The Nature of

Caneer

iri

.:*
,l

&
.i-l Volume One
:i

:
r*i
r. !.
: $.e

a.
,:

*
;i

!
1!i

h'
il

P,

!-;i€
 \

Volume One

The Nature of
Cancer

MANU L. KOTHARI
M.8., M.S., M.Sc.

LOPA A. MEHTA
M.8., M.S.

Department of Anatomy,
Seth G. S. Medical College,
Bombay, 400 012.

KOTHARI MEDICAL PUBLICATIONS,

Acharya
?:"d:^Ygq,
Bomkiray, 400 Ol2,
tudta.
 ' * ".":-:.ii''
f

Kothari, Ma,nu L. aqd Mehta, Lopa A; -

The:Nature..qf-Cancer, " :-:

Bombay: Kothari Medical publications. l9?5.

'*i?:titl:r i' .. :

Cldss Numbcrs:
Dccimal 616.99{ Colon L:47pb

{.
..- *
.:.
i copFshl'@ l9?3 by i

M. L. Kornenr & L. A. Mrnre

; .I'
!i;$
I
.*'..
t. -
!
;, ' Firgt.Eilition, Iunc 197j

Pringed.by
V. D. Limaye ai the India printing Works,
9 Bakehbuse Lane, Fort,
Bombay 400 001.

Published by
Mohanlal B. Kothari, for
The. Kothari noot Depot,
Medical .Publications .Division,
Achar?l.Donde Marg, Bonbll 40001?, India. .J
 *,
rff
1
l

t
l
., j

Deilicoteil sl 'l

with reuerence anil affection i

to

Veta Louise BaileY (Mumma)

g in iheeP ailmiration of the uork
ilone ba her wtth her husbanil,
Hamilton Bailey, in the

field of surgical inriting

I
I
iI
.t
,l
'I i

.t .1
't
ri

.t j
F

. My final word, before I'm done,

Is'Cancer can be rather fun.'
Provided one confronts the tumour
With' a.sufficient sense of humour.

Iknow that cancer often kills,

But so do cars and sleePing Pills;
And it can hurt one till one sweats'
So can bad teeth and unpaid debts.
F

i' A spot of laughter, I am sure,

Often accelerates 6ne's cure;
So let us patients do our bit
To help the surgeons make us fit.

J. B. S. Haldane
Cancer's a Fu,nny Thing

(Reprinted in part,
with permission
from the New Statesman\

'r{
 The big brag preceiled the btg bdng as a
human possibility. Any demonstration that
the earth retolues about the sun, while
oflensiue to authorities in charge, d,id not
presume that ue could, reueise its coursc;
Any prqof ol a natural law called grauity
did not presuppose that man .could' mske
apples fall up; d,esigners of supersonic
planes, indbed, still tahe account of the
apple. To the frontiersmen of science the
d,iscotery of natural lauts meant no rrorc,
than that ue hail explored certain forces
gouerning the dispositioins of man. But lot
ffiany a hoi-polloi scientific sEttler who eame Preface
after. the lrontier such. iliscoaeries. meant
something quite difierent. Man c.ould.rnaster
nature.
.. , ,. Rogurt AxnnrY
:

Alth.ough this may be regarilcd as a hereti-

cal statement beyonil the mainstream ol !'

biologic thought, let me remind you that

hercsy in the pursuit ol science is no aice
and conformity lor tltc salie of lashion is no
uirtue.
RrcHiuoND PREHN

...::r:i:,..:

i :. '.:. - :, '

'' : :.i
l

ilancer, a myst€rious Plague [1] and the g€n€rous scientismic promise of the cur€
greatest bugaboo of man [2), is itself for cancer, rnuch before the deqade,i$,oyqr,
plagued by scientific doublethink: On the This glorious doublethink, probably rngr,q
one hand, it has been sirpei'latively des- mysterious than cancer itself, cpuld ,!g
cribed as the most fascinating, formidable curativ€ly treated w€re we . to aqcept,
:[3,4] almost be- uis-a-ais cancer, vqp Bagr's observation
and wonderful problem
yond comprehension by' human intellect t\4t human wit is too p{o$e to convert
t5,6]. On the other. hand, mankind has Nature's simplicity into ':infinigely great3r
r been repeatedly promised a victory against and more incomprehensible wondgrs,'1,,,+g
also Ardrey's [8] candid generalizatio" qhll
cancer, the overpromise having been cli-
maxed recently ti] ty the formation of an even if we do discovCr th" ,g,"gr"l ,, gf
agency for the outright "conqu€$t" of can- certain natnral forces "eoverninc the
c€r. The 'Promethean conviction that
I
dispositions of man," our chances, o{,m?!;
I
,"M:an could rnaster nature" allows, in the tering them are as remote aS'is our ab,ility
1970's, the coexistence of science's ' uttCr to makc applcs fail up. Despiierialt"itb
l- ignorance of the nature of cancer with the bizzarc demeanors, caicer-the'pr€roghtidd

I
 PREFACE
of a single, normal diploid dividing cell- allows as many as 56 years between the
is far more comprehensible than vascular exposure to the postulated cause (radia-
disease, diabetes mellitus, or contra-auto- tion) and the occurrence of cancer [ll] is,
r€active-dis€as€ (auto-immune disease). because of the irreconcilable temporal gap,
Cancer is intrinsic, .time-governed, senesc- clearly against the causalisrn of cancerogen-
ence. Its intrinsicality precludes the cure ism. "All philosophers, of every school,
ar control of cancer by any extrinsic mea- imagine thar causation is one of the funda-
sure, including the rnuch-vaunred [9] im- mental axioms of science, yet, oddly
munotherapy. enough, in advanced science, such as gra-
Cancer is intri,nsic. Cancer does nor vitational astronomy, the word .caus€'
have a cure };rccauw it does not have a nev€r occurs. The Law of Causality,
c&use. Cancerogenism--{anc€rogen is an f believe, like much that passes among
"agent" that caus€s cancer-is too strong a philosophers, is a relic of a bygone age,
force to allow us to think of any cancer surviving like the monarchy, only because
without a corr€sponding -gen. The pro- it is erroneously supposed to do,no harm.,,
position that a -gen caus€s a cancer holds p2]. The foregoing commenrary by Ber-
no water in the light of the lattei occur- trand Russell U2] is as much applicable
ring without, and refusing to occur des- to cancerology as it is to gravitational astro-
pite, the former. This conund,rum of a nomy. Vist-ais chronic diseases, the only
cancer-cousalist could be expressed as experimentally produced condition to
follows: which a -gen concept is applicable is the
X causes Y. use of alloxan and allied agents for pro-
But why does Y ducing diabetes mellitus; but, even here,
Occur without, and the concept of alloxan as a diabetogeni,c
Not .occur despite, X? agent llSl is wrong: Alloxan produces the
diabetes by specifically destroying
A young Indian !ady, the wife of a so-called
the beta cells and producing absolute insu-
physiciarr-friend of the authors, recently
came to Bombay frorn Canada with an in-
lin deficiency U3]. On the other hand, in
most of the adult-onset diabetics and some
operable lung carcinoma. About her one
could pose a qu€stion in Erich Segal's of the
juvenile diabetics, ttre beta cells
style: "What can you say about a twearty- pour out more than normal quantities of
five-yearold girl" who got lung cancer insulin U8,l4f. Moreover, diabetes melli-
tus has been recognized [14] as a complex
without having had a single puff any time?
No cancerogen has yet proved to be syndrome, the angiopathic part of which
bears no relation to the degree of the
causa sine qua non of any particular can-
panmetabolic disorder. The idea of a
cer, in humans or in animals, in aiuo or
in aitro. Fuller [I0] puts down, as the d,iabetogen is as misconceived as that of a
cancerogen, for both do not exist. Hieger
earmark of causality, an inuariant relation
of event$ in which the cause must precede [3] wonders whether it is possible to con-
ceive of cancer without a cancerogen, and
it$ €ffect and the efiect rnust follow its of senescence
without a gerontogen. yes,
cause, in time. "It is this sense of rnusf
it is possible to, think so, provided- we
which distinguishes causal connection from realize the
intrinsic character of aging
coincidence." (Fuller) [0]. Further, Fuller process€s which
are, in Burnet's [lE] words,
emphasizes, the effect must immediately "no more than a facet of the
whole patt€rn
follow the cause: "Causality can no more of grorvth and difierentiarion.', It is time
jurnp gaps in time than it can gaps in we changed from Ptolemaic -genocentric
rpace." The conc€pt of "latency" that thinking, on cancerogene$is, to cytocenlric
 PREFACE xl

