Could life have started with Simplicity?

One of the perplexing questions people ask in the origin of Life is how did such complexity ever evolve from a simple broth of chemicals in the prebiotic world. The first person to ever attempt to try to answer it was Harold Urey and Stanley Miller who created a chemical soup of ammonia (reduced Nitrogen), methane (reduced C), and hydrogen (should be present in a reduced atmosphere) and subjected the soup to electric discharge (simulating lightning and solar radiation). This experiment was performed in the 1950s and was done to simulate early Earth condition. After this electric discharge passed through the soup, simple amino acids and sugars and the raw materials for nucleic acid bases such as adenine were found to be created in this mixture [1]. These are all the raw ingredients for biochemistry to start hence bringing evolution of the origin of life into the realm of experimental science for the first time. Even though, the conditions of early Earth have come into question since then, Urey and Miller deservedly received a Nobel prize for the novel aspect of their work. In fact, the experiments were repeated recently with nitrogen gas instead of ammonia, carbon dioxide instead of methane, and hydrogen or water (currently accepted conditions for early Earth), and the products from the broth were similar in nature to those found in the Urey-Miller experiment.

In the prebiotic world envisioned by most scientists, chemistry would have dominated the changing scenario and landscape found in Earth. Chemistry, unlike biochemistry, is very non-specific and would create a huge pool of chemicals. Under the assumption that there were signs of modern cellular organisms in that pool (and this is a big assumption made out of necessity), then all or most of the biochemical reactions would be a small subset of all the reactions occurring in this pool called protometabolism [2]. Somehow, after the first catalyst were formed (not as efficient as modern enzymes), those catalysts were more specific towards a subset of these reactions and made these reactions occur at a faster rate leading to a feedback mechanism by which these reactions became the dominant reactions leading to the biochemicals or life as we know it now.

One such theory of the origin of life states that an autocatalytic reaction cycle was present in the chemical gemisch in the prebiotic world and by the nature of it being autocatalytic, it started dominating this prebiotic world leading to the first signs of life [3-6]. One such autocatalytic cycle is the tricarboxylic acid cycle (TCA or Krebs or Calvin cycle), which is present in all modern organisms in one form or the other [7]. The TCA cycle is the only route of carbon fixation into biochemicals starting with carbon dioxide as the source of carbon [8,9]. In one form of the cycle, called the reverse TCA cycle (and found in few organisms), the overall reaction can be visualized as 2 molecules of carbon dioxide (found in prebiotic earth) reacting with a molecule of citrate and 6 molecules of hydrogen to form 2 molecules of citrate and 5 molecules of water. The important thing to note is that 2 molecules of citrate were formed from 1 molecule of citrate hence producing more of the reactant. In other words, 2 molecules of citrate can be used as reactant in the next round of the TCA and the cycle is hence called autocatalytic. As it is autocatalytic, once prebiotic conditions existed where this cycle could take place completely (all reactions in it have to take place), this cycle would have taken place much faster after some time and would have slowly dominated the early prebiotic metabolism.

In addition, in modern cells, the TCA or the rTCA cycle is at the center of a cell's metabolism. In other words, the intermediates of the TCA cycle form amino acids, nucleotides, and cofactors for the rest of the cellular machinery. So, after this cycle starts to dominate the prebiotic world, the side reactions would start producing amino acids and nucleotides leading to complexity required for biochemistry to begin [8]. However, the conditions required for this cycle to take place completely have not been found so far. Secondly, the source of energy of these reactions and the compartmentalization of these reactions (to cause insignificantly higher concentration of these biochemicals) is still a matter of speculation and further research.

It was postulated that in early prebiotic conditions, these reactions could have taken place on clay or on metal sulfide surfaces such as FeS. These metals would have themselves been oxidized to ferric sulfide providing energy to take place to completion [3,4]. Another theory is that it may not have been just the TCA cycle but some other cycle like the ribose cycle that could have been at the origin of metabolism [5]. The advantage of the ribose cycle is that unlike the TCA cycle, there are only 1 or 2 reactions in the cycle that do not take place at an appreciable rate without a catalyst and hence only 1 or 2 reactions need the clay or metal surface as a catalyst.

In either case, it is a question whether an autocatalytic cycle should be considered as life. In my opinion it should not, even though it is producing more of itself (chemical form of reproduction) at the end of the day and there is energy conversion in the cycle (metabolism). It is just that life is very specific and driven unlike early chemistry which would have been highly aspecific. But this is certainly a matter of speculation and discussion.

