based on the book: Katharsis
 by Andrzej Szczeklik
ISBN 83-240-0242-1
176 pp, 154 x 214 mm

About the Author:
Andrzej Szczeklik (1938-2012) was Professor and Chairman of Department of Medicine, Jagiellonian University School of Medicine in Cracow. He received his medical degree from University of Cracow, and continued his education in the USA, England and Sweden. In the years 1990-93 he was Rector of the Copernicus Academy of Medicine in Cracow, and from 1993 to 1996, Deputy Rector of the Jagiellonian University in charge of School of Medicine in Cracow.

RHYTHM OF THE HEART

The world which surrounds us is saturated with rhythms. We encounter them incessantly, from the very first moments of our lives. Rhythm is the movement of the cradle and the song which accompanies it, the blinking of a lighthouse and the pounding of waves against the shore, the rocking of a train and the croaking of frogs near the tracks. The rhythms of the world penetrate us, introducing their own meter and compelling us to respond. The first peoples associated rhythm with birth. A god in the Polynesian islands molded a small clay figurine of a woman-mother and danced before her for three days and three nights. Drums accelerated the rhythm, and with every movement of his dancing body he enticed and pleaded. Until, finally, as Czeslaw Milosz writes, matter could no longer maintain its inertia. The first tremor of rhythm ran through her awakening her from a timeless sleep. Her response was hesitant: she extended a knee as if testing to see whether she really was something other than earth.

And perhaps this rhythm, beaten out on drums, came from the depths of the universe? Maybe it was triggered by signals issuing from intergalactic spaces-regular, measured signals emitted from the interior of colossal bodies next to which our sun is a dust mote? This gigantic aggregate of matter, the sources of powerful magnetic and gravitational fields-neutron stars-send into the universe-and to us-radio waves of tremendous intensity. They possess such perfect regularity that the centers from which they come are called pulsars. Is it impossible to imagine pulsars imposing their rhythm on the beating drums, and then to imagine the first pulse of blood, coursing through man just awakening to life, as a response to their rhythm?


It is not just the external world that imposes its rhythms on us. There are also rhythms within us. In our organisms there are so many rhythmic phenomena-from the obvious, like sleeping and waking, to the most imperceptible, such as the release of hormones into the blood-that to explain their bizarre regularity and synchronicity people began to use the visual image of a biological clock. And long before it was discovered, everyone agreed that if this extraordinary chronometer actually existed, then all the cells of our body, without exception, could read time from its face.


Today we locate this clock in the brain--in the part we call the hypothalamus. It is there in two collections of gray matter, in the two subthalamic nuclei, that the biological clock and its most essential part-the circadian oscillator tick. It seems that the mechanism of a clock sets up the cycle of repeating reactions: the coding of genes and protein synthesis. These reactions arrange themselves into a feedback loop: genes, called "clock" genes code protein, which collect and thus put a stop to a reverse coding of genes. Together with the degradation (deterioration) of the protein the coding proceeds again and the protein producing cycle is resumed. This clock mechanism, characterized by rhythmicality, is common to all species-from a fruit fly to man. It is joined with the emission of circadian rhythms, dependent on changes in the cell membrane. Once they become active, they spread into the closest neighborhood, and also to other parts of the brain.

But of what use would a watch be if one could not set it to local time? The biological clock is hidden in the brain-directly over the intersection of the visual cortex. And the transformed light signals-using a shortcut-bring to it constant news of the world, just as the neurons creating its structure convey information to the brain from the interior of the organism. In our genetic clockwork, the rhythms of our inner and outer worlds coincide and harmonize with each other.

In some people the biological clock is in a hurry. At the threshold of the new millennium, in the state of Utah, a few families were found in which all members--from grandchildren to grandparents-wake up four hours earlier than anyone else. They get up, bright-eyed and bushy-tailed, while their neighbors continue to sleep much longer. It is as if their clock were set four hours ahead. In these early birds, there has been a change in a "single letter" - a nucleotide in one of their clock genes. And maybe the night owls carry in their clocks another delicate gene mutation? Medicine is already beginning to look for cures which will be able to intervene in the workings of the biological clock, to correct the annoying time changes such as those we experience after transoceanic flights in jets. Will the future produce a new group of doctor-clockmakers? In our country will the Minister of Health add one more medical specialization to the seventy-two already in existence? And will he call these specialists by the very scholarly name of "chronologists" to avoid confusion?