realism wherein we permit the cell to turn anism residing within the raould-be-
cancerous without, and to refuse to turn canceroqs nmmal cell. It is this mechanism
canc€rous despite, one or more canc€ro- rryhich determines the occurrence of cancer
gen$. Cancerogenesis is a property of all esophagus in a boy aged 14 or a man
aged 94 years. The timer inside the nor-
or most living systems and a-result of the
rnal cell us€s, as its time-ticket or calendar-
manner in which the form and function
event, some periodic activity of the cell;
of these systems are coded and controlled most probably cell-division, difierential
tl6]. This coding and controlling makes and/or nondifierential. The concept of
canceration of normal cells merely a form Finite Cell Doubling Capacity (FCDC) of
of difierentiation that is blessed, like life, a normal diploid dividing cell (Ch. 3) pro-
with invariable variability. Each cancer vides an operational mechanism for the
is a species by itself [17]. And this remark- working of such a timer, mediating the
able diversity is achieved rvithout, what cancerous change. The temporal gap be-
Ardrey [8] calls, "the accident of the night" tween the cancerous change at the cellular
that mediates "sexual recombination'" The level and the cancerous manifestations at
strict intrinsicality of cancer is independ- the clinical level is quite large (5-20 years)
ent of what has treen called somatic muta' and this cruelly foils all our attempts at
tion. A particular locus (or loci) in the early diagnosis and treatment of cancer.
human chromosomes-altered or original Cancer is a form of senescence. "In
not be specifically invoked for ex- fact, death is not natural at all. It's
-need
plaining cancerogenesis. We do not, and really an avoidable mistake." [9]. Fred
cannot, do so for explaining the genesis of Stewart [9] has envisioned the dis-
alpha cells of the islets of Langerhans, or covery of The Methuselah Enzyme
the pyloric sphincter, or the prepyloric that rvould "desenesce" human body and
vein of Mayo out of the unpreformation- make the aforequoted antideath hope a
ary, featurele ss human zygote. Smithers reality. With such an enzyme, the human
[4], while discussing the theories of cancer- body just would not senesce. flowever,
ogenesis, observes: "There does not, horv- Hans Selye [20], writing in 1965 on "The
ever, s€em to be any over-riding reason Future for Aging Research" as the con-
why a specific somatic mutation should be cludirig chapter to Perspectiaes in Experi-
invoked to account for tissue rnalformation mental Gerontology asserted that "aging is
urhen it is not thought necessary to bring ess€ntially an ineluctable manifestation"
in a mutation theory to account for normal of the entropy that affects both the living
development, regeneration and repair." and the non-living, and that science does
Cancer is time-gouented- Animal life, not have any evidence to pin its hopes on
fertilization onwards, is configured time some "desenescing" p9] enzyme. If death
p8]. The spontaneous--epigenetic-forma- is inevitable and renescence is ineluctable,
tion of the common bile duct ofi the fore- then surely there is some basis to link the
gut at about the 6th week of intra-uterine two: Senescence is the necessary prelude to
life, and the cancerous change*as much an inrinsically-timed ontolysis. If death is
spontaneous and epigenetic-therein at the
the ultirnate function of individual life,
6bth vear of postnatal life are, for an indi-
death-eventuating processes-cancer, vas-
vidual human being, examples of, what
Portmann [l8l calls, configured time. The
cular diseases-assume a physiologic role.
cancerous differentiation-canceration-of Walter Cannon would have called this the
a normal cell is a time-governed process, biolytic f ontolytic wisdom of the body.
tirned quite precisely by an intrinsic mech' Senescence eventtrating itr death is not the
 xlr PREFACE
result of a "loss of programme" [21], or dids of a senescent process. Ir dies of a
a "meaninglesi fade-out of genetic pro- process that was intrinsic, deleterious,and
gramming" p5]. It is an individual- progrissive and which when the child,was
specific, herd-serving, biolytic program alive had contributed to the increased,
that is, for the individual, no less import- probability of death. Nelson's [23] charac.
ant nor less purposeful than the biogenic teriz.ation of diabetes'mellitus. as a disease
forces that fashion his being and the bio- with wide age range-"infancy to old aget'
trophic forces that make h"im grow and which the disease may manifest
exert his ability to survive. "Why should -during
itself, should force us to revise our think-
a purely chemical process in a substance ing orr. senescence i If cancer and diabetes
like collagen which has essentially the mellitus in old age are looked upon as
same composition in all mammals, move senescent manifestations of aging, why
faster in some species than other? . should the same in young age, or even in
Senescence takes a generally similar'form infancy, be considered as anything but
in each species,, whether judged by 'the forms of senescence?
physico-chemical changes in collagen, the The ITS ioncept-cancer is a form
incidence of degenerative changes in blood of fntrinsic Time-governed Senescence-
-understanding
vessels or the high incidence of malignani allows unqualified of the
disease. . . . The essence surely is that there nature of cancer, heedful of Oicam's razor
is a genetic 'programme in rime' Iaid down [0], the law of parsimony ll0], and Feyn-
for each species. There must be a biolo- man's [24] invokation thar a theory niust
gical clock and a means by which a series allow us to take much more out of :it than
of processes can be made to occur earlier rve put into it. The present book is
or later according to the.expediencies of essentially a factual verification of the'ITS
evolutionary.survival." (Burnet) p5]' Can- :As an exercise
concept. in convergent
cer is but one of a series of senescent comprehension, both the volumes of this
forces. book can be reduced to 25 lines'in Chapter
The pantrajectorial occurrence of cancer, l; these can be reduced to three words ,e.
from intra-uterine life to old age in mani presented by ITS, and the same could'be
has prevented it frorn being called a expre ssed, r,vith little alteration, is It,s.
senesc€nt process, hS such a ,pfocess, for Cancer, for an individual, is-in prospectl
reasons etymologic,, is expected to occur it is, not anything introduced or inducgd
only in a senile individual. Senescence frotn outside. ITS represents an appropri-
has been defined as an intrinsic process ate concpplual sequence: fntrinsicality of
that increases the probability of the death cancer implies that an individual is born
of an individual U5,21,221. Cancer, at with a would-be carcinorna of the prostate
whatever age it occurs, is an intrinsic pro- or the pancreas, or an osteosu..ornl' ofiitht
cessthat increares the probability of death, lower end of femur, as,an integrallpart of
whether it be in a child of 2 years or a his or her biologic trajector|. - Time-
man of 80 years. In fact, its function of governedness indicates: that 'the particular
heightening the probability of death is cancer will mahifest its€lf at a certain age
more severe when it affects a young indi- of the' iildividual. ' Cancer u, ,"n"sc.rri"
vidual. fn an old person, multiple, mild implies that it may scrve, for the indi.
or moderate, senescent process€s prod.uce vidual, the linal function of ontolysis: or
an efiectively lethal aggregate. Strehler dying. "The characteristic pathriiogicai
[21] has put down, as criteria of senescence, qhange of age is an increase in'the nuinber
intrinpicqlity, pro gre ssiu e nes s and eri-
clel et of'pathologrcal changes; and rnost people
ousness. Now, a child dying of cancer who die late in life trom one of th6se
 PREFACE xlu

