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Chapter 17. Epilogue
Cross-word puzzle
and fox hunt: two models for scientific research
Science resembles
solving a cross-word puzzle. An ordinary cross-word puzzle can be
done easily by one person. In solving the scientific puzzle of Nature,
an inherent difficulty lies in its immense size. Inevitably, division
of labor is inaugurated and uncoordinated multiple starts are launched.
Thus with perfectly good intentions, fragmentation, the deadliest
disease of science, was set in motion. For a science like cell physiology,
there is a second pitfall.
In solving the
cell-physiological puzzle, correct basic physico-chemical concepts
rather than words are used to fill the blank spaces. Since these
physico-chemical concepts were being discovered at the same time
the cell-physiological research was on-going, the early cell physiologists
were bound to make wrong entries because the right ones were not
yet known. By the time the right physico-chemical ideas come along,
wrong entries have already been written into textbooks and taught
worldwide to generation after generation of young people at their
most impressionable age---with no end in sight.
The cross-word
puzzle analogy emphasizes that there is only one unique solution
for each man-made puzzle as well as for the puzzle of Nature. A
fox hunt is a cogent model in another aspect. It underscores the
critical need of a correct guiding theory. A guess (theory) must
be made early on the direction the fleeing fox has taken, before
the chase can begin. Once that guess is correctly made, the rest
of the hunt has a much greater chance to proceed fruitfully. If
not, the leader of the hunt must have the courage and wisdom to
make changes promptly. Nonetheless, if the discovery of a wrong
theory is made late in the game, changing direction is difficult.
The secret of
past success in paradigm changes
These great inborn
difficulties notwithstanding, science did make major directional
changes in the past. These changes are referred to as scientific
revolutions. What was the secret for their success in the past?
Before attempting to answer, let us not forget successful or not,
a scientific revolution has never been easy. For their role in a
scientific revolution, Bruno lost his life at the stake, Galileo
was imprisoned for life and Semmelweis died in an insane asylum.
Revolutionaries, who did live to see the success of their work,
were found more often at the time of, or after the Enlightenment
movement of Western Europe.
Replacing a broadly
accepted but wrong guiding theory in science with a correct one
has been as a rule initiated by one (or a few) individual(s). This
is what I call Step 1 of a scientific revolution. (107 p 319) However,
if science is to continue its progress as a continuing cooperative
effort, the new and closer-to-truth revolutionary theory must be
accepted by the scientific community as a whole. This conversion
of the scientific majority is what science historians call a scientific
revolution, but which I believe is Step 2 of that process. (In an
earlier writing, I called Step 1 a scientist's scientific revolution,
and Step 2 an historian's scientific revolution. (107 p 319 ) Step
2 is as a rule more difficult to accomplish than Step 1. Thus, the
great physiologist-physicist, Hermann von Helmholtz said in his
1881 Faraday lecture: "...it is often less difficult for a
man of original thought to discover new truth than to discover why
other people do not understand and do not follow him." (537
p.1.)
To illustrate how
Step 2 of past scientific revolutions actually did get accomplished,
I cite two specific examples.
(i) Joseph Priestley
(1733-1804) was the Unitarian minister-scientist who, as mentioned
earlier, discovered oxygen but believed it to be "dephlogisticated
air." When Antoine Lavoisier argued that it was really oxygen,
Priestley fought him tooth and nail----- until he realized at last
that Lavoisier was right. Then Priestley made a 180-degree turn
and praised Lavoisier's chemical revolution with overflowing admiration
and enthusiasm: "There have been few, if any, revolutions in
science so great, so sudden and so general....of what is now named
the new system of chemistry." (346) Rapid and broad acceptance
of Lavoisier's new theory soon followed.
(ii) Michael Faraday
(1791-1867) came from a poor family in London. He had no formal
education. Yet he revolutionized the field of physics with his iconoclastic
concepts of curved electric and magnetic lines of force and his
field theory. He was almost entirely rejected by his peers. Some
even suggested that "he ought to return to sixth form mathematics
before venturing into the deep ocean of Laplacian physics."
(54 p 507) But there were also striking exceptions.