Of the many rhythms active in our organism the heartbeat is the closest to us perhaps because it has always been a telling indication of life-biological as well as emotional. Doesn’t a doctor listen to a patient’s beating heart just as attentively as a writer listens to his hero’s? And don’t both, doctor and writer, borrow these words to describe their condition by saying that the heart pounds, flutters or fades?
For the heart has played an enormous role as the center of psychic powers, even as far back as in the oldest living homogenous world civilization, the Egyptian. It enters poetry, religion, hieratic texts, and grows to the rank of the chief organ not just in the body but also as the main center of emotion and becomes almost the "essence of the human being" in a person. In period of the Old Kingdom, five thousand years ago, only the heart of a man would be tossed on the scale in the last judgment by Osiris. A pure heart had to weigh less than the lightest feather on the scales standing before him. Otherwise the heart was immediately devoured by the monster waiting alongside and the afterlife of the Egyptian ended in disgrace for all eternity.

As for the heart, it is not its harmony with its environment as much as the independence of its rhythm that is most intriguing. Let us recall a school biology lesson. A heart removed from a frog and placed on the table beats for a few long-lasting minutes. Everyday, in dozens of operating rooms in our country, surgeons stop ailing hearts by freezing the organism, proceed to do complicated operations, and then activate the heart once again with an electrical current when they are finished. Even more amazing is that fact that during transplant operations, the human heart--removed from the body of the donor, placed in a foreign system, and awakened by an electric shock to its wall that lasts barely a fraction of a second-starts up again and beats rhythmically. These examples indicate that within the heart there must be a mechanism capable of rousing the heart to rhythmic work.

This mechanism is made up of specialized cells, generating and transmitting impulses. They are not distributed randomly but join into a coordinated system. We call it the autonomous system of the heart or, more frequently, the command center. The first name emphasizes the autonomy, first and foremost, the unfailing, mechanical regularity of the system’s work; the second underscores its role in the distribution of impulses. Large concentrations of cells in the system meet in terminals, or stations, between which the impulses travel on their tracks of fibers. 

The command system, like an army at the front, has its hierarchy, ensuring the succession of leadership in the case that earlier leaders die. At the top of the hierarchical ladder stands the sinoatrial node, setting the pace, that is, it makes the first move. It emits impulses with the greatest frequency. It represses, therefore, all the other potential starters and defines the heartbeat. If the node is injured, the leadership role is taken up by the next, lower echelon centers, imposing rhythms with a lower and lower frequency. When they go silent, the heart activates its last emergency mechanism, concealed in the muscle, and begins to beat with the slowest rhythm, which maintains circulation of systems at rest, but does not allow any activity. Then we are dealing with a complete heart block, as the direct terminals and heretofore navigable pathways have been destroyed or blocked.


What are these signals with which we have come the entire way, from the first station to the last? We describe them as electrical phenomena. And we say that they occur when there are fissures in the cell walls, small canals by way of which some charged atoms enter and others leave. This phenomenon repeats itself rhythmically, eliciting differences in potential. Electrical discharges flow through well-known circuits to muscle tissue which constricts. But who, within the cell walls, with exact rhythmic precision, opens the gates through which the charged atoms jump? What kind of metronome beats out the first rhythm from which is born the heartbeat? This we do not know. And we slide over the surface of phenomena with this electrical current.

Does our heart beat with the mechanical precision of a metronome? Not everyone’s. The explanation is as follows. The birth of impulses in the cells of the sinoatrial node repeats itself with an ideal rhythm, to the beat of the most sensitive of metronomes. But before the impulse leaves the node--to travel over the pathways created for it and makes the heart contract-before this happens, it will experience the unbelievably subtle influence of the sympathetic nervous system. This is a delicate response, which we are incapable of detecting with a stethoscope. We may, however, notice it by analyzing the long transcription of the electrocardiogram. When we measure the pauses between consecutive heartbeats over a period of a few minutes, we can see, that in many of us there are discreet differences between them; the deviate from the average by just one hundredth of a second.


This brings to mind tempo rubato, a characteristic feature of Chopin’s music. There are many descriptions of a Chopin rubato. It is supposed to be a way of performing a work "with a subtle disquieting rhythm." Rubato, according to others, relies on "minute shifts between notes of the melodic voice in the field of its own beat, against a background of a steadily mounting bass. Francis Liszt described a Chopin rubato by comparing it to a tree, "whose crown leans in all directions in a wind while the roots stand firm in the earth."
Chopin used the term rubato to mean playing senzo rigore in the years 1824-1835 in his mazurkas as well as his nocturnes. He stopped using the term in 1836. Gastone Belotti considers the reasons for this to be obvious: from the instant of maturity all of his performances became rubato.
There are hearts in which rubato, that "subtle disquieting rhythm" is clearly registered as in the mature work of Chopin; there are others in which, as in Chopin’s early, youthful work, the rhythm is imperceptible. The former, afflicted by serious illness, rarely stop suddenly, as if the lack of stiffness, their flexibility, tendency to rhythmic freedom had better prepared them for the advent of sinister, morbid rhythms. Analyzing these discreet deviations from the ideal rhythm under the influence of heart rate variability is finding wider and wider application in the assessment of the risk of sudden heart attack among those who have already had an obstruction.