qagryS also exhibit several o-ther patholo- ing of canc€r or guide cancer research, and
gical processes which would . problbly which betrayed inherent conlradictions
have killed them very soon, had theY and difficulties when scrutinized by logi-
survived the actual cause of their deaths." cal, observational, or experimental means.
(Comfor$ [22]. The foregoing general- Smithers [4] commenled that "no clear
ization on aging, akin to one by Smithers story" was available that. could unite the
[4] orl "people who die of neoplastic dis- diverse clinical and experimental data on
ease," should servc to de.emphasize the cancer. Perusal of this volume may make
legeudary "malignancy" or lethality of it clear how the apparently simple
cancer or, say, coronary artery disease. ITS concept unifies the oceanic mass of
Cancer is a means to an end, and an indi- data on cuttcer without indulging into
vidual body may decide not to be killed by self-excusing ifs and buts. Karl Popper
a seemingly lethal cancer. "And not so [29] proposed that the empirical method
rarely," Brooke [25] recently emphasized, of scientifrc investigation should aim not
'canqer itself is overtaken by another dis- at saving the livcs of untenable systems
order and beaten to the final post " Amidst but at selecting the one which by com-
all such vagaries of behavior, cancer in parison is the fittest, "by exposing them all
an individual manages tq. serve, wilh to th€ fiercest struggle for survival." The
fairly accurate timings, the function of ITS concept is offered to the world of
herd-mortality' wh;' otherwise, as willis science,.to be exposed to the fiercest strgg-
[26] generalizes, should the age distribu- gle for strrvival. A la Popper, the value
tion of a sufficiently large series of cancer of a concept on cancer would lie in its
necropsies provide a continuous ("ideal1') abilitl' to stand the rigors posed by the
smooth curve? different facetg of the problem-age inci-
Summarizing, ITS is a geslalt collcePt dence, sex difierences, clinical features,
I of ITS does not
on the nature of cancer: .occurrence without cancerogens and nQn-
admit of a cancerog€n; T allows cancer occurr€nce despite them, geographic differ-
stomach to occur in a girl of 18 and in a ences, survival without treatment and
woman of 80 years; the T part also allon's quick death because of treatment, .and
a so-called cancerogen to effect some time- so on, In the present volume, most
contraclion so that the occurrence of can- varied aspects of cancer have been
cer, in the tissue and the individual ex- integrated into an intelligible synthesis.
posed to the agent, is advanced in time, sg A distinct departure from the hackneyed
as to manifest at an earlier age; S places track has been to omit merely factual
cancer as one of the numerous pre-death statistical data from th€ text, packing the
forces. The ITS concept excludes cancer same, where necessary, into compact
as being necessarily a lethal Process. Tables. The text, at almost ev€ry stage,
A theory, Einstein [27] expressed, is the discusses the problem, using minimal des-
more impressive the greater the simplicity cription. The bold theorizing herein may
of its premises, the more difierent asp€cts be strongly objected to by the world of
it relates, and the more extended its area cancerology largely dominated by experi-
of applicability. Hieger [28] made an mental.ists. But, must we always insist on
exhaustive survey of the theories of can- experiments to reach the truth? What if
cerogenesis, in 1961, to conclucle that the our experiments have been misconceived
enormous theorizing (and experimenting) so that the results only double the pre-
on canc€r had failed to produce anything experiment confusion? If experimental
except an assortment of "theorytautology" cancerology were to help uu it would
which could not provide any understand' have done so, by now. It has been
 xrv PREFACIT
chastizinglv generalized by Dawe [30] and carcinogen" [15], and yer irradiation
that experimental work on cancer has not constitutes one of the commonest ways of
added one causal fact which was not al- "tr€ating" canc€r. The situation is similar
ready known from our studies on human to that in Anthony Burgess's I Cloch-
cancer. It is time we stop experimenting tuorh Orange f36]: ..Our subject is, you
on cancer, at least for a short while, so see; impelled towards the good by, para_
that the experimentalismic fog clears our doxically, being impelled towards ivil."
and we have a more realistic view of the The too generously funded cancer chemo-
things. "The ultimate goal of all science therapy research programs provide an
is to devise and explain conceptual "anticancer" drug which, by a semantic
schemes about the nature of the universe alchemy, turns anti-psoriasis when used by
in which we live. . . . The major aim of a dermatologist, anti-immunity when em_
most competent biologists is to discover ployed by a transplantologist, and. anti_
facts lnd to establish biological general- rheumatoid-arthritis when given by an
izations that can be applied to an under- internist. Most of the cancer chemothera-
standing of the phenomena of life." agents prove to be anri-everything,
(Hickman) [31]. The present work is an
ry1ti:
including the patient. These .g"rri, p.o-
attempt at presenting a conceptual scheme vide cent per cent failure against auto
and at oftering useful generalizations on a chthonous cancer and, sometimes, cent
phenomenon of life alleged to be linked per cent success against the so_called
inevitably with death. transplanted cancer which is not & cancer
The foregoing may smack of Rovakian at all but a borrowed mass of mitotically
anti-scientism [32], but as Roszak would actiue cells. It shouldn't be surprising that
agree, it is being scientific to oppose, tooth Glemser, in his globe-trotting surviy of
and nail if need be, scientism. The persist- Man Against Cancer, gathered. that surgery
ent, nay, the Perennial gap separating the should be eliminated ..at all costs,', ihai
promise and the performance of cancer irradiation is well-nigh obsolete, and that
research calls for a thorough reappraisal. chemotherapy is "an absolute farce." Dis_
Treatment of cancer, supposedly based on illusioned by the utter failure of what
the principles evolved through research, is claimed as treatment/cure for cancer,
betrays the mo$t unscientific aspect of our the crusading therapists have been ofier-
scientism and experimentalism. We want ing as effective, the last stronghold of
to treat or cure cancer with irradiation, early diagnosis and, treatment. The recent
chemicals, viruses, hormones and immuno- findings on the cytokinetics of cancer have
logic measures, holding at the same time forced many to conclude that the treat-
all these agents as cancerogenic. Karnof- mglt of what is genuinely cancer is always
sky's [33] recommendation that "carcino- a little too late. The apparent success of
gens" be used for therapeutic trial against these Diagnose And Treat Early (DATE)
"cancer" is but an example of the popular- programs is attributable to ..pragmatic"
ized medical magic of' creating i iancer diagnoses [37] and equally ..pragmatic"
with one agent and curing another cancer treatments so as to, as Collins and Wall
with the same cancerogen. Burnet [S4] [38] remark, inflate the statistics on rhe
attributes the occurrence of cancer to im- apparent incidence of cancer and the ap-
munologic inadequacy; yet a recent com- parent efficacy of treatment.
pilation [35], in a book on pathology, of With the failure of cancer therapy clear
the theories of cancer, presents a bold and unmitigated, the emphasis expectedly
heading: "Immunity as an Oncogen.', has been shifted onto that great bui
Ionizing radiation is "a potent mutagen unfulfilled hope of preventing cancer. The
 PREfACI xv

