Found Sci (2014) 19:387401

DOI 10.1007/s10699-014-9348-0

Serendipity and the Discovery of DNA

urea Anguera de Sojo Juan Ares Mara Aurora Martnez Juan Pazos
Santiago Rodrguez Jos Gabriel Zato

Published online: 19 March 2014

Springer Science+Business Media Dordrecht 2014

Abstract This paper presents the manner in which the DNA, the molecule of life, was
discovered. Unlike what many people, even biologists, believe, it was Johannes Friedrich
Miescher who originally discovered and isolated nuclein, currently known as DNA, in 1869,
75 years before Watson and Crick unveiled its structure. Also, in this paper we show, and
above all demonstrate, the serendipity of this major discovery. Like many of his contempo-
raries, Miescher set out to discover how cells worked by means of studying and analysing
their proteins. During this arduous task, he detected an unexpected substance of unpredicted
properties. This new substance precipitated when he added acid to the solution and it dis-
solved again when adding alkali. Unexpectedly and by a mere fluke, Miescher was the first
person to obtain a DNA precipitate. The paper then presents the term serendipity and dis-
cusses how it has influenced the discovery of other important scientific milestones. Finally,
we address the question of whether serendipitous discoveries can be nurtured and what role
the computer could play in this process.

Keywords Computational serendipity DNA Miescher Nuclein Serendipity

1 Introduction

Very few people, even biologists, know that it was Johannes Friedrich Miescher who orig-
inally discovered and isolated nuclein, now known as DNA, the molecule of life, in 1869,
that is, 75 years before Watson and Crick unveiled its structure (Watson and Crick 1953).

. Anguera de Sojo J. G. Zato

Technical University of Madrid, Madrid, Spain

J. Ares S. Rodrguez (B)

University of A Corua, A Corua, Spain
e-mail: santi@udc.es

M. A. Martnez J. Pazos
Madrid Open University (UDIMA), 28400 Madrid, Spain

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And still fewer know that this, like many other scientific discoveries, was serendipitous, that
is, made by chance when he was looking for something else.
On 26 February 1869, a young Swiss physician wrote a letter from the old university
town of Tubingen to his maternal uncle, Wilhelm His, a renowned physician and chair of
anatomy and physiology at the University of Basel. This letter announced a major discovery: a
substance that he had found in the cellular nucleus whose chemical composition was different
from other proteins and any other known compound at the time.
Strictly speaking, however, the first document written about DNA structure was a letter
that one of its discoverers, Francis Crick, wrote on 19 March 1953 to his then 12-year-old
son Michael, who was away at a British boarding school, weeks before the publication of
the article that he had co-authored with Watson. After instructing him to attentively read and
comprehend the contents of the seven-page letter (Watson and Crick 1953), he explained, as
shown in Fig. 1, the composition of deoxyribonucleic acid (DNA), listed its constituent bases,
plus its helical structure. The letter not only recounted the discovery but also conveyed to his
beloved son, who was also interested in the world of science, how excited Crick, the father,
was about the breakthrough. And, rightly so, as, further down, he wrote We think we have
found the basic copying mechanism by which life comes from life. You can understand that
we are very excited. Incidentally, and somewhat anecdotally, the manuscript was auctioned
by Christies for no less than four million euros.
The amazing thing about this discovery was that Miescher was unaware of the major future
repercussions that his research, called upon to trigger one of the major scientific revolutions of
all time, was to have. Also, Miescher was researching the chemical composition of cells, first
lymphocytes and then their close relations, leucocytes, by analysing their proteins in order
to find out how cells worked when he came across a substance that exhibited unexpected
properties. This substance, which he called nuclein, is now known as DNA.

2 Mieschers Biography

To write this section we have consulted the following biographies of Miescher: (Dahm 2005,
2008b; Greenstein 1943; Wolf 2003; Lagerkvist and Brenner 1998; Meuron-Ladolt 1970).
Johannes Friedrich Miescher was born into a family of scientists based in Basel, Switzer-
land, in 1844. His father and maternal uncle, Wilhelm His, were renowned physicians, and
both had held the chair of anatomy and physiology at the University of Basel. Scientists
often visited his home, where heated and interesting debates were held especially concerning
scientific and cultural questions. This was the environment and breeding ground that opened
up science, its ideas, problems, perspectives and prospects to Friedrich as of a very young
age. This milieu naturally led to Miescher developing a profound and early interest in the
natural sciences.
This interest led him to enrol at the age of 17 years for medical school at Basel, from
where he qualified with distinction in 1867. He originally had in mind to pursue the family
profession; however, an illness, typhus, which he contracted during his childhood, had left
him partially deaf. This was a substantial handicap for practising the teaching profession.
And, looking on the bright side, this was actually a great stroke of luck, as his passion for
science pushed him into research. And that is where his Uncle Wilhelms influence came
in. Wilhelm His was convinced that chemistry held the key to the outstanding questions
regarding tissue development. This encouraged Miescher to study biochemistry.
In spring 1868, he moved to Germany to work with two of the most renowned scientists
of the time: Adolf Strecker, a specialist in organic chemistry, at whose Gttingen-based