Doctors have always attached great important to measuring the pulse, and they became quite proficient at it. In the Third Century B.C., Herophilos of Alexandria determined the various stages of a pulse with the aid of a clock of his own construction; he carried it with him when visiting his patients. For centuries the waves of the pulse have been measured in all possible ways, in the belief, not without foundation, that this is the path to knowing the secrets of the heart’s workings and those of the entire organism. And not so long ago medical students had to describe, in one fell swoop, the basic characteristics of a pulse such as speed, filling, pressure, frequency and beat. The number of words used to try and capture these qualities must have seemed endless to them: twin pulse, thread pulse, anacrotic or, when all other adjectives failed, a weird pulse. Has all that knowledge been forgotten in the epoch of almighty technology? Not at all. The acclaimed Dorland’s Medical Dictionary, in the 2000 edition, advertised as a compendium of the most useful information for medical practitioners in the third millennium, describes... eighty-eight kinds of pulse!

Of course, measuring a pulse soon took second place to listening to a heart. The French doctor Rene Laennec invented auscultation one day when, wanting to avoid the inappropriate placement of his ear to the breast of a young female patient, he rolled a sheet of paper into a tube, tied it with a string, and placed it in the vicinity of her heart; he could not have imagined that his invention would open up an entire world of literally the closest sounds, a world unavailable to our ears up to that moment. Arrhythmias offer an excellent example. A single extra systole is like a slight misstep in a dance-one lilt, probably unnoticed, and in the next step we pick up the rhythm which carries us further along. The rhythm of the heart, punctuated by repeated premature contractions, makes us realize that syncopations were not a discovery originating with jazz musicians. In the irregularity of a complete pause between contractions, they change, the rhythmic accent shifts. The rhythm of a galloping horse resounds in a heart with an incapacitated left chamber; in English this is called a "gallop rhythm." The beating of a heart suffering a complete block is interrupted now and again by a loud "cannon blast" (the simultaneous contraction of atria and ventricles), followed by the quiet echo of contracting atria.

Echo: the name of a mountain nymph. Greek myths explained in various ways how she became the personification of an ethereal, returning voice. Having fallen in love with Narcissus, who did not return her affection, she fell into such deep despair that she began to disappear, until only her voice remained. Apparently it was also for her concealing of Zeus’s love affairs that Hera condemned Echo to repeat the last word of whatever was said to her. So it is not strange that languages new in the making were beginning to repeat her name. She came to inhabit them for good and became one of the most commonly used words in modern medicine. Echo, echolocation, echocardiogram... We penetrate the heart with voice waves and they bounce back and return to us like an echo from which we construct the image of the heart itself. This image is amazing for its accuracy of detail. The diagnostic apparatus is developing so quickly one might think it was trying to match in perfection the echolocation... of a bat.
And echocardiogram revealing the details of the anatomy of the heart or the contractibility of its muscle, allows us to understand the reason for the disruption of the rhythm. In an electrocardiogram we see it. Especially valuable is the portable electrocardiograph popularly known as the Holter monitor (named after an American doctor) which records the workings of the heart over a twenty-four hour period. In this memoir, written by the heart, every twitch is noted. And so is each, even the slightest, arrhythmia or lack of oxygen. This record is an invaluable aid in daily medical diagnoses. And even more advanced analytical tools are being developed for use in detecting delicate asynchronicities in the workings of the heart. Mathematicians and physicists are coming to the aid of doctors by applying non-linear systems dynamics and chaos theory to the examination of these exceptionally complicated phenomena.

How many conveniences there are today for medical students who want to divine the music of the heart! Over the bridge, where the ribs are attached, we place a membrane with an electronic amplifier. Out of it come six pairs of acoustic ducts, just like those in a regular stethoscope. Thus six people can receive the sound phenomena from the same place over the heart. On the screen of a portable computer runs a crooked electrocardiogram, and under it a phonocardiogram-a continuous record of tones, whispers, all the acoustical phenomena the heart emits. One can stop, "freeze" and analyze.