main bulwarks of preventionism are can- to contract lhe understanding of cancer.

cerogenism-the idea that almost every- (Cf. Boyd [a5]: ". . . the more we know
thing under the sun, including the sun it- about diabe tes, the less w€ s€em to
selt is or can be a cancerogen-and the understand it.") The unmanageable/
ever-expanding endeavor of epidemio- incurable factosis has only made the
logic studies. We are immersed, as Boyd researchers overpromise all the mor€:
[39], poetically describes, in a sea of can- Eisenberg [46], a non-researcher, has en-
cerogens, to the impressive components of visaged a cancer-free mankind by the 2lst
which has been recently added the human century, but some researchers have pro-
sperm whose more inrportant role s€ems mised that by 1976 s.o., the crab will have
to be to produce carcinoma cervix by been buried, for ever. Horv this elnc
somatic fertilization [40]. Glemser [6] ex- Utopie will be achieved in the next 4 years
pressed that humanity had reached a stage is a mystery, for as recently as in 1969, a
when, to pr€vent canc€r, it mu$t "stop critical perusal of Glemser's book Mara
breathing," "stop eating,"' and, we must Against Cancer [6] would have convinced
add, stop copulating. Burnet [15] describes anyone that the more realistic title could
the enormous research on cancerogens- have been Man Helpless Against Cancer.
including the much-hoped-in viruses-as a Man's helplessness does not, howeyer,
"major" disappointment which will not imply invariable hopelessnes$. Cancer does
turn into, a success by merely pouring not always kill even n'hen left untreated
more money into it. The relatively large 147, 48]. And rnany a benign lesion-
bibliography on cancerogens in Chapter 5 "that does not of itself destroy thc host"
represents but a fraction of the available [l]-in the adrenal [49], pituitary [50],
and expanding literature on cancerogens. parathyroid [51], nasopharynx [4,26], or
These references have been cited to stress the brain [26] wrecks and kills more pre.
that the concept of. there is nothing lihe dictably and inexorabl;' than a "frank"
a. cancerogen is in the teeth of all the cancer in the breast or thc prostate. The
publications on canc€rogens. And all the acquiescence of clinicians, pathologists,
chapters, beyond the fifth, bear out this and researchers in the debateless divorce
concept, by citing relevant "facts" from between the histologic/cytologic picture
cancer research. The hubristic urge to presented by a "cancer" and the realities
catch and eliminate the cancerogens so as of its behavior in the patient has allowed
to prevent over 80 Per cent [41] of all the creation of a universally accepted
cancer$ is highly laudable but the outcome myth that canc€r:death sentence. That
is nothing except scare-mongering that is explains the paralyzing cancerophobia
bound to arise out of etiologically linking both among the lay public and the learned
cafteine [42], coitus [6], salt [43], and medical men [52]. The immeasurable cli-
"going to school" [44] with the occurrence nical and experimental research on cancer
of cancer. has not helped to frame a realistic defini-
In the coming years, cancer research will tion of cancer, much less of what is do-
be pursued with fanatically funded vigor. goodistically called precancer. In the ab-
But what it will add is "facts," which, as sence of any precise definitions as guides,
Foulds f5l, Hieger [28], and Smithers [4] what gains dominance is that cancer is a
point out, we already have in unmanage- killer that must be killed before it kills
able quantities. fn nosologic Parlance, you. This makes every human being,
one could say that cancerology sufters frorn even when most remotely suspected of
cancerous factosis, that seems to obey some having cancer, feel utterly hapless. A
Parkinsonian law: Facts on cancer expand dispassionate, unemotive perusal of cancer
 xvl PREFACE
litgl4qrg could provide the medical men nation or. the co,ntinuing existence of
epo,ugh cancerrealism to enable lhem, to semantic confusion t60]. The chronic
ofier ,an average pati€nt the strengih to aneusemantics of cancerology betrays the
da.fg,, the d,i;ease and to liue with cancer. nearly zero progress that cancer research
Like immunology [6], cancerology sufiers has made. The zeroness of progress is
frpsl,. clronic semantic obscurantism: unpalatable, but.the bitter truth remains:
Cancer= malignant growth : neop-lasm: "The public has been oversold," Rutstein
qwelling=tumor p.1,, 26,. 39, 53, 54]. . And, 16l] lamented in his 1965 lectures at the
'.'. . a growing lump may well not be a M.LT. "Thus, responsible publications
malignant cancer-" (Roe) [55]. (You are cure cancer almost every week. At fund-
fo,rced ,1o coaclude that there is.something raising time, spokesmen for our great
likg a .beni,gn cancer.) How tumor, of national health agencies clearly imply
rvhiph Dorland's dictionary [56] lists ll4 that all thar is.lacking is money and that
Patentl)/ non-cancerous tyP,qs, came to be if , enough were made available the .big
squqtqd with. ganqeq will remain a my$tery, answer' would be just around the corner."
D.pq t!t", confu-sio.n ,that such. equating [61].; Arley [62] generalized that, despite
genexates is ,certainly avoidable. In the the. vast quantities of money and man_
prepnt, worl(, the insiqtence has been on Power put into cancer research during the
,e,Usemqntfcs in ,,the, various fields of can- past half century or more, whar has hap-
,cgrolqgy; hq.r.g for example, the replace- .
,pened is that we still do nor know whit
me.nt of '.ibenign tumor'l by eucytoma, ot is cancer or a cancer cell and that .,now
of 'fguqrorli by aneuplasm. While,on th€ mo, re people live on cancer than d.ie of
nged for eusemantics, the avoidable confu- . cancer." Yet, we are told that in this

