THE BEGINNING

5/19/202439 min read

THE BASICS OF PRODUCING LIFE

The formation of living things involves a complex interplay of molecular components and processes. While the exact origin of life on Earth remains a subject of investigation and debate, there are several key molecular components and theories that provide insights into how life may have emerged from non-living matter. Here's a simplified overview of some fundamental molecular components and processes involved in the formation of living things:

GENERIC ELEMENTS NEEDED FOR "EVOLVING LIFE FORMATION

1. Organic Molecules

: Organic molecules are carbon-based compounds that form the building blocks of life. These molecules include carbohydrates, lipids (fats), proteins, and nucleic acids (DNA and RNA). Organic molecules are essential for the structure and function of living organisms.

2. Water:

Water is a critical solvent for many biochemical reactions and is essential for life as we know it. It plays a crucial role in facilitating the interactions between organic molecules and enabling the transport of nutrients and waste products within cells.

3. Energy Sources:

Living things require a source of energy to carry out essential processes. Early Earth likely had various potential energy sources, such as geothermal heat, lightning, and ultraviolet radiation from the sun.

4. Prebiotic Chemistry:

The formation of organic molecules from simple chemical compounds in a non-biological environment is known as prebiotic chemistry. Several experiments have shown that under certain conditions, such as in the presence of certain minerals and energy sources, simple organic molecules like amino acids and nucleotides can be synthesized.

5. Self-Replication:

One of the defining characteristics of life is the ability to reproduce. In the context of the origin of life, self-replication refers to the ability of molecules to make copies of themselves. Some RNA molecules, for example, are capable of self-replication, which has led to the hypothesis that RNA may have played a crucial role in early life forms.

6. Protocells:

Protocells are hypothetical structures that are thought to have preceded the first true cells. These protocells would have had a lipid membrane-like structure and the ability to encapsulate and protect self-replicating molecules. The formation of protocells is a critical step in the emergence of life, as it would have provided a means for molecular organization and separation from the external environment.

7. Evolution:

Once life began, it would have undergone a process of evolution through natural selection. Mutations and variations in replicating molecules would have led to the emergence of more complex and diverse forms of life over time.

It's important to note that the exact details of how life originated on Earth remain the subject of scientific investigation and debate. Theories such as the RNA world hypothesis and the Miller-Urey experiment provide insights into potential mechanisms for the emergence of life, but the process is likely to have been highly complex and may have occurred over millions of years.

The study of abiogenesis, which is the process by which life arises naturally from non-living matter, continues to be an active area of research, and scientists are working to unravel the mystery of life's origins on our planet.

SUGGESTIONS FOR THE ORIGINATION OF LIFE'S MOLECULAR PRECURSORS

1. Prebiotic Chemistry:

· Prebiotic chemistry studies the chemical processes that could have taken place on early Earth, leading to the formation of organic molecules necessary for life. Under the right conditions, simple organic molecules like amino acids, nucleotides, and lipids can form through abiotic (non-biological) processes.

· Experiments, such as the Miller-Urey experiment in the 1950s, demonstrated that under simulated early Earth conditions (e.g., a reducing atmosphere, energy sources like lightning), simple organic compounds could be synthesized from inorganic precursors.

· Modern research continues to explore the chemistry of early Earth environments and the potential pathways for the formation of organic molecules.

2. Hydrothermal Vent Hypothesis:

· Some scientists propose that life could have originated at hydrothermal vents on the ocean floor. These vents release mineral-rich, high-temperature fluids into the ocean, creating a chemically diverse and energy-rich environment.

· The high-temperature conditions and mineral surfaces at hydrothermal vents may have provided the necessary conditions for the synthesis of organic molecules and the formation of prebiotic chemistry.

3. RNA World Hypothesis:

· The RNA world hypothesis suggests that self-replicating ribonucleic acid (RNA) molecules were precursors to life as we know it. RNA can carry genetic information and catalyze chemical reactions, making it a plausible candidate for an early genetic and catalytic system.

· Some experiments have shown that short RNA molecules can form spontaneously under certain conditions and may have been present on early Earth.

4. Extraterrestrial Delivery:

· Some scientists consider the possibility that the building blocks of life, such as amino acids and organic molecules, could have been delivered to Earth by comets, meteorites, or interstellar dust. These extraterrestrial sources could have provided the initial organic material needed for life.

5. Panspermia:

· The panspermia hypothesis suggests that life, or its precursors, could be distributed throughout the universe by space dust, meteoroids, asteroids, or even deliberate seeding by intelligent civilizations. This hypothesis posits that life may have originated elsewhere in the universe and then spread to Earth or other celestial bodies.

It's important to note that the origin of life is a complex and multifaceted problem, and the exact mechanisms remain a subject of ongoing research and debate. Scientists continue to investigate these hypotheses through laboratory experiments, computer simulations, and the study of extreme environments on Earth and in space to gain insights into how life's molecular precursors may have formed and evolved.

PRELIMINARY Prebiotic chemistry

1. Abiotic Synthesis of Organic Compounds:· Early Earth had a reducing atmosphere, rich in gases like methane (CH4), ammonia (NH3), and water vapor (H2O). These conditions were conducive to the formation of organic molecules through various abiotic processes.· One of the most famous experiments illustrating this is the Miller-Urey experiment conducted in the 1950s. In this experiment, a mixture of these gases was subjected to electrical discharges (simulating lightning) and heat. This resulted in the formation of amino acids, which are the building blocks of proteins, and other organic molecules.· Other abiotic processes, such as ultraviolet (UV) radiation from the sun, thermal cycling, and reactions at hydrothermal vents, could also have contributed to the formation of organic molecules.

2. Formation of Complex Molecules:

· Simple organic compounds, like amino acids and nucleotides, are important precursors for life. These molecules can form through chemical reactions involving the elements carbon, hydrogen, oxygen, nitrogen, and others.