People have dreamed about being able to freeze sounds, words, even music for a very long time. Antiphones, a member of Plato’s household, tells about a country whose winters were so severe that words froze in the air. In the summer when the words melted, the residents would find out what had been said during the winter, just as Plato’s students would learn only in old age the meaning of the words uttered by their master in their youth. Many centuries later a certain Italian merchant (described by Baldassare Castiglione) set off in winter for the Ukraine to get himself a sable fur. He got stuck on the frozen bank of the Dnieper where he was conducting negotiations with Muscovite merchants bivouacking on the opposite bank. The words were not getting across, however; they froze en route and hung in the air like icicles. Then the Polish translators made a fire in the middle of river. The thawing words contained such high prices, however, that the Italian quickly returned, empty-handed, to his sunny homeland.
But who could surpass Baron von Munchhausen’s stories about winterlands! Rushing once in a sleigh over the icy wastelands of Russia, he told the postilion to play his horn the entire way back. The fact that not a single sound made it out of the horn should not surprise us. All got stuck in the horn, frozen. But that evening at the inn, music began to pour out of the horn hung by the fireplace and "to joyously melt the hearts so cruelly frozen."
In an operating room, when the doctor "freezes" a heart, lowering the temperature by a few degrees, he stops the music and rhythm because the heart stops. Mechanical pumps replace the heart and push the blood through the blood vessels. After the operation the warmed heart starts up its work, emits tones. The circulatory system begins to function once again driven by the rhythm of the heart.

When I was a new doctor and Wroclaw was hit with the iciest winters of the century, a completely frozen man was carried into the hospital at three in the morning. He was found on the banks of the Oder, where the temperature read minus thirty-five degrees Centigrade. He was as stiff and cold as an icicle, he wasn’t breathing, and his heart had stopped beating. The EKG registered a straight horizontal line. People were just beginning to talk about resuscitation; we had no equipment. I was there with a nurse. I began to massage his heart, and she gave him mouth to mouth. Every breath he released filled the room with alcoholic fumes. His heartbeat returned after about an hour of massaging his heart, his breath after two. The next day the dead man walked out on his own two feet, having upbraided us earlier for losing his pack of extra strong cigarettes."

Concerned, we sent an account of what happened to Lancet even though we could not answer the editor’s question: what was the body temperature of the resuscitated man. Over twenty-five years later the same paper printed the story of an accident involving a world-class Norwegian skier in the far North. She had fallen into a deep ice pit from which she was extracted two hours later, showing no signs of life and with a body temperature measuring 13.7 degrees Centigrade. She was transported by rescue airplane to Tromso. Her heart began to function only after a few hours of pumping her blood through the heaters of an extrasystemic circulatory system. She left the hospital after five months of rehabilitation. Such incidents have lead people working in wards of intensive therapy with patients resuscitated on the streets and brought in, to use mattresses that cool the body at least a few degrees. They do this in the hope that they can stall the moment of irreversible damage to the brain and thus enable the pulse and heartbeat to return more quickly.

You would not be able to take the pulse or to measure the blood pressure of thousands of Americans who nonetheless move around quite freely. They have, sewn into their hearts, small pumps aiding blood flow from the left ventricle to the aorta in a constant, non-pulsating way. In the world there are also a few patients whose hearts have been removed and replaced with a completely artificial heart the size of a grapefruit-all titanium and plastic-"the latest in the most advanced technology that a human being has ever carried within." Also popular are electric fibrillators, and the choice of antiarrhythmic prescriptions is exceptionally wide and still growing. Yet there are times when the strongest medicines will not work but a good word does.

Years ago Jerzy Turowicz, the editor in chief of the Polish weekly Tygodnik Powszechny, came to our clinic because he had a terrible infection. We were able to bring the infection under control, but the arrhythmia remained. His heart beat with a bad, menacing rhythm, one of those which do not retreat by themselves and augur the worst danger. We prescribed strong medicines-without result. We had reached the limits of what we could do. One evening I visited Jerzy in a private room, listened to his heart and returned home depressed by my own sense of powerlessness. When early the next morning I put the stethoscope to his chest, I heard a pure, measured, correct heartbeat. I did not believe my ears, but the EKG confirmed my reading. Astonished, I asked, "Jerzy, did something happen last night?" He replied with his gentle, kind smile: "You know, the Pope called me, after midnight, from the Vatican."

The mystery of circulation in the human body was discovered almost two hundred years after the discovery that the earth and the planets revolve around the sun. Our inability to see a phenomenon so important and relevant to each of us must seem incomprehensible, especially since the combination of experiments necessary to determine this truth could have been conceived and performed without any impediments in the course of the previous millennia. William Harvey, the man who discovered the circulatory system, was an experienced anatomy-pathologist and a scholar with an insatiable curiosity. Before he got interested in man, he completed the dissection of around two hundred various animals, including an ostrich, which at the beginning of the seventeenth century in London was not the easiest task. Next, by using simple cuts and bandaging the human hand, he arrived at the conclusion that blood leaves the heart through the arteries and flows back through the veins.
Comparing the orbiting of the planets around the sun to the circulation of blood in the human body directs one’s thought to music. Pythagoras claimed that the rhythmic movement of the planets was the source of music. The music of the heavenly spheres, the expression of perfect harmony, always resounds even though we may never hear it. Similarly, we do not hear the rhythmic surging of the blood because it is with us from birth. It reaches us only in rare moments, when the harmony of the organism is seriously disturbed, when it feels bad-in illness.

