What is Life, Part III

Even armed with NASA’s pragmatic definition of life, it is almost impossible to know what Earth’s very first life form was like. One very real possibility is that planet Earth’s earliest life may have been vastly different from anything we know today. Many experts suspect that the first living entity was not a single isolated cell, because even the simplest modern cells incorporate bewildering chemical complexity.

Most researchers assume that the first life form did not use DNA, given its exceedingly intricate mechanism. It may not even use proteins, which today act as the chemical work horses of cellular life. Naturally, experts propose different ideas regarding Earth’s first life form. Geologists propose that the Earth’s earliest living entity which fits NASA’s definition was an extremely thin molecular coding on a rock. It is easy to imagine the simple behavior of such flat life. It would have just spread across minerals in a layer of only a few billionths of a meter thick. Flat life would have exploited energy-rich mineral surfaces, and slowly spread outwards, from rock to rock.

Whatever that life form looked like, it must have arisen from chemical reactions among the oceans, the atmosphere and rocks.

Our Tendency to Dichotomize

The French anthropologist Claude Lévi-Strauss investigated the mythologies of many cultures. In the process, he recognized deep human tendency to reduce all sorts of complex situations to oversimplified dichotomies. We tend to divide people into friend and enemy. We divide the afterlife into heaven and hell. We divide actions into good and evil. We all know that most situations are much more subtle and complex.

The long history of sciences reveals that scientists are in no way immune to the trap of this kind of oversimplification. In the 18th century, for example, one group of naturalists called the “neptunists”, favored a watery origin for rocks. They fought many battles with the “plutonitsts”, who favored heat to describe the origin of rocks. It turns out that both were right. Rock sometimes form by the action of water, and sometimes by the action of heat, and sometimes even by a combination of both.

A similar contentious and misleading dichotomy raged between 18th century geologists was the one between catastrofists and uniformitarians. Catastrofists espoused the view that brief and cataclysmic events like earthquakes and floods dominated the geological history of Earth. Uniformitarians countered that geological processes are for the most part gradual and ongoing. Again, both groups were correct. Geological changes occur gradually over millions of years, but discrete catastrophic events, like the impact of big asteroids, also influence Earth’s history.

Similarly, there was a time when sharp distinctions were seen between plants and animals, and between single celled and multicellular organisms. Now, those sharp distinctions have become blurred.

I believe that any attempt to formulate an absolute definition of life, one that tries to differentiate between “life” and “non-life”, must represent a similar false dichotomy. Here’s why. It is obvious that the first living cell did not just appear fully formed with all its chemical complexity and genetic machinery. Rather, life must have arisen through a stepwise sequence of emergent events. I see life’s origin as a process of increasing chemical complexity.

What now looks to us as a divide between non-living matter and living cells tends to obscure the fact that the chemical evolution of life occurred in a stepwise sequence. Most of that history is lost, because when modern cells emerged, they quickly consumed all traces of the earlier stages of chemical evolution. They ate the evidence.

Our challenge is to use every available clue to establish a progressive hierarchy of emergent steps, leading from a prebiotic Earth rich in organic molecules to clusters of molecules, to self-replicating molecular systems, to encapsulation and membranes, to cellular life.

This view of life as a stepwise sequence of emergent events also informs the central question “what is life”. Any attempt to define the exact point in which a system of gradually increasing complexity becomes alive is intrinsically arbitrary. Where you or anyone tries to draw such a line is a question more of perceived value than of science. For example, if you value the intrinsic isolation of each living thing, then, for you, life’s origin probably would correspond to the stage when encapsulated cell membranes appeared. Perhaps you most value life’s ability to reproduce. If so, self-replication would be the demarcation point for life.

Many scientists today place special value on information as the key to life. They argue that life began with a genetic mechanism to pass information from one generation to the next. In this context, the question “what is life” becomes fundamentally a semantic question. It’s a subjective matter of taxonomy, rather than any absolute divide. Nature supports a rich variety of complex emergent chemical systems. Scientists are learning to craft a wide variety of those systems in the laboratory as well, but no matter how curious or noble the behavior of these systems may be, none of them comes with a label “life” or “non-life”.

Don’t get me wrong, labels are extremely important. They are vital for effective communication. However, I think that defining life is not helpful because there is so much we don’t know. Early attempts to classify animals purely by their color or shape ultimately failed. Similarly, early efforts to classify chemical elements according to their physical state (solid, liquid or gas) were unhelpful in elaborating a chemical theory.