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Fig. 1 Extract from Cricks letter to his son with a drawing of the DNA spiral model

laboratory he spent 6 months, and Felix Hoppe-Seyler, a biochemist and pioneer of the recent
discipline of physiological chemistry. From 1860 to 1871, Hoppe-Seyler led one of the first
biochemistry laboratories in the world. It was located inside Tbingens medieval castle,
overlooking the old part of the town. His laboratory occupied what had been the laundry,
and Miescher worked in the former castle kitchens. Before Mieschers arrival, Hoppe-Seyler
had conducted innovative research into the properties of haemoglobin, which had a major
impact on later studies on the structure and operation of this and other proteins. He soon rose
to international fame.
Under the leadership of Hoppe-Seyler, Miescher started to research the chemical compo-
sition of cells and developed a method that led him to a capital discovery. In autumn 1869,
Miescher returned to Basel for a short holiday, where he started to write his first scientific
publication on the analysis of the chemical composition of leucocytes, which included the
discovery of nuclein (Miescher 1871). By that time he was sure about the importance of his
discovery and likened the substance to a protein.
After his vacation, he returned to the laboratory, this time based at the University of
Leipzig, where he started to work with Carl Ludwig researching, among other things, the
pain-transmitting nerve pathways of the spinal cord. And although Miescher went about his
new undertaking with his characteristic rigour and thoroughness, he was nowhere near as

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enthusiastic about his work as he had been in Tbingen. In fact, he spent his first few months at
Leipzig working on the draft of his first publication, which he completed just before Christmas
1869. He sent the completed manuscript to Hoppe-Seyler for approval and publication in the
journal that he edited. On 23 December 1869, Miescher wrote to his father, saying On my table
lies a sealed and addressed packet. It is my manuscript, for whose shipment I have already
made all necessary arrangements. I will now send it to Hoppe-Seyler in Tbingen. So, the
first step into the public is done, given that Hoppe-Seyler will not refuse it. And although it
was not rejected, it was not published until 1871 due to a series of unforeseen and events and
changing circumstances, including the Franco-Prussian War which broke out in 1870.
After his stay at Leipzig, Miescher was offered a position as faculty member at the Uni-
versity of Basel. He returned to the institution in 1870, after his scientific achievements had
earned him a notable reputation as a tenacious and ingenious researcher. In 1872, at the age
of 28 years, after qualifying as a university lecturer, he was offered the universitys chair
of physiology, the same position that his father and uncle had held. Miescher worked hard
at his new job, often to the point of exhaustion. Additionally, his passion for science gave
him the itch to demonstrate that he had been awarded the chair on his own merit and not by
inheritance.
At Basel, Miescher went back to his nuclein research, which he had broken off during
his stay at Leipzig. He was encouraged by the fact that Hoppe-Seyler was interested in
and accepted to continue research on the topic, provided Miescher redoubled his efforts.
Mieschers goal was to describe the features of nuclein in more detail. But his working
conditions were much worse than at Tbingen, which meant that the project progressed
slowly. In a letter to a friend, he complained, In the past 2 years, I have avidly yearned for the
laboratory in Tbingen Castle again, for I had no laboratory here and was merely tolerated
in a small corner of the chemistry laboratory, where I could hardly move, surrounded by
students; and above all the chemistry professor conducting his research here. He continued,
You can imagine how it must feel to be hindered in the energetic pursuit of an endeavour
on account of the most miserable conditions, knowing that I may never have such a fine
opportunity again.
Even so, Miescher did not give up. Moved by his uncles interest in developmental biology,
he set out to study nuclein in eggs and sperm cells. He soon found that the sperm cells,
composed almost exclusively of nuclei, were a perfect source of sufficient quantities of
nuclein. Basel, located on the banks of the Rhine, turned out to be a good spot for his
experiments. And the animal migration season, when salmon swim upriver to spawn, was
the optimal time for collecting raw material. Thus, salmon sperm, which he used to carry
out his increasingly complex research, became his new source of nuclein as of autumn 1871.
The results of this research were published in 1874 (Miescher 1874).
This contact with the salmon industry steered his interests towards other more mundane
fields, and he never published on the nuclein again. In the mid-1870s, he studied the changes
that took place in salmon anatomy during their annual migrations from the ocean to the
cold waters of the Rhine where they spawned, a journey during which the fish starve. He
was amazed by the fact that the fishs sexual organs grew enormously eventually accounting
for a quarter of their total body weight, taking up space left by their wasting muscles. By
virtue of this work on salmon metabolism, the Swiss government commissioned a report
on the diet of Basel prison inmates in autumn 1876. Miescher did not like the undertaking,
which lasted months, but the authorities were so favourably impressed by the results that
they commissioned similar reports for other prisons. Apparently every prison wanted its
own menu. And it did not stop there, as educational institutions, food associations and other
nutrition-related organizations sought Mieschers advice and opinion. He ended up loathing