William Thompson
(Lord Kelvin) and especially James Clerk Maxwell both recognized
the importance of Faraday's revolutionary concepts. Later Maxwell
was to introduce his own famous theory of light as electromagnetic
waves, which marked one of the great forward leaps in physics. Yet
through it all, Maxwell always insisted that the core of Maxwell's
advanced field theory were the ideas Faraday expressed in his life's
work. (54 p 509, p 513) Thus Step 2 of another major scientific
revolution was once more successfully carried out.
Eighty nine years
after Faraday's death, Albert Einstein--- possibly the greatest
scientist of all times----wrote: "For us, who took in Faraday's
ideas so to speak with our mother's milk, it is hard to appreciate
their greatness and audacity." (365 p 101) And Faraday did
all these "without the help of a single mathematical formula."
(537 p.1)
The two sets of
historical events cited above, tell us that the secret of the successful
scientific revolutions of the past lies in the deep belief in fair
play or sportsmanship among the key participants in particular
and the scientific community in general. One asks, "Is this
secret formula so lofty and idealistic that one cannot expect it
from ordinary people?"
Not so at all.
Indeed, every one, who participates in a competitive sport, accepts
and lives by it without a second thought. It is true that occasionally
one hears of someone in sports, who used illegal drugs or even attempted
to beat up a referee, but that is a rare exception. Almost all participants
of competitive sports know how to win and how to lose. In this obedience
to a widely accepted rule of fair play, the very sprit of sports
resides. This spirit is not inborn. It is taught from the day
the child learns to play the game --- by those who love the
game, understand it and teach its (ethical) rules which make the
game possible. But another factor in favor of fair play in the sports
is that everyone can see and fully understands what is going on.
After all, they are exhibitions.
I am sad to say
that the same spirit, which is as vital to the health and survival
of science as it is to competitive sport, has not done well in the
field of cell physiology in the later half of the 20th century.
The decay began slowly and almost imperceptibly after the introduction
in the 1940's of large-scale government funding of scientific research.
To determine who gets support and who is refused, the peer review
system was universally adopted. (348 ; 349)
Public funding
of research per se is a great blessing to science
and scientists, including myself. Unfortunately, those chosen to
serve on peer-review panels are---- unlike most referees and umpires
in competitive sports ---- often themselves competitors for the
money they control. All too frequently, they forget the vital role
of fair play and sportsmanship in science and see an impending scientific
revolution as a threat to their personal advantages and use the
entrusted power to suppress it. (247 ; 350) Unlike sports, these
activities are as a rule not open to public view.
(Creating and putting
into action a better system than the peer review in wide practice
today so that truly innovative ideas are encouraged rather than
suppressed is a great challenge for all concerned. Until this reform
is successfully accomplished, the peer review system will remain
a blemish on the integrity of a great democracy like the United
States, which rightfully would not tolerate infringement of the
freedom of expression in far less important issues.)
Fragmentation
and its impact on the future of science
In his "History
of Physiology," Karl E. Rothschuh pointed out that with the
increase in the number of practicing physiologists, the number of
scientific journals have risen to such an extent that "Physiology
has even ceased to be one whole and distinct teaching subject, a
fact which virtually spells the end of the discipline as a certified
field of scientific endeavor." (352 p 349)
This comment was
made by Rothschuh many years ago on what is known as organ physiology,
e.g., renal physiology, digestive physiology, etc. But cell physiology
has fared no better. It too has split into biochemistry, biophysics,
cell biology, molecular biology, mathematic biology, etc., etc.
Indeed, things have gotten much worse with the universal adoption
of the peer review system which further exacerbates fragmentation.
A verified unifying
theory to put the Humpty-Dumpty together again
"The eternal
mystery of the world is its comprehensibility" (Immanuel Kant).
To begin with, simple and coherent things are easier to understand
and to remember. Thus the comprehensibility of Nature may be tied
to its underlying simplicity and coherence, which are couched in
such admonitions like that of Occam's razor, "What can be done
with fewer is done in vain with more."
However, a fragmented
approach is like "viewing the sky from the bottom of a well"
(Chinese proverb). As such, it hides from view Nature's innate simplicity,
coherence and comprehensibility. The question is: How can we overcome
this fragmentation? The answer is: Begin with a unifying
theory.