· Chemical reactions involving these precursors can lead to the formation of more complex molecules. For example, amino acids can combine to form peptides and proteins, while nucleotides can combine to form RNA and DNA.

3. Polymerization Reactions:

· Polymerization is a crucial process in prebiotic chemistry, where smaller organic molecules, such as amino acids or nucleotides, join together to form larger, more complex molecules.

· In the case of the RNA world hypothesis, RNA molecules themselves are thought to have formed through the polymerization of ribonucleotides. RNA molecules can have both genetic information-carrying and catalytic properties, making them central to early life processes.

4. Mineral Catalysis:

· Minerals present on early Earth's surface or at hydrothermal vents may have played a role in facilitating chemical reactions and catalyzing the formation of organic molecules.

· Certain minerals can act as catalysts, providing surfaces where reactions can occur more readily. For example, clays and iron-sulfide minerals have been proposed as possible catalysts for prebiotic chemistry reactions.

5. Concentration and Selection:

· In natural environments, processes such as evaporation of water or concentration in geothermal pools could have led to the accumulation of organic molecules, increasing their chances of reacting with each other.

· The selective retention of molecules that had advantageous properties, such as self-replication or stability, could have driven the emergence of increasingly complex chemical systems.

It's important to note that prebiotic chemistry is a complex field of study, and researchers continue to explore various environmental conditions, reactants, and mechanisms to gain a better understanding of how life's molecular precursors may have arisen on early Earth. While significant progress has been made, many questions about the origin of life remain unanswered

MORE RECENT INFORMATION The RNA World Hypothesis

The RNA World Hypothesis is a concept put forth in the 1960s by Carl Woese, Francis Crick and Leslie Orgel.It proposes that earlier life forms may have used RNA alone for the storage of genetic material.

Walter Gilbert, a Harvard molecular biologist, was the first to use the term "RNA World" in an article published in 1986.

The hypothesis posists that DNA later became the genetic material as a result of evolution because RNA was a relatively unstable molecule. According to the RNA World Hypothesis, around 4 billion years ago, RNA was the primary living substance, largely due to RNA’s ability to function as both genes and enzymes.

The main reasoning behind the hypothesis is that RNA is capable of self-replication and could therefore have carried genetic information across generations independently. This concept has been highly debated in the scientific world over the last 50 years. Experts now generally agree that non-living chemicals could not have given rise to bacterial cells in a single step and that intermediate, pre-cellular life forms must therefore have existed. Of the possible pre-cellular life models considered, the most popular is the RNA World.

In 1968, Sir Francis Crick proposed that RNA must have been the primary genetic material as it is capable of self-replication, owing to its ability to act as an enzyme. Moreover, RNA can also be converted to DNA by reverse transcription, which further strengthens the idea that the RNA world could have been the initial pathway to cells.

Ribozymes and the RNA world It was previously thought that the only biomolecules that could catalyze essential chemical reactions in cells were proteins.

However, Sidney Altman, Thomas Cech and colleagues discovered a class of RNAs that is capable of catalyzing chemical reactions ─ ribozymes. Altman and Cech were awarded the Nobel Prize in Chemistry in 1989 for this discovery.

The discovery of ribozymes supported the RNA World Hypothesis. The strongest argument for proving the hypothesis is perhaps that the ribosome, which assembles proteins, is itself a ribozyme. Despite the fact that the ribosome is composed of both RNA and protein, the processes involved in translation are not catalyzed by protein, but by RNA, indicating that early life forms may have used RNA to catalyze chemical reactions before they used proteins.

Summary Research over the years has demonstrated the useful properties of random RNA sequences, such as the production of active RNA ligases from random sequences of RNA. However, this is not enough to prove the RNA World hypothesis. Based on what is known about present-day organisms, it is not possible to conclude that a self-replicating molecule was the primary source of catalytic mechanisms fundamental to living systems. Research on the RNA World Hypothesis is ongoing, although recent findings threaten to disprove the hypothesis. NASA apparently stated in a 1996 report that the “significant difficulties” that surround the RNA World concept include the chemical fragility of RNA and its narrow range of catalytic activities. Biochemist Harold S Bernhardt shares the same concerns and in a 2012 biology paper, he referred to the concept as ‘the worst theory of the early evolution of life.’ His paper states that the complexity of the RNA molecule means it could not have arisen prebiotically; that RNA is unstable and that it possesses limited catalytic properties.

The RNA World Hypothesis, proposed by Carl Woese, Francis Crick, Leslie Orgel, and later popularized by Walter Gilbert, suggests that early life forms may have used RNA as the primary genetic material before the emergence of DNA. This hypothesis is based on RNA's ability to self-replicate and function both as genes and enzymes. RNA's capacity for self-replication and its role in genetic information transfer make it a plausible candidate for the earliest life forms.

The central idea of the RNA World Hypothesis is that around 4 billion years ago, RNA played a crucial role in the origins of life. It is believed that RNA molecules could have carried genetic information independently and catalyzed essential chemical reactions in the absence of proteins. The discovery of ribozymes, RNA molecules capable of catalyzing chemical reactions, further supported this hypothesis.

Despite ongoing research into the RNA World Hypothesis, there are challenges and criticisms. Some scientists argue that the fragility of RNA and its limited catalytic properties raise doubts about its role as the primary source of early catalytic mechanisms in living systems. NASA has expressed reservations about the hypothesis, and biochemist Harold S. Bernhardt has referred to it as 'the worst theory of the early evolution of life.'

LIFE BEGINS

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NICK LANE

First, oxygen makes it difficult for life to emerge, and the presence of oxygen can halt the process.

Second, there is evidence of a single common ancestor for all life on Earth, suggesting that multiple origins of life may have failed and only one succeeded.

