Who wrote the laws of thermodynamics?

Circa 1797, Count Rumford (born Benjamin Thompson) showed that endless mechanical action can generate indefinitely large amounts of heat from a fixed amount of working substance thus challenging the caloric theory of heat, which held that there would be a finite amount of caloric heat/energy in a fixed amount of working substance. The first established thermodynamic principle, which eventually became the second law of thermodynamics, was formulated by Sadi Carnot in 1824. By 1860, as formalized in the works of those such as Rudolf Clausius and William Thomson, two established principles of thermodynamics had evolved, the first principle and the second principle, later restated as thermodynamic laws. By 1873, for example, thermodynamicist Josiah Willard Gibbs, in his memoir "Graphical Methods in the Thermodynamics of Fluids", clearly stated the first two absolute laws of thermodynamics. Some textbooks throughout the 20th century have numbered the laws differently. In some fields removed from chemistry, the second law was considered to deal with the efficiency of heat engines only, whereas what was called the third law dealt with entropy increases. Directly defining zero points for entropy calculations was not considered to be a law. Gradually, this separation was combined into the second law and the modern third law was widely adopted.

Laws of thermodynamics

The four laws of thermodynamics define fundamental physical quantities (temperature, energy, and entropy) that characterize thermodynamic systems at thermal equilibrium. The laws describe how these quantities behave under various circumstances, and preclude the possibility of certain phenomena (such as perpetual motion).

The four laws of thermodynamics are:There have been suggestions of additional laws, but none of them achieves the generality of the four accepted laws, and they are not mentioned in standard textbooks.

The laws of thermodynamics are important fundamental laws in physics and they are applicable in other natural sciences.

The zeroth law of thermodynamics may be stated in the following form:

The law is intended to allow the existence of an empirical parameter, the temperature, as a property of a system such that systems in thermal equilibrium with each other have the same temperature. The law as stated here is compatible with the use of a particular physical body, for example a mass of gas, to match temperatures of other bodies, but does not justify regarding temperature as a quantity that can be measured on a scale of real numbers.

Though this version of the law is one of the most commonly stated versions, it is only one of a diversity of statements that are labeled as "the zeroth law" by competent writers. Some statements go further so as to supply the important physical fact that temperature is one-dimensional and that one can conceptually arrange bodies in real number sequence from colder to hotter. Perhaps there exists no unique "best possible statement" of the "zeroth law", because there is in the literature a range of formulations of the principles of thermodynamics, each of which call for their respectively appropriate versions of the law.

Although these concepts of temperature and of thermal equilibrium are fundamental to thermodynamics and were clearly stated in the nineteenth century, the desire to explicitly number the above law was not widely felt until Fowler and Guggenheim did so in the 1930s, long after the first, second, and third law were already widely understood and recognized. Hence it was numbered the zeroth law. The importance of the law as a foundation to the earlier laws is that it allows the definition of temperature in a non-circular way without reference to entropy, its conjugate variable. Such a temperature definition is said to be 'empirical'.

The first law of thermodynamics may be stated in several ways :

More specifically, the First Law encompasses several principles:

where denotes the amount of energy transferred into the system as heat.

Combining these principles leads to one traditional statement of the first law of thermodynamics: it is not possible to construct a machine which will perpetually output work without an equal amount of energy input to that machine. Or more briefly, a perpetual motion machine of the first kind is impossible.

The second law of thermodynamics indicates the irreversibility of natural processes, and, in many cases, the tendency of natural processes to lead towards spatial homogeneity of matter and energy, and especially of temperature. It can be formulated in a variety of interesting and important ways.

It implies the existence of a quantity called the entropy of a thermodynamic system. In terms of this quantity it implies that
The second law is applicable to a wide variety of processes, reversible and irreversible. All natural processes are irreversible. Reversible processes are a useful and convenient theoretical fiction, but do not occur in nature.

A prime example of irreversibility is in the transfer of heat by conduction or radiation. It was known long before the discovery of the notion of entropy that when two bodies initially of different temperatures come into thermal connection, then heat always flows from the hotter body to the colder one.

The second law tells also about kinds of irreversibility other than heat transfer, for example those of friction and viscosity, and those of chemical reactions. The notion of entropy is needed to provide that wider scope of the law.

According to the second law of thermodynamics, in a theoretical and fictive reversible heat transfer, an element of heat transferred, "δQ", is the product of the temperature ("T"), both of the system and of the sources or destination of the heat, with the increment ("dS") of the system's conjugate variable, its entropy ("S")

Entropy may also be viewed as a physical measure of the lack of physical information about the microscopic details of the motion and configuration of a system, when only the macroscopic states are known. This lack of information is often described as "disorder" on a microscopic or molecular scale. The law asserts that for two given macroscopically specified states of a system, there is a quantity called the difference of information entropy between them. This information entropy difference defines how much additional microscopic physical information is needed to specify one of the macroscopically specified states, given the macroscopic specification of the other – often a conveniently chosen reference state which may be presupposed to exist rather than explicitly stated. A final condition of a natural process always contains microscopically specifiable effects which are not fully and exactly predictable from the macroscopic specification of the initial condition of the process. This is why entropy increases in natural processes – the increase tells how much extra microscopic information is needed to distinguish the final macroscopically specified state from the initial macroscopically specified state.