We are in no position to define life. We don’t know if life’s biochemistry is highly constrained, or if there are many chemical solutions to life. It is much better at this point to keep an open mind and just describe the chemical characteristics of whatever we find.

What is Life, Part II

So, here we continue with the “what is life” issue. A general definition that’s able to distinguish all imaginable living objects from the diversity of non-living objects remains elusive. Even today, we know relatively little about the cellular life on Earth. It’s been said that a shovel full of soil would contain hundreds of microbial species that are unknown to science. That’s not to mention the vast range of plausible non-cellular life forms that might be discovered elsewhere in the universe.

I have to conclude that endorsing any sweeping definition of life based on so little knowledge is like trying to define music after listening to a single Elvis Presley song.

Top-Down and Bottom-Up

So, what do we do? As you can imagine, scientists crave a definition of life. Such a definition remains elusive, but they adopted two complimentary approaches in their efforts to distinguish that which is alive from that which is not. On the one hand, many scientists have adopted the top-down approach. Top-down refers to the effort to scrutinize all modern living organisms and fossil entities to identify the most primitive forms that are or were alive. It turns out that primitive microbes and ancient fossils have the potential to provide relevant clues about life’s early chemistry.

I must say that I find this top-down strategy inherently limited. At least so far, all known life forms are based on biochemical sophisticated cells containing complex molecules, including DNA and proteins. Any definition of life based on top-down research is limited to what appears to be modern biochemistry.

By contrast, a small but determinate army of investigators adopt the so-called bottom-up approach. The principal objective of bottom-up researchers is to device laboratory experiments to mimic the emergent chemical process of environments in the ancient Earth. Ultimately, the bottom-up goal is to synthesize a self-reproducing chemical system in the laboratory. That’s an effort that might help clarify the ancient transition from non-life to life.

You might think that all bottom-up researchers hold a common view of what would constitute the first synthetic life form, but research actually leads to an amusing range of diverging opinions regarding what’s alive. Each scientist has a tendency to define life primarily in terms of his or her own chosen chemical or biological specialty. One notable group focuses on the origin of cell membranes. To them, life began when the first encapsulating membrane appeared.

Other well respected research teams study the emergence of metabolic cycles. Those are the process by which cells gather and use atoms and energy. Naturally, for them, the origin of life coincided with the origin of metabolism. Lots of other groups investigate the origin of primordial RNA, which many experts consider to be the first genetic material. For them, the origin of RNA is equivalent to the origin of life.

There are many other workers who focus on viruses, minerals or even artificial intelligence; and each researcher advocates his own definition of what constitutes life.

NASA’a Definition

Into this mix, quite a few philosophers, theologians and science fiction writers have injected a variety of more abstract views and speculations on the possible phenomena that might said to be alive. The possibilities seem endless: counscious clouds in space, high temperature silicate minerals, a self aware internet. Such proposals sound at times farfetched, but there is so much we don’t know.

Consequently, the scientific community, with the support of NASA and other governmental agencies, holds regular meetings to explore the definition of life. After all, if one of NASA’s primary missions is to look for life on other worlds, then we’d better have a clear definition for planning future missions. It’s amazing how the “what is life” question sparks passionate arguments.

Gerald Joyce, a biologist working at the Scripps Research Institute, developed a widely accepted definition for life, at least in the context of NASA’s space exploration. He concluded that “life is a self-sustained chemical system capable of undergoing Darwinian evolution”.

According to this opinion, life incorporates three distinctive characteristics. First, all life forms must be chemical systems. That means that computer programs or robots are not alive. The second characteristic is that life grows and sustains itself by gathering energy and atoms from its surroundings. That’s the essence of metabolism. Finally, all living entities must display some sort of variation. According to the concepts of Darwinian evolution, natural selection of more fit individuals inevitably leads to evolution and the emergence of more complex entities. A system that does not have the potential to evolve does not fit this definition of life.

There’s still so much we don’t know, but this NASA inspired definition is probably as general, useful and concise as anyone is likely to come up with, at least until we discover more about what’s actually out there.

