A COSMIC PERSPECTIVE ON LIFE AND DEATH

R.E.Davies

Benjamin Franklin Professor of Molecular Biology and University Professor, Emeritus Departments of Astronomy and Astrophysics, and Animal Biology University of Pennsylvania, Philadelphia, PA.

Although science progresses by observation, the creation and testing of hypotheses, by experiment, and the discovery of the regularities or Laws of Nature, rather than by revelation, intuition or appeals to authority, I will have to make a variety of statements without presenting all, and often any, of the evidence. The Universe is extremely complex and our knowledge is often quite tentative and not universally accepted. Most scientists do not claim absolute knowledge of “truth” although we hope to approach it more closely as experiments and their explanations proceed.

To start with, the very terms, "Life" and "Living", although convenient labels, are strictly meaningless. Like the shading from black to white in, say, 1000 steps, the passage from non-life to life is also a continuum and the line defining one or the other may be quite arbitrary. Like the terms solid, liquid and gas that seem all-encompassing but are not in fact precise, life and death are categories we try to impose on Nature. Things themselves may be much more complex. We have found and continue to discover that the various aspects of human life are not uniquely different from those of other animals. Life is found and expresses itself in many, many varied and unexpected ways on Earth.

Although biochemists and molecular biologists can be defined as those who ask the question, among others, "How is it that living things are composed of lifeless molecules?", and by now they believe that they know the outline of the answer pretty well, there is no simple short satisfactory definition of life based on breathing, movements, heart beats, electrical activity in the brain, metabolism, the utilization of energy, growth, reproduction, mutation, evolution or the activity and interactions of proteins and nucleic acids, etc., precisely because the situation is not simple and there is a continuum. Many assemblages of interacting matter exhibit all or most of these behaviors for some, but not all, of the time. Others don't, even though we call them living. Worse, many fairly simple atuocatalytic physical and inorganic, and organic chemical systems can exhibit them too, though we do not call them living. As far as we know, there are no residual fundamental mysteries concerning the basic life of living cells. There are many details to learn but we know of no reason why we must postulate a "life force". Living cells certainly obey, or I should rather say, behave in accordance with, the many Laws of Thermodynamics. In effect, the 34 volumes of the series "Comprehensive Biochemistry" constitute a description and definition of the life of living cells. Yet it is true that our detailed understanding of the activities of the enormously complex assemblage of chemically and electrically interacting cells that comprise the brains of mammals, and even any vertebrate or invertebrate, is still quite incomplete, but we are learning more every day.

Cells such as blood cells or sperm or ova, or the product of their union, the zygote, can be frozen for months and years in liquid helium at a temperature so cold that no "living" at all is going on. Yet they can be warmed and thawed and, if conditions are right, can be revived, the zygote then implanted in an appropriate uterus, and grown, be born, and then live a normal life. This has happened already to many domestic and farm animals and also to some humans. The pattern, if not the activity, of life survived during the deep freeze.

Some few organisms are autotrophs and live entirely on their own on simple molecules like carbon dioxide, nitrogen and the essential elements with energy from the sun, or a simple chemical reaction. Most others are heterotrophs. We are, and we live a life dependent on other species. Even as adults we need bacteria to turn the nitrogen gas in the air into a form we can use. We need plants to make the oxygen we breathe, the vitamins, essential fatty acids and essential amino acids that we cannot make ourselves. If photosynthesis stopped completely, say, following the dark night of a nuclear winter, or the impact of a major asteroid, we would eventually die out, unless a local closed ecology was built to house a few survivors. As children, babies, fetuses, embryos and unimplanted zygotes we had varying degrees of dependency on society and on our mothers for our immediate needs. Thus definitions such as "life is a process capable of self-duplication and mutation" will not do - ask any post-menopausal woman or castrated man. Even such general definitions as "living systems have the property of cycling bioelements to achieve complexity in a process driven by solar energy" or "life is a dynamic equilibrium in a polyphasic system" or "life is the mode of existence of proteins" are interesting but unhelpful. We have to look at individual cases.