My cherished Oxford Companion to Music defines rhythm as the face of music, turned in the direction of time. How could one relate this to the heart?
Blood surges into billions of our cells like an ocean wave licking the sandy shore, rubbing up against it and then going back out, only to return after an interval of time. Our great internal organs and the cells which make them are endlessly rocked by waves of incoming and outgoing tides. They feel, they hear the rush and rhythm of blood which "binds the distant shores together with a thread of understanding" and tells them about the passage of time.

AFTER THE GENOME
Explaining the mechanism of heredity is indisputably biology’s greatest accomplishment. What is this phenomenon of heredity? An organism locks into capsules a gamut of instructions on how to create its successor. These instructions pass to the fertilized egg cell and gradually unfold until a descendant appears. In the course of 150 years biologists have discovered that strict laws govern the transmission of these instructions, and that they are hidden, like a treasure, deep in the nucleus of a cell. It has the shape of a thread-DNA-and it is written in a special code as a recipe for the form of the organism and all its functions. The heredity mechanism amazes and astounds with its ordinariness. DNA sequences indicate how to assemble, from the tiniest bricks, each living creature on our planet-be it a snail, pine, whale or worm, gnat or human being. These instructions can be translated into a numerical code, saved in a computer and analyzed.


A few years ago we knew just a few bits of the information coded into the DNA. Success in deciphering these bits, these individual genes, gave rise to an altogether wild yet compelling idea: what if we went "for the whole thing"? Literally: to decipher, letter by letter, the entire DNA code? In 1995 this was accomplished for the bacterium, H. influenza, a one-celled organism. Three years later-for the tiny, transparent worm, made up of nine-hundred and fifty-seven cells: Caenorhabditis melanogaster. By March 2000 the entire DNA code of the fruit fly, Drosophila melanogaster, was sequenced. This insect had been the domain of endless and intensive research by geneticists. We know a substantial amount about the inheritance of its various traits. And because the language of DNA is universal, the code of a fly should be helpful in reaching an understanding of human DNA. It could be the Rosetta stone. Yes, but then we need to have the other, human code in order to lay the texts alongside one another. Just like on the Rosetta stone: Egyptian hieroglyphs right next to Greek. Those hieroglyphs, the most important record, were procured a few months later. In 2001 all three billion letters of the human DNA code, from A to Z, were deciphered, published and presented on the Internet. If we were to print this code with characters like those used in this book, it would extend from Warsaw to Montreal. The entire DNA code contained in a cell is called the genome. Thus people have begun to call medicine of the third millennium, medicine coming after the decoding of the genome, or post-genomeic medicine, for short.

Let us imagine three billion beads strung on a thread. The beads are of four colors, according to the letters of the genetic code. Let us place two strings of beads next to each other from two people. They appear to be identical, but upon closer inspection, we notice that one bead in a thousand is of a different color. Medicine is beginning to attribute greater and greater weight to these discreet differences. They can indicate a susceptibility to certain diseases or a specific response to a medicine. This has been demonstrated in the case of Alzheimer’s disease as well as in the case of pulmonary embolisms. Sometimes these discreet differences have no biological significance; in the majority of cases we don’t understand the first thing about them.


The variation in individual nucleotides (letters) of the genetic code we call polymorphism. With these words we refer to the beginning of the world when things were not yet imprisoned in forms or fixed into one shape. When Apollo reaches Daphne after long pursuit, clusters of leaves sprout from her fingers and she becomes a laurel tree. Alpheos, upon seeing his love change herself into water, agrees to become water, too: "...by refusing to allow himself to be imprisoned in the contours of his identity, he joins his beloved". And Zeus changes into a swan-when he loses his mind at the sight of Leda, or into a snow white bull-for Europe.


Thus polymorphism existed at the beginning of things. The Greeks wondered what happened to it, where it went. If Zeus is watching us today, he is probably smiling to himself, amused. He sees how, after millennia, people are returning to the first myth. And it is not in the world surrounding them but in themselves that they are rediscovering polymorphism which was supposed to have been, primarily, a divine attribute.
In order to understand genetic polymorphism, thirteen of the largest pharmaceutical corporations formed a consortium not long ago. In a very short time they discovered around two million single nucleotide polymorphisms. Apparently this is supposed to constitute about one half of the entirety. Why did these gigantic companies invest enormous amounts of money in this undertaking? Out of the conviction that the decoding of polymorphisms would allow for individualized diagnoses in a few years. We will look into genes, see the misplaced letter and say: this patient will respond best to this and that drug. The drug will then be tailored to the patient.