Early on, I pointed
out why the membrane theory at one time appeared to be a unifying
theory (Chapter 4). Unfortunately, as more and more new facts came
to light, they left no doubt that the membrane theory is not headed
in the right direction.Then alternative theories based on the concept
that cells are solid and made of protoplasm were introduced. Unfortunately,
the protoplasm-oriented cell physiologists did not produce a unifying
theory. The time was not right yet.
Not only were the
essential basic physico-chemical sciences themselves still in a
stage of early development or not yet in existence (Chapter 7),
powerful modern scientific tools, like radioactive tracer technology,
which have played key roles in critically testing the alternative
theories--- were still to come. Nor did these investigators enjoy
the benefits of public financial supports, which were not in place
until after the end of World War II in the United States, for example.
All these had undergone
profound changes when my generation came on the scene as I have
pointed out repeatedly in the text of this volume. Whether or not
the AI Hypothesis is the one and only unifying theory as I believe
it to be, is a judgement that can be made only in the future. Notwithstanding,
there is no denial that the AI hypothesis is the first-in-history
physico-chemical theory of life at the cell and below-cell level.
And this whole volume testifies to how it agrees with the experimental
studies designed to test its validity.
How a dedicated
biology teacher can brighten the future of basic life science
Let us begin with
what a teacher does not want. No teacher worthy of that title wants
to teach or present a wrong theory as truth knowingly. Nor teach
only (beautifully-illustrated) trivia.
However, a great
teacher does more than just not doing wrong or meaningless things.
He or she can expose the students to the right underlying rules
of fair play and sportsmanship in the same way that volunteer coaches
teach youthful sand-lot baseball players. And in the process inspire
in a few students an abiding love for the subject taught, and prepare
him or her for a career in the service of all mankind that is always
interesting and unswervingly relevant. To find out what specific
tool may help our teachers to fulfill this critical role, let us
return to the life of Michael Faraday once again.
At the age of fourteen,
Michael Faraday was an apprentice to a small book-binding business.
He could easily have continued with what he had learnt as an apprentice
and spent the rest of his life as a journeyman bookbinder. But that
was not to be. What then inspired this young bookbinder's apprentice
to dream of a career of a modern Galileo or Isaac Newton? From what
I could gather, his dream---where it all began---started with two
articles on the history of science.
As young Faraday
was glueing together the pages of a set of Encyclopedia Britannica,
something in the printed pages caught his eyes. It was an article
entitled, "History of Electricity" written by a Mr. James
Tytler. Tytler , in turn, took most of his materials from Joseph
Priestley's book , "The History and Current Status of Electricity."
(379) Faraday was so excited by what he read that he began to conduct
experiments on the mantle-piece of his employer's shop. His scientific
equipments were fashioned out of two glass bottles, which he bought
from an old rag shop for six pence and one penny respectively. Next
thing you know he was defending his own theory of electricity among
a gathering of young friends intent on "improving their minds."
Unfortunately, as his love for science grew more and more fervent,
the prospect of becoming a professional scientist, or even just
continuing as an amateur scientist, became dimmer and dimmer. His
apprenticeship was drawing to a close. He felt hopeless and depressed.
Then suddenly and
unexpectedly came a lucky break. The janitor of the Royal Institution---
home of such illustrious scientists like Sir Humphrey Davy----got
fired for engaging in a brawl. And Michael Faraday was hired to
replace him. This was how Faraday began his life career at the Royal
Institution of London.
At the beginning,
he was mostly engaged in helping Davy and others. But before long,
he was on his own. Despite its resounding name, the Royal Institution
had no regular income. Faraday, like the other members, had to earn
his expenses. One way on which he relied was giving public lectures
on scientific subjects. He took great pains to learn how to be an
effective speaker. In the end, he became good at it. On one occasion,
his lecture was so engaging that school children gave up their Christmas
parties to hear the series of his talk, which bore the title: "The
Chemical History of the Candle."
So it seems that
in the early intellectual environment of Michael Faraday, narratives
on history of one sort or another, kept on popping up. Is
there something special about history that reaches out to
the young mind? If so, it would not be surprising. After all, the
English word, history, is synonymous with the word, story.