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this job. Inquiries into the Swiss diet, cookery books for workers, nutrient tables for national
exhibition, disagreements with the Chamer dairy gave Miescher the feeling that he was the
stomach warden of three million Swiss.
Years later in 1885, Miescher took on another challenge: the foundation of Basels first
anatomicalphysiological institute, which he directed successfully and responsibly. This
foundation set out to promote scientific activity. He engaged renowned and accredited tech-
nicians that developed machines and instruments for performing exceedingly accurate phys-
iological measurements. He researched the change in blood composition at altitude and
discovered that it was the concentration of CO2 and not O2 that regulated breathing.
With time, his increased commitments wore him down. His obsession for his work and
his perfectionism led him to cut down on hours of rest. He slept less and less, kept up with
his social commitments and relations and worked nonstop without respite. Exhausted, his
body weakened day by day. In early 1890, he contracted tuberculosis and had to give up his
work altogether and retire to a sanatorium in Davos in the Swiss Alps. He attempted to make
a comeback soon afterwards and even return to his research on nuclein, but his health broke
down completely, and he died in 1895. After his death, Wilhelm His published a collection
of his research with a foreword reading, The appreciation of Miescher and his work will not
diminish; on the contrary, it will grow and his discoveries and thoughts will be seeds for a
fruitful future. Not even His could imagine how true these prophetic words in honour of his
nephew would be.

3 The Discovery of Nuclein

The references that we have used for this section are (Dahm 2008a; Harbers 1969; James
1970; Maderspacher 2004; Ostrowski 1970; Portugal and Cohen 1977). When under Hoppe-
Seylers leadership, Miescher started to research the chemical composition of cells, he focused
on lymphocytes. Lymphocytes were the most simple and independent type of cell, from which
he hoped to unravel the secrets of cellular life. However, lymphocytes were hard to purify
in sufficient quantities for chemical analysis from the lymph nodes. Hoppe-Seyler, who had
been looking into the makeup of blood for some time, suggested that he should use leucocytes,
which were closely related to lymphocytes. To do this, Miescher, isolated the raw material
for this experiments, leucocytes, from the pus on surgical bandages which he collected from
a nearby hospital. This was a rather uninspiring start. At the time, seeping wounds were
considered to be the bodys cleansing mechanism whereby it excreted harmful substances.
As antiseptics were not much used, there was no problem at all in gathering large quantities
of pus-filled bandages.
The first thing that Miescher had to do was to develop a method to extricate the leucocytes
from the surgical material. To do this, he tested several saline solutions always checking the
results under the microscope. Once he had established the extraction protocol, he proceeded
to characterize and classify the proteins and lipids that he isolated from the cells. Like many
of his contemporaries, his ultimate hope and aim was to analyse cellular proteins in order to
discover how cells worked, which is why Miescher went about describing and classifying
proteins. Now, his path was riddled with obstacles. The diversity of cellular proteins surpassed
the primitive methods and instruments of the time. Even so, he unexpectedly detected a
substance that he was not actually looking for, a substance which exhibited unpredicted
properties. It precipitated when he added acid to the solution and dissolved again when an
alkali was added. Without realizing it and by pure luck, Miescher had for the first time
obtained a precipitate of DNA.

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Table 1 DNA-related timeline

Year Event

1865 Gregor Mendel discovers that traits are inherited according to specific laws
1866 Ernst Haeckel states that the nucleus contains the factors responsible for transmitting
hereditary traits
1869 Friedrich Miescher isolates DNA, which he calls nuclein
18841885 Oscar Hertwig, Albrecht von Klliker, Eduard Strasburger and August Weismann
demonstrate that the cell nucleus is the basis of inheritance
1889 Richard Altmann changes the name of the nuclein molecule to nucleic acid
1928 Frederick Griffith proposes a transformation principle underlying the transmission of
properties of one type of bacteria to another
1929 Phoebus Levene identifies the components of DNA
1944 Oswald T. Avery, Colin MacLeod and Maclyn McCarty demonstrate that DNA is
responsible for Griffiths transformation principle
19491950 Erwin Chargaff finds that the composition of DNA bases varies from one species
to another but that the proportions of bases are unchanged in each species
1952 Alfred Hersey and Martha Chase use viruses to confirm that DNA constitutes
genetic material
1953 Rosalyn Franklin and Maurice Wilkins use X-rays to demonstrate that
DNA has a regularly repeated helical structure
1953 James Watson and Francis Crick discover the molecular structure of DNA, which is a
double helix
1954 Researchers continue to sequence the genome of many organisms
2001 The human genome is sequenced

Where did that substance come from? While Miescher was extracting leucocytes using
acids, he observed that the prolonged exposition of cells to diluted hydrochloric acid produced
a cellular residue similar to isolated nuclei. He found that those nuclei were not stained
yellow by iodine, which provided unquestionable proof that no proteins were present. Slightly
alkaline solutions caused the swelling of, but did not dissolve, the nuclei. Miescher thought
that the mysterious precipitate must come from the nucleus.
Hardly anything was known about that organelle at the time. Although its cellular function
had been discovered back in 1802, it was still a cause of speculation and controversy. In
1866, however, 3 years before Mieschers discovery, Ernst Haeckel claimed that the nucleus
contained the factors responsible for transmitting hereditary traits, whose laws Gregor Mendel
had discovered. This hypothesis again raised interest in investigating the role of the nucleus.
The chance finding by Miescher provided the key to gather more information about the nature
of the mysterious organelle. Later, as of this discovery, a powerful, and today still buoyant,
line of research was developed, whose highlights are reported chronologically in Table 1.
Before he could identify the nuclear precipitate, Miescher had to develop several proce-
dures for isolating highly pure nuclei. After numerous trials and errors, he came upon an
effective method. This finicky and tiresome method (Dahm 2008b) had to be carried out at
low temperatures to prevent the degradation of the samples and consisted of the following
steps:

1. Wash the pus-filled bandages in a diluted solution of sodium sulphate to extract the
leucocytes.
2. Filter the result to remove cotton fibres, leave to stand for several hours and then examine
the leucocytes under the microscope to check that they are intact.

