Medical Hypotheses (2004) 62, 635–640

http://intl.elsevierhealth.com/journals/mehy

The quest for questions – on the logical force

of science
Thomas C. Erren*

Institute and Polyclinic for Occupational and Social Medicine, School of Medicine and Dentistry
University of Cologne, Germany

Received 25 August 2003; accepted 26 October 2003

Summary Questions and the logical principle of contradiction became a formal basis of scientific research and
education in the newly founded universities in the 1200s. With the advent of experimental methods in the 1700s, the
scholastic method of disputing questions as exclusive source for research and teaching disappeared. However, those
times’ stringent continuum of questions, answers and further questions corresponds to today’s empirical science with
hypotheses, tests and new hypotheses. This paper summarizes background information to the scientific methods of
disputing questions and testing hypotheses. While both questions and answers are necessary for research and
education, it is suggested that the generation of questions and hypotheses, i.e., propositions about observations or
ideas which can be disputed and empirically examined, drives scientific progress. Importantly, questions are necessary
tools to challenge locked-in concepts and to instigate new avenues. It is concluded that questions and hypotheses as
their formal expression must be strongly encouraged: appropriate answers and crucial tests will ultimately follow.
c 2004 Elsevier Ltd. All rights reserved.

The important thing is not to stop questioning.
Albert Einstein
To raise new questions, new possibilities, to
regard old problems from a new angle, re-
quires creative imagination and marks real ad-
vance in science.
Albert Einstein
Recall the many talks with children: the infinite
flow of questions and answers is really perpetuated
by children’s unlimited reservoir of questions
*
Present address: Institut und Poliklinik fu€r Arbeits-Sozial-
medizin, Klinikum der Universita €t zu Ko
€ln, Joseph–Stelzmann
€ln 50924, Lindenthal, Germany. Tel.: +49-221-478-5819;
St. 9, Ko
fax: +49-221-478- 5119.
E-mail address: tim.erren@uni-koeln.de (T.C. Erren).
which do or do not build upon our answers to all the
WHYs, WHENs, HOWs and so on. Without doubt, our
kids’ questions are immediate expressions of their
curiosity and wish to understand and need be en-
couraged. For similar reasons, i.e., to understand
or challenge past and present observations as a
basis to predict and possibly shape future events,
we pose questions in the scientific arenas as well.
There, a specific advantage is that many questions
can be answered by a trip to the library.
This paper is not about the use of questions as
a means to ask for what we – may erroneously –
consider as facts, for instance in the setting of an
exam. To the contrary, it shall focus on questions
as a means to express uncertainty about facts and
concepts. In this vein, according to The Oxford
English Dictionary [1], questions constitute “the
interrogative statement of some doubtful point to