MANY also point out differences between bacteria and archaea, which are both ancient forms of life. They share some similarities, like having membranes and DNA, but their DNA replication processes differ. Despite these differences, there is likely a single common ancestor due to the fundamental similarities between them. this common ancestor might have originated in hydrothermal vents, with potentially many vents hosting different common ancestors.

However, only one of them could have successfully dominated and become the ancestor of all life forms.

The fundamental unit of life is a single cell, and even though there are various populations of cells, the single cell is the basic building block.

When these cells left the vents and entered different environments, they needed to power up their own membranes, which required pumps to create electrical charges. The differences in these pumps and other cellular components contributed to the divergence between different groups of cells.

It is possible that life may have started multiple times on Earth, but due to certain constraints and evidence, it's more likely that there was a single common ancestor for all life, with various populations of cells evolving from it and diverging over time.

It is possible that life originated from this space prebiotic chemistry to create molecular machines like ribosomes is that the first thing that you would say is life . I’m thinking about RNA molecules reproducing itself then any changes in sequence allowed to do.

one is selected by perfectly normal natural selection but within the system so that’s when it becomes alive-same composts into like an object that keeps information and involves that information over time

Changes that informational metastases in response to the notice always positive us out since your sense that it started only once because it is difficult or is it possible started in multiple locations on earth

it’s possible just on multiple occasions to provisos to that one of them is--- oxygen makes it impossible ready for life stopped , so soon as we got oxygen in the atmosphere ,than life is to keep stalling over

life starts in the race you got one hydrogen’s agreement with s oxygen. hydrogen reacts with oxygen instead this explosive reaction is rocket fuel

is by the other foot for the origin of life early and not all we know is that this is a single common ancestor for all of life that could have been multiple origins and they all just dissipated.

this is a very interesting team’s place in life between bacteria unwanted calls can wish you look just the same as bacteria found that no class is diverse but nearly on the day of very different in biochemistry makes me think that life probably days arise only once can you describe the difference

that’s interesting there will how their similar other different while there a difference in the genes behind it for replicating DNA so that both have membranes both have DNA replication yes the process of that is different than ½ day they both have DNA genetic code is identical in both the way in which case transcribed into RNA into the copy of the gene way the Boston translated into a protein

that so basically the setting both these groups are like playing the shack common ancestor is to set that difference in fundamental ways as well and if you think about what will kind of processes could drive the divergence variability

I can think about is in terms of membranes and times of the electrical charges on membranes is not that makes me think public though probably many unsuccessful attempts

only one really successful it can explain why that divergence makes you think there’s one as one common ancestor of taking described intuition on Lupita there about why they divert the leap from the divergence

is there is one did you mean like the divergence indicates that there was a big convention at that time yet one was if if you thoughts as I imagine if you have a common ancestor living in a hydrothermal vent that say that millions of vents and millions of potential common ancestors living in all of those fact---s but only one of them then he could imagine that Sal is then given current take over the welding and wipeout everything else and so you point would see would be a single common ancestor for all of life but with no lost also different vent systems old, providing said created the first life forms you might say this thing is a cell single so I would always talk about populations of cells.

the fundamental life form as a single cell right it’s the unitive selection singles bus selection operates over generations and changes over generations in populations cells so it will be impossible to say the salad is the unitive selection

You must have a top population involving the change ---there was one Chuck Norris the American reference -- The cell that made it out of the vents I like the first one

imagine then that this woman cell gets out and he takes over the world and gets out in the water flowed Nora went deep in the ocean somewhere yet but actually to cells and they appear to have guns out from the same event because they both share the same code everything else so nice all you got a million different common ancestors in the Lea’s different bands so either they all have the same code into cells spontaneously much different places

Two fundamentally different cells could come from the same place -either way

one of the constraints with one came out form ½ million came out but to came out thus, with us what you doing inside event is relying on the electrical charges down to power this reaction between hydrogen to make yourself grow when you leave the event you got to do that yourself you go to power up your own membrane so the question is how do you power up your own membrane and the answer is well you need to pump you need to pump iron is to give an electrical charge right so one of the pumps look like will the pumps look different in these two groups faces if they they both emerge from a common ancestor soon about that ancestor things move very quickly I’m divergent why does the DNA replication of different while strong to the member membranes are different the DNA replication is different because it showing to a different kind of membrane that is interesting to see the detail you I say it is also fundamental because it's about the two one organism and that organized to start replicating the heck out of itself with some mutation on the DNA so that there is some there’s a competition t

Life may have started in multiple places on Earth, but the journey from prebiotic chemistry to complex molecular structures like ribosomes is challenging. Life is defines as the introduction of information into growing systems, even if it's random bits of information like RNA molecules. When introduced into a system that's already growing and reproducing, any changes in this information are selected through natural selection, leading to life.

However, two conditions must be considered. First, the presence of oxygen can make it difficult for life to begin, as oxygen inhibits the process. Second, there is evidence of a single common ancestor for all life on Earth, suggesting that multiple origins of life may have failed.

Spock also highlights the differences between bacteria and archaea, which are both ancient life forms. While they share similarities like having membranes and DNA, their DNA replication processes differ. Despite these differences, there is likely a single common ancestor due to fundamental similarities.

Spock speculates that this common ancestor might have originated in hydrothermal vents, with many vents potentially hosting different common ancestors. However, only one of them could have succeeded in dominating and becoming the ancestor of all life forms.

When these cells left the vents and entered different environments, they needed to power up their own membranes, requiring pumps to create electrical charges. Differences in these pumps and other cellular components contributed to the divergence between different groups of cells.