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3. Wash the cells several times with heated alcohol to break down the cells and remove most
of the lipids.
4. Wash pigs stomachs with hydrochloric acid to extract pepsin, the enzyme that digests
proteins.
5. Heat and shake the cells with pepsin repeatedly for 1824 h to form a fine, grey, grainy
sediment of isolated nuclei separated from a pale yellow liquid.
6. Stir the nuclei in ether several times to remove any trace of lipids, wash with water, stain
with iodine, and examine under the microscope. If they do not stain, the proteins have
been successfully removed.
7. Wash again with heated alcohol and start checks. Add diluted sodium carbonate (alkaline
solution) whereby they should swell and become translucent.
8. Add hydrochloric acid to obtain an insoluble, flocculent precipitate: nuclein or DNA.

Through these experiments, Miescher demonstrated that the observed precipitate came
from the nuclei on which ground he called it nuclein, a term that is still conserved in todays
deoxyribonucleic acid.
Despite nucleins unusual behaviour, Miescher was not absolutely convinced that it was
not a protein. This led him to conduct other experiments to further examine the nature of this
strange molecule. First of all, he set out to determine its elementary composition. To do this,
he had to purify nuclein. To eliminate the contaminating cytoplasm, he decided to apply the
method that Wilhlem Khne had described one year before in his physiology manual.
Unfortunately, pepsin was not sold commercially at the time, and he had to isolate it on
his own account. The second, equally or more disagreeable, part of his scientific enterprise
began. This was to wash pigs stomachs in diluted hydrochloric acid and filter the extracted
contents in order to obtain a crude solution of digestive enzymes. By treating the cells with
this solution, he managed to demonstrate that nuclein was not a protein because the pepsin
would have digested all the proteins. At that time, fundamental analysis was one of the few
methods for identifying molecules. The procedure included heating the sample together with
several chemical agents that reacted selectively with the different components. The resulting
products were weighed to determine the amount of each element in the sample. Although
this was an extremely laborious and slow process, factory work in Mieschers words, it was
successful.
Mieschers isolation method showed that nuclein behaved differently to lipids and proteins,
as it was not degraded by the enzymes capable of breaking down proteins, nor could it be
extracted by means of strong organic solvents. The analysis of its composition caused another
surprise: apart from containing carbon, oxygen, hydrogen and nitrogen, elements that were
known to abound in proteins, the molecule also contained large quantities of phosphorus but
no sulphur. This was a surprising finding that certainly was a distinguishing feature of the
substance as there was no other known organic molecule containing phosphorus. This result
convinced Miescher that he had discovered a new type of fundamental cellular substance.

4 Getting the Results Published: A Calvary

In autumn 1869, Miescher started to write his first scientific publication on the analysis of
the chemical composition of leucocytes, which included the discovery of nuclein. Months
later, he moved to Leipzig, where he completed the manuscript just before Christmas. Its
off-putting, even repulsive, title, On the chemical composition of pus, obscured the crucial
discovery that it reported. The body of the text did, however, underline the innovative finding

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of nuclein as follows, Wir haben vielmehr hier einen Krper sui generis, mit keiner jetzt
bekannten Gruppe vergleichbar; that is, Rather we are dealing with a sui generis entity that
is not comparable to any hitherto known group.
Hoppe-Seyler considered the manuscript rather circumspectly and guardedly as he dis-
trusted such innovative results. This is not a surprising attitude taking into account that a pro-
found debate about the existence of a molecule containing phosphate in brain tissue had been
held at his laboratory not long before. Hoppe-Seyler was sceptical about a young and inexpe-
rienced scientist having discovered a new fundamental molecule. Additionally, Mieschers
manuscript was to be published in Medizinisch-chemische Untersuchungen. Hoppe-Seyler
was the editor of this publication, on which ground he had to be specially demanding and crit-
ical. After checking Mieschers results, Hoppe-Seyler was very favourably inclined towards
the article, although his initial analyses of the elementary composition of nuclein differed
from Mieschers. They were unimportant differences, but they were going to delay the pub-
lication process. In face of this delay, Hoppe-Seyler suggested that Miescher submit the
manuscript to another publication. However, Miescher preferred to wait until his results had
been confirmed and have them published in the journal of his former mentor.
In July 1870, when the Franco-Prussian War broke out, the situation worsened and there
was further delay. Miescher became increasingly concerned about the hold-up, among other
things because his qualification as a university professor at the University of Basel was
at stake. Moreover, he feared that others might discover nuclein and publish their discovery
before his article came out. And, as is known, there are only gold medals in scientific research.
Desperate because of the long delay, he wrote to Hoppe-Seyler several times to get things
moving. He even considered the option of submitting his work to another journal and asked
Hoppe-Seyler to return the manuscript. Finally, after a year-long lapse, Miescher received
the response to his letters. Hoppe-Seyler had confirmed his results and told him that he would
try to publish the paper in the next issue of the journal. Pleased to hear that this work would
soon see the light, Miescher immediately wrote back to Hoppe-Seyler noting his satisfaction
and including some comments on the latest findings that he had been sent. A few weeks later
he received the proofs of his first publication. These, anecdotally, were accompanied with a
letter from the editor apologizing for all the typos which were the result of printers having
found his handwriting hard to decipher.
The paper was finally published in 1871. It headed the table of contents of that issue
of the journal edited by Hoppe-Seyler. The publication contained another two articles on
nuclein, one written by one of his disciples, which proved the presence of the molecule in the
nucleated leucocytes of birds and snakes, and another by the editor, confirming Mieschers
results.
In 1871, Miescher again took up his research on nuclein, which he had broken off during
his stay a Leipzig. Despite the difficulties of experimenting at Basel, he returned to his nuclein
research, driven by his uncles interest in developmental biology. During his stay at Tbingen,
Miescher had, as already mentioned, isolated a great deal of the very purest nuclein. Thanks
to this, he was able to carry out the thorough analyses that he had projected to undertake
at Tbingen. The new observations confirmed the initial results and precisely determined
nucleins phosphorus content.
In 1874, he published his results on the presence of nuclein in vertebrate sperm. At the
time, scientists were researching embryonic development and the transmission of hereditary
traits. Miescher had the answer at his fingertips and even went as far as to write, If one
wants to assume that a single substance is the specific cause of fertilization, then one should
undoubtedly first and foremost consider nuclein. However, he did not believe that a single
molecule was responsible for inheritance, as he could not conceive how a single substance