What is Life

We usually think that life is easy to recognize, that it would be obvious if something is alive or not. It turns out that is not that easy. The question “what is life” is asked in very different contexts by different groups of people. For centuries, theologians have hotly debated life’s definition and relation to the beginning of human life. Does life start at the moment of conception? Or does it begin when the brain’s first response, or with the heart’s first beat? In some theological doctrines, life commences not with a physical process, but rather at the unknowable supposed instant known as “ensoulment”.

At the other end of our human journey, doctors, lawyers and politicians require a definition of life in order to deal ethically with patients with brain death. As we saw with the contentious case of Terri Schiavo (the woman who spent more than a decade in comma), lots of people have intense and emotional views on this issue.

In sharp contrast with these ethically difficult and emotionally charged issues, are the more abstract ongoing scientific efforts to define life. A must read book on the origin of life is Noam Lahav’s “Biogenesis”, which was published in 1999. Lahav’s works in the Hebrew University at Jerusalem, and he has been involved in origins research for almost 40 years. His book is filled with insights, as well as countless technical details. As part of his text, he prepared an appendix with lots of different scientific definitions of life, which are written by over 48 different authorities.

These definitions span 150 years period, from the mid 18th century to the late 20th century. It’s worthwhile thinking about a few of those:

- Alexander Oparin: he reflects the view of many authorities. Life can be defined by a combination of traits. He says: “Life may be recognized only in bodies which have particularly special characteristics. These characteristics are peculiar to living things, and are not seen in the world of the dead.” What are these characteristics? In the first place, there is a definite structure or organization. Then there is the ability of organisms to metabolize, reproduce others like themselves and the response to stimulation. The problem is that Oparin’s characteristics are not unique to life. Many non-living systems have definite structure and organization (think about your car or your PC). Oparin says that organisms obtain energy from their surroundings to grow and reproduce, but fire does that also. Many natural non-living systems, such as flowing water or drifting clouds, respond to stimulation.

- John Desmond Bernal: an influential 20th century biological theorist, who provides a longer list of characteristics. He says: “Life is a partial, continuous, progressive, multi-form, and conditionally interactive self-realization of the potentialities of atomic electron states”. I don’t know about you, but that definition seems to be hopelessly fussy and unhelpful in distinguishing life from non-life.

- Stuart Kauffman offered a more promising definition of life in 1993. He claimed: “Life is an expected collectively self-organized property of catalytic polymers”. Embedded in this statement are a couple of key ideas. Kauffman said that life is self-organized. That is, life is a collective emergent phenomenon. He also states that life relies on chemicals to promote the production of more copies of themselves. In Kauffman’s view, life might be a relatively simple collection of self-replicating chemicals. That includes much more primitive entities than modern cellular life.

- John Maynard Smith proposed a short and persuasive definition of life in 1975. He describes life as “any population of entities which have the properties of multiplication, heredity and variation”. Here Smith introduces two key ideas and thus comes closer to a useful set of criteria. First, all life possesses information that’s passed from one generation to the next. That key idea of heredity may not be unique to life, but it is certainly one of life’s most important characteristics. Second, life displays variations. In life, heredity isn’t perfect like a Xerox copy. Variation, in turn, leads to evolution by natural selection.

Lahav goes on and on citing definitions of life, and remarkably, no two definitions are the same. I think you can see this lack of agreement might represent a problem for those of us who search for signs of living organisms in other worlds, as well as for anyone interested in the origin of life. After all, how can you be sure that you discovered life, or that you figured out the process of life origin, when you can’t come close to defining what exactly life is? In spite of generations of work by hundreds of thousands of biologists, we still have no universally accepted definition.

To be continued…

Spontaneous Generation

What is spontaneous generation? Why did people accept it? Let’s look back at old Greece. By the 4th century B.C., a significant debate regarding the nature of matter arose between the school of Democritus and Aristotle. Democritus argued for a world of atoms: tiny particles that combine to form the variety of matter in our world. In his view, life arose spontaneously through the combination of atoms of soil and fire. Aristotle opposed this atomic hypothesis with its supposed chance mixing of elements. Nevertheless, he too embraced the spontaneous and naturalistic generation of life on Earth. At the core of this belief was the doctrine of vitalism: the idea that every organism is imbued with a life force different from the forces that act on inanimate matter. That’s the way things remained for almost 2000 years.