MANY believe that life may have started in multiple places on Earth, but due to constraints and evidence, it's more likely that there was a single common ancestor for all life, with various populations of cells evolving from it and diverging over time.

we know is that this is a single common ancestor for all of life that could have been multiple origins and they all just dissipated. the process of that is different than ½ day they both have DNA genetic code is identical in both the way in which case transcribed into RNA into the copy of the gene way ribosome translated into a protein that so basically the setting both these groups are like playing the shack common ancestor

that difference in fundamental ways as well and if you think about what will kind of processes could drive the divergence variability on I can think about is in terms of membranes and times of the electrical charges on membranes is not that makes me think public though probably many unsuccessful attempts and only one really successful it can explain why that divergence makes you think there’s one as one common ancestor

if you have a common ancestor living in a hydrothermal vent that say that millions of vents and millions of potential common ancestors living in all of those facts but only one cell is then given current take over the welding and wipeout everything else you would see would be a single common ancestor for all of life

the fundamental life form as a single cell , together with the machine ,marrying each one individual yes it’s the unitive selection singles bus selection operates over generations and changes over generations in populations cells so it will be impossible to say the salad is the unitive selection i

there was one Chuck Norris the American reference cell then made it out of the vents and this winner cell gets out and he takes over the world and gets out in the water.Other cells flowed out from the same event because they both share the same code everything else so l you got a million different cells---either they all have the same code into cells spontaneously much different places all to two different cells fundamentally different cells came from the same place so either way

one of the constraints that say they come out relying on the electrical charges down to power this reaction between hydrogen to make yourself grow

when you leave the event you got to do that yourself you go to power up your own membrane so the question is how do you power up your own membrane- the answer is well you need to pump iron is to give an electrical charge --so one of the pumps look like will the pumps look different in these two groups faces if they they both emerge from a common ancestor soon about that ancestor things move very quickly I’m divergent

why does the DNA replication of different while strong to the member membranes are different the DNA replication is different because it showing to a different kind of membrane that is interesting to see the detail you I say it is also fundamental because it's about the two one organism and that organized to start replicating the heck out of itself with some mutation on the DNA so that there is some there’s a competition t

It suggests that life may have started in multiple places on Earth, but the journey from prebiotic chemistry to complex molecular structures like ribosomes is challenging. Spock defines life as the introduction of information into growing systems, even if it's random bits of information like RNA molecules. When introduced into a system that's already growing and reproducing, any changes in this information are selected through natural selection, leading to life.

However, two conditions must be considered.

First, the presence of oxygen can make it difficult for life to begin, as oxygen inhibits the process Second, there is evidence of a single common ancestor for all life on Earth, suggesting that multiple origins of life may have failed.

One must recognise the differences between bacteria and archaea, which are both ancient life forms. While they share similarities like having membranes and DNA, their DNA replication processes differ. Despite these differences, there is likely a single common ancestor due to fundamental similarities.

I speculate that this common ancestor might have originated in hydrothermal vents, with many vents potentially hosting different common ancestors. However, only one of them could have succeeded in dominating and becoming the ancestor of all life forms.

When these cells left the vents and entered different environments, they needed to power up their own membranes, requiring pumps to create electrical charges. Differences in these pumps and other cellular components contributed to the divergence between different groups of cells.

In summary, I believe that life may have started in multiple places on Earth, but due to constraints and evidence, it's more likely that there was a single common ancestor for all life, with various populations of cells evolving from it and diverging over time.

The question arises about how these cells came out and whether they will continue to function.

Inside an event, electrical charges power reactions between hydrogen, allowing cells to grow.

However, when you leave the event, you need to power up your own cell membrane.

To power up your own membrane, you need to pump and provide an electrical charge.

The appearance of pumps may differ between the two groups of cells that emerged from a common ancestor.

There's rapid divergence in these cells' evolution, affecting DNA replication and membrane characteristics.

DNA replication is different because it corresponds to different types of membranes.

This differentiation is fundamental as it involves the competition between organisms replicating with DNA mutations.

Nick Lane (PhD, FRSB, FLS) is Professor of Evolutionary Biochemistry in the Department of Genetics, Evolution and Environment at University College London.

Prof Lane’s research is on the way that energy flow has shaped evolution over 4 billion years, using a mixture of theoretical and experimental work to address the origin of life, the evolution of complex cells and downright peculiar behaviour such as sex. He was a founding member of the UCL Consortium for Mitochondrial Research, and is Co-Director of the UCL Centre for Life’s Origin and Evolution (CLOE). He was awarded the 2009 UCL Provost’s Venture Research Prize, the 2011 BMC Research Award for Genetics, Genomics, Bioinformatics and Evolution, the 2015 Biochemical Society Award for his outstanding contribution to molecular life sciences and 2016 Royal Society Michael Faraday Prize and Lecture, the UK’s premier award for excellence in communicating science.

SELF-ORGANIZATION

SELF-ORGANIZATION ( ALSO NEED TO CHECK OUT MIKE LEVIN'S NEW WORK on electricy in cells )

This section is primarily the classical thinking--- by explanation of heat exchange energy and entrophy

Self-organization ( FIRST RECOGNIZED BY ALLEN TURING ) is one of the most fascinating and pervasive phenomena in our world from sand grains assembling into ripple dunes to cells combining to create highly structured tissues to individual insects working to create sophisticated societies to the coordinated movement of a school of fish what these diverse systems hold in common is their emerging global patterns being derived solely from the local interactions among relatively simple components--- researchers are finding in such patterns a new approach to understanding ecosystems through the process of self-organization .Turing observed colored perticles independent arranging themselves in patterns spontaneously - Imaning that the event that started his career was " finding out how leopards made their spots")

Main section

Understanding biological systems challenges us because they consume energy and are therefore far from equilibrium thus classical thermodynamics which has been so successful in developing an atomic understanding of physical and chemical properties such as temperature and pressure does now apply to these systems instead of self assembling into lower energy states such as the crystal these energy dissipating components self-organized into highly dynamic structures through which there is a constant flux of energy of materials