The third law of thermodynamics is sometimes stated as follows:
At zero temperature the system must be in a state with the minimum thermal energy. This statement holds true if the perfect crystal has only one state with minimum energy. Entropy is related to the number of possible microstates according to:

Where "S" is the entropy of the system, "k" Boltzmann's constant, and "Ω" the number of microstates (e.g. possible configurations of atoms). At absolute zero there is only 1 microstate possible ("Ω"=1 as all the atoms are identical for a pure substance and as a result all orders are identical as there is only one combination) and ln(1) = 0.

A more general form of the third law that applies to a system such as a glass that may have more than one minimum microscopically distinct energy state, or may have a microscopically distinct state that is "frozen in" though not a strictly minimum energy state and not strictly speaking a state of thermodynamic equilibrium, at absolute zero temperature:

The constant value (not necessarily zero) is called the residual entropy of the system.

The second law of thermodynamics may be expressed in many specific ways, the most prominent classical statements being the statement by Rudolf Clausius (1854), the statement by Lord Kelvin (1851), and the statement in axiomatic thermodynamics by Constantin Carathéodory (1909). These statements cast the law in general physical terms citing the impossibility of certain processes. The Clausius and the Kelvin statements have been shown to be equivalent.

Second law of thermodynamics

The second law of thermodynamics states that the total entropy of an isolated system can never decrease over time. The total entropy of a system and its surroundings can remain constant in ideal cases where the system is in thermodynamic equilibrium, or is undergoing a (fictive) reversible process. In all processes that occur, including spontaneous processes, the total entropy of the system and its surroundings increases and the process is irreversible in the thermodynamic sense. The increase in entropy accounts for the irreversibility of natural processes, and the asymmetry between future and past.

Historically, the second law was an empirical finding that was accepted as an axiom of thermodynamic theory. Statistical mechanics, classical or quantum, explains the microscopic origin of the law.

The second law has been expressed in many ways. Its first formulation is credited to the French scientist Sadi Carnot, who in 1824 showed that there is an upper limit to the efficiency of conversion of heat to work, in a heat engine.

The first law of thermodynamics provides the basic definition of internal energy, associated with all thermodynamic systems, and states the rule of conservation of energy. The second law is concerned with the direction of natural processes. It asserts that a natural process runs only in one sense, and is not reversible. For example, heat always flows spontaneously from hotter to colder bodies, and never the reverse, unless external work is performed on the system. The explanation of the phenomena was given in terms of entropy. Total entropy ("S") can never decrease over time for an isolated system because the entropy of an isolated system spontaneously evolves toward thermodynamic equilibrium: the entropy should stay the same or increase.

In a fictive reversible process, an infinitesimal increment in the entropy () of a system is defined to result from an infinitesimal transfer of heat () to a closed system (which allows the entry or exit of energy – but not mass transfer) divided by the common temperature () of the system in equilibrium and the surroundings which supply the heat:

Different notations are used for infinitesimal amounts of heat () and infinitesimal amounts of entropy () because entropy is a function of state, while heat, like work, is not. For an actually possible infinitesimal process without exchange of mass with the surroundings, the second law requires that the increment in system entropy fulfills the inequality

This is because a general process for this case may include work being done on the system by its surroundings, which can have frictional or viscous effects inside the system, because a chemical reaction may be in progress, or because heat transfer actually occurs only irreversibly, driven by a finite difference between the system temperature () and the temperature of the surroundings (). Note that the equality still applies for pure heat flow,

which is the basis of the accurate determination of the absolute entropy of pure substances from measured heat capacity curves and entropy changes at phase transitions, i.e. by calorimetry. Introducing a set of internal variables formula_4 to describe the deviation of a thermodynamic system in physical equilibrium (with the required well-defined uniform pressure "P" and temperature "T") from the chemical equilibrium state, one can record the equality

The second term represents work of internal variables that can be perturbed by external influences, but the system cannot perform any positive work via internal variables. This statement introduces the impossibility of the reversion of evolution of the thermodynamic system in time and can be considered as a formulation of "the second principle of thermodynamics" – the formulation, which is, of course, equivalent to the formulation of the principle in terms of entropy.
The zeroth law of thermodynamics in its usual short statement allows recognition that two bodies in a relation of thermal equilibrium have the same temperature, especially that a test body has the same temperature as a reference thermometric body. For a body in thermal equilibrium with another, there are indefinitely many empirical temperature scales, in general respectively depending on the properties of a particular reference thermometric body. The second law allows a distinguished temperature scale, which defines an absolute, thermodynamic temperature, independent of the properties of any particular reference thermometric body.