sion exemplified by CEA could be ryen- golden age of medicine characterized by

tionqd . here. Gold and Freedman l57l the triumph of the experimental method,
found in the (cancerous) tissue$ of certain I'we are very close to success" in our battle
.cancer. patients some "unique tumor anti- against cancer [2]. The Babylonians cured
ggn(s)" which they christened as "carcino- cancer with strange stones [68], and, for
embryonic antigen(s):' or CEA, This was all we know, the moon rocks may harbor
in the year 1965. In a recent issue of such a cure [64]. There can be no deny-
Nature (London), there appeared an ing such a wishful vision, but as things
article [58] which reported the presence of stand today, cancer research has provide"d
"Carcinoembryonic Antigen in Normal truths that have been unable to go beyond
Ifuman Plasma." The article rightly the capsule of confusion; in that, they
concluded that "with CEA the difference haye remained benign, non-iconoclastic
between normal adult. plasma and the and incapable of providing any under-
plasma of cd,ncer patients is quantitative standing of cancer. No mutation has oc-
rath€r than qualitative." Fair enough; curred therein in the past 200 years. The
but if CEA becomes a pr€rogative of fault has been of the science of cancerology
all normal-non-cancerous.-humans, then which, instead of being one of unprejudic-
could it still be called CEA, and that too, ed objectivity and biologic scholarship,
in Nature? Would it not mean, as it must, has been one of cancer-conquering crusa-
that all normal persons are, antigenicallv. des llli,65l in which even the scienrists
cancerous? Aneusemantics, in any science, have rarely remained frre of clo-goodistic
is a dangerous thing. bias. This is evident from Rutstein's
Words stimulate or stifle the.progress.of [6lj candor: "scientists, being human,
science [59] and the progress or stagnation tend to be overly optimistic about the im-
of , gcience,. in. turn, determines the elimi- plications of their research results. All of
 P,RE F A CE xvll