Self-organization is a process in which patterns at the global level of a system emerge solely from numerous interactions among the lower-level components of the system the rules specifying interactions among the systems components are executed using only local information without reference of the global pattern--- what is also intriguing about this pattern formation in biological systems and lends excitement to the study of self-organization in animal groups is the recent realization that interactions among systems components can be surprisingly simple even when extremely sophisticated -----patterns are built such as the complex nests of termites the coordinated movement of birds in a flock or even human consciousness out of a network of nonlinear interactions between simple components self-organization can give rise to complex phenomena on the macro level which then in turn feeds back to both enable and constrain the components on the local level

The theory of self-organization helps us to approach one of the big questions within biology and ecology that of organization and order how and why do we get this extraordinary level of organization we see within ecosystems as we previously discussed the second law of thermodynamics tells us that the disorder or entropy of a physical or chemical system and its surroundings must increase over time in other words systems left to themselves must become increasingly random the ordered energy of a system must degrade eventually to this randomness ---but there are many instances in which physical systems spontaneously create emergent patterns of order for example despite the destruction that they cause hurricanes have a very orderly vortex motion when compared to the random motion of the air molecules in a closed environment---- even more spectacular is the order created by chemical systems, the most dramatic being the order associated with life of all kind

But of course the second law only really tells us about closed systems what we're dealing with --in ecology though are in fact open systems if the system has a high enough exchange with its environments order can be created in the system by an even greater decrease in order of the system surroundings --in the hurricane example hurricanes are formed from unequal heating within the atmosphere the Earth's atmosphere is then far from thermal equilibrium-- the order of the Earth's atmosphere increases--- but at the expense of the order of the Sun , the Sun is becoming more disorderly as it ages and throws off lights are material to the rest of the universe--- the total disorder of the Sun and Earth increases despite the fact that orderly hurricanes are generated on earth these examples help to illustrate the nature of dissipative systems--- dissipative systems such as the Barnard cells created by boiling water can exhibit dynamic self-organization ---such structures are necessarily open systems---- energy and all matter are flowing through them the system is continuously generating entropy but this entropy is actively dissipated or exported out to the system -

Thus ,it manages to increase its own organization at the expense of the order in the environment the system circumvents the second law of thermodynamics simply by getting rid of excess entropy ---plants and animals take in energy a matter in a low energy form as light or food they export it back in a high entropy form as waste product ---this allows them to reduce their internal entropy thus counteracting the degradation implied by the second law----- it is this dissipative catabolic process within ecosystems that constantly produces disorder in the form of exported low-grade heat that paradoxically makes possible the maintenance of order in system through self-organization

It is this feature to dissipative systems .like ecologies that creates the conditions for self-organization , what we can think of a dissipative system as a context where energy is imported and entropy is exported--- given that context elements within the system will then self organize to process whatever resource is flowing through the system ----- this is part of the essence of biological creatures ---not only are biological systems dissipative but also they perform some internal function all biological creatures process energy a matter in some form and elements internal to the system have to self-organize

To do that biological creatures somehow have evolved orderly internal structures that enable their functionality and this internal functionality to biological entities has no equivalent within inert physical systems this can be understood ---with reference to the maximum power principle and construction law previously talked about where during self-organization the system designs develop and prevail the maximize power intake energy transformation --those uses that reinforce production and efficiency or according to the constructor law for a flow system to persist in time, it must evolve freely such that it provides greater access to its currents thus where the second law commands that things should flow from higher to lower energy potential-- the constructor law posits that they evolved in configurations that flow more and more easily over time and elements in the system will self organize to achieve this in so doing producing some macro level pattern of organization

We can ask then why do all the different parts of an ecosystem appear to fit together so well --what is responsible for organizing all the parts there are functional connections and results in feedback loops in a way that allows everything to function together--- the amazing answer is that ecosystems organise themselves because the ecosystem is a dissipative system inside of which is available free energy this exergy can be used to create some form of order and functionality through the process of self-organization