This has not turned out to be so straightforward, however. Even though searching for links between some polymorphisms and illnesses have lead to establishing such correlations in the case of diabetes and Crohn’s disease, the amount of human effort and financial investment required have cooled the initial enthusiasm. The problem is technological. Even if we were to give up searching the entire genome and to concentrate on "suspect genes," we would need research to screen tens of thousands of polymorphisms in thousands of people. The efficiency of the methods we currently use for this would have to increase twenty fold.
Certain genetic variants, most often caused by the aforementioned polymorphisms, are inherited together as they lie close to one another. This allows us to separate the blocks of letters within the DNA. These stretches of nucleotides are called haplotypes. Biologists, followed by doctors, are looking for haplotypes. In this, they remind us of travelers who begin to recognize individual words, and perhaps even sentences, in a language in which they had only recognized letters.

The cloning of Dolly the sheep demonstrated that every organism cell contained the instructions for making the whole sheep. It is the same with a human being. However, if we could see a thread of human DNA from a bird’s eye view, then we would see over its vast extent, night. Thousands upon thousands of genes sleep. And elsewhere the lights are on and work is proceeding apace. Clusters of illuminated genes send their signals directing the life processes of a cell, of an organism. These lights and shadows may change, especially in illness. We have recently been able to see them. Here is an example: we take a small lump from the patient. Let it be a tumor, lymphoma, for example. We extract its DNA and after preparing it, we put it on a slide the size of a fingernail. Earlier we have coated the slide with the detectors for five thousand genes. The active genes, coiling like boiling hot water, will light up with a bright, phosphorescent light. Those which sleep will show up as shadows. The instrument will decipher the slide and identify the active genes. The information obtained may influence the diagnosis of the disease and its cure. This technology is known as DNA microarray and is comparable to the discovery of the telescope. Like a telescope, it reveals the limitless multiplicity of, not stars, but genes. In order to take in, digest, and understand the vast amount of information, special computing methods and new, sought after bioinformatics specialists are needed.

Active genes set into motion the machinery of a cell which makes proteins. Getting to know all the human proteins became the next goal after decoding the genome. This is an undertaking on an unprecedented scale next to which decoding DNA was "child’s play." Some want to recognize the expression of proteins in diseases, others-their interactions. And still others-functions dependent on spatial structure. All of them are joined in the hope of finding drugs which will act through the discovered proteins. The first step of the race is to the patent office. Thus, for instance, the large firm of Perkin-Elmer anticipates around four thousand patent applications by the end of 2002, one patent per protein, linked to one illness.


Proteomics, as this discipline is called, is unfolding in a futuristic space. In a labyrinthe of multi-storied laboratories robots are working noiselessly. Their shoulders are circling in all directions and in spite of their 150 kilos of weight, they are capable of executing the most delicate functions. From the cells they are given, they isolate a mixture of proteins and separate them into distinct collections. They break up each ingredient in the collection into fragments and locate them in mass spectrometers. Every second these machines transcribe the identity tag, the fingerprint of an examined fragment. The supercomputer arranges them into a protein model. As a result, in a few hours we get a printout of a few thousand proteins present in an examined cell. Until not long ago, the identification of just one of these took years.


It is estimated that we carry in us from 200,000 to two million proteins. The barrier to getting to know them is not the number, however, but their changeability. While genes, in principle, remain unchanged throughout our lives, proteins are ever-changing-depending on the cell, organ, age-or even on what we have eaten for breakfast. Proteins are like Proteus (in Greek, the "first")-The Old Man of the Sea, one of the oldest beings inhabiting the mythological universe. For the Greeks he was the archetype of transformations, which so fascinated them and constantly recurred in their mythology. Many people sought Proteus the way we look for proteins today. He had the gift of infallible prophecy. Finding and holding him was extremely difficult as

Such was Proteus, changing now into a dragon,
Or becoming rain, fire, or the color of a cloud.

Proteomics does not, however, match the popularity of cloning. One has the impression that cloning has a brief history and that it exploded in 1997, the day the photos of Dolly the sheep were made public. But all this really began 170 years earlier when it occurred to people that life is irrevocably joined to the cell and Rudolf Virchow advanced this idea in the sentence: Omnis cellula e cellula ("Every cell comes from a cell"). Out of the following decades of careful observation of the first cells, developing from the egg cell, came embryology. In 1938 Hans Spemann conducted a "thought experiment" which, as he wrote, "might at first seem somewhat fanciful": What would happen if one extracted a cell nucleus from an adult organism and introduced it into an egg cell whose nucleus had been removed earlier? Fourteen years passed before the technique to transfer the nucleus in amphibians was developed and another fifty-eight years before Dolly was born. "What is proven today was once imagined."


