inexorably
more human—or should we ever have forgotten this limit to
objectivity ?

Man’s future as a biologist surely depends on the rationaliza-
tion of scientific communication. Society makes many demands
on the energies of the global community of science. We must
also take care to look to the preservation of our own future by
the modernization of our own techniques for efficient but free
expression.

The theme of this paper was to have been molecular biology,
the transfer of information from one macromolecule to another.
It has become an essay on communication, under the same logic
by which man has evolved from substance to concept.

BIBLIOGRAPHY

. Huxley, J. (ed.) (1961). The [Humanist Frame. London: Allen & Unwin.

. Lederberg, J. (1958). A View of Genetics. Stockholm: Les Prix Nobel.

. Medawar, P. B. (1959). The Future of Man. London: Methuen.

. Muller, H. J. (1962). Studies in Genetics. Bloomington, Ind.: Indiana
University Press.

wD

273

sB