we've been talking about self organization on a generalized level but we'll use the rest of this video to discuss in more detail its basic workings today this process of self-organization is understood to take place through a number of key stages the dynamics of a self-organizing system is typically nonlinear because of circular or feedback relations between the components this involves some form of initial randomness or fluctuation positive feedback groups that can then amplify these small events when this positive feedback reaches its limits it dies out creating negative feedback with closed attractors forming and finally out of all of this we get the emergence of some global pattern nonlinear systems have in general several staple States and this number tends to increase or bifurcate as an increasing input of energy pushes the system further from its thermodynamic equilibrium the basic dynamics underlining self-organization is one of variation which explores different regions in the system state space until the enters an attractor this precludes further variation outside the attractor and thus restricts the freedom of the system's components this is equivalent to the increase of order or decrease of statistical entropy the defines self-organization will go over each of these stages in the process separately in more detail many theories surrounding self-organization involve an initial state of randomness within which fluctuations or noise can take hold for example British aim proposed the principle of order from fluctuations this may be understood with reference to a simple observation that if the components in the system are already held within some global form of organization this will likely resist alteration when an ecosystem organism or some of the system is held in an auditory strong basin of Attraction it is difficult for small events to take hold through self-organization we need some initial state of entropy and randomness for this process to take hold some small fluctuation can only really gain traction given positive feedback positive feedback can take hold around some small events and by compounding on his presence with every iteration work to amplify it into a large systemic effect one example of this will be the process whereby bees from swarm attacks against enemies when a potential enemy is identified an email tag but the bee also releases a pheromone a pheromone communicating to others to do likewise thus for every new bee that attacks we get a stronger accumulation of pheromones placing an ever greater attraction on other bees to join this is an example of a positive feedback process synchronizing the states of the bees as they come to form a swarm around the enemy similarly positive feedback through pheromone excretion is present in the formation of patterns within ant colonies another example would be any form of auto catalytic chemical process a single chemical reaction is said to have undergone Auto catalysis if one of the reaction products is also a reactant and therefore a catalyst in the same or coupled reaction the more reactions we get the more catalyst we'll have which will then generate more reactions and so on these are examples of runaway positive feedback the worse a cascade through the system aligning all the elements into some coordinated regime as self-organization is an inherently nonlinear process the transition to order as the distance from equilibrium increases is not usually continuous order typically appears that properly as characteristic of nonlinear systems the threshold between the disorder of chemical equilibrium and order is known as a phase transition the conditions for phase transitions can be determined with the mathematics of non-equilibrium thermodynamics once the process of positive feedback has run its course and met some boundary or formed a number of different local attractors their negative feedback starts to take hold once again creating a stable State the British siphon addition W Ross Ashby proposed what he called the principle of self-organization noting that a dynamical system independently of its type of components always tends to evolve towards a state of equilibrium or what we now call an attractor this reduces the uncertainty that we have about the system state and therefore reduces the system statistical entropy this is equivalent to self-organization the resulting equilibrium can be interpreted as a state where the different parts of the system are mutually adapted and balanced as they form local attractors closing in on themselves creating what we call closure for the outside observer closure determines a clear distinction between inside and outside and therefore a boundary separating system from environments this boundary can encompass all components of the original system if the system settles into a negative feedback regime it will be relatively impervious to external perturbations the system has now become responsible for its own maintenance and thus become largely independent from its environments it is thus also closed against influences from the outside although in general there will still be exchanges of matter and energy between the system and environments the organization is to term largely by its initial dynamics thus who may say that the system is at this stage thermodynamically open but organizationally closed more generally a self-organizing system may settle into a number of relatively autonomous organizationally closed subsystems but these subsystems will continue to interact these interactions too will tend to settle into self-sufficient closed configurations defining subsystems at a higher hierarchical level which contained the organizational subsystems as components these higher-level systems themselves may interact until they hit on a closed pattern of interactions thus defining a system of yet higher order this goes some way to explaining why complex systems tend to have the hierarchical architecture we previously discussed where at each level we can distinguish a number of relatively autonomous closed organizations for example a cell is an organizationally closed system encompassing a complex metabolic network of interacting chemical cycles within a membrane that protects it from external disturbances however cells are themselves organized into networks and tissues that together form multicellular organisms these organisms themselves are connected by a multitude of food webs collectively forming the ecosystem in this video we'll be covering the topic of self-organization within biological systems we talked about how the theory of self-organization helps us to approach one of the big questions in biology and ecology that of organization or order in particular how biological systems can evolve to exhibit greater structure and complexity over time by harnessing a dissipated process to enable the self-organization of their constituent elements into a functioning organism we then discussed the basic workings to this process and self-organization as one that requires some initial state of entropy or randomness where small fluctuations can gain hold and become amplified through positive feedback into new patterns as they come to form stable basins of attraction that close in on themselves producing an emergent global pattern

THE NEW BIOLOGY

Michael Levin,PHD Tufts University.

People tend to think of intelligence as being of two kinds: There's the quote, unquote "real" intelligence, which is what we are supposed to have, and then there's this idea of a 'collective intelligence,' so swarms of bees, colonies of ants, shoals of fish, and so on. And people tend to think of those as radically different things. But the reality is all intelligence is collective intelligence, and this is because we are all made of parts. So you and I are collections of cells, and these cells, including neurons and various other cells in our body, have many competencies- this is because they were once separate individuals by themselves.

They were unicellular organisms with all of the skills needed to survive in a complex world. And that journey that we all took, those progressive steps by which we construct ourselves- we construct our bodies, we construct our minds- that journey is maybe the most profound question in all of science.

I'm Michael Levin, and I'm a developmental biologist at Tufts University. Developmental biology is maybe the most magical of all the sciences because you get to see with your own eyes that journey that we all take from physics to mind. We all start out life as an unfertilized oocyte, and then slowly, gradually, step-by-step, that oocyte turns into a bunch of cells that self-construct an embryo, and eventually that embryo matures and becomes a large-scale adult. In the case of a human, it will be an individual with metacognitive capacities and the ability to reason. But we all have our origin in that chemistry and physics of that initial oocyte.

And the magic of developmental biology is that there is a mechanism by which all of these cells get together, and they are able to cooperate towards large-scale goals. This is the notion that biology uses what I call a "Multi-scale competency architecture," which basically means that we are not simply nested structurally in terms of cells which comprise tissues, comprising organs, and bodies, and then ultimately societies and so on- that's obviously true on a structural level.

But more interesting is the fact that each of these layers has certain problem-solving competencies. Each one solves problems in their own space, so cells are simultaneously solving problems in physiological spaces and metabolic spaces and gene expression spaces, and tissues and organs are solving those problems.

But, for example, during embryogenesis or regeneration, they're also solving problems in anatomical space. They're trying to navigate a path from the shape of an early embryo or a fertilized zygote all the way up to the complexity of a human body with all of the different types of organs and structures

. So the competency architecture refers to the fact that all of the parts inside of us and inside of all other creatures are themselves competent agents with preferences, with goals, with various abilities to pursue those goals, and other types of problem-solving capacities.

What evolution has given us is this remarkable architecture where every level shapes the behavioral landscape of the levels below- and the levels below do clever and interesting things that allow the levels above not to have to micromanage, and to be able to control in an interesting top-down capacity. One of the most important things about this emerging field of diverse intelligence is that we, as humans, have very limited capacity and finely-honed ability to see intelligence in medium-sized objects moving at medium speeds through three-dimensional space. So we see other primates and we see crows and we see dolphins, and we have some ability to recognize intelligence.

But we really are very bad at recognizing intelligence in unconventional embodiments where our basic expectations strain against this idea that there could be intelligence in something extremely small or extremely large.

