Ah fl C huK A
lh nery WE

BIOLOGISTS HAVE ACHIEVED SO MUCH IN THE LAST cecruRy.
AND PARTICULARLY IN THE LAST TWENTY-FIVE YEARS, THAT YOU
MAY WONDER WHY I CHOSE TO TALK %eSe@F ABOUT THE FUTURE
RATHER THAN CONCENTRATE ON THE PRESENT. ESPECIALLY AT MY
AGE, AT THE THRESHOLD OF RETIREMENT, IT WOULD SEEM MORE
APPROPRIATE TO SUM UP THE ACHIEVEMENTS THAT I HAVE BEEN
LUCKY ENOUGH TO WITNESS RATHER THAN TRYING TO FORECAST
WHAT OTHERS WILL BE DOING AFTER MY TIME.

My REASONS FOR CONCENTRATING ON THE FUTURE RATHER THAN
is A A |

THE PAST ARE TWO. THE FIRST “MB GENERAL ONE x CAN BEST
EXPRESS IN THE WORDS OF BERTRAND RusseLL:(47 a IS IMPORTANT
TO CARE IMMENSELY ABOUT THINGS THAT ARE GOING TO HAPPEN
AFTER ONE 1S DEADM’’ WHAT RUSSELL MEANT, OF COURSE, IS THAT
THE TEST OF ONE’S HUMANITY IS TO IDENTIFY, NOT WITH ONE TIME
OR ONE GROUP/OR ONE JOB/ BUT WITH THE CONTINUITY OF THE

, h
[HHEELEESSHAL) ENTERPRISE OF MANKIND, SUCH BELIEF WAS SURELY

MF PART OF THE SECRET OF LONG Lire THAT MADE RUSSELL LIVE

et eee

TO BE A STURDY 98!

My SECOND REASON FOR LOOKING AT THE FUTURE IS THAT THERE
HAS RECENTLY BEEN A CERTAIN GLOOM IN THE WORLD OF BIOLOGY,
IT MAY JUST BE THE GLOOM THAT FOLLOWS EVERY ruRrerT OF SUCCESS,

MAY
BUT IT MUST BE TAKEN SERIOUSLY BECAUSE TT ALNDICATEY SH

LO
UNHEALTHY SITUATION. FAN
ON THE ONE HAND, THERE ARE THE PROPHETS OF DOOM, WHO
TELL US THAT ALL THAT WAS EXCITING TO SOLVE IN BIOLOGY HAS
BEEN SOLVED: THAT, ALAS, NO NEW COSMIC LAWS HAVE BEEN
DISCOVERED; AND THAT ALL THAT REMAINS TO BE DONE IS TO MOP
UP -- EXCEPT PERHAPS FOR EXPLAINING THE HUMAN BRAIN. A
SMALL ORDER INDEED; LIKE SAYING THAT, HAVING LEARNED TO
CLIMB BEACON HILL, ALL THAT REMAINS IS TO CLIMB ANNAPURNA!
THIS TREND 1S, OF COURSE, PURE WELTSCHMERZ OR SNOBBERY, AND
I SEE LITTLE DANGER OF ITS SPREADING FAR /AMONG THE NEW

GENERATION OF BIOLOGISTS. f

THE SECOND SOURCE OF QUESTIONING, ON THE OTHER HAND, IS
MORE SERIOUS AND MORE DANGEROUS. IT IS THE “SO-WHAT” TYPE
OF QUESTIONING. IT IS THE SOURCE OF A REAL CRISIS, OR
RATHER PSEUDO-CRISIS, WHICH TAKES THE FORM OF ANTI-REDUCTIONISM:
OF AN ATTACK ON SCIENTIFIC REDUCTIONISM, AN ATTACK CARRIED
OUT IN THE NAME OF WHAT IS VARIOUSLY CALLED WHOLISM OR

A TON
INTEGRATIONISM, THE ARGUMENT /OF THE ANTI-REDUCTIONISTS IS
BIND

SIMPLE: THE MORE 3#® MOLECULAR BIOLOGISTS PPYNS OUT ABOUT THE
MOLECULAR STRUCTURE OF ORGANISMS, AND THE RELATION OF THAT
STRUCTURE TO ORGANIC FUNCTIONS, THE MORE THE INTEGRATIONISTS
COMPLAIN THAT WHATEVER THE REDUCTIONISTS FIND @# IS NOL THE
IMPORTANT PART OF BIOLOGY. WE ARE TOLD THAT THE ORGANISM,
AND THE HERD, AND THE SPECIES, AND THE ECOLOGICAL NICHE ARE
WHAT MATTERS. IT ALL SOUNDS AS IF THESE MOST COMPLEX LEVELS

OF ORGANIZATION DERIVED THEIR REALITY, NOT FROM THEIR
COMPONENT ELEMENTS, WITH THEIR SPECIFIC MOLECULAR STRUCTURES
AND FUNCTIONS, BUT FROM SOME ALMOST MYSTICAL ELEMENT OF
“WHOLENESS” COMING SOMEHOW FROM SOMEWHERE ELSE -- IN OTHER

t

WORDS, THE MYTH OF “EMERGENCE.” 10 CITE ONE EXAMPLE, AN
EMINENT WHOLISTIC BIOLOGIST WHO READ THE MANUSCRIPT OF A

BOOK OF MINE, WROTE ME A SERIOUS AND URGENT PLEA TO INTRODUCE
SOMEHHERE AT LEAST THE IDEA THAT “SOMETHING SPECIAL,”

SOMETHING OUTSIDE CURRENT EVOLUTIONARY THEORY, MAY HAVE ENTERED
THE PICTURE TO MAKE POSSIBLE THE EMERGENCE OF MAN. SINCE I AM
AGAINST DISCRIMINATION OF ANY SORT, 1 WONDERED$ WHY SHOULDN’ T
THE HONEY BEES, OR THE BIRDS OF PARADISE, OR THE WHALES /FEEL
ENTITLED TO THE SAME EXCEPTIONALITY WITHIN EVOLUTION, JUST
BECAUSE THEY DON’T HAVE A CHANCE TO REVIEW MANUSCRIPTS PRIOR

TO PUBLICATION?