this creates extravagant public expectations of cancer can go a long way towards
and, often cruelly raises and. dashes the unmaking the anxiety that mankind
hopes of sufierers from mortal illnesses." is plagued with, uisqtis this cellular
Cancer research should take its inspira- repertoire.
tion from Nature and not frorn any utility; fn Volume One, Chaptets 2, 3, and 4
its proper reward is understanding, not provide operational concepts, helpful in
practical application [65]. If researchers comprehending canceration of a cell. The
keep their eyes and minds adequately remaining chapters are syntheses that rest
open, the reward of understanding cancer on the cold facts of cancer. Chapter 23,
is not difficult to attain. Notwithstanding the largest, is essentially on the biology of
the failure of the so-called research, one cancer as determines the outcome of vari-
can assert, in Einsteinian style, that the ous modes of treating cancer; the closing
most incomprehensible thing about cancer part of the chapter discusses the rather
is that it is comprehensible. Let us controversial issue of the rights of a can-
put aside, for the moment, all that cancer c€r therapist. All chapters stand on their
research claims regarding the genesis and own and can be read out of context with-
the cure of cancer. l,et us appreciate, out loss of value or understanding. We
heretically though, that evegr at the level hope that this volume, as also the next
of the human body-to use Ardrey's 18] one, will serve as a useful reference work
words-"Order and disorder are intimately presenting and correlating diverse data on
entwined," and that the body is endowed cancer.
both with the will-and-ways-to-live and Volume Two, in preparation now, deals
the will-and-ways-to-leave. The clisorder- with the biologic-non-clinical, non-
ordered disorder, rather-looks, prima experimental-aspects of cancer. The
facie, dysteleologic, but it is not; most chapter on biomechanics elaborates upon
organic phenomena strive towards an certain natural laws that govern the bio-
end, and their whys and wherefores can logic trajectory of a species, a herd, or
sometimes be understood onl,v by realizing an individual. The concluding chap-
what the end is [0]. Cancer is a cellular ter is a treatise on research in general,
innovation to serv€, "with fine disregard and on cancer research, in particular. The
for individual fate," the functional neces. appendix is a collation of theories of
sity of programed ontolysis, thus serving cancerogenesis.
the herd at large. And in that, it is not
necessarily merciless, and mutilating. In Bombay Mexu Korrrenr
fact, a true comprehension of the nature May 1973 Lop.l Mrnre
xvllr PREFACtr
REF'ERENCES ;22.. Comfort, A.: Ageing: The Biology of
Senescence. Routledge & Kegan Paul, London,
l. Foote, T.: Books: The taste of hemlock. 1964.
Time, June 12, 1972, p. 62. 23. Nelson, W. E. : Diabetes mellitus. In,
2. Tainter, M. C.: Medicine's golden age: Textbook of Pediatrics. (Ed.. Nelson, W. E.),
The triumph of the experimental method. Tran. W. B. Saunders, Philadelphia, 1969, p. t155.
N.Y. Acad. Sci., 18:206, 1956. 24. Feynman, R. P.,-Leighton, R. 8., and
3. Hieger, I.: Theories of carcinogenesis. In, Sands, M.: The Feynman Lectures on Physics.
Ciba Foundation Symposium on Carcinogenesis: I. Addison-Wesley Publishing Co., London, 1g63.
Mechanisms of Action. (Ed. Wolstenholme, 25. Brooke, B. N.: Understanding Cancer.
G. E. W., and O'Connor, M.), Churchill, London, Heinemann Health Books, London, lg7l.
1959,p. 3. 26. Willis, R. A.: Pathology of Tumours.
4. Smithers, D. W.: A Clinical Prospect of Butterrvorths, London, 1967.
the Cancer Problem. Lif ingstone, Edinburgh, 27. Einstein, A.: In, Albert Einstein: philo-
London, 1960. sopher-Scientist. (Ed. Schilip, P. A.), Tudor
5. Foulds, L.: Preface. In, Neoplastic Deve- Publishing Co., New York, 1957, p. 3.
lbpment. Academic Piess, London, Nerv York, 28. Hieger, I.: Carcinogenesis. Academic press,
1969,p. v. London, Nerv York, 1961.
6. Glemser, B.: Man Against Cancer. Funk 29. Popper, K. R.: The Logic of Scientific
and Wagnalls, New York, 1969. Discovery. Hutchinson, London, 1968, p. 42.
7. Page, I. H.: Cancer-conquest or turmoil? 30. Dawe, C. J.: Phylogeny and oncogeny.
Modern Medicine, 39:73, 1971. Nat. Cancer Inst., Monogr., 3l : l, 1969.
8. Ardrey, R.: The Social Contract. Collins,
31. Hickman, C. P.: Integrated Principles of
Zoology. C. V. I\{osby Co., Saint Louis,' 1966,
London, 1970.
p. 3.
9. Cover Story: Torvarcl cancer control. Time, 32. lVade, N. : Theodote Roszak: Visionary
March 19, 1973, p. 30.
critic of science. Science, 178:960, 1972.
10. Fuller, B. A. G.: A History of Philoso- 33. Karnofsky, D. A.: Experimental cancer
phy. Oxford & IBH Publishing Co', Calcutta, chemotherapy. In, The Physiopathology of Can-
1955. cer.(Ecl. Homburger, F.), Hoeber-Harper, New
ll. Kark, W.: A Synopsis of Cancer' John York, 1959, p. 783.
Wright, Bristol, 1966. 34. Burnet, M.: Immunological factors in the
12. Russell, B.: On the notion of cause. In, process of carcinogenesis. Brit. Med. Bull., 20:
Mysticism and Logic. W. W. Norton & Co., Nerv r54, t964.
York, 1929. 35. Prehn, R. T.: Neoplasia. In, Principles
13. Stauffacher,. W', and Renold, R. E.: of Pathobiology. (Ed. Lavia, M. F., and Hill,
Pathophysiology of diabetes mellitus' In, Joslin's R. B., Jr.), Oxford Univ. Press, London, 1971,
Diabeies Mellitus. (Ed. Marble, A., White, P., p. l9l.
Bradley, R. E., and Kralt, L. P.), Lea and Febiger, 36. Burgess, A.: A Clockwork Orange. Ballan-
Philadelphia, 1971, p. 35. tine Books, New York, 1963, p. 125.
14. Metz, R.: Diabetes mellitus. In, Internal C7. Park, W. W., and Lees, J. C.: The abso-
Medicine Based on Mechanisms of Disease. (Ed' lute curability of cancer of the breast. Surg.
Talso, P. J., and Remenchik, A. P.), C' V. Mosby Gynec. Obstet., 93:129, 1951.
Co., Saint Louis, 1968, p. 580. 38. Collins, V. P., and Wall, J. A.: The
15. Burnet, F. M.: Immunological Surveil- cervix. In, Management of the Patient with
Cancer. (Ed. Nealon, T. F., Jr.), W. B. Saunders,
lance. Pergamon Press, Oxford, 1970.
Philadelphia, London, 1965, p. 758.
16. Wellings, S. R.: Neoplasia and primitive 39. Boyd, W.: A Textbook of Pathology.
vertebrate phylogeny: Echinoderms, prevertebrates, Structure and Function in Disease. Lea and
and fishes-A review. Nat. Cancer Inst. Monogr.' Febiger, Philadelphia, 1970.
3l :59, 1969.
Coppleson, M., and Reid, B.: Preclinical
40.
17, Huxley, J. : Biological AsPects of Cancer.
Carcinoma of the Cervix Uteri. Pergamon Press,
.George Allen and Unrvin, London, 1958'
Oxford, London, 1967.
18. Portmann, A.: Time in the life of the 41. Payer, L. J.: IARC: An environmental
organism. In, Man and Time. Pantheon Books, approach to cancer research. Science, 178:844,
New York, 1957, p. 308. 1972.
19. Stervart, F. M.: The tr{ethuselah Enzyme. 42. Kuhlmann, W., Fromme, H., Heege, Eva-
Bantam Book, Nelv York, 1972. Maria, and Ostertag, W.: Mutagenic action of
20. Selyc, H.: The Future for aging research. cafieine in higher organisms. Cancer Res., 28:
In, Perspectives in Expedmental Gerontology. 2375, 1968.
(Ed. Shock, N. W.), C. C. Thomas, Springfield, 43. Hirayarna, T.: Thc epiclemiology of can-
Illinois, p. 375.
1966, cer of the stomach in Japan; rvith special refer-
21. Strehler, B. L.: Time, Cells and Aging. ence to the role of diet. Gann Monogr., 3:lb,
Academic Press, New York, London, 1968. r968.'
 PRtrFACE xlx
44. Mendelson, J. A.: Breast cancer and re- 55. Roe, F. J. C.: Cancer as a disease of the
productive history. Lancet, l:675, 1970. whole organism. In, The Biology of Cancer.
45. Boyd, W.: Pathology for the Physician. (Ed. Ambrose, E. J., and Roe, F. J. C.), D. Van
Lea & Febiger, Philadelphia, 1967, p. 517. Nostrand Co., London, 1966, p. l.
46. Eisenberg, P.: Are rve ready for the 56. Dorland's Illustrated Medical Dictionary.
trventy-first century? Span (Rombay), January, W. B. Saunders, Philadelphia, London, 1957.
1970, p. 20. 57. Gold, P., and Freedman, S. O.: Carcino-
47. Ho, J. H. C.: The natural history and embryonic antigens of the human digestive system.
treatment of nasopharyngeal carcinoma (NPC).
In, Oncology. IV. (Ed. Clark, R. L., Cumley, J. E*p. Med., 122:467, 1965.
58. Chu, T. M., Reynoso, G., and llansen,
R. W., McCay, J. E., and Copeland, M. M.), H. J.r Demonstration of carcinoembryonic anti-
Year Book Medical Publishers, Chicago, 1970, p. l. gen in normal human plasma. Nature,238:152,
48. Peeling, W. B.: The diagnosis and treat- t972.
ment of carcinoma of the prostate. In, Some 59. Asher, R. : Making sense. Lancet, 2:359,
Aspects of the Aetiology & Biochemistry of Prosta-
I 959.
tic Cancer. (Ed. Griffiths, K., & Pierrepoint, 60. Lavoisier, A.: Quoted by Max Kleiber,
C. G.), Alpha Omega Alpha Publishing Co., in, Ann. Rev. Physiol., 29:5, 1967.
Cardiff, 1970, p. 135.
49. Forsham, P. H.: Diseases of adrenocorti- 61. Rutstein, D. D.: The paradox of modern
cal hyperfunction. In, Textbook of Endocrinology. medicine. In, The Coming Revolution in Medi-
(Erl. lVilliams, R. H.), W. B. Saunders, Philadel' cine. Vakils, Feffer and Simons Pvt. Ltd., Bombay,
phia, London, 1970, p. 339. 1967,p. 9. "
- 50. Daughaday, W. H.: The adenohypophysis. 62. Arley, N.: Applications of stochastic
Ibid., p. 27. models for the analysis of the mechanism of car-
51. . Rasmussen, H. : Hyperfunction of the In, Stochastic Models in Medicine
cinogenesis.
- 52. Day, glands.
parathyroid Ibid., p. 922. and giology. (Ed. Gurlarid, J.), The Univ. Wis-
E.: The patient with cancer and consin Press, Madison, 1964,p. 3.
the family. New Eng. J. Med., 274:883' 1966. 63. Caldwell, T.: Dear and Glorious Physi-
59. Harris, R. J. C.: The history of cancer cian. Bantam Book, New York, 1962, p. 3.
research. In, What We Knon' about Cancer. 64. Editorial: Serendipity lost. The Tirnes of
(Ed. Harris, R. J. C.), George Allen & Unrvin,
London, 1970, p. 55.
India, Bombay. November 18, 1970, p. 10.
54. Lajtha, L. G.: The nature of cancer. 65. Smithers, D. W.: Clinical cancer research
Ibid., p. 54. Lancet, l:253,1956.
 Thc ha,rm,onious cooperation of all beings
arose, not frorn the ord,ers of a superior
authority external to themselves, but from
the fact that they uere aII pafis in a hie-
rarchy of wholes forming a cosmic pattern, Appreciation
and uhat they obeyetl were the internal
dictates of their own natures'
CHvNq TZU