People often criticize this approach by saying, "Well, then anything goes. If you can pick up a rock and say, 'I think this rock is cognitive and intelligent, you know, there's a spirit with hopes and dreams inside of every rock.'" That's not what this is. This is quite different. As an engineer, what you have to do is you have to come up with a way to look at a particular system that doesn't overestimate its intelligence or underestimate its intelligence. If you treat complex animals as if they were clockwork, you're gonna miss everything that's important and exciting about how they work. If you treat a clock as if it had a complex intelligence, you're going to waste a lot of time- but getting it right is fundamentally important. And so, you have this spectrum where the engineer has to pick the right level for the right system, and it's critical not to then say, "Well, that doesn't sound like human intelligence," right?

We're looking for the basic minimal version. So I think it should have two things: The first thing it should have is some degree of goal-directedness, some ability to take different paths to get to the same goals; so this is William James's definition of intelligence. And it has to have some ability to undertake actions that are not completely determined by local circumstances.

So you start with all of that, and systems that have scaled up, those basic, very fundamental, non-zero levels of agency, we call that life. So it is a spectrum, and I think that in this Universe it goes all the way to the bottom. It's very hard for people to think about these unconventional kinds of intelligences that may be either too large or too small. And of course, they often work in other spaces.

So we're good with three-dimensional space, but imagine if we had a primary sense of our own blood chemistry. If you could feel your blood chemistry the way that you currently see and smell and taste things that are around you, I think we would have absolutely no problem having an intuitive understanding of physiological-state space the way we do for three-dimensional space

. I think that we would immediately be able to recognize our various internal organs as intelligent agents navigating that space and solving these kind of problems, all the various things that happen during the day. And here's one of my favorite examples of problem solving in physiological and transcriptional spaces: So we have these worms. These are Planaria, these are flatworms. And if you put these flatworms in a solution of barium- barium is a non-specific potassium channel blocker; it blocks the ability of these cells to exchange potassium with the outside world- the cells really don't like it, especially cells in the head, because the head is full of neurons; neurons love to pass potassium. And so what happens is that overnight their heads explode. Literally, it's called head deprogression; they literally lose their heads. But if you leave them in the barium, within a couple weeks they grow back a new head. And the new head is completely barium-adapted, has no problem with the barium whatsoever. We said, "How could this be?" We looked at the original heads, the original naive heads, we looked at the barium-adapted heads, and we simply did a subtraction and asked, "What are the different genes that are expressed here?" And we found out that the barium-adapted heads have just a small number of genes that were turned on and off to allow them to adapt to this novel stressor.

Now, here's the amazing part. Planaria never see barium in the wild. There's no evolutionary history of knowing what to do when you're hit with barium. This is not an ecological stressor that they normally have to deal with. So just imagine you're a bunch of cells and you're hit with this incredible physiological stressor you've never seen before.

You've got tens of thousands of genes. What do you do? How do you know which genes to turn on and off? You don't have time to try combinations. You don't have time for an exhaustive search. You don't have time for hill climbing. You don't have time to try random things because you'll probably kill the cell long before you solve the problem.

And yet, you are able to navigate from where you are to where you need to be to escape this physiological stressor. And so, what I think evolution has done is pivoted some of the same tricks from very simple systems that only solve metabolic problems eventually to physiological and then to transcriptional problems.

And when multicellularity comes on the scene, large-scale anatomical problems. And so it's never a question of: Is something physics and chemistry, or is it cognitive? The question is: What kind of cognition, and how much?

MICHEAL LEVIN

Non-neural Bioelectricity Techniques to Manipulate

the Layer of Physiological Software

Your brain your body tissues form electrical networks that make decisions these are decisions about dynamic anatomy and that we now have the ability to target the system to control large-scale editing that can even override all kinds of genomic default states with lots of advantages and opportunities for regenerative medicine and synthetic bioengineering

we all start life roughly like:

a collection of embryonic blastomeres and then thereafter a complex process----- you get something like a cross section through a human torso- think about this incredible invariant order all of these organs are the correct shape size -position - orientation everything is next to the right stuff. It's absolutely staggering amount of amount of order

we know THAT genomes specify the DNA specifies proteins there's nothing directly that specifies how is it that cells use the genomically specified hardware that they have to know what to make and when to stop. in regenerative medicine we would like to know if a piece of this is missing how do we get the cells to rebuild it

a single cell organism called the lacrimaria HAS is no brain -there's no nervous system t- no stem cells there's no cell to cell communication-- just one cell handling all of its local goals

their ability to pursue states in various kinds of problem spaces, including anatomical amorphous space, physiological space BUT a single cell can give rise to a collection of cells -that self-assembles into incredibly complex morphology.

in a standard developmental biology ,that we're told is a kind of feed-forward ,open-loop system which is very much based around "emergence".

When a singular cell is operating at this level ,we must ask about the algorithms-- how are these decisions being made what do the cellular collectives measure, what are , are there modules ,or subroutines ,how are these global patterning goals specified ,and stored and,how reprogrammable is any piece of the biological hardware involved

this information comes in many flavors so chemical extracellular matrix tensions and stresses or biomechanics all kinds of things and of course bioelectricity so bioelectricity doesn't do this alone it works with all of this other stuff

it's actually a computational layer that gives some privileged access to the control of complex anatomical features it is the medium in which the computations are being made to make decisions

you have a collection of cells ,each cell has ion channels in this in the plasma membrane they set voltage values across- that's produces the resting potential ,which can go up and down, and can it propagate to the neighbors via these electrical synapses. Those kind of networks underlie this amazing software ,

We need to understand the electrical activity, the commitment of neuroscience , if we are able to decode this .