In the 17th century, the theory of life’s spontaneous generation was accepted knowledge. In fact, the only real challenge to the Aristotelian view came from a few theologians who argued that all living things were formed by God during the first days of creation. A famous quotation by Jan Baptiste van Helmont(1577-1644) exemplify the common views at the time: “If you press a piece of underwear soiled with sweat together with some wheat in an open mouth jar, after about 21 days the odor changes and the ferment, coming out of the underwear and penetrating through the husks of the wheat, changes the wheat into mice." Van Helmont was describing the spontaneous generation recipe for mice.

Redi’s Experiment

The first experiment to challenge this conventional wisdom was performed by the Italian physician Francesco Redi (1626-1697). Redi tackled the problem of preserving raw meat, which deteriorates rapidly on air. In the first part of his experiment, he used open containers. If you let flies land on the meat, then maggots would invariably appear a few days later. In the second part of the experiment, he covered the containers to protect them from the flies. In that case, no maggots grew. He described all these studies in his influential book “Experiments on the Generation of Insects”. Redi’s discovery that maggots only appear in meat contacted by flies let him to conclude that flies, not spontaneous generation, cause maggots.

Redi’s experiment was brilliantly conceived and executed, and it provides us with one of the earliest examples of the scientific method. Even so, Redi accepted the idea that microscopic organisms arise spontaneously all around us all the time.

For the better part of the next two centuries, well until the 19th century, the doctrine of vitalism was widely accepted. Many naturalists felt that this “life force” was not only different from the well studied forces of the non-living world, but also that it was inherently unknowable. The influential philosopher Immanuel Kant (1724-1804) wrote: “It is absurd for men to hope that another Newton will arise in the future who shall make comprehensible by us the production of a blade of grass according to natural laws which no design has ordered”. In other words, the origin of life is an ongoing supernatural phenomenon.

Why People Believed It

Why so many people accepted this idea of spontaneous generation? Think for a moment about your own experience and you’ll get a feeling for why this idea isn’t such a strange point of view. Worm-like maggots form in meat and every spring new leaves appear and flowers blossom in season of renewal. It is not surprising that many people accepted unquestioningly that life arises trough spontaneous generation.

This view continued well into the 19th century, when there were an increasing number of respected deniers of it. One important factor in the spontaneous generation controversy was the 17th century invention of the microscope and the surprising discovery that microscopic life is everywhere. Microorganisms, however, fail to resolve the controversy. After all, anyone who favors spontaneous generation could say that microbes are just one more manifestation of the life force.

As anyone who does experiments would tell, the interpretation of data is seldom unambiguous. This fact of scientific life was highlighted by a marvelous 18th century exchange. Lazzaro Spallanzani, who was opposed to spontaneous generation, explored the subject by comparing flasks filled with nutrient rich water. He boiled flasks that were sealed, and he observed that those flasks remained sterile indefinitely as long as they remained seal. However, when he boiled unsealed flasks, they rapidly took on a cloudy appearance due to the growth of microbes. Spallanzani concluded that ubiquitous microscopic life forms must have contaminated all of his unsealed flasks.

Spallanzani’s conclusions were challenged by Englishman John Needham. Needham agreed that boiling kills microbes, but he found that microbes soon reappear in abundance when the flask is cooled. That was a result that led him to a very different conclusion. He claimed that this new population of cells arose by spontaneous generation.

Naturally, Spallanzani countered that Needham’s new microbes came from the air contamination. To prove his point, he undertook a new set of experiments in which he pumped air out of his flasks, and then boiled the water. No microbes appeared in these trials. Needham countered with a new argument: It was a property of the air, not the water, that must carry the life force.

Today, we’re likely to react to this historical incident with a rather biased worldview. It seems obvious to us that Spallanzani’s conclusions about microbial contamination were correct. It seems just as obvious that Needham’s support of spontaneous generation was misguided. But put yourself in the place of an impartial observer of the time. You wouldn’t be that familiar with the nature of bacteria, nor with their ability to replicate rapidly. Faced with these conflicting claims you would have had a hard time choosing between invisible microbes on the one hand, an invisible life force on the other. Indeed, both arguments were internally consistent, so doubts remained.

Pasteur Takes Care of the Issue

By the 19th century, experiments had clearly disproved spontaneous generation of larger organisms, such as mice and flies. The origin of microbes was still a matter of much debate. It was the great French chemist Louis Pasteur (1822-1885) who resolved the issue once and for all. Pasteur was a giant of experimental research and he contributed many fundamental ideas to biology.