When one tells a bedside story to a child, be it Winnie the Pooh
or Peter Rabbit, it is as a rule a history. A story or history is
always moving and coherent and it involves experiences with which
the reader or listener can identify.
With these examples
in the background, one can see why cell physiology has been losing
ground steadily (to such a degree that knowledgeable scientists
could be led to believe that (all) science is approaching an end.)
Being fragmented and, in my view, wrongly-headed, the conventional
cell physiology has no story to tell ( and, of course, is at its
end.) With no story to tell, students and teachers would be hard
put to develop a genuine interest in it---- like Faraday himself
and his young audience did. But all this is changed now.
With the introduction
of the AI Hypothesis, cell physiology has become coherent for the
first time. Convinced that the best way to bring the future generations
of the like of Michael Faraday into the field of cell physiology
is to tell them its story or history, I gradually convinced myself
of the need of a book like this one, which too is a story and bears
that magic word history in its subtitle.
While teachers
and their students are an important segment of the audience I am
trying to reach, they are not the only audience I am looking for
---- as I briefly mentioned in the Preface. Others I am trying to
reach include all kinds of scientists especially those close to
biology and medicine who want to update their basic knowledge; molecular
biologists seeking the link between genetics and cell and subcellular
physiology; physicists looking for new fertile terrains to apply
their talents and knowledge; researchers in medicine and in pharmacological
companies searching for new ways to cure diseases and invent drugs;
school-board members eager to offer the right and up-to-date guidelines
for school curriculum they supervise; science reporters and editors
who may open the eyes and minds of the even larger body of intellectually
adventurous book readers. True, teachers and their wards hold the
key to reverse the senseless unending teaching of meaningless long-ago-disproved
ideas. But we need the help of everyone to accomplish the momentous
task lying ahead.
"Science,
The Endless Frontier" can be as shining and as promising as
ever
Fifty-five years
have gone by since Vannevar Bush wrote his report to President Franklin
D. Roosevelt, bearing the title: "Science, The Endless Frontier."
(400). Those, who have read only Horgan's "End of Science"
(see Preface), may be misled into thinking that Bush was wrong and
that science does not offer an endless frontier. Those, who have
gone through the present volume, may realize how right Vannevar
Bush was and still is. And in all probability will continue to be.
As an illustration,
the invention of MRI shows not only that cell physiological science
is burgeoning, it also shows how physics is as alive as ever, because,
among other reasons, advanced cell physiology is physics. And then,
advanced physics is also advanced cell physiology. For after all,
it is the cell physiological activities of the trillions of brain
cells in men and women, who call themselves physicists that have
created physics.
It would be wonderful
if I could present a list of all the exciting open avenues of cell
physiological research to the future. But my space is too limited.
So I must satisfy myself with a more limited objective. First, a
reminder that many of the seemingly dead-end scientific accomplishments
now gathering dust in some unreachable storage libraries---and sooner
or later in danger to be in some garbage dump--- be they biochemistry,
or biophysics or molecular biology etc. etc. will become alive again
, when viewed through the new light of the unifying AI Hypothesis.
Better still, in them will be found truths that show conflicts,
real or apparent, with the predictions of the AI Hypothesis. They
will be the spring-board for the continued growth in the future
cell physiological science.
Second, one specific
direction that answers the question with which I began this story.
How to develop an inexhaustible arsenal of weapons against cancer,
AIDS and other deadly diseases, which are the true enemies of our
species? These weapons are in the form of drugs, which unlike the
kind we have, are rationally designed and thus on target
and without untoward side effect. And they can be cheap.
It is truly astonishing
to listen to political debates on how to stave off the impending
bankruptcy of the Medicare/Medicaid programs as the US population
ages and more and more people consume larger and larger quantity
of prescription drugs. For this to happen in as wealthy a country
as the US tells just how extremely inefficient and expensive it
is to obtain useful and safe drugs through random trial and error---as
it is being done now, a process which leaves patients of AIDS in
a poor country to die like abandoned cats and dogs.
What chance is
there for improvements if we just do more of the same along the
line of the membrane-pump theory? Indeed, the theoretical mechanism
of drug action now being taught in textbooks remains not much more
than the same ancient lock-and-key model mentioned earlier. The
conventional concept of drug action begins and ends with receptor-site
fitting. The fitting drug does not do anything. Because there is
nothing proposed to respond to drugs other than site fitting, one
cannot go very far on such a dead-end road.