THE EMPHASIS ON THE COMPLEX AND THE HARD-TO-EXPLAIN AS
BEING THE ONLY VALID CENTERS OF INTEREST /IMPLIES A MYSTICAL
ATTITUDE, ALMOST A HOPE THAT BRIDGES WILL NQT BE FOUND BETWEEN
THE COMPLEX, INTEGRATIVE LEVELS AND THE SIMPLER LEVELS OF
INTERPRETATION. [| USED TO ATTRIBUTE, CYNICALLY, THE ANTI-
REDUCTIONIST ATTITUDE OF ORGANISMIC BIOLOGISTS/TO AN
UNWILLINGNESS TO LEARN BIOCHEMISTRY. BUT ANTI-REDUCTIONISM
IS NOT JUST AN ODDITY AMONG BIOLOGISTS. IT IS AN ATTITUDE
THAT BIOLOGISTS BORROW, UNCONSCIOUSLY, FROM THE SOCIAL
SCIENCES, WHERE A NONREDUCTIONIST, PHENOMENOLOGICAL APPROACH
IS NECESSARY AND JUSTIFIED. LET ME ILLUSTRATE WHAT I MEAN
WITH AN EXAMPLE.
I RECENTLY HAD THE EXPERIENCE OF DINING WITH A GROUP OF
DISTINGUISHED SOCIAL PSYCHOLOGISTS. DURING DINNER, I BROUGHT
UP CONVERSATIONALLY SOME FACTS OF NEUROPHYSIOLOGY THAT I HAD
LEARNED A FEW DAYS EARLIER AND I HAD D EDUND EXCITING, AND 4
THOUGHT WOULD INTEREST MY COMPANIONS. anERE WAS AN
EMBARRASSED SILENCE, F, 1 HAD MENTIONED DEATH AT A WAKE;

Sf thew a
OR AS IF | oo ah ee DEVIL IN THE HOME OF A METHODIST
MINISTER. LATER THAT EVENING, ONE OF THE PSYCHOLOGISTS ASKED
ME, WITH SOMETHING LIKE COMPASSIONATE UNDERSTANDING, “YOU ARE
A REDUCTIONIST, AREN'T YOU?” IN THE TONE AN ENLIGHTENED
LIBERAL MIGHT USE TO ASK, “ARE YOU A COMMUNIST?” OR “ARE YOU
A HOMOSEXUAL?”

UPON REFLECTION ,IT SEEMS TO ME THAT ANTIREDUCTIONISM IS
AN UNDERSTANDABLE AND PROPER ATTITUDE IN THE SOCIAL SCIENCES,
AFTER ALL, BETWEEN BIOLOGY (INCLUDING PHYSIOLOGICAL PSYCHOLOGY)
AND THE SOCIAL SCIENCES (STARTING WITH SOCIAL PSYCHOLOGY)
THERE EXISTS A TRUE GAP OF SUBJECT MATTER. THE GAP REFLECTS
OUR CURRENT IGNORANCE OF THE PHYSICAL AND BIOLOGICAL BASIS
OF HUMAN COGNITION. PHILIP MORRISON, WHO W&6 ONE OF Bs (oLag &,
MeREPENG=S- SPEAKERS, ONCE DEFINED CHEMISTRY Seen TO DO
WHILE YOU WAIT FOR THE SCHROEDINGER EQUATION,” “Gee tae GAP
BETWEEN PHYSICS AND CHEMISTRY IS ONLY A TECHNICAL GAP. we Dal Lh
GAP BETWEEN NATURAL AND SOCIAL SCIENCE IS WIDER, BECAUSE AN
ENTIRE LEVEL OF COMPLEXITY, THAT OF THE HUMAN MIND, REMAINS
TO BE EXPLORED, SOCIAL SCIENCES DEAL WITH THE STRUCTURE OF
HUMAN SOCIETY, THAT IS, WITH MEN AND WOMEN AS SOCIAL ANIMALS,
5

HUMAN BEHAVIOR IS CONDITIONED BY SOCIETY AS WELL AS BY THE
HUMAN BRAIN. BUT HOW THE HUMAN BRAIN WORKS STILL ESCAPES
US. PHYSIOLOGICAL PSYCHOLOGISTS, WHO ARE REALLY BIOLOGISTS,
ARE HARD AT WORK ON THIS, BUT PROGRESS IS SLOW. AS A RESULT,
THE SOCIAL SCIENTISTS HAVE TO OPERATE STRICTLY AT THEIR OWN
THEY
LEVEL OF PHENOMENOLOGY. IF -S@GhAL-SCLENTE8F6=HAB—FO WORRY & DP)
THEMSELVES ALL THE TIME ABOUT THE POSSIBLE BIOLOGICAL |
SUBSTRATE OF THEIR SUBJECT NATTER/THEIR WORK WOULD BE BADLY
HAMPERED. IN FACT, I BELIEVE THAT SOCIAL SCIENCE IS ACTUALLY
ENDANGERED BY MISGUIDED EFFORTS TO BIOLOGIZE HUMAN BEHAVIOR,

AS I SHALL MENTION LATER IN THIS LECTURE.

WITHIN BIOLOGY THE ANTI-REDUCTIONIST ATTITUDE HAS NO
VALID JUSTIFICATION. IN THIS LECTURE | INTEND TO SET FORTH Af
FIRE 9€ Revuctionist CREED: NOT A NEGATIVE CREED, THAT DENIES
THE VALUE OF DEALING WITH PHENOMENA AT THE LEVEL OF
OBSERVABLE PATTERNS, BUT A POSITIVE REDUCTIONIST CREED.

A POSITIVE REDUCTIONISM IS FOUNDED ON THREE PRINCIPLES,
EIRST, THAT ANY INTERPRETATION OF PHENOMENA AT ANY LEVEL MUST
BE CONGRUENT WITH THE LAWS OF PHYSICS AS GENERAL LAWS OF - \
NATURES SECOND, THAT THE INTERPRETATION MUST POTENTIALLY BE

REDUCIBLE TO THE PROPERTIES OF STRUCTURES FULLY INTERPRETABLE
IN TERMS OF 38 PHYSICAL LAWS, AND THIRD, THAT IT IS THE
PROPER TASK OF THE SCIENTIST TO FOSTER THE ACHIEVEMENT
OF SUCH REDUCTION,

REDUCTIONISM SHOULD OF COURSE BE HISTORICAL RATHER THAN
MECHANICAL, TO SAY THAT CHEMISTRY OR GEOLOGY OR BIOLOGY MUST
BE INTERPRETABLE IN TERMS OF PHYSICAL LAWS DOES NOT MEAN
THAT THE STARS, THE PLANETS, THE SPECIES THAT EXIST ARE