We are thankful to the Editor of the worked the way we did but for his kinc,
New Statesman, London,,for kindly allow. paternal interest in the project. 'Wc are
,

lng u$ to reprint a part of Prof. J. B. S, grateful to Dr. C. K. Deshpande, our Dean,

Haldane's poem "Cancer's a Funny Thing" and to Dr. T. ,H: Rindani, our ex-Dean
which first appeared in the New Statesman for guidance and enconrag€ment, We are
of 2lst February, 1964. We also thank thankful to Dr. C. V. Fatel for his con-
the Fditor of the lournal of Postgraduate structive criticisrn .based on his rich ex-
Medicine, Bombay, for allowing us to te: perience in,clinical cancerology. Dr. D. S.
print Figures I in Chapter .2t 1,2,3,4,5,6,7 Pardanani cleserves a special word of thanks
in Chaptcr 3, I in Cnlapter 5, and 3,4,5 in for his keen intere.st and kind help. We
Chapter lS, from our articles which ap- are indebted, to Mr. Chandrakant Shah
peared in thb journal. for providing us an easy access to general
Many persons around us have urade our literature and for.serving,continually as a
task easier through their ltindness, and 'it non-medical critic ,of the book. Dr. Bindu
gives us gr€at pleasure to thank them. T. Desai introduced us to Prof. Haldane's
,

I,l/e owe a large debt of gratitude tg poerq, and.read part of the ,manuscript;
Prof. S. M. Bhatnagar of the DePartment we arg grateful; to her. We thank MisS
of Anatomy, and Dr. S. K. Pandya of the Saraswati ,Bakta; Dr. Aroona Mehta; Drr
Department of Neurosurgery. They have Poornima Patel and Dr. Sunil Joshi for
mo$t willingly extended their help at their help.
every stage in the preparation of the We are happy to acknowledge here the
book. Each page carries the benefit of unstinting cooperation and professional
their patient scrutiny, criticism, and ins- expertise of many individuals within
piring appreciation. Often we spent hours Messrs. Kothari Medical Publications-
with them discussing an idea, or an illus- the publishers, and Messrs. India Printing
tration. The frequent search with them Works-the printers. In the former group,
for the mot iuste has been most r€warding. the help given by Mr. V. B. Kothari is
Prof. K. D. De'sai, our Chief, has en- particularly noteworthy. His patient under-
couraged us all along. We couldn't have standing of the many problems of author-
xxi
xxll APPRECIATION
ship and his willingness to extend to us Despite her very busy practic€ as a con-
every courtesy and indulgence has turned sulting gynecologist and obstetrician com-
our relationship with him into a warm, bined with motherhood, Jyoti has not
responsive and lasting friendship. We spared any efiort in making MLK's task
express our. sincere appreciation of the comfortable. Her minute attention to
pains taken by Mr. V. D. Limaye of India various aspects of the book and her con-
Printing Works. Always ready to help, stant encouragement has been of great
patlent, full of cheer, Mr. Limaye seemed help to both the authors. MLK's son
to have but one aim-to give of his best Vatsal, at a young age, responded to his
for the printing of the highest standard. Daddy's need of being spared frequent
We thank him. visits to a swimming pool or a movie.
Our thanks are due to Mr. M. R. MLK is indebted to his parents-parti-
Chavan who drew the illustrations to our cularly his Father who discussed with him
specifications. The introductory illustra- the problem of cancer and read the proofs.
tions and the jacket were prepared by Special thanks are due to his sister Dr.
Messrs. Derek and fan Pinto. We thank Meena L. Kothari, for assisting in the
them. Our typists Mr. S. R. Khanvilkar reading of proofs and the preparation of
and Mr. V. K. Godhia deserve kudos indices. He is also indebted to his
for immaculate manuscripts. We were brothers, Dhiraj, Jashwant, Mukund, Dr.
indispensably helped by the librarians of Dipak, Devidas, and Mukesh and to his
our institute and the institutions around. sisters and sisters-in-law, Jaydevi, Drs.
Spceial mention must be made of Mr. ffansa, Poorvi, Nila, and Jayashree. The
N. G. Wagh of Seth G. S. Medical College, junior author most sincerely thanks her
Mr. V. M. Mathkar of the Tata Memorial family members for serving her comfort
Hospital, and Mr. M. S. Pawar of the and conveniences' at every stage. IIer
Cancer Research Institute. mother spared her the burden of manag-
It is but natural that families of irg the home. Her Father has taken
authors share to a considerable extent the personal interest in the making of the
burdens involved in the writing of a book. book-the choice of the style, as of thc
Often they must help in the forrnulation printers. LAM's brothers-Harish, Anil,
of clear ideas, in the preparation of the Mayur-have given generous help, parti-
manuscript, as well as share the physical cularly in the preparation of bibliography
and emotional strains of long and arduous and indices. LAM cannot forget thank-
hours of writing stretching into years. ing her sister Madhu, and her brother-in.
It is a matter of great pleasure and pride law Mr. A. V. Parekh, for kind encourage-
for thc senior author to acknowlcdse the ment.
willing and gracious acceptance of these M. L. K.
burdens by his wife, Dr. Jyoti Kothari. L. A. M.
 :i'

Contents

Volume One

PART ONE. FT]ITDAMENTAL CONCEPTS

Chapter I
FuNonnanNrer CoNcrPTs .........

Chapter 2

CvrouonpHosls '.,..'.....'.... 3
. Cytomorphosis in vitro 4
cytomorphosis in vivo ....::.........:.....::....::........' 5

Chapter 3
FrNrrr Lrrrrru4 or NoRuer- Drprom DrvrnrNc Cur,r,s ;........ 7
Finite Cell Doubling Capacity @CDC) Concept 12
FCDC and Cancerogenesis 14
FCDC Postulates

Chapter 4
CeNcnR GnNoun .....".:..'... ...'..'...;"'..... 2r

Chapter 5

CeNcnnocnNs: MvrH AND Moous Opnnennr 21

Myth of Cancerogens 30
Modus Operandi of Cancerogens .... 39

Chapter 6
Trrnrponar, Dtur,NsroN IN CeNcrnocENEsIS: Pnonr,nu 'oF
LernNcv .......'... 87
xxiv coNTENTs
Chapter 7

TnnurNor,ocv, DnrrNrrroNs nNn CrassrFrcATroN 93

Suggested,Telminology 97
Defining,Cancer 98
Biologic definition 102
Cytomorphotic definition ............. .t02
Cytologic definition t02
Histologic definition r03
Ontogenic definition 103
General definition r05
Clinical defrnition 105

PANT TVO. CEII,TILAN ASPECTS OF CANCEN

Chapter 8

Cnrrs IN CANcERous SrATE .....:.......... .. lll

Structural Features
Metabolic Features
' Defining Cancerous State 130
Genetics of Cells in Cancerous State l3Z
Basis of Cancer Cell Structure and Function t39
Raison d'6tre of Cells in Cancerous State ......... ls2
, Chapter 9

CaNcnn-pnorin CoNorrroNs lZb

Precancerous or Cancer-prone? l7b
': Classification of'Cancei:Ilrone'Conditions..:............1,....:.......... llb
'. Congenital Malformationr........i.l::.....:...:.,........-.........,....... 176

Hyperplasia 180
Metaplasia 186
Atrophic states .... ... .,. . .... ...... , .. . .. ...... r89
Reparative stat€s ... l9l

Chapter l0
 \*,*.

