by Dov Michaeli

What is life? A recent opinion article inThe Scientist” By Edward Trifonov of Haifa University, Israel, transported me back to my junior year in high school. They used to have public lectures given by university professors on all matters scientific. Yes, people used to go to such “shows” in those days in Israel; the hall, which as I recall could sit about 500 people, was three-quarter full, and the audience was a mixture of union members (they got subsidized tickets), soldiers (their tickets were complimentary), shopkeepers, clerks, some obviouly religious, and one high school nerd. In short, regular people. The subject was “What is Life?”. How many people would this subject draw today?

What follows is a somewhat “scientific” description of of the inquiry into the the subject, but if you stick with me you’ll arrive at a surprisingly “humanistic”, dare I say poetic, conclusion to the story.

The definition of life has occupied human beings since the days they had time to think about their existence. Mythologies of the earliest cultures grappled with the issue. The Bible dealt with it in the story of the creation. The classical Greek philosophers spun theories out of deep analytical thoughts, or maybe just plain navel-wathching. My favorite is Empedocles (430 B.C), who speculated (it wasn’t much more than that) that cosmos and all life within it are made up of  of a combination of four eternal “elements” or “roots of all”: earth, water, air, and fire. Now,  before we dismiss this “theory” willy-nilly, we’ve got to give him some credit. What he is actually proposing is life is a product of some combination of basic elements of  nature. He couldn’t possibly know about atoms and molecules, so he surmised that his “eternal elements” (meaning indivisible, immutable, permanent) are the basic building blocks of life. But the overarching idea is still valid: life is made up of basic elements.

Preceding Empedocles by a generation, Democritus (460 B.C.) proposed  that the essential characteristic of life is having a soul (psyche).  He thought the soul was composed of fire atoms, because of the apparent connection between life and heat, and because fire moves. Before we dismiss this philosopher as an idle navel-gazer, consider this: The theory of Democritus and Leucippus (his mentor and co-author) held that everything is composed of “atoms”, which are physically, but not geometrically, indivisible; that between atoms lies empty space; that atoms are indestructible; have always been, and always will be, in motion; that there are an infinite number of atoms, and kinds of atoms, which differ in shape, and size. And how about anticipating Darwin and the science of Anthropology?  He suggested that humans originally lived like animals, gradually developing communities to help one another, originating language, and developing crafts and agriculture. Amazing analytical powers!

C’est ne pas le homeless

These two Greek philosophers established the two schools of thought that debated the nature of life for the next 22 centuries. As late as the end of the 19th-early 20th century one school of thought argued that living organisms are made of inanimate matter and a soul (Henri Bergson, Friedrich Nietzsche), and the other that life is essentially mechanistic and there is no need to postulate any additional inanimate forces such as a soul (Descartes, in the 17th century).

As almost always in science, the reductionist approach gets us closer to the truth. So the key to life may be found in the simplest organization of molecules that a living organism can function.

Sounds straightforward, until you start asking questions like, what is that simplest form? It is not enough to have amino acids or nucleotides; they cannot fulfil the attributes of life, like metabolism, growth, replication, adaptation. For that we need a genome, an assembly of genes that constitute the “instruction manual” for the living organism. When we say genome, by association we think DNA. That was true until about 50 years ago, when accummulating evidence showed that  RNA is able both to store genetic information, like DNA, and to catalyze chemical reactions, like an enzyme protein. It may therefore have supported pre-cellular life and been a major step in the evolution of cellular life.  So preceding our “DNA world” there was an “RNA world”.  Do we stop here in our quest for ‘life’? Not quite.

In a seminal 2011 paper titled “ Role of Everlasting Triplet Expansions in Protein Evolution”  Zohar Koren and Edward Trifonov made the observation that both genes and genomes appear to have emerged originally as simple tandem repeats, with subsequent mutations increasing their complexity. “Tandem repeat” simply means that three nucleotides in the DNA sequence repeat themselves in different permutations, for instance: CCG, GCC, CGC, CCG, GCC, and so on. What they found in their analysis is that all genomes probably started as those triplet repeats and then acquired more and more mutations leading eventually to the creation of a functional gene.

The implication of this discovery verge on the philosophical. As Trifonov states ” One can view a genome as molecular habitat for emergence of “new life” in the form of expanding and mutating simple repeats. In that sense, and under the above minimalistic definition, life never stopped emerging, starting some 4 billion years ago with replicating RNA, and continuing to this day within the genomes of every living organism.

Think of it: life never stopped emerging. This is wonderful poetry arising from the deceptively dry scientific endevour.


Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.


  1. Hatha yoga groups poses as either water, earth, fire and air. The real purpose of Hatha yoga is to find your soul, however you define it. Yoga poses were developed by people looking at the natural world and copying what they saw in nature. Seems like the Greeks and the yogis were on the same path – self discovery.

    • Jim,
      It is indeed curious that such disparate, and geographically distant cultures would end up describing life in the same terms. There is another explanation, though, than just coincidence. There is quite a bit of evidence that the the Phoenicians and the Hebrews were trading with the ancient Hindus, both through land routes going through the Arabian desert and through maritime routes. The phoenicians traded with the Greeks, and in fact introduced them to the written alphabet. And through this route there was a diffusion of Hindu and Budhist concepts to the Hebrew and Greek culture.


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