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could produce such a broad assortment of animals as those whose sperm he had examined.
He believed that the chemical structure of the molecule occasioned such variations, but that
their variability was limited; not large enough to explain the differences observed among
individuals of the same species and much less so among different species. Contrariwise, he
defended that mechanical stimuli caused by the movement of sperm and other processes such
as were observed during nerve and muscle fibre excitation were responsible for developing
the fertilized egg.
Miescher likewise put forward a hypothesis on the transmission of hereditary informa-
tion, which, although he got the details wrong, is very close to the current description of
information storage in DNA. It speculated on the possibility of information being encoded in
the stereochemical arrangement of carbon atoms or, alternatively, their organization inside
the molecule. In the same way that a 26-letter alphabet is enough to express all the words
and concepts of most languages, molecules would be composed of different stereoisomers or
specific forms of their constituent atoms. In other words, if there were a great many asymmet-
ric carbon atoms in organic micromolecules, like proteins, there would be an extraordinarily
large quantity of stereoisomers. For example, a molecule with only 40 asymmetric carbon
atoms could contain 240, that is, over 1,012 stereoisomers. Miescher thought that such a fig-
ure was sufficient to encode the hereditary information of all forms of life. He later suggested
that molecular errors during the embryo development could be prevented by merging the
information of two germ cells during fertilization. These opinions anticipated what today we
know to be true: intact progenitor alleles offset the defects in an allele inherited from another
progenitor.

5 An Overlooked Discovery

Why is Mieschers name not associated with DNA today? The first reason is that, unlike many
diseases, species, anatomical structures, etc., molecules are not named after their discoverer.
Second, Miescher was a reserved and introverted person. This meant that he moved in a
very small circle and had few disciples, most of whom ended up leaving him. On top of
this, he publicized and promoted his discoveries poorly. Could there be anything worse?
Finally, and perhaps most importantly, irrespective of his passion for scientific research, he
was an irresolute perfectionist to the point that he repeated his experiments more often than
necessary. This delayed his publications and reduced his visibility enormously.
Miescher was himself aware that research on nuclein was being increasingly associated
with other researchers. In 1889, Richard Altmann changed the name of the molecule that
Miescher had discovered to nucleic acid. This irritated Miescher beyond measure, as he had
always highlighted that nuclein was an acid, but his outburst got him nowhere. However, the 75
years that elapsed between his discovery and the subsequent realization of its importance were
perhaps what ended up being most decisive for Mieschers contribution being overlooked.
That was when, despite all the mysteries that the molecule still holds, DNA became the icon
of modern life sciences.

6 Serendipity in the Discovery of Nuclein

In terms of what it both denotes and connotes, the word serendipity has, as shown in Table 2,
a very long and interesting past. Technically speaking, it means to look for something and
fortuitously, by chance, slip-up, accident or luck, end up unexpectedly finding something