Just as cows depend for their lives on the microorganisms in their rumen or first stomach (they have four!), so some very small disease-causing entities, the viruses, can "live" inside living cells and get themselves reproduced. They are extremely simple, usually a bit of DNA or RNA, a few thousand base-pairs inside a protective protein coating. The viroids are even smaller, a few hundred RNA bases in a circle. The complete chemical structures of many of these are now known. Several of them can be crystallized and kept in a bottle indefinitely. Their chemical names are among the longest words in the English language. They live a more or less borrowed life and, for many, their contribution to their own reproduction is rather like that of a sheet of typescript in a photocopy machine or of the latest popular song that gets people who hear it, to sing it - often with extensive mutations. Prions cause disease, get themselves replicated, seem to be small proteins, and don't seem to have any nucleic acids. The DNA that encodes them is already in the cells they invade and they may act like derepressors. We should know soon.

Many people argue over when life starts - at, soon after, or a long time after, fertilization. For a molecular biologist the particular sperm and ovum from which we came were certainly both "alive" and "human". There is very convincing evidence that life on Earth started about 4 ± 0.2 billion years ago and that all living organisms in our biosphere are related, i.e., there is only one "life" on Earth; the one that started that has continued, and that we see all around us. If other types of incompatible life started about then, then they left no traces that we have yet found.

Just like the Universe itself, we have more nuclei of hydrogen atoms in our bodies than those of any other element. In fact we have several billion, billion, billion of them and virtually all were made early in the first second of time since the Big Bang which itself began, perhaps from a preceding quantum fluctuation, between 10 and 20 billion years ago. The rest of the elements in our bodies (which make up most of the mass of our bodies) evolved in nuclear furnaces by fusion reactions over the next few billion years mainly in large and very large stars and sprayed back as atoms and dust into interstellar space as stellar winds and following various very violent catastrophic stellar events like ring nebulae formation, novae and supernovae. Though hydrogen is really primordial most of the mass of our bodies and the things we see around us are made from stardust produced more than five billion years ago when an interstellar cloud of atoms, ions, molecules and dust collapsed under the influence of gravity. This collapse was probably initiated by a pressure wave from a nearby exploding supernova. This led to the formation of the Earth, the solar system, and our Sun, which is a late-generation G2 yellow dwarf star.

Most of the helium in the Universe was made from hydrogen in the first three minutes after the Big Bang, and it is remarkable that over three billion (3 X 109) supernovae were needed to make the elements heavier than helium that exist in our Milky Way Galaxy. Some of these are used in our bodies. 36 different elements are known to be essential for some form of life on Earth; 27 of them for human life and 17 for the life of the microorganism Escherichia coli. It is even more remarkable that because of the mixing of our rotating Galaxy, the existence of stellar winds and the production of matter and anti-matter from energetic gamma-rays, our bodies contain some atomic nuclei from all the older stars in our Galaxy and even from nearby galaxies such as M31 (the great spiral galaxy in Andromeda). Phosphorus and potassium atoms are the ones in shortest supply and a volume of the Galaxy, twenty million times that of the Sun, is needed to make an average (70 kg) human body.

Thus the evidence is overwhelming that the Universe has evolved and that the elements have evolved. Virtually all biochemists believe that life started under water without free oxygen by a process of chemical evolution of the small molecules that are the building blocks of proteins and nucleic acids and that could be made abiotically by the action of ultraviolet radiation and other energy sources. Many of these small molecules, in fact, have been found in comets, meteorites and in interstellar gas clouds.

Now life as we know it has been confined to Earth, although the Moon has been contaminated inadvertently with Earth bacteria during the Apollo missions and Mars will be when the Viking Orbiters finally crash onto Mars. No certain trace of life out there has yet been discovered but many scientists in the field believe that there is a good chance that life, even civilized, intelligent, technologically advanced life may be wide-spread throughout our Galaxy and the Universe, and by the way scientists involved in SETI - the Search for Extraterrestrial Intelligence - define intelligence as the ability to build and use large radio telescopes.
In 1985 i presented an invited paper before the 36th Congress of the International Astronautical Federation in Stockholm, where I discussed the evidence for the possibility that desiccated spores of some radiation-resistant bacteria might spread life from star system to star system. And yes, it is unlikely but just possible. This possibility has been made less unlikely by the work of Weber and Greenberg (Nature 316 403-407, Aug. 1, 1985).