COULD EXISTED
THE ONLY ONES THAT MB@HF HAVE BEER} AND THAT IF WE KNEW THE
ENTIRE HISGORY OF THE UNIVERSE WE COULD CALCULATE THE
ABUNDANCE OF CHEMICAL ELEMENTS ON JUPITER OR THE GENE
FREQUENCIES AMONG PYGMIES IN CENTRAL AFRICA. WHAT REDUCTIONISM
MEANS IS THE CONFIDENCE THAT THE DECISIVE ELEMENTS IN BIOLOGICAL
EVOLUTION, FROM THE EARLIEST TEMPLATE MOLECULES TO THE MOST
COMPLEX INTERACTIONS BETWEEN SPECIES AND POPULATIONS/ HAVE
INVOLVED PHYSICAL PROCESSES ONLY; THAT THESE PROCESSES HAVE
NOT BEEN DIFFERENT IN ANY RESPECT FROM THOSE OBSERVED IN
PHYSICAL PHENOMENA; AND THAT ALL BIOLOGICAL PHENOMENA CAN
ULTIMATELY BE INTERPRETED IN TERMS OF THE BEHAVIOR OF ATOMIC

AND MOLECULAR STRUCTURES,

THE MOLECULAR BIOLOGY OF THE GENE, TO USE THE FELICITOUS

en

TITLE OF WATSON’S TEXTBOOK, HAS BROUGHT TO BIOLOGY A UNIFYING

CENTER, COMPARABLE TO THAT PROVIDED TO PHYSICS BY wecszaurc actly,

THEORY. JUST AS THE ACHIEVEMENTS OF PHYSICS INTERPRET THE
As VET
BROAD LINES OF CHEMISTRY WITHOUT MAKING THE EXPLANATION
FULLY EXPLICIT, THE MODERN THEORY OF THE GENE EXPLAINS BIOLOGY

* Wd Sane.
WITHOU RAKING ALL OF IT EXPLICIT. WHERE DO WE GO FROM #HERE?
6A

AN ORGANISM OPERATES, NOT WITH GENES BUT WITH GENE
PRODUCTS, THAT IS, WITH PROTEINS. PROTEINS ARE THE LOVE
OF PROTEIN CHEMISTS, BUT TO THE MOLECULAR BIOLOGIST THEY
ARE A NIGHTMARE. WHEREAS GENES ARE ALL (oR ALMOST ALL) DNA,
WITH A UNIFORM TAPE-LIKE STRUCTURE AND A CODED SET OF
SPECIFICATIONS AND SIGNALS, PROTEINS START WITH SPAGHETTI-
LIKE FILAMENTS AND FUNCTION ONLY WHEN THE FILAMENTS HAVE
BALLED UP IN THEIR OWN SPECIFIC SHAPES, THOUSANDS OF DIFFERENT
SHAPES. DESPITE SOME HELPFUL PRINCIPLES, IT STILL TAKES YEARS
OF WORK TO UNRAVEL THE SHAPE OF ONE, PROTEIN AND THE RELATION
TO ITS FUNCTION, AT THE MOMENT/WE CAN NO MORE PREDICT THE
PROPERTIES OF A PROTEIN FROM THE SEQUENCES OF ITS AMINO
ACIDS THAN A CHEMIST CAN WRITE THE WAVE EQUATION FOR A NEW
COMPLEX ORGANIC COMPOUND. THE FRONTIER OF PROTEIN CHEMISTRY
WILL CONTINUE TO BE EXPLORED FOR DECADES, BUT MEANWHILE THE
MOLECULAR BIOLOGIST MUST SEEK OTHER AND GREENER PASTURES.

THE FIRST FIELD I WISH TO TAKE UP IS THAT OF ONTOGENY,
THAT IS, EMBRYOLOGY: THE MAKING OF A COMPLEX ORGANISM OUT
OF CELLS WITH IDENTICAL GENES. IN A COMPLEX ORGANISM
DIFFERENT GENES / FUNCTION DIFFERENTIALLY IN DIFFERENT CELLS.
IN A UNICELLULAR ORGANISM LIKE A BACTERIUM, DIFFERENTIAL GENE
FUNCTION IS ELICITED DIRECTLY BY THE ENVIRONMENT: SPECIFIC
SUBSTANCES CAUSE THE ACTIVATION OR INHIBITION OF THE FUNCTION
OF SPECIFIC GENES. WE KNOW HOW THIS IS DONE IN BACTERIA,
BUT WE ALSO KNOW THAT IN THE CELLS OF HIGHER ORGANISMS IT
MUST BE DONE DIFFERENTLY. WE DO NOT YET KNOW HOW, BUT WE
ARE CONFIDENT THAT WE SHALL SOON FIND OUT.
ARE of TéEW

IRREVER SIBL

7

BuT WHEN A HUMAN EMBRYO, CONTAINING ONLY A FEW THOUSANDS
CELLS, BEGINS TO TURN SOME OF THESE CELLS INTO PRECURSORS
OF THE BRAIN, OTHERS INTO THE ANCESTORS OF THE GUT, AND
OTHERS STILL INTO THE SOURCES OF MUSCLES AND BONES, THE
SIGNALS CANNOT COME FROM THE OUTSIDE: THEY MUST COME FROM
WITHIN, FROM THE GENES THEMSELVES. IHE SIGNALS MUST BE
PROGRAMMED IN TIME AS WELL AS IN SEQUENCE OF EVENTS. WHAT
IS THE MOLECULAR BASIS OF THIS PROCESS? SURPRISINGLY, THE
BEST ANALOGY TO DATE COMES FROM CERTAIN VIRUSES. WHEN
VIRUSES ENTER A SUITABLE CELL THEY UNFOLD A SEQUENTIAL
PATTERN OF EVENTS THAT IS FULLY PROGRAMMED WITHIN THE VIRAL
GENES, THIS PROGRAM, WHICH IS REGULATED BY A SERIES OF FEED-
BACK AND FEED-AHEAD COMPONENTS, HAS BEEN ALMOST COMPLETELY
UNRAVELED FOR ONE OR TWO VIRUSES. IT SUGGESTS AT LEAST
THE KINDS OF MECHANISMS THAT COULD BE INVOLVED IN
EMBRYOGENESIS: TURNING®ON MECHANISMS SPECIFIC FOR ACTIVATING
THEN OR OFF
A GROUP OF GENES, WHOSE PRODUCTS CAN E=eeRN TURN ON OTHER
A
GENE SETS, anil So or,