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better. Roberts (1989) noted that serendipitous discoverers share dominant characteristics,
such as sagacity, perception (also described as awareness), curiosity, flexible thinking and
intensive preparation. And van Andel, who has catalogued over 1,000 cases of serendipity
and agrees with Roberts on this point, claims that there are three personal characteristics of
serendipitous discoverers: sagacity, adequate preparation and curiosity (Van Andel 1994).
Serendipitous discoveries include champagnization by Dom Prignon, pasteurization by
Louis Pasteur, penicillin by Alexander Fleming, X-rays by Wilhem Rntgen, vulcanization
of rubber by Charles Goodyear, quanta by Max Plank, the universal computer by Alan M.
Turing and von Neumann, America by Christopher Columbus, nuclear fission by Otto Hahn,
Fritz Strassmann and Lisa Meitner, cosmic background radiation by Arno Penzias and Robert
Wilson, radio astronomy by Janski, vaccination by Jenner, etc.
Of the many, albeit evidently equivalent definitions of serendipity, the popular catchphrase,
Its like looking for needle in a haystack and rolling out with the farmers daughter or son, is
the one that we think is best, because it is illuminating, that is, plain and simple, productive,
and useful for drawing analogies and modelling. Its descriptiveness is beyond question, and
we say it is productive since the needle in the haystack metaphor, which, trivially, means
something that it is hard to find, can be apprehended and, consequently, modelled differently
and thus equated to the following search and/or research scenarios (Koll 2000):
Finding a known needle in a known haystack
Finding a known needle in an unknown haystack
Finding an unknown needle in an unknown haystack
Finding any needle in a haystack
Finding the sharpest needle in a haystack
Finding most needles in a haystack
Finding all the needles in a haystack
Being able to confirm that there are no needles in a haystack
Identifying each new needle that appears in the haystack
Finding where the haystacks are
Finding any needless in any haystacks, etc.
Now, what might look more like a play on words makes absolute sense when needle is
switched for issue, question, etc., and haystack for internet.
The Physics Nobel laureate Yuval Neeman and his colleague Aharon Kantarovich and
Neeman (1989) and years later, more specifically, Antonio Dias de Figueiredo and Jos
Campos Dias De Figueiredo and Campos (2001), expounded qualitative ways for discerning
whether or not a discovery and/or experiment is serendipitous. Neeman and Kantarovich
used the Oxford English Dictionary definition: The faculty of making happy and unexpected
discoveries by accident. The dictionary contains, however, the following sharper definition:
looking for one thing and finding another. This second definition refers to cases where one
looks for A and finds B. This way, scientists following a procedure to solve a problem discover
that the final result provides a solution to another problem, of which they were not aware.
The notion of serendipity implies that the discoverer knows that he or she has discovered
B or, at least, that he or she found something unexpected and/or relevant and meaningful.
Sometimes, the scientist that made the discovery is not aware of the outstanding importance
of his discovery and other scientists finish the job. Accordingly, Neeman and Kantarovich
divide serendipitous events into two classes, as follows:
1. Scientists solve and/or explain B when they intended to solve and/or explain A.
2. Scientists solve and/or explain B plus A when they intended to solve and/or explain
only A.

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Table 2 Timeline of the term serendipity (Merton and Barber 2004)

Year Event

Undated The Greeks had a god for the unknown, to whom they attributed the unexpected finding of
something good. It was the Arcadia-born Hermes, son of Zeus and a lesser goddess called
Maia, from whom the month of May takes its name. Hermes was also the inventor of the
alphabet, music, weights and measures and fire. He was the patron of orators, travellers,
tradespeople and thieves, who, as a newborn jumped out of his cradle to steal Apollos oxen.
Additionally, he was a psychopomos, that is, responsible for conducting lost souls to the
Underworld. In his honour, the two-faced milestones, signposts placed by the ancients at
crossroads and/or forks in the path, land boundaries and even in gardens and at altars are
called herms, a name still in use today
504501 BC Heraclitus said, Unless you expect the unexpected you will never find [truth], for it is hard to
discover and hard to attain
385 BC Through Socrates, Plato criticized the sophists (500300 BC) in his Meno, as follows: I
understand the point you would make, Meno, Do you see what a captious argument you are
introducing that, forsooth, a man cannot inquire either about what he knows or about what
he does not know? For he cannot inquire about what he knows, because he knows it, and in
that case is in no need of inquiry; nor again can he inquire about what he does not know,
since he does not know about what he is to inquire
1302 Delhi-based Amir Khusran, the greatest Persian poet of India, published Hasht Bihisht (The
Eight Paradises)
1557 Christoforo Armeno published his book Peregurinagfio di tre Giovani Figliuoli de Re di
Serendip (The Three Princes of Serendip). This is the first time the word Serendip, the
mediaeval name of Ceylon, now known as Sri Lanka, appeared in print. These princes had
the talent of making unexpected discoveries by sagacity. This book is a loose adaptation of
Hasht Bihisht
1679 Robert Hooke signalled the role that luck plays in scientific discovery and invention in the
preface of his book
1754 Horace Walpole coined the word serendipity, which he defined as the unexpected discovery of
something one is not in quest of, in a letter to his namesake Horace Mann dated 28 January
1754
1775 Priestley referred to luck as being the observation of events arising due to unknown causes
1833 Lord Dover published Walpoles meticulous correspondence, and the word serendipity
appeared in print for the first time and became known to the scholarly world
1854 In his opening address as dean of the new School of Sciences of Lille, Pasteur recalled that
rsteds experiment suddenly opened his eyes, one might say, by chance, but reminded his
audience that, in the observational sciences, chance favours only the prepared mind
1865 Claude Bernard wrote that Experimental ideas are very often born by accident or on the
occasion of a fortuitous observation
1875 Antiquarian, booklover and former chemist Edward Solly used the word serendipity in Notes
and Queries, the newspaper founded by John Thoms in 1857, in response to a reader and
introduced the term into literary circles, to which it was confined until 1930
On 12 May of the same year, R.S. Charnock of Grays Inn explained in the same medium, that
Serendip was the Arabic corruption of Sinhala-devipa (island of lions), later corrupted down
to Ceylon
On 26 June again in the same newspaper, R.C. Chielders corrected Charnock and claimed that
Sinhaladvipa means island of the Sinhalese people, and that Ceylon is a corruption of
Sinhala only
1911 The great physiologist Walter B. Cannon, discoverer of homeostasis, described the role that
chance plays in research at a lecture to Yale Medical School graduates, titled Career of
Investigator, without mentioning the word serendipity
1930 Cannon started to use the term serendipity on a regular basis; he introduced and popularized
the term in scientific and medical circles
1938 E. McDonald used the word serendipity in the annual report on the work of the Biochemical
Research Foundation of the Franklin Institute in Philadelphia

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398 . Anguera de Sojo et al.