In the 1850’s and 1860’s, Pasteur helped to abolish belief in vitalism and the theory of spontaneous generation with a brilliant series of experiments on sterilized solutions. Like others, he prepared a nutrient rich sugar solution and poured it into several beakers. As with previous researches, one set of beakers was tightly sealed to prevent any contact with ambient air. Pasteur’s innovation was to prepare other beakers that were left open to the air but with a narrow twisted neck. Thus, the sugar solution was in contact with the ambient air, but microbes were unable to traverse that long glass passage.

Pasteur also ran a serious of controlled experiments by leaving beakers wide open or contaminating them with ordinary dust. Over the course of several years, she showed that boiled water, if isolated from air microbes, remains sterile indefinitely. His conclusion: only microbial contamination causes new growth; cells do not arise by spontaneous generation.

This unambiguous result had more than purely intellectual appeal. His discoveries and subsequent perfection of techniques to sterilize sealed containers of food and beverage proved to have a tremendous practical use. This helped to reduce the incidence of infectious diseases.

In the course of this elegant work, Pasteur also contributed in a significant way to the study of life’s origins. By experimentally verifying the dictum that no cellular life can occur without prior cellular life, he pushed back life’s origins to an inconceivable remote time and place. If life does not arise spontaneously, then where and when did it come from? How could anyone make useful observations and make experiments to study an event so ancient and inaccessible?

Mitochondrial DNA

In women there is a DNA sequence that is passed on just through them. This is the sequence called mitochondrial DNA. The fact that is passed only by mothers to their sons and daughters has to do with the mechanics of fertilization. The sperm is extremely small compared to the egg. The sperm has its DNA concentrated in a very small area, the head. That’s indeed the only part of the sperm that gets into the egg. Included in the parts that don’t get into the egg is an organelle called mitochondria, which has a very small amount of DNA.

A molecular clock looks at differences between DNA sequences or proteins between two organisms, and then calculates back to their last common ancestor. If we have 20 differences between them, and their last common ancestor lived 20 million years ago (according to fossil evidence), one difference per million years is piling up. These differences are caused by non-selected mutations that are simply piling up over time. Then, considering a constant rate of mutations, if we have two organisms that have only 5 differences between them, we can infer that their common ancestor lived 5 million years ago.

If we want to make this argument for human genetics we have to use DNA sequences that are not subject to natural selection. If they are selected they would not be piling up over time. The sequences we can use in humans for looking at evolutionary clocks are sequences on the Y chromosome that is passed through males, and the mitochondrial DNA that is passed only through females. Both of these DNA sequences are not subject to selection.

First, let’s look at the Y chromosome sequence. On the Y chromosome are regions that are non-selected and mutate at a constant rate. The Y chromosome has very few functional genes, the most notable of which is that one that determines maleness. If we look at these DNA sequences, my brothers and I probably have identical sequences. Our last common ancestor is our father. We didn’t give our DNA much time to change; we just got it from our father.

My first cousins and I have a common grandfather, so maybe there might be a change. My third cousins might have slight differences, because we have a common ancestor longer time ago. And so on, to the most diverse humans.

A survey of Y chromosome sequences in different men from all over the world was conducted, and the group with most diversity, who obviously had a common ancestor the longest time ago, was from Africa. That says that humans’ last common ancestor for this particular sequence lived in Africa. How long ago? We can calculate the rate at which it changes. The Y chromosome “Adam” lived, according to Spencer Wells, 60000 years ago.

This is not necessarily the first man, but the one who’s Y chromosome was passed on uninterrupted to the current Africans.

Mitochondrial Eve

The small sequence of DNA in the mitochondria is not subject to natural selection and is passed only from mother to offspring. With mitochondrial DNA we can do the same analysis as with the Y chromosome in males. We can look at sequences of DNA, compare Africans to Africans, Asians to Asians, and so on. Using this method, we find that the greater diversity in mitochondrial DNA is found in Africans. The mitochondrial “Eve”, who’s DNA has been passed uninterrupted all the way to us lived about 150000 years ago. Wait a minute; she didn’t live at the same time as Y chromosome Adam. That’s just because of who passed on what. If a woman doesn’t reproduce, her sequence doesn’t get passed on.

We don’t have the first man or the first woman, but this is an interesting calculation. Maybe it is a pointer to where we originated.