IN EMBRYOLOGY, HOWEVER, THERE IS THE ADDED PROBLEM OF
DIFFERENTIATION. THE PROGRAM PRESCRIBES, NOT ONLY WHEN AND
IN WHICH SEQUENCE THE CHANGES OCCUR, BUT WHERE: THAT IS,
WHICH CELLS OR GROUPS OF CELLS WILL GO IN WHICH DIRECTION. ANY /HE

YIT IS EVIDENT THAT WE ARE DEALING/HERE|WITH SOMETHING OF A

i

\ DIFFERENT ORDER OF COMPLEXITY FROM WHAT MOLECULAR BIOLOGISTS

=,
4,

HAVE ENCOUNTERED IN BACTERIA @eemcentts#s, THE SITUATIONS THAT
ARE RELEVANT TO DIFFERENTIATION ARE NOT LIKE THOSE IN WHICH
ONE GENE IS TURNED ON OR OFF ACCORDING TO HOW MUCH OF ITS
PRODUCT IS NEEDED IN A GIVEN ENVIRONMENT, THE ESSENCE OF
DIFFERENTIATION IS STABILITY AND OFTEN IRREVERSIBILITY,
SUPERFICIALLY AT LEAST, THE BACTERIAL SITUATION DIFFERS FROM
DIFFERENTIATION IN HIGHER ORGANISMS AS A TELEPHONE CALL
DIFFERS FROM A WEDDING. AT THE MOLECULAR LEVEL, IN OTHER
WORDS, WE KNOW HOW SWITCHES ARE TURNED ON AND OFF BUT WE DO
NOT YET KNOW HOW CELLS MAKE COMMITMENTS “PA LAST TILL DEATH
B® THEM PART. FOR THAT REASON, EMBRYOLOGY HAS REMAINED
PHENOMENOLOGICAL, NONREDUCTIONIST FOR A VERY LONG TIME.

Now, HOWEVER, THIS CITADEL BEGINS TO YIELD TO THE STRATEGIES
OF MOLECULAR BIOLOGY, THAT IS, TO THE CONCERTED APPLICATION

OF GENETIC AND BIOCHEMICAL ANALYSES.

ESSENTIALLY, WHAT IS BEING DONE IS TO BREAK DOWN THE
COMPLEX SITUATION INTO MANY, POTENTIALLY LESS COMPLEX
ELEMENTS. IF THE PROBLEM OF HOW GENES ARE REGULATED IN THE
CELLS OF HIGHER ORGANISMS STILL BAFFLES US, WE TURN FIRST
TO THE MOLECULAR ORGANIZATION OF CHROMOSOMES, WHERE THE
GENES ARE LOCATED. ONE BEGINS BY HOMOLOGIZING SPECIFIC
STRUCTURES WITHIN CHROMOSOMES WITH THE LOCATION AND SIZE
OF THE GENES. ONE IDENTIFIES THE PROTEINS OF THE CHROMOSOMES,
HOPING TO UNDERSTAND WHICH OF THEM ARE INVOLVED IN REGULATION
OF GENE ACTIVITY. ONE CAN ISOLATE THE PRIMARY MESSAGES THAT
CODE FOR PROTEINS MADE BY SPECIFIC DIFFERENTIATED CELLS.

THIS TELLS US THAT THE MESSAGES ARE IN FACT SPECIFICALLY
ail Kept

MADE ,IN THOSE CELLS, RATHER THAN MADE IN ALL CELLS AND
SPECIFICALLY USED ONLY IN SOME CELLS.

THE METHODS OF GENETIC ENGINEERING CURRENTLY UNDER
DEVELOPMENT, ATTACHING PIECES OF J)NA FROM CELLULAR CHROMO-
somes TO DYNA DERIVED FROM BACTERIA, <-PROMESESTS LEAD Ue
FURTHER TOWARD THE ISOLATION OF THE PIECES OF CHROMOSOME
THAT CONTAIN SPECIFIC GENES,

BESIDES PURSUING THE GENES IN ACTION BY WAY OF CHROMO-
SOME STRUCTURE, THE MOLECULAR BIOLOGIST IS AFTER THE SECRETS
OF DIFFERENTIATION BY STUDYING THE SIGNALS THAT CAUSE
DIFFERENT CELLS TO ACT IN SPECIFIC WAYS AND TO BECOME
COMMITTED TO DIFFERENT DESTINIES. JHE PROBLEM IS STILL
BEWILDERING, NOT FOR LACK OF CLUES, BUT BECAUSE OF THEIR
ABUNDANCE AND VARIETY, PROTEIN FACTORS, PEPTIDES, AND
STEROID HORMONES ELICIT IN DIFFERENT CELLS OF THE ADULT
ORGANISM OR OF THE EMBRYO SUCH A VARIETY OF SPECIFIC
RESPONSES THAT MAY Ay aR T SEEM TO PROMISE NOTHING BUT

EGU!
CHAOS. BUT THE CHAOS BESS TO YIELD TO BIOCHEMICAL
OME OF THE MYSTERY DISAPPEARS AS THE PROCESS

Wn
THE ENCOUNTER OF A CELL WITH AN EXTERNAL
fhe ell

  
  

DISSECTION,
THAT
FACTOR TO THE RESP NSE(TS BROKEN DOWN INTO A SERIES OF
STEPS, FOR EXAMPLE, A STEROID HORMONE MUST ENTER A CELL
AND COMPLEX WITH A CYTOPLASMIC PROTEIN. THE COMPLEX --
NOT EITHER OF THE TWO COMPONENTS SEPARATELY -- THEN MOVES
TO THE CELL NUCLEUS AND ACTIVATES SPECIFIC GENES. THE
10

DIFFERENT RESPONSES OF DIFFERENT CELLS MAY REFLECT DIFFERENCES
IN ENTRY OF THE HORMONE, OR IN ITS COMBINATION WITH CARRIER
PROTEIN, OR IN THE AFFINITY FOR VARIOUS CHROMOSOMAL SITES,

OR IN THE RESPONSE OF INDIVIDUAL GENES. TITHE LAST POSSIBILITY
SEEMS TO BE THE IMPORTANT ONE: IN THOSE CELLS THAT RESPOND

