Life at the Cell and Below-Cell Level. The Hidden History of a Fundamental Revolution in Biology
"Dr. Ling is one of the most inventive biochemist I have ever met."
With no exception, each one of us began as a single cell. That tiny fertilized egg, scarcely larger than a speck of dust, then divided into two daughter cells. The daughter cells grew and divided into four cells. And this repeated itself many times over. Somewhere in the course of the development, the daughter cells ceased to be copies of each other through differentiation. Division, growth and differentiation over a period of nine months, transformed that single fertilized egg cell into trillions upon trillions of cells of diverse shapes and functions. Together they made up or will make up the baby that was you, I and anyone else who is living, had lived or will live in time to come.
Smiling, laughing and other normal physiological activities tell us that a baby is well. This is just a short way of saying that the trillions of cells making up the baby are well. Similarly, when the baby is sick, it is a short way of saying that some or all of the baby's cells are sick. When we give medicine to the sick baby (or sick grown-up), our hope is that the medicine will make these sick cells well again. But unfortunately we are not sure.
Why are we not sure? For an answer, let us consider one illness, cancer.247
From the time of her birth to her death, a female American child has approximately a 1 in 3 chance of contracting invasive cancer; a male child, 1 in 2.358 table 5 In America alone, cancer kills 1500 men, women and children everyday, notwithstanding America has the best medicine of the world. Beginning in the 70's, a quarter of a century of "war on cancer" did not bring victory. On the contrary, the cancer death rate rose from 158 per 10,000 population in 1970 to 210 in 1997.553 Part of the increase can be attributed to the aging of the population and the fact that older people are more cancer-prone. But that alone cannot explain why a Nation so proficient in other difficult scientific undertakings—be it the landing of a human on the moon, the creation of computer science and technology or the unraveling of the human genome—should be so bogged down in attempting to control diseases from the common cold to cancer. There must be a special cause for this pointed tardiness. What can it be?
Prof. Alfred Burger offered a clue. In his monumental treatise on thousands of drugs, "Medicinal Chemistry," he wrote: "Almost all the problems of medicinal chemistry would become more amenable if we had even an inkling of the reactions of any drug with body chemicals."345 p 19
By body chemicals. Prof. Burger referred to the chemical components of the living cells. The failure to gain an inkling of how any drug works reveals something few are aware of: an unbelievably poor understanding of how the living cell functions in general and its response to drugs in particular—as currently taught at virtually all levels of education under the heading of cell physiology or another name to the same effect..
Thus the magical formula, which gave us the "many-splendored" world of today, seems to have lost its magic in this specific quest for scientific truth. That magical formula was invented in the 17th century in Europe and is known as the scientific method.
The scientific method comprises four steps: (i) observation; (ii) introduction of an explanation of the observation, known as hypothesis or theory, which also generates testable predictions; (iii) experimental testing of these theoretical predictions; (iv) conclusion based on the result of the experimental testings, which confirm or refute the theory.
Not explicitly stated, but implied as a matter of course, is a crucial fifth step. A theory that has been unequivocally disproved by extensive experimental testings must be replaced by one more promising. Or better, by one that has already been consistently confirmed. It is my opinion that the current poor understanding of cell functions mentioned above reflects a failure to implement the fifth step when due.
The science of how living cells work (cell physiology), currently taught at different levels of education with varying degrees of detail, is founded on an old theory. Beginning well over a century ago, it is known as the membrane theory. Later it was modified and called the membrane-pump theory. Some 50 years ago I first published my suspicion that the cell may not have enough energy to operate the pumps postulated in this membrane-pump theory.96 The initial response,382 which was quickly answered,550 did not continue, but petered out into total silence. As years went by, the contradictory evidence against the membrane-pump theory have grown in number and in consistency (see Chapter 12). Nevertheless, the membrane-pump theory continues to be taught as the truth by many innocent teachers all over the world. And it still serves as the foundation for research on cancer, AIDS, and other deadly diseases by mostly innocent investigators.
By the same token, the great majority of teachers, students and researchers do not know that an alternative theory—already extensively tested and verified in its essence—has been in existence and steadily developing for nearly 40 years. It bears the name, the association-induction (AI) hypothesis. Unlike the membrane-pump theory, the AI Hypothesis does offer, from its very inception, a broad outline of a theoretical mechanism of how drugs work, based on state-of-the-art understanding of modem physics and chemistry (Section [14.3(3)]).
No one can tell how much closer we would be to conquering cancer, AIDS and other fatal diseases if, say, half of the money, talent and effort spent on research projects based on the membrane-pump model had been diverted to support projects based on the association-induction hypothesis. Nonetheless, history shows that useful inventions as a rule follow progress in pure science quickly. Thus 50 years after Michael Faraday discovered magneto-electric induction (1831), electric power plants came into being (1880).54 p 196 Thirty years after Maxwell introduced his unified theory of electromagnetic waves (1867-1873), Marconi obtained a British patent for the future radio industry (1900).254 Only 15 years after the introduction of the association-induction hypothesis (1962), Raymond Damadian invented the medical breakthrough now known as magnetic resonance imaging or MRI15 p vii; 98 p xxv (1977) [11.3(1)]. (In contrast, despite a far longer history, neither the original membrane theory nor its pump version has produced anything useful to the best of my knowledge.)
Thus pure science, if wisely and unwaveringly nurtured, will continue to spawn new inventions, which in return will nurture and protect our species as well as our fellow living creatures who share this beautiful but fragile planet with us. That is, if we do not forget that to reach these goals it takes more than just money—though money is indispensable—but human effort and dedication as well. And over time, nothing can replace a continual flow of young talents who are eager to engage in this, the greatest adventure of all—the search for (relevant) scientific truth in the service of Mankind, living and yet to come.
This volume provides a summary of the (scientific) rise and fall of the membrane (pump) theory, the emergence and growth of the association-induction hypothesis, and important but nearly forgotten alternative theories and their experimental support. It is written with the hope that a reader familiar with its contents knows what is, in my opinion, the essence of all cellular and subcellular physiology—from its beginning (and even earlier) to this day. In short, this is a story of the largely hidden saga of man's search for understanding of life at the most basic cell and below-cell level.
"It is highly dishonorable for a Reasonable Soul to live in so Divinely built a Mansion as the Body she resides in,
altogether unacquainted with the exquisite structure of it." (Robert
"...we have this further duty, the care for what is eternal and highest amongst our possessions, that which gives to life its import and which we wish to hand on to our children purer and richer than we received it from our forebears." (Albert Einstein) 365 p 151
"Unfortunately, school teaching keeps up certain traditional views , which have been out of date for many years and which obscure the understanding of the actual state of affairs." (Erwin Schrödinger on school teaching of physics in 1944)363 p 58