functional cognitive structures are to be read out from the electrical activity of the brain that's what we believe well it turns out that actually all cells do this okay all cells have ion channels most cells have electrical synapses known as gap junctions to their neighbors and we have undertook uh undertaken this this project to try to do the same kind of decoding so

an embryo and we would like to read all the electrical conversations that bind the individual cells into a collective that uh can undertake undergo anatomical homeostasis towards large uh states like like build a limb build a kidney and and so on and on the one hand it'

strange and surprising to many people to think about somatic cells as having this kind of neuroscience-like um aspect to them as if they're processing information they're having having goal states

we know what ion channels and pumps are in the membrane can we explain why the voltage is the way it is and why it changes as a function of time the way it does and so let me show you a couple of native bioelectrical patterns

the bioelectrical properties set up a pre-pattern a scaffold that tell you where everything is going to be

once you're electrically disconnected from this grid the rest of the animal becomes just external

you can control in any tissue you can control which cells electrically couple to which other cells and so we target these gap junctions we can mutate them we can open them close them or and this is basically synaptic the controlling synaptic plasticity or we can control the various ion channels opening again opening and closing them to actually set the voltage of the individual cells and this would be the equivalent of some sort of intrinsic plasticity

these bioelectrical states are not just readouts just yet molecular machinery but the information-bearing medium for these large-scale modifications so one thing you can do is you can take some cells in the frog that are going to become gut

in this region that's going to be part of the gut we'll set up a voltage pattern a distribution of voltage that's very similar to what happens when the native eyes if you recapitulate that pattern somewhere else the cells are using that pattern to decide what they're going to build and that pattern tells them to build an eye and here they go they will build an eye out of endodermal cells e round lens so so it's a non-cell autonomous effect and when we see this again and again that there's this this this ability of these bioelectrical signals to uh not just to specify cell fate but but to actually specify organ type and position and things like that so we can make eyes we can make h what this is all about is is predictive control over large-scale anatomy the idea is that we can show how much of this is actually under bioelectrical control and then use computational techniques to gain uh to gain good good predictive control over

this tissue already knows how to do and the decision for what it's going to do scar or produce various types of organs can be is is part of an electric circuit that we can guide we can we can we can manage

the second thing is that in keeping with this idea from the beginning that that one of the hallmarks of the collective intelligence of these cells in in responding to novel situations is that they can get to the final outcome through through novel paths and if you actually look at this at this intermediate stage of this leg this is nothing like what frog

we've done we've done some work um with david kaplan and um lauren black and others uh on human mesenchymal stem cells and cardiomyocytes and you can control the kinds of things that you can see in vitro um differentiation proliferation wound healing but i think that's not what the bioelectricity is for what the bioelectricity is really for in terms of why evolution uses

we should be interested in is because it allows us to exploit the modular nature of the anatomical decision making because we can control very large scale outcomes not micromanage the the um the details and uh here i have to do a disclosure so david kaplan and i are both um co-founders of this company called morphaceuticals inc where we're trying to take the things that we learned about frog leg regeneration and move them towards mammals so our goal is net where we're now in rodents trying for limb regeneration using the same strategies and using these wearable bioreactors

it is already known how it is that voltage change impacts the transcriptional machinery --at if we understood how voltage controls gene expression we basically do there are we already know about six ways that that voltage change transduces down into second messenger pathways and controls gene expression

e voltage-sensitive phosphatases um neurotransmitter transporters we already know how this works at a single cell level this transduction machinery -all of these kinds of things are in fact the redistribution of morphogens in the examples that i showed you uh all of this this is known both from specific candidates and

what allows us to do is to build models of both molecular uh networks like grns together with the various biophysics steps that happen and you can simulate every cell having these various circuits and then you can try to build a full stack model that integrates from the molecular steps to the tissue level physiology like every cell has various channels what is the electrical pattern and going to be in this tissue

i think is the kind of the the future of using this for regenerative medicine

the cancer issue so so i've shown you that you can you can track the uh the the the the shrinking of these kinds of um computational boundaries from from from that of the organ or whole body scale to single cells and you can use this as there's an obvious uh application here as a kind of diagnostic modality right um is screening for cancer and so on

but functionally what's what's really important is that first of all you can induce basically a a conversion of normal melanocytes

instructor cells for an obvious reason they those cells tell the melanocytes what to do in particular to stay nice cooperative melanocytes under control if you block their ability to signal what happens is basically metastatic melanoma these normal melanocytes convert to these crazy uh really really um kind of a long stringy things that start to crawl a crawl away they dig into the brain they dig into the neural tube they start to invade here they are all through the blood vessels this is basically exactly like a melanoma type of behavior

and the melanocytes are just at this point they're they're they're going on their own so it's a voltage change in the environment --there's nothing genetically wrong with these animals there are no oncogenes there were no carcinogens no um uh nothing nothing like that but but this voltage change is this is a physiological switch away from the cooperation of cells toward embryogenesis and towards single cell

despite what the oncogene is trying to get them to do and here while while that uh dominant negative uh k ras p53 whatever while they're uh blazingly expressed there's no tumor it's the same animal there's no tumor because these cells are coupled to this electrical network that forces them towards a uh to a proper tissue

uh try to use this to target target carcinogenic behavior in human cells the other thing that is important is again to think about the the level of control that's possible with this

you can build a computational model that asks a simple question what determines the shape and size of the brain and there's a particular bioelectrical pattern that's required for the brain to get back to the correct you can get back to a normal brain shape a normal brain gene expression

choose your tissue and and so on and the idea is that something like 20 of all drugs are ion channel drugs and these things form an incredibly convenient toolkit of what we call them electroceuticals because if you have the right computational model you can repurpose these they have a massive applicability in tweaking the bioelectrical signals now another nice thing about this kind of approach is that once the bioelectric circuit has made its decision the downstream steps that are in second messengers than gene expression everything else it can be as long as you want

we think that cracking this bioelectric codes can help reveal how cell networks make decisions in large-scale anatomy not just how individual cells decide what type of cell they're going to be but actually the question of growth and form where where do these comple patterns reside ,and we can now rewrite some of these patterns for all kinds of uh all kinds of applications ollaborators

MOST LIKELY TO WIN THE NEXT NOBEL PRIZE IN BIOLOGY