TO THE HORMONE, THE HORMONE-CARRIER COMPLEX BINDS TO

HUNDREDS OF CHROMOSOMAL SITES, BUT ONLY ONE OR A FEW GENES
RESPOND. EVIDENTLY, THE GENE SET IS PROGRAMMED TO RESPOND
SPECIFICALLY TO A RELATIVELY UNSPECIFIC STIMULUS. How? WE
HOPE THE ANSWER WILL COME SOON,

THE THIRD AND MOST POWERFUL REDUCTIONIST APPROACH TO
EMBRYOLOGY IS BY GOING FROM ORGANISMS OR ORGANS TO CULTURES
OF CELLS. APART FROM THE RANGE OF EXPERIMENTATION THAT
CELL CULTURES MAKE POSSIBLE ON THE PROBLEMS I HAVE ALREADY
MENTIONED -- CHROMOSOME-GENE RELATION AND GENE-SIGNAL
INTERACTION -- CELL CULTURES MAKE IT POSSIBLE TO ANALYZE A
KEY ASPECT OF DEVELOPMENT, THE CONTROL OF CELL PROLIFERATION,
FOR IN THE COURSE OF DEVELOPMENT, DIFFERENTIATION IS
INTIMATELY TIED UP WITH CONTROLLED PROLIFERATION, AT ONE
EXTREME, CELLS LIKE NEURONS OR MUSCLE FIBERS DO NOT DIVIDE
ANY MORE IN THE ADULT BODY. EVEN WHEN THEY STILL PROLIFERATE.
DURING EMBRYOGENESIS, THEY PROLIFERATE IN A CONTROLLED WAY,
WHICH GENERATES THE SPECIFIC SIZES AND SHAPES OF THE ORGANS,
AT THE OTHER EXTREME ARE STEM CELLS, WHICH CONTINUE TO PROLI-
FERATE THROUGHOUT LIFE, BUT ONLY IN A LINEAR FASHION:
11

FOR EXAMPLE, WHEN A STEM CELL OF THE SKIN DIVIDES, IT
GENERATES ONE STEM CELL AND ONE CELL COMMITTED TO DIFFEREN-
TIATION, THIS COMMITTED CELL WILL NO MORE DIVIDE, BUT

WILL CHANGE INTO A HORNY SKIN CELL AND THEN DIE.
DIFFERENTIATION, THEREFORE, IS CLOSELY TIED TO CONTROL OF
CELL PROLIFERATION. THE CANCER PROBLEM, INCIDENTALLY, IS

A VARIATION ON THIS THEME,

CULTURED CELLS ARE AN INEXHAUSTIBLE SOURCE OF INFORMATION
IN THIS RESPECT. THEY MAKE IT POSSIBLE TO CLARIFY THE CONNECTION
BETWEEN THE CELL CYCLE FROM ONE DIVISION TO THE NEXT AND THE
PROCESS OF GENE DUPLICATION. THEY HAVE REVEALED THE ROLE
OF HORMONES AND OTHER SUBSTANCES ON THE TRIGGERING AND
INHIBITING OF THE CYCLE. THEY HAVE REVEALED THE UNSUSPECTEDLY
CENTRAL ROLE THAT THE OUTER MEMBRANE OF THE CELL PLAYS /IN
ACTIVATING VARIOUS PHASES OF CELL PROLIFERATION, THE
MOLECULAR BIOLOGY OF THE CELL MEMBRANE HAS BECOME A CENTRAL
ASPECT OF THE STUDY OF DIFFERENTIATION. FOR EXAMPLE, THE
SPECIFIC DIFFERENTIATION OF BONE MARROW STEM CELLS INTO RED—
BLOOD=CELL= PRECURSORS/ IS TRIGGERED, IN CELL CULTURE AS WELL
AS IN THE INTACT ORGANISM, BY A PROTEIN CALLED ERYTHROPOIETIN,
Pree WHICH NEVER ENTERS THE CELL BUT COMBINES WITH A SPECIFIC
MEMBRANE SITE, THE SAME CELL, IN RESPONSE TO A DIFFERENT
STIMULUS, WOULD HAVE GENERATED WHITE BLOOD CELLS. EVIDENTLY,
THE MEMBRANE OF THE UNDIFFERENTIATED BONE MARROW CELL HAS A
MULTIPLICITY OF RECOGNITION SITES, WITH SPECIFIC AFFINITIES
12

FOR DIFFERENT SIGNAL MOLECULES, EACH OF WHICH TRIGGERS A
DIFFERENT RESPONSE ~~ THAT IS, ACTIVATES A DIFFERENT SET
OF GENES.

AT THIS POINT THE MOLECULAR BIOLOGIST FEELS EXCITED.
HE HAS NOT YET BROKEN THE CODE OF DIFFERENTIATION, AS HE
HAD SUCCESSFULLY BROKEN THE GENETIC CODE AND THE SIGNAL
CODE OF BACTERIAL GENE FUNCTION. BUT THE FORTRESS IS
BEGINNING TO CRUMBLE. WHAT IS NEEDED NEXT, AND IS Al L READY
BEGEANENG—F6 BECOMe AVAILABLE, IS A SET OF SYSTEMS SIMPLI-
FIED ONE STEP FURTHER: SYSTEMS IN WHICH A PIECE OF CHROMOSOME,
PLACED IN A TEST TUBE WITH THE APPROPRIATE ENZYMES AND
FACTORS, WILL GENERATE ITS MESSAGE AND ITS PROTEIN PRODUCT,
THEN THE ROLE OF THE STIMULANTS OR INHIBITORS THAT ACT DURING
DEVELOPMENT AND IN VARIOUS ADULT ORGANS WILL BECOME TESTABLE,
] PREDICT THE FIRST OUTPUTS OF THIS PROGRAM ARE LESS THAN
FIVE YEARS AWAY AND THE MOLECULAR UNDERSTANDING OF THE
CONTROLS OF CELL PROLIFERATION LESS THAN TEN,

Oo

IF UNDERSTANDING EMBRYOLOGY, THAT IS, UNRAVELING THE
PROGRAM THAT MAKES ALL OF US WHAT WE ARE IN OUR GROWTH,
HEALTH, ILLNESSES, AND DEATH SEEMS A STAGGERING TASK, THE
OTHER TASK THAT I PROPOSE FOR MOLECULAR BIOLOGISTS IS
POSSIBLY MORE DIFFICULT. [| REFER TO THE MOLECULAR