Table 2 continued
Year Event

1941 In a lecture given at Cornell Medical School, Bronson Ray described how he had recently
discovered the term serendipity, and recalled that Elliot Cutler, a Harvard professor of
surgery, had given a talk mentioning serendipity as a desirable quality for students
1945 In his book The Way of an Investigator, Cannon published a chapter titled Gains of
Serendipity, explaining the concept
1949 An article titled Choice of Research Projects published in the Journal of the Franklin Institute,
247, revealed that the word had been discovered in 1938 in a detective story!
1958 Robert K. Merton and Elinor G. Barber produced a 338 page typed manuscript (to be revised
and perhaps extended) titled The Travels and Adventures of Serendipity, A Study in
Historical Semantics and the Sociology of Science. The book is a clear example of
anti-serendipity as it was not published until many years later, in the early 21st century.
Merton had previously given a precise definition of the meaning and importance of
serendipity in 1957

Fig. 2 Dias de Figueiredo and Campos serendipity equations

In the light of the above works, Dias de Figueiredo and Campos introduce a simple notation,
which they somewhat imprecisely denote serendipity equations. These equations, shown in
Fig. 2 with their respective examples, highlight the key differences between serendipitous
and non-serendipitous situations. To do this, they use P to describe a problem; KP for the
problem knowledge domain; M for the unexpected metaphor or inspiring idea; KM for the
metaphor knowledge domain; S for the solution; KS for the solution knowledge domain.
The four equations actually rely on a spark, the metaphor, as a means of provoking insight:
metaphor, unexpected metaphor, no inspiring metaphor and ignorance as a metaphor.
In the first equation, the unexpected metaphor inspires the sought after solution, and is
hence classed as pseudoserendipity. In the second equation, the unexpected metaphor leads
to a new problem and a new solution, apart from solving the original problem. In the third
equation, pragmatism takes the place of metaphor, a problem finds an echo in another problem
and thus leads to a new solution. In the fourth equation, ignorance as a metaphor leads to an
incorrect description of the problem domain, which implies a new problem and then a new
solution.

7 Conclusions

Two conclusions can be drawn from Mieschers research. Following on from the above, an
immediate inference is that the discovery of nuclein can be classed, according to Neeman

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Serendipity and the Discovery of DNA 399

and Kantarovich, as a type-2 serendipitous discovery and, according to Dias de Figueiredo

and Campos, as a type-3, or laxly type-2, discovery. According to Neeman and Kantovarichs
classification, it can be pigeonholed as a type-2 discovery because Miescher was trying to
find out how cells worked by analysing proteins. He did actually make a lot of progress in this
field, while he, serendipitously or unexpectedly, came upon DNA, that is, two for the price of
one. Applying Dias de Figueiredo and Campos equations, his discovery is classed as type-3
serendipity, because Hoppe-Seylers recommendation to switch research from lymphocytes
to leucocytes can be considered to be the metaphor in this case. Now, if we were to be
very strict and not consider this advice as a metaphor, then Mieschers discovery would be
equation 2, serendipity without a metaphor. In sum, Mieschers discovery can unquestionably
be classed as serendipitous, because, as discussed in Sect. 3, he was researching the chemical
composition and arrangement of cells, analysing their proteins, and unexpectedly found
something much better: what he referred to as nuclein, now known as DNA, the molecule of
life.
The other deduction is further flung. Serendipities, or sudden illuminations, are the result of
the general schematic anticipation latent in a researchers mind and triggered by a fortuitous
and unexpected external event. Now, only a mind prepared by some pre-existing interest,
idea, thought or experience will grab the chance or window of opportunity. This raises the
following, open question, which we are researching: Can serendipity be programmed, planned
or, in principle, generated computationally? The definition of serendipity would appear to rule
out any such possibility. And Van Andel (1994), for instance, states that pure serendipity
cannot be produced by a computer. Because of this, no computer would ever be able to
pass a modern Turing test containing this question. But, it could be arranged for something
unforeseen to always happen. The person, and of course the computer, experiencing this would
then react autonomously to at least try to understand the unexpected observation or event.
The examples of true serendipity suggest that knowledge-based systems, and particularly
expert systems, can at least help, and perhaps in the future link up with, the researcher to
achieve serendipitous discoveries more efficiently. Additionally, it certainly is possible for
a computer searching for patterns of association or related interests to contribute something
that its user would take as a coincidental discovery. Therefore, a computer could automate,
speed up and provide support for the discovery of a new information item, which is the first
part of the above concept of serendipity. The second part of the concept, the sagacity and
the wisdom required to make the connection between items of information, continues to
be dependent upon the individual person. Therefore, serendipity, defined as the attitude of
making unexpected discoveries, can be developed with computational assistance insofar as
it is a precious faculty in research. But, at the present time, as Hamlet said, readiness is all;
hence, no surprise element, situation, etc., should be overlooked, and whatever prompted the
surprise, including, anomalies, novelties and enigmas, should be taken into account.
Regarding the state of readiness, that is, grasping the opportunity, the only course of
action open is training. Save at a small number of elite establishments, people are taught,
from primary school through to higher education, that knowledge flows from a question to
an answer, from a hypothesis to a thesis. As a result, student learning is increasingly tested
using multiple choice questionnaires. These questionnaires contain pre-stated questions that
are followed by several likewise pre-stated answers, of which only one response is correct.
Indeed, contrary to its name, the choice is single and not multiple. This may, inadvertently,
convey the idea that knowledge in scientific research grows from a correct hypothesis to a
correct response. This could not be further from the truth, as there is no a priori correct question
or answer in research. Precisely, there is no way of knowing whether any such question or
answer really exists or whether or how it can be discovered. Additionally, scientific practice