However for Earth there are so many plausible hypotheses for the way in which life could have started here that there seems to be no need to postulate panspermia for the origin of our form of life. A lot of new information has become available in the last few years from research on the possible ways that life could have originated on Earth. These include the possible role of clay crystals in acting as templates, of a type of ribonucleic acid called ribozymes that can carry information and also act as catalysts, of thioesters as energy sources even before high energy phosphorus compounds became ubiquitous, and studies of hypercycles and on autocatalysis of small organic molecules. Although we do not yet know the precise way in which chemical evolution led to systems that we could call "alive", the possible pathways are becoming clearer and a self-replicating system make from abiotically produced molecules with the properties of life may well be put together in our lifetime or that of our students. Given an energy supply and the right building blocks, both of which would have been available, some of the type of proteins called enzymes can assemble nucleic acids, and nucleic acids can specify the structure of enzymes through the genetic code. These together form a primitive self-replicating system that could have arisen naturally and continued within cells generation after generation until now.

Most of our cells, the soma, are destined for death (unless we learn to clone the nucleus of these cells - it's already been done for frogs and happens in human cancer cells, which are potentially immortal). However in our germ cells we have strands of the famous double helix of DNA that have been copied and copied billions of times with all sorts of mutations, transpositions and serial gene-doubling in an unbroken, so-far immortal chain back for about 4 billion years. What an astonishing finding this is! We believe that all the over a million species we have on Earth now have arisen by biological evolution and these are the survivors from many extinctions and die-outs that have destroyed all but about one of every thousand species that ever existed here. Samuel Butler's statement that "the hen is the egg's way of making another egg" has a lot of truth. By the way the egg came before the hen because hens evolved from reptiles who laid eggs well before there were any hens.

Although we think that life started under water in a virtually oxygen-free environment and used the available molecules as building blocks, chemosynthetic and photosynthetic organisms then evolved in a few hundred
million years and could make all the molecules they needed themselves. They eventually also made the oxygen of our air, that made it possible for air-breathing animals to evolve and that also made ozone that blocked the ultraviolet radiation from making more molecules and made it possible, over 440 million years ago, for plants and then animals to colonize the land. Without that ozone the intense ultraviolet radiation would kill unprotected organisms on land in a few hours. Thus the process that started life on Earth led to a form of life whose products now prevent the initial abiotic reactions from proceeding. We do not believe that life is developing from non-life any more on Earth.

How long will it all last? Even if we, or our progeny, do not destroy the so called higher forms of life by all-out nuclear warfare, the human race or its evolved offspring or for that matter, every life form on Earth, will still have only about seven billion years before our Sun becomes a Red Giant and engulfs the Earth. At that time life on Earth, even Earth itself, will cease to exist and we-they will need a space colony twice as far out as Neptune, currently the most distant known planet, in order to survive. Perhaps before then we-they should go and colonize a younger star system, preferably one that has not even been formed yet. Don't lose any sleep over this. Seven billion years is a long, long time - longer than life on Earth, or the Earth, or the Sun itself has existed, but less than the length of time the Milky Way or the whole Universe has been here - or there.

Well, now! To return from the sublime to the by-no-means ridiculous, what of us and the decisions we are continually making, consciously or not, about who, or what, shall live or die? What is an individual? It is not an easy question. Cells of slime molds can live individually or cooperate temporarily to make multicellular organisms that can move and produce separate fruiting bodies.