INTERPRETATION OF EVOLUTION.
13

EVOLUTION, OF COURSE, TAKES TIME. IT TOOK FOUR
BILLION YEARS OF EARTH HISTORY TO PRODUCE ANIMALS; IT
TOOK 200 MILLION YEARS TO GENERATE MAMMALS FROM THEIR
REPTILE ANCESTORS; IT MAY HAVE TAKEN TWENTY MILLION YEARS
TO GENERATE MAN FROM OUR COMMON ANCESTORS WITH TODAY'S
LIVING APES,

SUPERFICIALLY, THERE WOULD SEEM TO BE NO GREAT HURRY TO
FIND OUT HOW ALL THIS HAPPENED. IT IS NOT LIKELY TO START
HAPPENING MUCH FASTER, NOR IS THERE MUCH WE CAN DO ABOUT IT
EXCEPT BEING SENSIBLE ABOUT ATOM BOMBS AND POLLUTION. BUT
THIS IS NOT THE WHOLE STORY, WE DO HAVE A STAKE IN
UNDERSTANDING THE MECHANISMS OF EVOLUTION, AND UNDERSTANDING
THEM SOON, BECAUSE THE CONSEQUENCES OF EVOLUTION ARE
PRESSINGLY UPON US, MATERIALLY, MORALLY, AND INTELLECTUALLY,
ALL THE TIME,

SINCE DARWIN'S TIME WE UNDERSTAND THE GRAND LINES OF
EVOLUTION: VARIATION PROVIDES THE MATERIAL UPON WHICH NATURAL
SELECTION PLAYS. BUT THIS AWARENESS OF THE MAIN FORCES IS
ABOUT AS ILLUMINATING TO AN EVOLUTIONIST AS QUANTUM
MECHANICS IS TO A CHEMIST. WHICH VARIATIONS CONTRIBUTE
TO THE EMERGENCE OF NEW SPECIES? BY WHAT COMBINATION OF
EVENTS DO SOME LINES OF DESCENT PETER OUT, OTHERS BECOME
IMMOBILIZED, OTHERS STILL BLOSSOM INTO THOUSANDS OF
DIRECTIONS? A PRESSING QUESTION IS THAT OF THE TIME SCALE

OF EVOLUTION, Is THAT SCALE CONGRUENT WITH THE TIME
(PARAMETERS
14

PARAMETERS OF VARIATION AND SELECTION AS WE MEASURE THEM?
AND ARE VARIATION AND SELECTION INDEPENDENT FORCES, THE
LATTER JUST ACTING ON THE OUTPUT OF THE FORMER, OR ARE

THEY TIED TOGETHER INTO AN INTERACTING SYSTEM BY STRUCTURAL
FEEDBACKS?

FoR MANY YEARS BIOCHEMISTS HAVE COMPARED A FEW HOMOLOGOUS
PROTEINS, THAT IS, PROTEINS WITH SIMILAR FUNCTION IN
ORGANISMS RANGING ALL THE WAY FROM YEASTS TO HUMANS. THIS
IS LIKE STUDYING THE HISTORY OF SPECIFIC GENES. [THROUGH
THIS KIND OF MOLECULAR EVOLUTIONARY HISTORY THE AMOUNT OF
VARIATION PER UNIT OF GEOLOGICAL TIME CAN BE ESTIMATED,

I WILL NOT GO HERE INTO THE QUESTIONS OF CALCULATING THE RATE
OF EVOLUTION FROM THESE DATA, EXCEPT TO SAY THAT THE RESULTS
NOT ONLY FIT QUITE WELL THE CLASSIFICATION PROPOSED BY
TAXONOMISTS, BUT ALSO THE TIME SCALE OF PALEONTOLOGISTS.

THE HARD PROBLEMS COME UP, HOWEVER, WHEN WE COME TO THE BIG
QUESTIONS: THE ORIGIN OF N W GEMS. THE 1OQ-FOLD DIFFERENCE
IN AMOUNT OF DNA AND OF GENES, FROM YEAST TO MAMMALS, AND,
MORE DRAMATIC, THE RAPID EVOLUTION OF CERTAIN LINES OF
DESCENT AT SPECIFIC TIMES.

NOT SURPRISINGLY, NAIVE CALCULATIONS BASED ON DATA
AVAILABLE AS RECENTLY AS 10 YEARS AGO LAND US INTO TROUBLE.
THE MUTATIONS THAT THE GENETICIST KNOWS BEST -- CHANGES OF
INDIVIDUAL DIGITS OF THE GENETIC SCRIPT OR REARRANGEMENTS
OF PIECES OF CHROMOSOME -- SEEM TO BE NEITHER FREQUENT
ENOUGH NOR VARIED ENOUGH TO REASSURE THE EVOLUTIONIST THAT
15
Kou!

THEY 22g THE WHOLE STORY OF GENETIC VARIATION. HENCE,
HYPOTHESES OF UNKNOWN FORCES, OR OF LIFE HAVING BEEN
IMPORTED FROM OUTER SPACE TO COLONIZE THE EARTH, HAVE
BEEN SERIOUSLY ENTERTAINED,

FORTUNATELY, THE SITUATION HAS IMPROVED IN TWO IMPORTANT
WAYS. FIRST, MOLECULAR BIOLOGISTS HAVE UNCOVERED THE
EXISTENCE OF -panEeus KINDS OF GENETIC VARIATION THAT MAY
SERVE TO SPEED UP EVOLUTION BY GENERATING A GREATER VARIETY
OF CHANGES. AMONG THEM ARE, TQ NAME A FEW, MUTATOR GENES’
THAT CAUSE THE FREQUENCY OF MUTATION TO INCREASE BY A
FACTOR OF 10 or 100; GENETIC CONTROL OF CROSSING OVER,
WHICH MAY ALTER THE FREQUENCY OF RECOMBINATIONS INSERTION
SEQUENCES, WHICH PERMIT THE INSERTION OF FRAGMENTS OF
GENETIC MATERIAL INTO CHROMOSOMES AND BRING ABOUT NEW
GENE COMBINATIONS; AND CONTROLLING ELEMENTS, WHICH CAN
TURN [ON OR OFE/GROUPS OF GENESHIN: DIFFERENT LINES OF
DESCENT. THESE/AND OTHER PROCESSES THAT MAY STILL AWAIT
DISCOVERY/B&l- PROVIDE A GREATER RANGE OF GENOTYPES FOR