In contrast, the
AI Hypothesis in its very name, association and induction, has already
spelled out that the basic mechanism of drug action is an electronic
one, a direction also more specifically pointed out in Chapters
14 and 15. Thus, based on the theoretically derived relationship
between the c-value and the rank order of selectivity of K+, Na+
and other alkali metal ions (and other criteria) and the c-value
analogue and the rank order of selectivity between helical structure
and water polarization-orientation , one can already determine whether
a drug or other cardinal adsorbent functions as an electron-withdrawing
cardinal adsorbent or EWC or an electron-donating cardinal
adsorbent or EDC. This is already a big step forward. Nothing
like this has ever occurred before.
In addition, this
type of experimentation has already begun to produce new valuable
information from a variety of intact living cells, normal as well
as cancerous. Among the cardinal adsorbents---which include all
drugs--- the most important is ATP. And from our studies of its
influence on different physiological manifestations in living cells,
we reached the conclusion that ATP is an EWC. Ouabain, in contrast,
is an EDC. Why is ATP an EWC and why is ouabain an EDC are questions
that will challenge the best of the coming generations of new biologists,
chemists and physicists, but especially those who have mastered
the essence of all three fields of science. And hopefully this volume
may stimulate the training of scientists of this kind. But all that
is for the future. For the moment, we return once more to something
at our current rather primitive level of progress.
As pointed out
repeatedly, a crucial step in verifying a cell physiological theory
is the invention or discovery of an inanimate model. An inanimate
model shares major attributes with living cells, but one upon
which it is much simpler and easier to test the theory. In almost
all the subsidiary theories of the AI Hypothesis, one or more suitable
inanimate model(s) has been found by 1992--- with one important
exception.
That exception
is an inanimate model showing how drugs and other cardinal adsorbents
at minute concentrations can induce an across-the-board change of
the c-value of a large number of beta- and gamma-carboxyl groups,
and that with their c-value change, the theoretically predicted
change in the relative adsorptive preferences for K+ , Na+ , for
example, can follow.
It is thus with
great pride and joy that I, together with my associate, Dr. Zhen-dong
Chen (as well as Margaret Ochsenfeld) can now make the preliminary
announcement that a few of these inanimate models have been found
and the essence of the changes predicted by the AI Hypothesis tentatively
confirmed. Having said that, I must add that the demonstrated changes
are very small though statistically significant. They are, after
all, models and not the real thing.
Not the least earnest
message, which we want to share with the next generation of cell
physiologists and their teachers, is about our experience as what
I shall call less-than-popular scientists---- though even now we
have more facilities than Faraday had to make do at his time. For
all these experiences suggest that if you always do your best with
whatever you may have, you will one day be at a better starting
position for a scientific career than Faraday, when he learnt with
unspeakable joy that he was appointed the "fag and scrub"
man of the Royal Institution.
References
54 Williams, I.P. 1965 "Michael Faraday: A Biography",
Da Capa Press, Plenum Publ. Co., New York
107 Ling, G.N. 1992 "A Revolution in the Physiology
of the Living Cell", Krieger Publ. Co., Malabar, FL
247 Ling, G.N. http://www.gilbertling.org
346 Cohen, I.B. "Revolutions in Science", Harvard
University Press, Cambridge, MA
348 Ling, G.N. http://www.gilbertling.org/lp11.htm
349 http://www.queensu.ca/~forsdyke/peerrev.htm
350 Ling, G.N. http://www.gilbertling.org/lp12.htm
352 Rothschuh, K.E. 1973 "History of Physiology"
(English translation by G.B. Risse) 2nd ed. Pergamon, London
365 Einstein, A. 1956 "Out of My Later Years"
Wings Books, New York
379 Priestley, J. 1767 "The History and Current
State of Electricity" 1st ed.2 volumes, London
400 Hagen, R.S. 1986 "Windows to the Origin",
Naval Research Reviews 38: 4
537 von Helmholtz, H. 1881 in: "The Modern Development
of Faraday's Conception of Electricity" The Faraday Lecture, delivered
before the Fellows of the Chemical Society in London on April 5,
1881
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