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shows that the reasoning in a serendipitous observation or finding is retroductive, flowing not
from the question to the answer but from a surprising event to a new problem (hypothesis).
In todays education and assessment system, however, students seldom learn to reason out an
original problem from a surprising observation. What is more, serendipity is rarely used in
the classroom, and abductive inference is never explained. Additionally, outside the English-
speaking countries, the term serendipity, and the concept that it denotes, is not even in the
dictionary. And this is another field of action where there is a lot of interesting work to be
done, shifting the stress from teaching towards learning, because, ultimately, it is impossible
to learn for somebody else. In this respect, todays education system is plainly failing the
subject of serendipitous learning, that is, using stories, cases and hypothesis statement to turn
the application of the faculty of serendipity into a regular practice in training centres.

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urea Anguera de Sojo received a B.A. Degree in Law and a B.A. Degree in Economics from the Uni-
versidad Pontificia de Comillas (ICADE) (Madrid, Spain). She obtained her Ph.D. in Computer Science
from the Universidad de Corua (Spain). She has worked at Universidad Nacional de Educacin a Distan-
cia (UNED) since 1996 until now teaching about Human Research, Law and e-Commerce. Since 2002 she

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Serendipity and the Discovery of DNA 401

is Associate Professor at Informatics and Law Department of Universidad Politcnica de Madrid (UPM),
imparting classes in e-Commerce and Social, Professional, Legal and Ethics Aspects of Engineering. Her
research interests include information systems, information retrieval and ICT social, economic and legal
implications.

Juan Ares received his Ph.D. in Computer Science from the University of A Corua, A Corua, Spain, in
1994. He is Associate Professor of the Information and Communications Technologies Department at the
University of A Corua, A Corua, Spain. He has worked as director and consultant in several organizations,
including Norcontrol Soluziona and Arthur Andersen. He has edited several books and authored numerous
chapters and publications. His research interests include conceptual modelling, knowledge management and
software process assessment. Dr. Ares is codirector of the Software Engineering Laboratory at the University
of A Corua and he has been invited to review papers for numerous prestigious computer science journals.

Mara Aurora Martnez is Associate Professor at the Madrid Open University (UDIMA), Spain. She has
a Ph.D. in computer science by the University of A Corua. She has worked on several projects in several
organizations. She has published a few book chapters and papers on several journals and international con-
ferences. Her research interests in computer science include Artificial Intelligence, knowledge management
and e-learning.

Juan Pazos received the first Spanish doctorate in computer science from the Universidad Politcnica de
Madrid, where he is currently Full Professor at the Department of Artificial Intelligence. He set up the first
Spanish Artificial Intelligence Laboratory, and was a visiting professor at Carnegie Mellon University and
Sunderland University, among others. He has been/is a member of the editorial board of the following jour-
nals: AI Magazine, Heuristics, Expert Systems with Applications and Failure and Lessons Learned in Infor-
mation Technology Management, among others. He is author and co-author of 10 books on computer sci-
ence and of over 100 publications. His current research is on the construction of an Information Theory that
integrates Computing Science, DNA and the brain. Currently, he is Emeritus Professor at the Madrid Open
University (UDIMA).

Santiago Rodrguez received his Ph.D. in Computer Science from the University of A Corua, A Corua,
Spain, in 2002. He is Associate Professor of the Information and Communications Technologies Depart-
ment at the University of A Corua, Spain. He has been a project leader in several Spanish organizations.
He has authored of several book chapters and publications on software engineering. His research interests
include conceptual modelling, knowledge management and e-learning. Dr. Rodrguez has been invited to
review papers for numerous prestigious journals.

Jos Gabriel Zato was born in La Corua, Spain in 1944. He received the B.E. and M.E. degree in Physics
engineering from the Universidad Complutense de Madrid (UCM), Spain, in 1973. He got the Ph.D. in
Physics at UCM in 1982. From 1989 to present he is professor of the School of Computer Science of the
Technical University of Madrid (UPM). He is the head of the Intelligent Systems for Accessible Mobility
and Communication Group, with a wide experience in leading regional, national and international projects,
funded through public as well as private funds. His research interest includes intelligent systems, usability
and accessibility and rehabilitation technologies.

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