NATURAL SELECTION TO ACT UPON,

BUT THE PROBLEM OF THE SPURTS OF FAST EVOLUTION STILL
REMAINS. THESE ARE INSTANCES IN WHICH EVOLUTION SEEMS TO
HAVE PERSISTENTLY CONCENTRATED ON IMPROVING SOME SPECIFIC
DEVICE, IGNORING EVERYTHING ELSE, LIKE A GAMBLER WHO BETS
ALL ON ONE HORSE OVER AND OVER AGAIN. IN THIS WAY
EVOLUTION BRINGS ABOUT ASTONISHING CHANGES. AN ELECTRIC
 

  
 

16

FISH, WHICH GENERATES AND MONITORS AN ELECTRIC FIELD FOR

ITS OWN Lael ala AND PROTECTION, HAS IN ITS BRAIN AN
Q

ENORMOUS Lope’ WHICH IS ENTIRELY DEVOTED TO DECODING AND

ein aes
EMITTING ELECTRIC stenacs anal (HICH IS MISSING IN ITS NON )

——
tt

“ELECTRIC RELATIVES, Afore IMPORTANT STILL, THE HUMAN BRAIN
SEEMS TO HA 1 IN LESS THAN ONE MILLION YEARS TO
ALMOST DOUBLE ITS SIZE, CONCOMITANT WITH THE DEVELOPMENT

OF HUMAN MENTAL FACULTIES, ESPECIALLY LANGUAGE.

THE PROBLEM OF SUCH EVOLUTIONARY SPURTS IS UNRESOLVED"
BECAUSE THE MECHANISMS ARE NOT YET KNOWN, BUT IT IS NOT
INSOLUBLE. WE REALIZE Now /THAT WHAT IS NEEDED IS SOME
ADDITIONAL FEEDBACK, SUCH ‘AS COULD BE PROVIDED BY A TIE-UP
BETWEEN RATES OF VARIATION AND OF SELECTION. IF, AT
SPECIFIC TIMES AND IN SPECIFIC ENVIRONMENTS, SELECTION
WERE FAVORING A CERTAIN CLASS OF GENOTYPES (FOR EXAMPLE, MORE
COMPLEX CEREBRAL FUNCTIONS) AND IF THE SELECTIVE VALUE OF
THOSE GENOTYPES WERE ENHANCED BY INCREASED RATES OF GENETIC
VARIATION OR RECOMBINATION, THEN SELECTION WOULD FAVOR
ENHANCED VARIABILITY AND ACCELERATE THE RATE OF EVOLUTION
IN A NON-LINEAR WAY. SUCH A COUPLED SELECTIVE PRESSURE, ON
GENETIC VARIABILITY AND ON A SPECIFIGCLASS OF GENOTYPES,
MAY HAVE CONTRIBUTED TO THE RAPID EVOLUTION OF HOMINIDS,
AND MAY ALSO EXPLAIN THE HIGH DEGREE OF POLYMORPHISM OF THE
HUMAN SPECIES COMPARED TO OTHER PRIMATES. (A CONVINCING
ANALYSIS OF THE CONCEPT OF SELECTION FOR VARIABILITY HAS
RECENTLY BEEN PRESENTED BY PROFESSOR LAYZER).
17

AN UNDERSTANDING OF THESE PHENOMENA, MORE PARTICULARLY
A CLARIFICATION OF FEEDBACKS BETWEEN VARIATION AND SELECTION,
IS IMPORTANT FOR SEVERAL REASONS. ONE OF THEM IS THE NEED
TO DISPEL CONFUSIONS THAT ARISE WHEN PEOPLE DEAL WITH HUMAN
FACULTIES IN A BIOLOGICAL WAY. IF ONE IGNORES THE HIGH
RATES OF EVOLUTION THAT BRING ABOUT A DOMINANT SPECIES LIKE
MAN, THERE CREEPS INTO BIOLOGY A TENDENCY TO HOMOLOGIZE
TRAITS AND BEHAVIORS BETWEEEN DIFFERENT SPECIES, ORDERS,
OR PHYLA, AS THOUGH EVOLUTION HAD STAYED PUT IN SOME WAYS
WHILE MOVING RAPIDLY IN OTHER WAYS. THUS SOME ETHOLOGISTS HAVE
sume ROM OBSERVATIONS OF INSTINCTUAL AGGRESSIVITY IN
INSECTS OR FISHES, TO INTERPRETING VIOLENCE AMONG HUMANS AS
RESULTING FROM COMPARABLE MECHANISMS. SOCIOBIOLOGISTS MAY
JUMP FROM DESCRIPTIONS OF RELATIONS BETWEEN MEMBERS OF ONE
SPECIES TO SIMPLISTIC INTERPRETATIONS OF THE BEHAVIOR OF
OTHER SPECIES. THIS IS UNJUSTIFIED AND, AT TIMES,

SEM AIST ICS
renesronsia.e. f Te SEMANTIC IMPLICATIONS OF #HE, CONFUSIONS
BETWEEN BIOLOGY AND HUMAN AFFAIRS CAN BE OMINOUS. LOOSE
TALK OF GENES FOR AGGRESSION IN A STICKLEBACK FISH /May BE
RIGHT OR WRONG, BUT IS CERTAINLY INNOCUOUS. TO SUGGEST,
HOWEVER, THAT THERE ARE GENES OR CHROMOSOME FOR VIOLENT
BEHAVIOR IN HUMANS IS NOT A BIOLOGICAL STATEMENTg IT IS A
SOCIOPOLITICAL ACTION. IT IS AN INCURSION INTO THE FIELD
OF VALUES, AN INCURSION THAT MAY INFLUENCE THE TREATMENT
OF INDIVIDUALS AND THE PASSAGE OF LEGISLATION ON SOCIAL
PROBLEMS. SUFFICE IT TO RECALL HOW FIFTY YEARS AGO THE

INSISTENCE OF SOME BIOLOGISTS TO IDENTIFY PELLAGRA AS A
18

GENETIC DISEASE OF THE LOWER CLASSES/AND TO IGNORE THE

ee HAVE
EVIDENCE THAT PELLAGRA WAS A VITAMI DEFICIENCY, DELAYED
FOR DECADES THE PROPER SOCIAL INTERVENTION AT THE

NUTRITIONAL LEVEL,

AS WE BIOLOGISTS APPROACH THE STUDY OF EVOLUTION OF OUR acti
itv .
OWN SPECIES WE OUGHT TO BE MINDFUL OF wnat Léon EISENBERG HAS