[1] Biochemistry - Stryer.
[2] Singularities - de Duve.
[3] Wechterheuser - Evolution of the first metabolic cycles - PNAS, 87:200-204, 1990.
[4] Wechterheuser - On the chemistry and evolution of the pioneer organism - Chemistry and Biodiversity, 4:584-602, 2007.
[5] Orgel - Self-organizing biochemical cycles - PNAS, 97:12503-12507, 2000.
[6] Smith and Morowitz - Universality in intermediary metabolism - PNAS, 101:13168-13173, 2004.
[7] Wikipedia entry on Citric acid cycle.
[8] Morowitz, Kostelnik, Yang, and Cody - The origin of intermediary metabolism - PNAS, 97:7704-7708, 2000.
[9] Srinivasan and Morowitz - Ancient genes in contemporary persistent microbial pathogens - Biol. Bull., 210:1-9, 2006.

PS: Stanley Miller passed away this year at the age of 77 and this post is dedicated to him.

Is there anybody out there?

This piece in November promised a lot more and I have failed to deliver on my promise so far. This is my first attempt to catch up with what I had promised. This post will deal with the chemicals that one finds in asteroids that land on Earth and with it questions the possibility that the raw materials for life on Earth could have started by the availability of these chemicals and also discuss the possibility of panspermia.

First, I will start with astronomical spectroscopy. This is the method by which chemists identify the compounds present in space. When light or any electromagnetic radiation is passed through a sample, the sample absorbs and emits certain wavelengths of light better than others and the wavelengths that are emitted and absorbed can be used as a fingerprint analysis of the chemical nature of the compound itself. Unfortunately, the science is not as simple* as I mention here but will suffice for the discussion that follows.

There have been many meteors that have hit the Earth's surface and some of these impacts have been seen as the reason for major climate change in the Earth. The interest in astronomical spectroscopy was purely to understand the physical and chemical nature of the universe around us. But as soon as astronomical spectroscopy developed into a reliable science, it stood to reason that it could lead us to understand how life on Earth originated and whether there are traces of life elsewhere in the universe. Afterall, if life evolved on Earth, the chemicals responsible for life should have been present on Earth before that (and possibly elsewhere) and hence the chemical nature of these meteors became important to biology as well, but all these studies have not been localized to the meteors alone.

The interstellar medium is divided into the dense and diffuse kind. The diffuse interstellar medium is cold and icy material that is not too dense and is made up of neutral and charged ions of compounds of C, H, and N, and also contain compounds such as naphthalene, which are aromatic compounds. In the dense interstellar compounds, the temperature is close to 10K to 200K (freezing point is 273K) important compounds such as hydrogen gas, carbon monooxide, water, carbon dioxide, methane, methanol, ammonia and hydrogen disulfide were found among others. That is, it has a source for H, C, N, O, and S. Later, in some clouds they have also found organic acids and higher alcohols such as ethanol (pure delight!).

The meteorites that have hit close to home were found to be quite rich in the lower and higher organic compounds of the classes mentioned above but were also found to have trace quantities of natural as well as unnatural amino acids (natural defined as biologically natural), purines, and pyrimidines (the base compound in DNA and RNA). In addition trace quantities of phosphonates and other P containing compounds were also found (also found in DNA and RNA). What was also interesting is that some of these amino acids was found to be chiral in nature (like in biological systems). In other words, there is a way in space to make optically active compounds and not synthsize all the isomers in equal quantities. It is actively debated whether these meteors were contaminated by biologically active components on their way to the ground even though there is evidence that says that it was not contaminated.

To summarize, the raw materials for life to start could be found in meteors and other components of space and indeed, these compounds under the right condition could lead to life anywhere. I will deal later with attempts by scientist these days to understand how life started from these raw materials.

I would like to end with panspermia and I think wikipedia has a good definition - Panspermia is the hypothesis that "seeds" of life exist already in the Universe, that life on Earth may have originated through these "seeds", and that they may deliver or have delivered life to other habitable bodies.

It is kind of a whacky theory and people either do not believe it or do not want to believe it because it is a theory like intelligent design - once you have said it, there is no way to prove it right or wrong. It is a theory which is unscientific in nature. But one of the leading scientists believing in the theory was none other than the Nobel Laurette - Francis Crick. Finding these organic chemicals in space has only led to more evidence for this hypothesis.

* Before one performs spectroscopy of a sample, one has to attempt to purify all the compounds present in the sample which is not an easy job because the chemical nature of the substance is an unknown at the beginning. A variety of chromatographic techniques are used for this. In addition, even after the spectroscopy of the individual samples are performed, it does take some time to realize the exact chemical nature of the substance being examined.