0306-9877/$ - see front matter c 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.mehy.2003.10.022
636
be investigated or discussed”. At their best,
questions constitute both, critical syntheses of
existing knowledge and starting points for dis-
cussions and new research. To drive knowledge
forward, scientists must be encouraged to con-
stantly challenge observations and ideas via ap-
propriate questions. And, at the same time, we
should be aware and make it clear that what we
teach as knowledge in academia is based on those
answers which have not yet been proven wrong in
detail or context. Accordingly, please note that
“perhaps the most important thing for a student
to realize is that while his teachers may differ
from him in experience, with rare exceptions they
will not differ in intelligence. They are not indi-
viduals to fear, but individuals to question and
challenge” [2]. That scientific advance is ulti-
mately fueled by a continuum of generating
questions appears intuitively obvious. However, to
understand as to how questions became the
logical force of science requires more detailed
considerations.
Quaestiones
Etymologically, “question” derives from the Latin
for “to ask” (quaestio, quaerere, quaesitum: to
ask, to seek for, to inquire). The symbol “?” which
formally indicates a question is believed to be de-
rived from the first and last letters of “quaestio”.
Interestingly, the latter reference does not only
provide one origin for the question or interrogation
mark but also evinces the fundamental role which
the scholastic process quaestio played for research
and teaching in the Middle Ages and thereafter.
The quaestio method which has also roots in legal
circles and the foundation of universities became
the intellectual expression of a young Europe in the
13th century. Thomas Aquinas (1224/5-1274) [3,4]
referred the method’s principles back to Boethius
(480–524)1 [5]: “After suggesting some necessary
facts for the discussion of the question he does
three things. He poses the question, he provides
the answer and, finally, excludes objections to his
answer”. The logical reasoning in the course of the
quaestio disputata developed as an essential part
of lecturing. A necessary condition being that a
thesis or a fact was disputable. If so, interpreta-
tions of the material in question were formulated
as quaestiones which were then discussed exten-
1
Boethius, 1048D. Questio vero est dubitabilis proposito. “A
real quaestio is a proposition which can be disputed”. A.M.T.S.
Boethius. Topica Ciceronis, lib. I (PL 64) (Boethius 1988).
Erren
sively. In this vein, the quaestio provided a logical
tool for analysis and perspective in research and
teaching which was expressed by Robert de Melun
(1100–1167): “Quaestiones were sometimes posed
because of a doubt and sometimes in order to
teach” [6].
It is important to note that a paramount principle
of logic, i.e., that of contradiction, was crucial for
disputing questions in the course of a quaestio.
Key components had been suggested by Abaelard
(1079–1142) who based himself on Aristotle
(384–322 BC) when he introduced the ideal of
“question or doubt”. While Abelaerd had primarily
religious intentions, his “sic et non” (yes and no;
thesis and antithesis; pros and cons, if you will)
embedded this logical form of question technique in
Medieval universities in general and in medicine and
science in particular [7]. The use of this multidis-
ciplinary approach throughout centuries permitted
a level of analysis and perspective that could not
have been achieved by other means of those times.
As a result, the method of quaestiones helped to lay
the foundations of what has been called the Scien-
tific Revolution of the late 16th and early 17th
century but it was abandoned from research and
teaching in the late 17th century for reasons which
were described by Lawn [8]: “. . . What eventually
led to the disappearance of the quaestio disputata
from the curriculum was the rise of the experi-
mental method, the realization of the inadequacy
of Aristotelianism and scholasticims to explain
phenomena in the physical world, and the substi-
tution of reasoning based on measurement and
mathematics for the old logic of the schools. Once
these changes had taken place the methods of
teaching also changed. The essentially Aristotelian
disputation was displaced by the straightforward
question-and-answer technique without argument,
by the classroom lecture, and in the written field, by
learned essays, dissertations, and treatises”. Em-
pirical research, however, continued to build upon
the quaestiones’ cycle of questions, answers and
contradictions and new questions which were to find
a formal expression and elaboration in hypotheses,
empirical tests and refutations and new hypotheses
in the following centuries.
Hypotheses
The ancient Greeks introduced deductive methods
to determine truth about the world around us.
Initially, the process of deduction – as suggested
by Aristotle – was used to prove the validity of
mathematical propositions. The method started
The quest for questions – on the logical force of science
out with a – limited – set of definitions and axi-
oms, i.e., statements assumed to be or self-evi-
dently true, and then rules of logic were applied.
The method of deduction was later applied beyond
investigating mathematical propositions: based on
a hypothesis, i.e., an indicative supposition or
conjecture put forth to account for some phe-
nomenon in nature, outcomes were predicted and
deduction meant an inference from the general to
the specific. In the 1600s, Francis Bacon was the
most important philosopher of science to point out
that assertions about the world are very different
from arbitrary axioms in mathematics because they
are based on observations. The latter, however,
are fallible and often – if not always – incomplete.
As the alternative, Bacon suggested a method now
known as induction: we start out here with obser-
vations and provided that these evince a pattern, a
more general statement about nature may be for-
mulated. In other words, the process of induction
meant inferences from the specific to the general.
Such general propositions fell into the broad range
of rather simple hypotheses to the formulation of
natural laws. Any statements about natural rela-
tionships were then reinforced or refuted by addi-
tional observations.
On the one hand, induction was an advance