Our germ cells need never die though they, or their products, must usually fuse with other germ cell products to produce another organism. But monozygotic twins, quadruplets etc. can occur and can be made artificially by separating cells at an early stage of development. How many individuals are really there (especially if the twinning is incomplete as in so-called Siamese twins or in teratoma or some moles on the skin? What of animals made by artificial fusion of these early cell stages so they have four or six parents and are true chimeras (as has been done for mice and cows, etc.)? What of parthenogenesis or virgin birth which occurs or can be induced, in many animals, such as frogs, lizards, turkeys, etc. and has been claimed in humans? In some insects the male has never been found because the females make fertile eggs all on their own. What of animals that change their sex once or many times as they grow older or change their environments or are unilateral gynandromorphs, female on one side and male on the other as has happened in several butterflies and birds, and what of those animals that are always true hermaphrodites (Hermes, Aphrodite)? These situations all occur in different animals. Many strange and complicated anomalies can occur in humans besides the normal XX females and XY males. Well over twenty different types of sex chromosome mixtures have been found, such as a variety of human chimeras, also the famous XYY males who were once suggested as being genetically programmed for lives of violent crimes and thus were of great interest to lawyers.

A Past Chair of the Faculty Senate of the University of Pennsylvania once wrote to the University journal Almanac (3/7/72) and disapproved of undergraduates telling members of the faculty to perform "certain physically impossible acts upon themselves". I replied (3/21/72) "He may be interested to know that Dr. Cawadias in his book 'Hermaphrodites - the Human Intersex', published in 1943 by Heinemann, London, recorded that Affaitatus Fortunius stated that the magician Merlin was the product of a self-fertilized hermaphrodite. So who knows what is really impossible for some people?" In case any one is worried, this claim is not widely accepted by modern medical scientists.

It should now be clear that the situation is far more complicated than appears on the surface, When Owen Edmonston wrote in the Daily Pennsylvanian of Feb. 13, 1985: "But science can never give us the answer to when life begins, because science cannot define what constitutes life. But simple common sense can. Simple common sense tells us that an unfertilized ovum or a solitary sperm will go no further."

Well, so much for "simple common sense". Those three sentences are nonsense. Unfertilized ova of many species have produced functional adults. There is a famous picture made by Jacques Loeb with the caption "This frog had a pin for a father". Parthenogenesis in mice has already been taken to the 10 day stage, i.e. about a half-way gestation period, with heart, limb buds and nerves, equivalent to about a 3 months embryo in humans. Virgin birth may eventually be routinely possible in humans, to produce, of course, only females. Men, or some gene or genes on the Y-chromosome, may only be needed to make other men.

It is very important to distinguish between the "life" of the DNA in cells, that of a whole cell, that of the whole organism and that of a species. The basic pattern in the DNA goes back and has been modified over billions of years. A cell nucleus containing it can potentially be removed, implanted in an appropriate embryonic cell (after removal of its nucleus) and then grown as a clone, to make a complete adult even after the death of the original cell or organism. Most individual cells can be grown in tissue culture for long after the death of the whole organism. The whole organism usually has a measure of independent organismal life that for most animals starts at viable birth and continues until the death of that organism. Many organisms, and not just ants and termites, require the cooperation of many other members of their species, and even of other species too, in order to survive.

There are clearly many problems that are relevant to decisions concerning abortions and when to turn off a life-support system.

Over 13 years ago in the Daily Pennsylvanian of Feb.2, 1972 Dr. Charles C.Price, Benjamin Franklin Professor of Chemistry wrote "The Supreme Court decision on the basic right of women to abortion will please millions of Americans and displease millions of others. It may be helpful to the latter to consider carefully the distinguishing feature of human life which must be protected by law and which is the essence of the reverence for human life.

"This feature cannot be the amazing plumbing chemistry and physics of a living cell. It cannot be the amazing chemical structure of the genetic information in a fertilized egg, since every single cell in the human body contains all of this genetic information, and no one fights for the right of an appendix or a finger to survive.

"Perhaps we could agree that the essential feature distinguishing human life is human consciousness, the feature which endows us with the creative human spirit and the capacity to communicate facts, opinions and emotions. It is being increasingly recognized that it is this feature of human life which distinguishes man from other forms of life and which is then the foundation for the basic respect and legal protection for human life. Until and unless this spark of consciousness and the functioning brain which makes it possible exists, human life does not exist. We can, of course, show concern for all forms of life, prehuman and subhuman, but our society and our laws are designed to protect the rights of human life itself.

"Perhaps Americans could achieve more unity on the issue of abortion if we could see that we all, proponents and opponents of abortion alike, agree on the issue of protecting the distinguishing feature of human life, human consciousness and the human spirit."