Because the nucleus from which Dolly came was derived from an adult sheep (earlier researchers were unable to clone even a frog from mature cells) and because this was the replication of a mammal, for some [the possibility of] human cloning suddenly appeared with the speed of light. It ceased to be a fantasy out of Aldous Huxley’s Brave New World. We instinctively feel that cloning threatens our identity. Will there come a day when I stop being the only one like me and see-like Narcissus in his watery mirror-the reflection of myself, except that it will be real? Heredity will no longer be a lottery; it will be subject to human control. The individuality of each of us is composed not just of genetic material which we inherit, however, but a history, character and traits which our environment shapes. My identity is not changed by the fact that I possess an identical twin, with the same genetic equipment. Identical twins are born almost simultaneously and they make their way into the world, which is equally open to each. It is different in the case of a clone, called a "delayed twin." The world cannot be such an open place because the road has been indicated by the parent. He sees her and knows he will follow in her footsteps. His knowledge extends farther than Rafael’s knowledge in Balzac’s "La peau du chagrin" (Wild Ass’s Skin). He knew only the time of his death; this one knows the fate left to him. One can only wonder whether this genetic determinism is not exaggerated. Is the predicament of a "delayed twin" so diametrically different from the predicament of a child whose excessively concerned parents never leave him alone and who influence his decisions for years, sometimes even making them for him?


While contrary to the assurances of the Italian gynecologist seeking fame, the cloning of people is subject to unimaginable numbers of complications and also raises basic ethical reservations, the cloning of animals has nonetheless become a reality. It realizes the centuries-long desire of man to breed the most beneficial races of domestic animals. This also holds true for reproductive cloning, which tries to implant the cloned embryo in the uterus and to produce a child. Biologists and doctors are equally interested in therapeutic cloning which takes genetic material from a patient and tries to generate cells of the heart muscle in order to implant them in the patient after a heart attack or the generation of pancreatic islets to cure diabetes. In this technique cloned egg cells are raised for a few days until they reach 100 hereditary cells of which they isolate so-called embryonic stem cells. We say that they are totipotential, that is, after sufficient stimulation, they change into a free cell type, which we then graft into the patient. These technologies are, however, far from practical application, and their ethical evaluation arouses understandable doubts since they involve the manipulation of reproductive cells.
Lack of availability and ethical issues hamper clinical applications of embryonic stem cells. Very recently focus has been shifting to therapeutic applications of adult stem cells. These can be obtained from the bone narrow of the patient and then re-injected to target-zones, like, say, myocardium in a patient with coronary artery disease. Thus, within each one of us may lay a treasure-trove of renewable life that can be directed toward healing and revitalizing cardiac function.

The human genome has been endowed with the loftiest metaphors. It has been called the bible of Creation, the Book of Man, a recipe for life, a manual of evolution, a code of nature, the Holy Grail and the language of God. Decoding the genome has been compared to "the smashing of the atom, the landing of man on the moon, the attainments of Galileo, Shakespeare, and Rembrandt, and the discovery of the wheel." And what did the decoding bring? Many surprises.
The number of genes turned out to be smaller than people thought at first and appears to be around thirty thousand. How could this be reconciled with the multiplicity of proteins far exceeding this number? Until recently it was generally accepted that one DNA segment, described as a gene, contains the code for just one protein. Thus people said: each gene encodes one protein. Meanwhile the phenomenon of one gene coding various proteins turned out to be quite common. The mechanism which does this is common and is called alternative splicing.

Genes make up only 1.5% of DNA. Thus they have been compared to oases scattered in a desert. What is this desert, crushing in its enormity? It consists of tens of thousands of motifs repeating themselves. Some are very simple, made of two letters, in pairs, as in CACACACA.... Others are incomparably more intricate. Many of them are mobile and can move from place to place in a chromosome; in this sense they resemble the shifting sands in a desert. There are also, among them, the scattered genomes of viruses, usually "relics incapable of replicating." Sometime in the evolutionary process they must have become incorporated into us. These desert spaces are also full of elements regulating gene activity, pseudogenes and "immigrants’ (for example, DNA fragments transferred from bacteria).

