The chicken and the egg of life

Scientists are looking for the minimal cell sufficient to function as an independent living cell. In any case, the most basic question - how life was created in the first place, remains one of the open questions in science. Life as software

By: Avi Blizovsky, Galileo

They are inside us, and they fill the earth around us in every possible corner, from bacteria to elephants, from algae to redwood trees. Life. But most of those involved in the scientific field known as "life sciences" examine this or that aspect of life and accept life itself as a given. Sometimes it is a search at the basic level of this or that mechanism operating inside the living cell, such as ubiquitin, which oversees the breakdown of proteins that are not needed, as discovered by this year's Nobel Prize winners in chemistry - Professors Avraham Hershko and Aharon Chachanover from the Technion and Irving Rose from the United States. Some are looking for the function of this or that gene, and there are also animal lovers who follow their behavior.

But the most basic question - how life was created in the first place, remains one of the open questions in science. We know, or at least we have theories that have stood the test so far, how the universe was created and what was in its first seconds and also how life developed after it was created, but in the middle there is a huge black hole in knowledge, waiting to be filled.
Life is a collection of processes, of building and splitting molecules and of ceaseless genetic changes. The basic features of life are: reproduction within heredity, development and metabolism. These processes require external material and energy resources; That is - life involves the utilization of energy and matter from the environment and turning them into the configuration of the living creature (the organism) itself. This process of turning external matter into living matter is metabolism.
Four chemical elements mainly, out of the approximately 85 stable elements existing in nature, serve life: hydrogen, carbon, nitrogen and oxygen. These four, together with other elements, which are found in the body in smaller quantities, such as: phosphorus, sulfur and iron, are the components of many different combinations of living substances.
The special properties of the element carbon are what make it unique to life, at least as we know it. The property that makes it particularly important is its ability to form long chains, consisting of millions of atoms. This ability is due to the fact that the carbon atom has four bonds, and its ability to form complex molecules. The second important component is water (H2O) - a molecule with two hydrogen atoms and one oxygen atom. Water is essential for basic life reactions - a significant part of the chemical processes in the bodies of animals takes place in an aqueous solution.

proteins and nucleic acids
Two types of molecules are responsible for the development and reproduction of animals and plants: proteins and nucleic acids. These two types of molecules are polymers, meaning - molecules built as long chains, consisting of monomers, which are relatively small and simple units. The properties of the polymers are determined by the particular arrangement of the monomers.
The proteins are responsible for the structure of the living cell and most of its actions, and they consist of a small number of monomers, called amino acids. Only about twenty such acids, in various combinations, are the building blocks of the huge number of proteins that make up the living matter on the face of the earth. In every nucleus of every cell, both in animals and in plants and bacteria, there are very long molecules built as a double helix: DNA (DeoxyriboNucleic Acid=DNA).
In addition to this, there is also a nucleic acid of the RNA type (RNA = ribonucleic acid); Exceptions to this rule are the viruses, which have only one type of nucleic acid, DNA or RNA. These molecules form a kind of book, written in the four-letter alphabet, that is, four basic units, assembled as a long chain. Their number and order determine whether the creature will be a bacterium, a frog, a fish, a monkey or a human... in other words, they are the software.

All together, and each one separately
But all these molecules together, and each one individually, are still not life. Something had to "breathe life into them". There is also the basic problem that in today's living cells, RNA is needed to dictate the order of the amino acids in the protein chain, but it is impossible to build RNA without the help of protein enzymes. This is like the chicken and the egg problem.
And here recently, at the beginning of December 2004, we were informed of an interesting experiment in this arena. Researchers at Rockefeller University in the United States have taken what they call the first step in principle towards creating a type of artificial life. They created a synthetic vesicle that expresses genes, and resembles a crude type of biological cell.
All the components of what the scientists call "vesicle bioreactors" come from a variety of branches of life. Cell membranes are made of lipids from a hen's egg; And the enzymes are from the common bacterium E. coli, stripped of its genetic material. The "heart" of the mechanism includes ready-made components of the biological machine needed to produce proteins, which were provided by the bacterium. When genes were added to the machinery, the cell components began to produce proteins, just as a normal cell does. It should be noted that this kind of combination is very common, and is applied in many biological laboratories, but the innovation was in the inclusion of these components in an "independent" fatty vesicle.
A gene that causes phosphorescent green color is taken from a species of jellyfish. The cell glowed as a result of the presence of the protein, which proves that the genes were indeed transcribed into RNA and translated into protein. Using a second gene, from the bacterium Staphylococcus aureus, the researchers were able to "convince" their cells to produce a protein that builds pores in cell membranes. This allowed nutrients from the environmental soup to penetrate, so that the cell could function in some cases for several days.
Albert Libchaber, who headed the project, says that the bioreactors are not living beings - but perform basic chemical reactions, which can also take place in a biological fluid without cells, but the researchers nevertheless took one step forward into a new field, known as synthetic biology, whose goal is to redesign A whole organism or create it from scratch.