CALLED “THE HUMAN NATURE OF HUMAN NATURE” -- OF THE FACT THAT,
IN BRINGING ABOUT LANGUAGE AND MIND, EVOLUTION HAS CREATED A
COMPLETELY NOVEL AND UNIQUE SET OF FORCES -- CULTUREs AND
TRADITION, AND VERBALIZABLE IMAGINATION. THESE Forces HAVE
{
NOT ISOLATED Nan Rom ITS BIOLOGICAL NATURE, BUT HAVE
SUPERIMPOSED UPON IT A NEW LEVEL, THAT OF COGNITION, EHAT t/ WICH
CONDITIONS AND FILTERS ALL HUMAN ACTIVITIES. ANY ATTEMPT
TO SINGLE OUT BEHAVIORS FOR BIOLOGICAL INTERPRETATIONS MUST,
PYALVA TE
NOT ONLY G@BRR@e=S6R- SOCIAL AND CULTURAL INFLUENCES, BUT TAKE
ACTIVELY INTO ACCOUNT THE INTERPLAY BETWEEN BIOLOGICAL AND
nn
CULTURZAL FACTORS, JUST AS IN THE BIOLOGY OF DOMESTIC ANIMALS
{ND
OR PLANTS WE CANNOT IGNORE THE ROLE THAT NanHxS-PLavED, so
IN ATTEMPTING TO BIOLOGIZE HUMAN BEHAVIOR WE MUST BE AWARE
THAT IN Nan| EVEN BIOLOGY IS SUBJECT TO CULTURE AND

UNDERSTANDING,

IN CLOSING, LET ME SINGLE OUT ONE FRONTIER THAT TODAY
MAY SEEM AS UNREACHABLE AS MounT EVEREST SEEMED TO BE 50
YEARS AGO. AND YET, IT IS EXCITING ENOUGH TO WARRANT
SERIOUS ATTENTION. [| REFER TO WHAT I MAY CALL BIOLINGUISTICS,
19

OR THE BIOLOGY OF HUMAN LANGUAGE. THE REASON FOR SINGLING
OUT THIS FIELD IS TWO-FOLD. FIRST, HUMAN LANGUAGE IS THE
SPECIAL FACULTY THROUGH WHICH ALL CONSCIOUS HUMAN ACTIVITY
IS FILTEREDs A FACULTY WHOSE DEVELOPMENT MAY WELL HAVE
PLAYED THE DRIVING ROLE IN THE ALMOST CATASTROPHIC EVOLUTION

FROM APE-KIND TO HUMANKIND. AND SECOND, LANGUAGE ALONE,

 

“To THE SCIENTIST A SYSTEMATIC THEORY, THE STRUCTURAL LINGUISTICS
CHorisky AMD HIS Fotloweks »
4, DEVELOPED BY Mepehi—erweuretes WHICH E AMENABLE TO
CONFRONTATION WITH BIOLOGICAL DATA, HAT I MEAN IS THAT
FORMAL LANGUAGE STRUCTURE, PLUS SOME FACTS ALREADY KNOWN
ABOUT LANGUAGE AND BRAIN STRUCTURE, PLUS THE ADVANCING

KNOWLEDGE OF BRAIN ORGANIZATION PROVIDED BY PHYSIOLOGISTS, g&

 

 

 

 

  
    
 

as

Thar may | HOLD SOME PROMISE THAT BETWEEN LINGUISTICS AND NEUROBIOLOGY
Provr0é A KIND OF CONVERGENCE MAY SOON BE POSSIBLE, -tikE—THE—

ov? : _
A WEDGE 0 BROUGHT FORMAL
INTo THE ‘
BioloG Cat TOL (Wi 7 OS — Ty =
Cc cplorATIOW ATIHISPONT D6 PAL FEEL THAT (HAVE
oF THE
Arran D PUSHED SPECULATION TOO FAR, PROJECTING BIOLOGY MUCH

MHP * TOO FAR INTO THE FUTURE. But, AS I MENTIONED AT THE START,

I AM TOO OLD TO LOOK ANYWHERE BUT AHEAD,
19

OR THE BIOLOGY OF HUMAN LANGUAGE. THE REASON FOR SINGLING
GUT THIS FIELD IS TWO-FOLD. FIRST, HUMAN LANGUAGE IS THE
SPECIAL FACULTY THROUGH WHICH ALL CONSCIOUS HUMAN ACTIVITY
IS FILTEREDS A FACULTY WHOSE DEVELOPMENT MAY WELL HAVE
PLAYED THE DRIVING ROLE IN THE ALMOST CATASTROPHIC EVOLUTION
FROM APE-KIND TO HUMANKIND. AND SECOND, LANGUAGE ALONE,
AMONG THE UNIQUELY HUMAN FACULTIES OF THE HUMAN BRAIN, OFFERS
TO THE SCIENTIST A SYSTEMATIC THEORY, THE STRUCTURAL
LINGUISTICS DEVELOPED BY CHOMSKY AND HIS COLLEAGUES, WHICH
MAY BE AMENABLE TO CONFRONTATION WITH BIOLOGICAL DATA, WHAT
I MEAN IS THAT FORMAL LANGUAGE STRUCTURE, PLUS SOME FACTS
ALREADY KNOWN ABOUT LANGUAGE AND BRAIN STRUCTURE, PLUS THE
ADVANCING KNOWLEDGE OF BRAIN ORGANIZATION PROVIDED BY
PHYSIOLOGISTS, HOLD SOME PROMISE THAT BETWEEN LINGUISTICS
AND NEUROBIOLOGY A KIND OF CONVERGENCE MAY SOON BE POSSIBLE,
LIKE THE CONVERGENCE WHICH FORTY YEARS AGO BROUGHT FORMAL
GENETICS TOGETHER WITH BIOCHEMISTRY TO CREATE MOLECULAR
BIOLOGY.

] FEEL IN THE AUDIENCE A MOVEMENT OF IMPATIENCE, AS IF
] HAD PUSHED SPECULATION TOO FAR, PROJECTING BIOLOGY INTO
A TOO DISTANT FUTURE, AS I MENTIONED AT THE START. | AM
TOO OLD TO LOOK ANYWHERE BUT AHEAD.