The desert metaphors seems inexact. "Desert spaces will certainly turn out to be fertile ground for science." In its structure, the genome conceals the riddle of evolution. One could compare it to "the archaeological ruin of an unknown civilization." As in archaeology, that which is valuable is hidden in the layers of earth.
Many human genes are astoundingly similar to the genes of other multi-celled organisms. It is amazing that entire identical segments of the genome in humans and mice have remained the same even though these species are divided by at least two hundred million years of evolution. Comparative studies of the genomes of humans and other living organisms should reveal the mechanisms of evolution. Are they capable of explaining those which are the cause of passionate disagreements and may even constitute the basis for an instinctive rejection-by some-of evolution? Rejection-in spite of the fact that biological evolution is only the next link in the grand cosmic process of transformations. It inscribes itself logically into the image of the world, outlined by contemporary cosmology. This image is "evolutionary through and through": from the Big Bang, through the synthesis of chemical elements, the appearance of galaxies, stars, planets, and, finally, living organisms. Clear, too, is the position of the Papal See, expressed in Pope John Paul II’s well-known letter dated October 22, 1996 to the Pontificial Academy of Sciences. It is summarized in the sentence: "The scientific theory of evolution does not contradict any tenet of the Christian faith."

Yet resistance to the theory of evolution exists, even persists. It unites "a considerable number of theologians and religions" as well as "practicing Christians." This does not just mean that "man does not want to accept the truth about his ancestors." More frequently this is a reaction to a rather evident "epistemological abuse" of contemporary Darwinists suggesting that science excludes the existence of God.


The resistance to evolutionary theory may also be tied to the language in which it is presented, to its metaphors. Scholars have a weakness for metaphors and sometimes they are as sensitive to them as poets though they create incomparably fewer of them. An accurate metaphor, thought-provoking comparison, or intentional ambiguity has contributed as much to the development of science as rigorous analysis based on objective data. The language of evolutionists arouses the ire of the poet:

Gene wars, traits assuring success, loss and gain.
For God’s sake, what language are these
People in lab coats speaking?

The metaphors of neoDarwinists (though Charles Darwin himself avoided them), originating in the period of flowering capitalism, have been revived in the last decades. Richard Dawkins "selfish gene" has attracted the most attention. People have begun to look at the human organism as a carrier of DNA in which a mass of egotistically inclined genes has one goal: to reproduce in the line of fire. Self-love, struggle, egotism, ruthlessness, the triumph of the fittest-these words return over and over again in the writings of prominent contemporary biologists. Occasionally they warn us not to take these words too literally: "These warnings have the same value as those on cigarette packages warning smokers about the health hazards of smoking tobacco."

"In biology cooperation and concerted action are as common as competition." The survival of life on earth may depend on maintaining a balance between all beings. What is more, organic and inorganic matter are joined to one another by a system of interwoven feedbacks, which calls for looking at Earth as a whole, as one living organism. That is how James Lovelock imagined it around three hundred years ago and this became the Gaia hypothesis. Gaia was one of the first mythological beings to emerge from Chaos. She was a living organism-with hills and valleys, like enormous limbs. The poetic Gaia hypothesis holds that even though organisms compete with one another on a local level, from a broader perspective their interactions create a realm more suited to life, more favorable to life. Many feel this is too outrageous a deviation from Darwinian theory, but the advocates of Gaia, whose numbers are growing, claim she completes and deepens evolutionary theory.


A similarly soothing picture, far from the ruthless competition of individuals, is painted by evolutionary theology. From its perspective nature is neither the blind play of random forces, nor does it contain a concealed evolutionary scheme which the Ruling Projectionist imposes with ruthless necessity. Evolutionary theory speaks of a divine vision of transformations in which it is somewhat reminiscent of modern physics, holding forth on God’s mind. God does not unambiguously determine the distant states of the universe, but "makes man His trustee co-responsible for the future work of creation." Evolution-already indicated by the Biblical description of Original sin-could therefore occasionally deviate from God’s vision of it. Poetic theories, like that of Gaia, as well as those of the evolutionary theologians, remain on the sidelines of the main current of scientific evolutionism.

The theory of evolution introduces randomness into our life, exploding the concept of the harmony and cohesiveness of the world. In the fall of 1996 at the Pontifical Academy of Sciences, at a session devoted to evolution, the discussions reached beyond the walls of the Vatican to the students of Rome, and they reacted with a characteristic poster, printed in hundreds of copies. The poster depicted the earth and over it the rising capsule of a rocket. It is moving upward with some resistance, and in it sits a serious, powerful Darwin, the one we remember from school etchings, in a long coat, with a neatly trimmed beard. He is rising toward heaven. The vault is the fresco from the Sistine Chapel in which God touches Adam’s extended finger. The force, here in the figure of Darwin, thrusting itself from Earth causes the vault to crack, pushing God’s hand away from man’s.
Is this separation the inevitable consequence of an autonomous and random evolution? Does it transform time into a "strip unwinding from nowhere to nowhere?" Or perhaps accidents are not free of causes. And then what the physicist sees in terms of quanta and the biologist in terms of evolution, this intrusion of randomness, is in fact the intrusion of a different kind of causality, incomprehensible to us yet consistent. Studying the history of the human genome, penetrating its oldest and deepest layers may one day bring these mysteries a bit closer.