CONTENTS XIGV

Chapter I I
IuuuNor,ocrc Aspncrs oF CANcrn "'' 221
r)C,9
Antigenic Adaptation by Cancer Cells ........

*flfiitrl'i:"i'lJ':1il"J
Permissive role .........
lill : :: :
226
227
227
99(l
Perverse role .................."'.'...
Protective role ....... 230
Therapeutic Implications ...'....... 233
Choriocarcinoma ..........'..... 234

Chapter 12
243
CnucnnocENESIS IN vITRo
Normal Cells in vitro '...... 243
Cancerogenesis in vitro "'i""" 247

Chapter 13

ExprnrunNrer- CencrR ........ 255

Nature of Experimental Studies 255
Inferences from Experimental Cancerogenesis .""""' 256
Limitations of Expirimental Studi€s 257

PART TIIREE. CANCJR IN AN INDIVIDUAL

Chapter 14
265
GnNns eNn HnnnDITY IN CaNcnn
Genes and Cancer(ogenesis) '......:..'. 263
Genes and Cancerog€ns .... 278
Role of HereditY 282

Chapter l5
Frrr,n or OrucrN: RncuRnnNcE oF CeNcrn 801
Unicentric View .... '....'.'....""'j""" 301
Multicentric View ........ 303
Mode of Origin of Tumors " 308

. RecurrencS/Neooccurrence 309

Chapter 16
ceNcnn IN AN INurvrnuar-
Procancerous State .........::.......:....:........:..: ;i3
Initiation
progression ...........::.::::::::,:.::::...::.......3;l
, Induction ........
, Initiation and Promotion: Two-stage Cancerogenesis '....;'."" 324

ul
 JO(VT CON T E,N T S

Cancer: Occult, Dormant, Latent 324

Cancerogenesis in an Individual ............ 328
Built-in Clock that Strikes Cancerous Change 33I
Symptoms and Signs in Cancer 334
The FoLoNoS Perspective 342
Regression of Cancer 346
Cancer as. an Associated Disease .......... 350
Prognostication: Grading and Staging .......... JJJ
Cause, of Cancer Death 359

Chapter 17
Mrresrasrs oF CeNcnn 381
' Semantics ..... B8l
Paraprimal Cancer ZB2
Hemal Dispersal of Cancer Cells .... 888
Lymphatic Dispersal of Cancer Cells ....... Bgb
Spatial Dispersal of Cancer Cells ........ gg7
Evolution o1 Puruprimal Cancer
Nature gf Paraprimalization 409

Chapter 18
THr PnosABrlrry oF f)EvEr.oprNc CANCER ......... 42t
Species-specific Probability ........... 42t
Geographic and Racial Variations 422
Ag. and Probabiiity ................i. 433
Sex and Probability 433
Role of Heredity 434
Role of Exposur-e to a Cancer€en .,.......... 435
Probability at Cell Level 438
Site-specific Probability 439
Cancer-prone Conditions and Probability .... 442

Chapter l9
'Acr exo Cencnr 4bl
The Cancer Age .......... 4bl
',. Cancer in the Young .........:......
ASrg and Cancer ..:......... 4bb
Cancerogenic Bioclock .. 460
The Three Ages . 460

Chapter 20
Srx Du'TtRENCES rN CANcER
Important. Sex Difierences ..... 4jl
Cancer in the Two Sexes 472
Reproductive Gapacity.and,Selection .pressure
 \

CONTENTS x!(vr.t

Chapter 22
PRrvrNrroN or CeNcsnt ......... 499
Meaning of Prevention ............. 500
Erroneous Bases of Prevention ....'......"..:...':r'....... 501
Prevention of Preponement of Cancer 508
Future of Prevention ............. 5I0

Chapter 23
TnrervrnNr or CeNcER.'-1..:.....
Biologic Bases of Therapeutic Failure 516
Treatment: General Features
Surgery ....... ' '.?...... '..... 5?8
Principles ."'......'.......'..'..'..., ,...... 528
Procedures
Merits ...... ,.. ' ':. r
.. 534
. Radiotherapy .":..,.:'.. ---.--.54?
Principles !........; ..'.....'. "-.'542
' Procedures .j...................i.......... 560
Merits 562
Borrowed Cancer ."....:.'. 564
Chemotherapy ....... 577
Defining cancer chemotheraPy ...'....".
Procedures ','..', 199
Merits 600
ImmunotheraPy ....1 .. .:.,.......'..1;... 607
Principles '.....'.':.........:..'.'......":...."......." 613
Procedures
Merits 620
Ilormonotherapy ...................."r.'.......... 621
Principles ......:........ 622
Procedures ....... .............:.. 624
Merits 625
Nostrums
Palliative Measures :'....'.,. 629 ;

Therapy of Future 630 .

Cure Rates in Cancer Therapy ,...'......,..'. .........' 631 ':

Whither Cancer Therapy? ,.......".1.'... 634

Diagnose And Treat Early (DATE) ......... "'...',.......... 1.....'.. 6E7

Outcome of DATE Program

i
Ll
$:
 x"\|iii coNTENTs

" ' Aicptance

Do We
of Therapeutic Failure
Really Treat Cancer? ............
......'.....,........... 701
I ,.. ................. 7t2
;,, Rights of the Cancer Therapist 7t7
The right to tr€at 718
,. .. The right not to tr€at ............:... 732
ll i,, The nght to control treatment 756
,. : The right to prqlnose ....:........... 762
Summing Up .......... 79r

Aurxon
!',
lNnrx 839

punpcr lNusx

Volunie Two

P4m Foun. Bror,ocrc sreNrFrcANCE oF cAl\-cER

I Chaoter 24
'L

,Tnn RersoN D'ETRE or Ceucrn

Chapter 25
Ceucrn es e SrNrsceNr Pnocrss ;'

BrouncHeNrcs oF Huuer.r Sunvrver, eNo MoRrarrry

i, ,Chapter 27
oF CeNcnn
,UNrvtnser.rry
.'", Chapter 28
rl?irrto""Nrc EvorurroN oF CaNcrn
I

P. ART FIVE. A PERSPECIIYE .:'

nitr
l: '
; .-.1
t,:
A PnnspECTrvE I
'ri.
b,.* Appendix
ft..
.:''
ir'r '
.
THnoruns or CeNcERocENEsrs
i.
a,:
i:::
AurHon lNorx
,SirBJEcr
i,I
lxnnx l 1,;#
:,,::: ,{