Table Of ContentSpringer Biographies
Ma Vie en Noir
Fifty Years with Melatonin and the
Stone of Madness
DANIEL P. CARDINALI
Springer Biographies
More information about this series at h ttp://www.springer.com/series/13617
Daniel Pedro Cardinali
Ma Vie en Noir
Fifty Years with Melatonin
and the Stone of Madness
Daniel Pedro Cardinali
Facultad de Ciencias Médicas
Pontifi cia Univ Católica Argentina
Buenos Aires , Argentina
Springer Biographies
ISBN 978-3-319-41678-6 ISBN 978-3-319-41679-3 (eBook)
DOI 10.1007/978-3-319-41679-3
Library of Congress Control Number: 2016944796
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Pref ace
A Contagious Stone?
The objective of this book is to summarize; to recapitulate the eventful life of the
pineal gland as a historical entity related to the legend of the stone of madness, in
large part forgotten; to assess the impact in the life of a scientist who serendipitously
linked his scientifi c career to an issue like melatonin at a moment when the ground-
work for the “hormone of darkness” was being laid; to ponder the meaning of the
work of a scientist and to conclude that it is simply to push a little further the borders
of science and to perpetuate this endeavor by nurturing disciples who scientifi cally
exceed their teacher’s achievements.
This work is not a scientifi c review but what memory has left in the mind of this
author after having lived half a century with an objective: to elucidate the mecha-
nism and meaning of the main pineal product, melatonin, and to take it to a stage of
therapeutic application. Today we know that in humans pineal melatonin begins to
be released every day toward the evening and there is evidence that this serves as
the trigger of the sleep process (the signal that “opens the gates of sleep”). Thus a
brief account of the historical development of concepts about sleep will be included.
There is no doubt that the understanding of sleep has been central to the develop-
ment of the concept of mind and consciousness, and many famous passages in lit-
erature illustrate how the ideas on sleep evolve.
Miguel de Cervantes (1547–1616), who refl ected on many aspects of sleep in
The Ingenious Hidalgo Don Quixote de la Mancha , puts into the mouth of Sancho
the following words:
All that I know is that so long as I am asleep I have neither fear nor hope, trouble nor glory;
and good luck betide him that invented sleep, the cloak that covers over all a man’s thoughts,
the food that removes hunger, the drink that drives away thirst, the fi re that warms the cold;
the cold that tempers the heat” and, to wind with, the universal coin wherewith everything
is bought, the weight and balance, that makes the shepherd equal with the king and the fool
with the wise man. Sleep, I have heard say, has only one fault, that it is like death; for
between a sleeping man and a dead man there is very little difference (II, 68).
v
vi Preface
P edro Calderon de la Barca (1600–1681), another prominent Spanish writer,
wrote in Life Is a Dream a famous sonnet with the following lines:
…What is life? A thing that seems / A mirage that falsely gleams / Phantom joy, delusive
rest / Since is life a dream at best / And even dreams themselves are dreams
A nd William Shakespeare (1564–1616) wrote in H enry IV, Part II, Act III, Scene 1:
O sleep, O gentle sleep, Nature’s soft nurse, how have I frighted thee
That thou no more wilt weigh my eyelids down
And steep my senses in forgetfulness?
B ut no one was more anticipative than Thomas Dekker (c 1572–1632), who
wrote about sleep the following words:
Sleep is that golden chain that ties health and our bodies together.
Today it is clear that the major pandemics we face (obesity, cardiovascular dis-
ease, dementias) have as a comorbidity, and presumably as a cause, insuffi cient
sleep. As we will see in this book, it is important to understand that we have not
always slept in the same way we do today. The invention of the electric lamp by
Thomas Edison (1847–1931) was a major landmark in this respect. While Edison
emphasized that the use of the electric lamp “ did not affect the quality of sleep and
was harmful to health,” we sleep today about 3 h less per day than in the pre-Edison
era! The inhibition of melatonin secretion by artifi cial light plays an important role
in these changes.
M elatonin is the prototype of the “chronobiotic” drugs used to synchronize and
increase the amplitude of the sleep/wake cycle. In Argentina melatonin was intro-
duced to the market as an over-the-counter medicament for insomnia in 1995, and
analogs of melatonin are used for this purpose in the USA (ramelteon, tasimelteon)
and for the treatment of depression (agomelatine, approved by the European
Medicines Agency in Europe). But none of this explains the reasons for the evolu-
tionary persistence of melatonin already detectable in organisms that neither sleep
nor suffer emotional distress. And this is one of the most exciting aspects of mela-
tonin functioning: it is a substance that is present in most living organisms, from
unicellular with aerobic respiration, to plants, to higher mammals, an irrefutable
proof of its importance for life. We will discuss in this book how the cytoprotective
function of melatonin may be of relevance in the prevention of obesity, cardiovas-
cular diseases, or neurodegenerative processes.
There is much in the history of pineal melatonin that attracts and that will be
recapitulated in this book. But before moving on to that, I feel it necessary to explain
the reason for the title, which might puzzle the reader. The discoverer of melatonin,
Aaron Lerner, christened the molecule with that name (m elano , Greek for “black”)
by its action on the pigment cells of the amphibian skin. Mimicking “La vie en
rose,” the immortal Edith Piaf song written in 1946, I call this story on melatonin
Ma vie en noir .
Preface vii
Following the ideas of Jorge Luis Borges one could imagine memory as a
b reakdown of oblivion. And somehow the breakdown of the stone of madness is
behind this story: perhaps the stone itself has infected the author.
For more information on the work and interests of the author visit w ww.daniel-
cardinali.blogspot.com
Buenos Aires, Argentina Daniel P. Cardinali
Contents
1 Brief History of the Stone of Madness .................................................. 1
2 The Prescientific Stage of the Pineal Gland.......................................... 9
3 The Beginnings of the Pineal Scientific Era: From the Late
Nineteenth Century to Melatonin’s Discovery ..................................... 23
4 Sleep/Wake Cycle: History and Facts ................................................... 33
5 When This Chronicler Enters the Story: The 1960s ............................ 53
6 The Stone of Madness as a Neuroendocrine Organ and Model:
The 1970s ................................................................................................. 61
7 Peripheral Innervation of Neuroendocrine-Immune System:
The Challenges to Change a Physiological Paradigm ......................... 87
8 Melatonin as a Potential Therapeutic Agent: The 1980s ..................... 115
9 Melatonin as a Chronobiotic That Opens the “Gates of Sleep”:
The 1990s ................................................................................................. 131
10 Melatonin and the “Diseases of the Soul”: The Stone
of Madness Returns ................................................................................ 155
11 Twenty-First Century: The 24/7 Society
as an Environmental Mutation .............................................................. 171
12 Melatonin as a Medicament for the 24/7 Society:
Metabolic Syndrome ............................................................................... 185
13 Melatonin as a Medicament for the 24/7 Society:
Normal and Pathological Aging ............................................................. 215
14 Melatonin as a Medicament for the 24/7 Society: Cancer ................... 245
15 Melatonin as a Nutraceutical ................................................................. 283
Epilogue ........................................................................................................... 289
Index ................................................................................................................. 293
ix