I replied (Daily Pennsylvanian Feb.5, 1972) "In the hope that Americans could achieve more unity on the issue of abortion, my fellow Benjamin Franklin Professor, Dr. Charles C.Price, wants us to agree 'that the essential feature distinguishing human life is human consciousness".

I too welcome the Supreme Court decision on abortion, but mainly as a major step towards the acceptance by both men and women that women should have the right to determine what happens to their own bodies.

"Just as the terms life and living are meaningless (see Pirie, N.W. in "Perspectives in Biochemistry" Ed. Needham,J. and Green, D.E., Cambridge, 1939) so consciousness as a criterion raises severe problems. This is quite apart from the problem of recognizing it. Some highly sophisticated computers have been programmed with so-called expert systems to present (over a teletype) a very lifelike impression of being both human and conscious. (This is the famous Turing test for artificial intelligence.)

'What is to be done about a sleeping person, one who is knocked out, dead drunk, or under anesthesia, or in a coma? None of them are conscious. Thus, one thinks about potential consciousness or the hope that consciousness will come with the passage of time. But this is precisely the difficulty with an unborn fetus. You can hope that it will eventually become conscious and have a functioning brain. However, the human consciousness of a child even a few weeks after birth and its 'capacity to communicate facts, opinions and emotions' are very rudimentary.

"In my view, human consciousness fails as the essential feature for a decision on abortion. In any case, I remain firm in the conviction that no man has the right to father a child on an unwilling woman, or to demand that any fetus be carried to full term. I believe that the decision on abortion is one solely up to the woman herself.

"Incidentally, not 'every single cell in the human body contains all this genetic information'. Dr. Price has inadvertently overlooked the very sperm and ova which are, in part, the cause of all the trouble."

The Oxford English Dictionary defines a "person" as a human being having the rights and duties recognized by law (1444 A.D.) and a human fetus as an offspring in the womb from the end of the third month of pregnancy until birth. (Before that it is an embryo or a conceptus.)

But what is a human being? This cannot be answered by "simple common sense". How much human DNA etc. can you inject or insert on plasmids and viruses into cells of other species by genetic engineering and when do they then become human? Human insulin, growth hormone, the anti-hemophilia blood-clotting protein Factor Vill etc.etc. are now grown in bacteria or yeasts and are absolutely identical to those isolated from human cells.

Just to make matters worse, the only cells in our body that don't respire are the red cells in our blood that carry oxygen, but don't use ft. All our other cells do respire. They need and can use oxygen only because they contain extra-nuclear cytoplasmic organelles called mitochondria. Now mitochondria contain their own DNA and reproduce inside cells by binary fission, like bacteria. Their DNA is circular like that in bacteria, not in strands, organized in chromosomes, as in the nucleus of the cell. We get these mitochondria entirely from our mothers and not from our fathers. Their respiratory biochemistry is almost exactly like that of a present-day small microorganism Paracoccus denitrificans. Much evidence leads to the astonishing view that all advanced living organisms contain two or, for plants with plastids, even three separate genetic systems and that this began about one and a half billion years ago when an early paracoccus-like bacterial cell invaded a primitive mycoplasma-like cell to produce a viable symbiont and to make a hybrid or actually a chimerical cell that could have a nucleus and respire or even photosynthesize. These cells have lived and evolved more-or-less happily ever after, and we are one of their many products.

It's bad enough that there are ten times as many bacterial cells in and on our bodies than there are human cells. It is a shock that some primitive bacterial-type DNA that invaded our ancestor's cells over a billion years ago still functions within all our cells that have to breathe. So much for the "breath of life". Parts of the Tree of Evolution are networks. Certainly 'the new-found ability to tamper with human genetic material will raise certain fundamental ethical dilemmas in the near future". But it has happened already in the past (lysogeny) and still happens with some viruses.