Minimal bacteria
In a different approach to this problem, Craig Venter, who heads the commercial company that decoded the human genome at the same time as the American government project, recently tried to condense a bacterium to the minimum of genes necessary for survival.
Liebshaber's hope is to build a minimal synthetic creature, with a cell membrane and a gene system, that can survive as a living cell (and see also: "The Craft of Life", Galileo 53). "As these structures become more and more reminiscent of life, we will have to start rethinking the nature of life. This is a philosophical question," said Dr. Liebshaber in an interview with the BBC. "For me, life is just another kind of machine - a machine with a computer program. No need to add more. However, not everyone adopts this point of view."
Livshaber chooses to open his article with an example that is not from the field of biology. "In his theory of automatons, John von Newman compared calculating machines to living beings. The self-replicating ability of the automaton was discussed and linked to a Turing machine-like principle. At the same time, biological science raised the question of how to engineer a minimal cell that would also replicate. Building a protocell will give us clues as to how self-replicating systems appear, but may also help researchers engineer self-replicating machines. Although several theoretical models have been proposed, attempts to simplify the process have not been successful.
Based on the concept of a minimal cell and one possible definition of life - a critical step in building an artificial cell is the creation of a closed enclosure that exhibits the ability to exchange materials and use external energy that comes through nutrients, through a semi-permeable membrane. In fact, enclosing active ingredients in a bubble in a two-layered environment of phosphorylated lipids can be considered a big step in building an artificial cell."
And Liebshaber adds: "Two complementary approaches were generally considered to build an artificial cell. The "bottom up" approach begins with the construction of a minimal cell from the molecular level; The world of RNA is one of the main models for this. In a "top-down" approach, scientists try to create a minimal cell by reducing the bacterium's genome to the minimal set of genes or proteins. In this article (by (Vincent Noireaux and Albert Libchaber), the first step was to assemble a mesoscopic bioreactor (meaning not tiny, but not that big either) using a membrane wrapping of a phospholipid vesicle that performs all metabolism outside of a cellular environment."

What does this actually mean?
Prof. Doron Lantz, from the Department of Molecular Genetics at the Weizmann Institute and a colleague of Liebshaber, answers our basic question, what is the meaning of the experiment, in light of the fact that over fifty years ago (in 1953) the results of an experiment conducted by the American chemist Stanley Miller (Miller) under the guidance of the British Harold Yuri were published (Urey). Miller put gases in a test tube that he believed represented the composition of the primordial atmosphere, passed an electric current through them (imitating lightning) and checked the results; To his delight, amino acids were found in the test tube, which are the basic component of proteins.
"Amino acids by themselves are not life, and don't even come close to being life." says Lantz. "The claim of many people today is that the scientists did not ask the right question at all. They did not ask how life is created, but how the building blocks of life are created. What is it similar to? To a situation where you would ask how a watch was made, and they would tell you about how the metal from which the gears are made is made. The material itself is not interesting, but the shape and the relationships between the parts."
"The experiments that create the minimal cell are closer to answering this question, but perhaps go a little too far. The criticism that can be made about them is that if materials such as DNA and protein enzymes are taken from a living being, what good did the sages do in regulating them. But here they try to at least define a collection of all kinds of materials, which together have the properties of a living cell. If we compare this, for example, to the road from Tel Aviv to Jerusalem, then Miller's experiments bring us roughly as far as the Genot interchange, and the experiments on the minimal cell are already in the Sakharov Gardens, and no one knows the route of the road between these two points.

Have the scientists already reached this minimum value?

"not for now. The work we do - albeit in a computer simulation - is actually a compromise between stacked and overly simple building blocks, and overly complicated systems that have too many of the materials found in the cells. We are trying to find some kind of golden trail, which might give a first clue about the missing section of the road."
"Under the conditions that existed on the ancient Earth a little less than four billion years ago, the building blocks of the molecules of life could indeed have created life. But many scientists claim that the chances that the small units (the monomers) will join together and produce a long key molecule (polymer) such as RNA that is capable of self-replication are very low. What, then, was the first step that ultimately led to the creation of living cells?" says Lantz.
"We decided to look for simpler molecular structures, capable, under the conditions that prevailed on the surface of the ancient Earth, of replicating themselves. According to our model, life arose from the organization of structures made of small molecules of lipids, such as those that make up the living cell membrane, and also the vesicles of Liebshaber. It has been shown that such fats could also have been formed under the conditions that prevailed on the ancient Earth. The computerized model presents a new phenomenon that belongs to the field of complex systems: the clusters of fat molecules show the ability to store information and replicate."

How does this happen?

"It is possible to base an evolution-like process on the fact that the entire cluster 'sucks' fat molecules from the environment and grows while maintaining its original composition. This happens due to a network of mutual help between the molecules, similar to a human society, in which people of different professions organize themselves into a collective entity with the power of adaptation and self-preservation. When the collection of molecules exceeds a certain size, the cluster splits into two parts (a well-known phenomenon in the world of lipids), and this is actually the simplest possible mechanism for self-replication. And this, without the involvement of DNA or RNA. Later, in Darwinian evolution, these primitive clones will go and be perfected, and nucleic acids and proteins will appear."
Lancet's theory has appeared since 1998 in several respected journals, but it is not the only innovative theory. Paul Davis's book "The Fifth Miracle - The Search for the Origin of Life" recently appeared in a Hebrew translation (Maariv Publishing House). A significant part of the book is devoted to a new radical theory about the origin of life - the super bacteria theory. "Since the days of Darwin," Davis writes, "there have only been two comprehensive theories about biogenesis (the scientific term for the concept of the origin of life).
According to the first, life began by chemical self-association in a watery medium somewhere on Earth - Darwin himself wrote about a 'warm little puddle'. The second is a version that life came to Earth from space, in the form of microbes that are already alive - a theory known as the panspermia hypothesis. In the latter scenario, the ultimate origin of life remains a mystery. In recent years, however, more and more evidence presents a third alternative, which holds that life began inside the Earth.
Not in the very deep part, of course, but most likely under the seabed, where the geothermal activity creates cauldron-like conditions. The intense heat and chemical power of the subterranean region, especially near volcanic vents, will instantly kill almost all known organisms. However, such an environment was ideal for biogenesis, and scientists have discovered bizarre microbes that still live in these hot places today, at temperatures well above the boiling point of water. The super bacteria are actually living fossils, which have survived since the dawn of life."

They know evolution - the beginning of life