from the medieval scholastic methods because the
latter to an important extent relied on clerical
faith and authority rather than on actual obser-
vations. On the other hand, David Hume empha-
sized in the 1700s that a scientific method which
based itself exclusively on observations must be
considered unreliable because the underlying
sense perceptions can be misleading and wrong.
Only in the 1900s, Karl Popper provided a solution
to this puzzle of scientific logic by suggesting that
science really advances by deductive falsification
rather than by inductive generalizations [9–11].
Popper’s philosophy holds that while propositions
about nature can be corroborated by empirical
evidence, no amount of evidence can proove or
ultimately verify such statements. On the other
hand, any statement about nature may be un-
equivocally refuted or falsified by one experiment
or one observation. In effect, as illustrated by the
“white swan” example (the statement “all swans
are white” cannot be verified by whatever large
number of white swans but it may be falsified by
identifying a single black swan), Popper assigned a
maximum weight to “negative or refuting” evi-
dence and gave very little weight to “positive or
supporting evidence” [9–11]. In the context of
this paper, the asymmetrical implications of such
imbalance correspond to the dominant role of
questions and their formal expression, viz, hy-
637
potheses: In Popper’s logical universe, we are
looking at an endless cycle of conjecture and
refutation. But what perpetuates this logical cy-
cle? More generally, the driving force is a contin-
uum of questions and hypotheses which account
more and more for the observations at hand and
have the power to predict the results of other
phenomena. Specifically, rather than many an-
swers to one question it is the next – logically
refined – question which a forteriori drives the
progress of science.
But how do we arrive at our questions and hy-
potheses? While some will be obvious, others of a
more critical nature can be difficult to formulate.
More generally, the hypothesis – or conjecture –
is a product of insight and imagination which
requires no justification except that it either ac-
counts for or challenges past observations. More
specifically, to most of us, research questions
come only after much reading and extensive
thinking. Some researchers, though, may arrive at
a critical question or conceptual hypothesis in the
luxary of a shower or bathtub or while watching
kids a flash of inspiration or intuition may do the
job. Interestingly, it is attributed to Newton that
“no great discovery was ever made without a bold
guess”. With regard to the latter, though, it is
important to note that science will not rest on
unanalyzable intuitions rather than on logic and
law. What may appear as “a bold guess” or as in-
tuition is commonly the result of an individual’s
perception of the data at hand, i.e., biological
knowledge, results of animal, clinical and epide-
miological studies, etc. What any one individual’s
perception of identical data leaves for interpre-
tation and, ultimately, for the formulation of
questions and hypotheses, depends critically on
the nature and amount of prior experience and
training [12]. Therefore, what may at first seem as
“a bold guess” or intuition can – on further anal-
ysis – often be explained by the andividual’s
background and tacit knowledge. In any case: Ra-
ther than how the questions arise, be it exclusively
in the head [13,14] – Einstein could study the
universe with no more than a piece of chalk – or
be it in other laboratories, it is important that we
constantly pose them.
Questions and hypotheses in
biomedical research
That hypotheses and observations are generating
scientific progress together has been recognized by
physical and chemical sciences for a long time. In
638
contrast, in the bio-medical fields, the role of hy-
potheses appears to have been somewhat inferior
to experimentation and observation [15]. Only in
the 1800s, a gradual but steady transformation of
scientific medicine was pioneered by a number of
impressive researchers. In fact, one of the most
important physiologists of all times, Claude Ber-
nard (1813–1878), established with his systematic
experimentation into metabolism and neurology,
that biomedical research needs specific study
questions and a guiding hypothesis [16]. Thereaf-
ter, the prevailing empirical methods of conduct-
ing experiments without a guiding hypothesis were
slowly abandoned.
In the 1900s, the value of specific questions
which have been convincingly answered to some
extent2 and continue to drive research3 is, clearly,
undisputed. However, the general value of ques-
tions and hypotheses for biomedical research of
the last decades is, equally clearly, more difficult
to assess. In my view, the principal value which
should be and effectively is assigned to questions
and hypotheses can be approximated from theory
and publication practice: more theoretically, the
aforemade conceptual considerations should con-
vey the critical value of questions per se, i.e., to
maintain and feed the crucial cycles of discussion,
debate, determined experimental testing and thus
new observations and new questions. More empir-
ically, we may look at the number of and space in
peer-reviewed Journals devoted exclusively to
questions and hypotheses. Indeed, where can
questions and hypotheses be developed as the
publications’ key objective rather than being
raised only in the discussion sections? In other
words: how could and how can suppositions or
2 Fifteen years after the foundation of Medical
One seminal example is: What is Life? The Physical Aspect of
the Living Cell [17]. “We wanted to answer the question: What is
life?” James Watson in a February, 2003 Spiegel interview [18];
see also: Watson JD. The Double Helix: A Personal Account of
the Discovery of the Structure of DNA [19].
3
Another key example is: Do rods and/or cones and/or other
uncharacterized retinal photoreceptors contribute to the ad-
justment of biological rhythms to light [20]? In the past 6 years,
this question posed by a small group of scientists has been
answered insofar as non-rod, non-cone light-sensitive cells have
been discovered in the retina of mammalian eyes which are
expected to guide the circadian, or the daily inner clocks of
human beings. In the light of serious interest and abundant