Most people do not realize that their bodies, that many believe will be resurrected after death, are not uniquely defined but are in a state of constant flux. Individual atoms and molecules are constantly entering, being incorporated and later leaving to be used temporarily by others. The histories of the hydrogen atoms in our bodies this instant, for example, are very complicated. Some have been part of many stars. Some have been repeatedly incorporated into many individual molecules such as water, glucose, individual proteins, etc. Most of the approximately 6 X 1027 atoms in a 70 kg. lean human being are hydrogen atoms combined with oxygen as water. With a mixing time of about a thousand years for virtually all the water on Earth this means, that each adult human contains about one hydrogen atom from every average milligram from all of every species of organisms that ever existed before a thousand years ago. This, of course, includes every dinosaur and most of our own and every one else's ancestors.

Particularly in a closed room, humans continually re-inhale part of the same water and carbon dioxide molecules that have recently been exhaled by others in the room. Some atoms from these molecules become part of their own structural proteins, bones, etc. even in a few hours.

There is another way in which our bodies do not remain unchanged. They contain important numbers of the radioactive forms, or isotopes, of many elements, for example 109 (3H) atoms. 3.7 X 1019 (40K) atoms and 1014 (14C) atoms. These decay radioactively to form about 7 (3He), 600 (40Ca) and 3000 (14N) newly-formed atomic nuclei every second.

Thus more than a trillion (1012) carbon atoms are turned into nitrogen atoms in each of our bodies in a 70 year lifetime; we breathe out more helium than we breathe in, and excrete more calcium than we eat and drink.

In the Middle Ages the Philosopher's Stone involved the search for a way to transmute lead into gold and, unbeknownst to most of us, the human body is and was a source of transmuted elements all the time.

So much for "life". What of "death"? It is interesting that the inability to breathe or the cessation of heart beats became somewhat obsolete for a definition of human organismal death with the development of iron lungs for victims of poliomyelitis, and of heart transplants or artificial hearts for those needing them. States such as Texas where many heart transplants have occurred and that used as a definition of death that the owner's heart had ceased to beat were in a quandary. Just who was legally alive or dead when the heart's original body and the recipient's original heart had both been cremated?

Many states now define human organismal death as "irreversible cessation of total brain function". But what is "irreversible"? and there is the difficulty that an overdose of barbiturates or hypothermia can both mimic brain death. There needs to be a time limit. There really seems to be no good purpose in keeping alive most of the individual cells of a brain-dead ex-person for weeks, months or years, unless it be to provide viable tissues for transplants to help those still organismically alive. If "irreversible cessation of total brain function" becomes universally accepted as a criterion for human organismal death then logically the organismal life of that human could hardly be considered to begin before brain function and electrical activity began, quite apart from other questions of a lack of independence and possible harm to the life and future of the pregnant woman. This might help some people in deciding whether to have an abortion or not, legally or otherwise, since nerve and brain activity and heart beats start long after conception, and breathing air directly does not start until birth. Another major question is the "right to die", especially when terminally ill, or if one wishes to risk sacrificing oneself to save others. It is a decision not lightly to be taken, and I feel deeply that I have that right, and so should others.

This account has not included any mention of the postulated activities of the many gods, goddesses, devils, spirits, etc. that are considered by the adherents of the many religions held by people on Earth to have been central or important in creating the Universe, the Earth, life and human kind. This is because there is no scientifically accepted evidence for the existence of these entities, their heavens and hells, or that there are any purposes in the Universe other than our own and that of other living beings.

Almost certainly we are the only human life in the observable Universe, and we are not yet sure that life on Earth, of which we are a part, is not the only life there is in our Milky Way Galaxy and even in the whole observable Universe. We are thus very, very precious and should not be fruitlessly wasted or destroyed in either peace or war.

The material from which our bodies are made was forged in enormous nuclear fires in the Big Bang and in stars many billions of years ago. Surely we must make every effort to prevent our bodies and our DNA from being incinerated in the relatively small, but still very lethal, nuclear fires that mankind now knows how to make, but perhaps may not be able to control. How to control this is one of the most important problems that we face. I hope we solve it.

Another problem is how to get a proper balance between the size of the human population and the energy sources available in an unpolluted world, where the political systems are such that everyone can develop themselves physically and intellectually in ways that don't harm others but leave them happy and fulfilled, without the misery, poverty, medical problems and wanton destruction of ourselves and other species that we see now. That will surely take a long time, but nothing is more important.

(5/30/91)