References:
Wikipedia as usual - on Origin of life and Astronomical Spectroscopy and Panspermia.

Extraterrestrial Organic Matter: A review - William M. Irvine - Origins of Life and Evolution of Biospheres - Volume 28, 1998, 365-383.**
** I can provide the pdf of this document on request.

What is Life?

As one takes an evening stroll, one can probably distinguish between all the living and non-living objects that one encounters. In spite of a classic book by Erwin Schrodinger, with a title that seems to ask one for a definition of life, published in 1943 [1], the scientific community has still not been able to come up with a single answer to this fundamental question that satisfies every scientist. Part of the reason for this ambiguity is because, to date, there remains a controversy over which objects should be considered as living beings [2]. For example, can a virus be considered as a living being?

But, first let's try to discuss some of the traits of living things:

1. Metabolism: A living being consumes energy from the surroundings by converting one form of energy to other forms of energy by a process called metabolism. Metabolism, the Greek word for change, designates all the chemical reactions carried out within a living organism.

2. Organization: The energy gained from metabolism helps organisms to remain far more organized than non-living things. Organization here refers to the fact that one can not reduce an organism into smaller independent parts. All living organisms are formed of the basic biological unit called the cell. Within each cell, there are membranes that divide the living world from the non-living world and within the membranes, the cellular constituents are organized hierarchically to form a live entity. All the molecular constituents within the cell serve a function. These molecules are organized into an integrative system and serve the activities of the cell as a whole. Some people even argue that keeping this organization going is the basic entity of life, and the minute an object is dead, this organization is lost. One can study independent parts (as molecular biology) or cells for that matter, but in reality, life as we know it, can not exist without being organized at various levels hierarchically.

3. Reproduction: Living things can reproduce on their own to produce new organisms of the same kind. The instructions to reproduce are also inherent within an organism and are inherited by each generation from their parents.

4. Evolution: Living things are able to evolve over time on their own according to their environment. They evolve due to the occasional errors that crop up while copying the instruction from one generation to another. These errors track changes in the environment and an organism that is better adapted to the environment survives. Darwin's central contention was that this adaptation stems from the interplay of random variation and natural selection. So, the history is as important as organization to understand the workings of the present day organism.

An object is traditionally considered to be living if it has all the above characteristics [3]. In addition, the definition is applied at a global level to a whole species and not to individual beings [4]. In other words, sterile organisms are also considered to be alive even though they may have lost the ability to reproduce.

Non-living things may have one or more of the above mentioned traits, but do not possess all the above mentioned characteristics. For example, a flame can use up energy and convert chemical energy to light and heat energy, using up energy in this process. However, it can not reproduce on it's own and neither does a flame evolve according to it's environment.

Viruses on the other hand are a little more difficult to distinguish. They can evolve and they can reproduce (albeit, inside another organism and not on their own), but they do not possess any metabolic capabilities, and hence, it may be argued, should be considered as not living. A small minority of the biologists have postulated that the abilities to reproduce and evolve are the only criteria for life, and that viruses should hence be considered alive.

Seeds also form an interesting example. Do we consider seeds as living or non living? Well, I did a google search and they are considered to be alive. They certainly have the ability to reproduce and, hence, evolve under the "right conditions". In addition, they are as organized as a living organism, but the real question was whether metabolism takes place in a seed under dry storage conditions. I was pleasantly surprised to find many papers reporting that seeds do undergo metabolism even during storage (an example is [5]), and hence, they do have all the criteria to be considered alive.

Physicists and chemists tend to argue over whether all the four properties are really required for life. While some chemists argue that metabolism is the real criterion for life, physicists argue that the level of organization in a cell is what really demarcates the difference between a living cell and a non-living cell. In fact, an algebraic information theoretic framework was developed to define the amount of information required to define an organism and the amount of organization in an organism [6].

What should be considered as living is not only an academic issue, but is equally important for space probes that look for signs of extraterrestrial life. In addition, it is equally important when one studies the origin of life from non-living entities. When does one consider that there is enough complexity in a system to call it a living cell? I will continue this post with a post on the quest for the origin of life and also, on a separate series of posts, on molecular evolution of living organisms.

References:
[1] What is Life? by Erwin Schrodinger.

[2] Chapters 1 and 2 of The Way of the Cell by Franklin Harold.

[3] Wikipedia entry on Life.

[4] Brittanica Encyclopedia.

[5] Metabolic activities of dormant seeds during dry storage. Naturwissenschaften, 59:3, 1972, 73-74.

[6] Toward a Mathematical Definition of "Life" by Gregory C Chaitin.