research into the eye and the retina since the 1800s, it is clearly
astonishing that – beyond the classical rods and cones - there
are photoreceptors which had been overlooked until the right
question was posed. Indeed, the discovery of these “chronore-
oreceptors” [21] has been identified as one of the ten most
important scientific achievements in 2002 by Science magazine
[22] and research into non-rod, non-cone photoreception and
transduction can become very important for scientific disci-
plines which study health and disease effects in man.
Erren
conjectures put forth to account for bio-medical
ideas or observations find their place in the liter-
ature which is reviewed and discussed by peers?
In view of Popper’s advocacy of deductive fal-
sification through a continuum of conjectures and
refutations and his appreciation of the virtue of
improbable hypotheses (scientific progress is much
more likely to occurr if a hypothesis which most
people expect to be wrong turns out to be true,
i.e., it cannot be falsified), it should come at no
surprise that he was on the editorial board of a
journal devoted exclusively to hypotheses – or
questions and ideas – in the biomedical sciences,
i.e., Medical Hypotheses (MH; [23]).4 Of some 3000
journals which published bio-medical research
about 25 years ago, only three (The Journal of
Theoretical Biology; The Lancet; Perspectives in
Biology and Medicine) provided space as a matter
of explicit policy for papers which merely discussed
ideas and suggested hypotheses [15]. Of the others,
quite a few occasionally published theoretical
material but only if it was provided by scientists
with outstanding reputations. It is worthwhile to
look back at two key points which were made by
the editor of MH in the journal’s first issue in 1975
[15]. With regard to the actual occurrence of sci-
entific advance it was stated – in analogy with
“The Emperor’s New Clothes” [24] “. . . Outdated
concepts can persist for prolonged periods because
the evidence against them is scattered through
hundreds of papers and no one is allowed to gather
it together in one article to mount a sustained at-
tack”. Moreover, “. . . people with ideas (who may
often be inept experimenters) could generate a
steady flow of new concepts which might rejuve-
nate the work of those whose primary skill is in
observation”.
Hypotheses, Horrobin provided an informative look
at obstacles to get fundamental work and ideas
published and illustrated again the pivotal role of
Medical Hypotheses for providing the opportunity
to discuss possibly innovative ideas in the medical
and biomedical fields [25]. One bottomline being,
that – particularly those “very few” – questions or
hypotheses which may promise radical progress
need a hearing. But, as there is no way to reliably
anticipate what question or hypothesis shall enable
scientific progress – and, ultimately, improvement
of patient welfare – all ideas should have a public
forum. Only if open to public discussion, many – or
4
Medical Hypotheses Advisory Board: Sir Macfarlane Burnet,
Sir John Eccles, Arthus C. Guyton, Linus Pauling, Sir Karl Popper.
Editor: David F. Horrobin. (Medical Hypotheses Advisory Board
1975)
The quest for questions – on the logical force of science
most – ideas can and will be rigorously dismissed
but some may help to shape new and important
research avenues [14].
In this vein, as of December 2003, more than
4700 papers have been published in Medical Hy-
potheses. In addition, space in further journals in
the medical and public health fields to promote
questions and ideas has increased. For instance,
the Lancet publishes much more hypotheses – as
characterized by “a substantial jump in thinking
that is testable but not so easily testable that
readers will wonder why you have not already done
it” – today than in 1975 [15]. Most other journals
consider letters to the editor which can be stimu-
lating vectors for questions and hypotheses as well.
In the latter case, though, the average 300–600
words can be too little to make a convincing case of
a question or hypothesis to be discussed and fol-
lowed-up. A further opportunity to promote hy-
potheses in the public health fields is explicitly
provided by Epidemiology. Finally, many journals
today publish perspective or commentary papers
which also provide the much-needed room for
questions and hypotheses. But, similar to 25 years
ago, an important qualification being that it is
much easier for a reputable scientist to publish
such papers than for a relative unknown. A further
explicit means to pose questions has been provided
this year by the British Medical Journal: Indeed, the
BMJ printed medical questions and solicited an-
swers by experts in the paper journal some 20 years
ago and now encourages the submission of ques-
tions which shall be posted on and can be answered
via the journal’s website. “This revived feature
aims to capitalise on our website visitors’ enor-
mous willingness to share their ideas, opinions, and
experience with others” [26] and clearly illustrates
the principal appreciation of questions.
Conspectus
Questions and, ultimately, hypotheses need be
encouraged as much as possible because they drive
scientific research and advance. With regard to the
absolute impetus for refining our questions and
hypotheses, i.e., a scientific truth or proof is shown
to be wrong, actual answers will rarely yield an
unambiguous “yes or no” and tests cannot verify
and rarely lead to an unambiguous “falsification”.
Rather, we shall receive answers with “degrees of
yes or no”, i.e., “conceivably, plausibly or probably
yes or no” and, similarly, we shall be confronted
with “degrees of verification” such as “an over-
whelming amount of evidence in favor” on the one
639
hand or “degrees of falsification” [12] on the other.
It follows that we must be aware of and commu-
nicate that scientific theory can never be proved
but only be considered highly likely on the basis of
the available evidence. The latter is clearly rela-
tive and limited by any current state of knowledge.
In order to gain firmer and more permanent re-
search answers it remains but to constantly refine
what we ask nature.
When (experimentation) is going well, it is like
a quiet conversation with Nature. One asks a
question and gets an answer; then one asks
the next question, and gets the next answer . . .
George Wald [27]
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