The historical origin of the second law of thermodynamics was in Carnot's principle. It refers to a cycle of a Carnot heat engine, fictively operated in the limiting mode of extreme slowness known as quasi-static, so that the heat and work transfers are between subsystems that are always in their own internal states of thermodynamic equilibrium. The Carnot engine is an idealized device of special interest to engineers who are concerned with the efficiency of heat engines. Carnot's principle was recognized by Carnot at a time when the caloric theory of heat was seriously considered, before the recognition of the first law of thermodynamics, and before the mathematical expression of the concept of entropy. Interpreted in the light of the first law, it is physically equivalent to the second law of thermodynamics, and remains valid today. It states

The efficiency of a quasi-static or reversible Carnot cycle depends only on the temperatures of the two heat reservoirs, and is the same, whatever the working substance. A Carnot engine operated in this way is the most efficient possible heat engine using those two temperatures.

The German scientist Rudolf Clausius laid the foundation for the second law of thermodynamics in 1850 by examining the relation between heat transfer and work. His formulation of the second law, which was published in German in 1854, is known as the "Clausius statement":
Heat can never pass from a colder to a warmer body without some other change, connected therewith, occurring at the same time.

The statement by Clausius uses the concept of 'passage of heat'. As is usual in thermodynamic discussions, this means 'net transfer of energy as heat', and does not refer to contributory transfers one way and the other.

Heat cannot spontaneously flow from cold regions to hot regions without external work being performed on the system, which is evident from ordinary experience of refrigeration, for example. In a refrigerator, heat flows from cold to hot, but only when forced by an external agent, the refrigeration system.

Lord Kelvin expressed the second law as

Suppose there is an engine violating the Kelvin statement: i.e., one that drains heat and converts it completely into work in a cyclic fashion without any other result. Now pair it with a reversed Carnot engine as shown by the figure. The net and sole effect of this newly created engine consisting of the two engines mentioned is transferring heat formula_6 from the cooler reservoir to the hotter one, which violates the Clausius statement(This is a consequence of the first law of thermodynamics, as for the total system's energy to remain the same, formula_7, so therefore formula_8 ). Thus a violation of the Kelvin statement implies a violation of the Clausius statement, i.e. the Clausius statement implies the Kelvin statement. We can prove in a similar manner that the Kelvin statement implies the Clausius statement, and hence the two are equivalent.

Planck offered the following proposition as derived directly from experience. This is sometimes regarded as his statement of the second law, but he regarded it as a starting point for the derivation of the second law.

It is almost customary in textbooks to speak of the "Kelvin-Planck statement" of the law, as for example in the text by ter Haar and Wergeland.

The Kelvin–Planck statement (or the "heat engine statement") of the second law of thermodynamics states that

Planck stated the second law as follows.

Rather like Planck's statement is that of Uhlenbeck and Ford for "irreversible phenomena".

Constantin Carathéodory formulated thermodynamics on a purely mathematical axiomatic foundation. His statement of the second law is known as the Principle of Carathéodory, which may be formulated as follows:
In every neighborhood of any state S of an adiabatically enclosed system there are states inaccessible from S.
With this formulation, he described the concept of adiabatic accessibility for the first time and provided the foundation for a new subfield of classical thermodynamics, often called geometrical thermodynamics. It follows from Carathéodory's principle that quantity of energy quasi-statically transferred as heat is a holonomic process function, in other words, formula_9.

Though it is almost customary in textbooks to say that Carathéodory's principle expresses the second law and to treat it as equivalent to the Clausius or to the Kelvin-Planck statements, such is not the case. To get all the content of the second law, Carathéodory's principle needs to be supplemented by Planck's principle, that isochoric work always increases the internal energy of a closed system that was initially in its own internal thermodynamic equilibrium.

In 1926, Max Planck wrote an important paper on the basics of thermodynamics. He indicated the principle

This formulation does not mention heat and does not mention temperature, nor even entropy, and does not necessarily implicitly rely on those concepts, but it implies the content of the second law. A closely related statement is that "Frictional pressure never does positive work." Using a now-obsolete form of words, Planck himself wrote: "The production of heat by friction is irreversible."

Not mentioning entropy, this principle of Planck is stated in physical terms. It is very closely related to the Kelvin statement given just above. It is relevant that for a system at constant volume and mole numbers, the entropy is a monotonic function of the internal energy. Nevertheless, this principle of Planck is not actually Planck's preferred statement of the second law, which is quoted above, in a previous sub-section of the present section of this present article, and relies on the concept of entropy.

A statement that in a sense is complementary to Planck's principle is made by Borgnakke and Sonntag. They do not offer it as a full statement of the second law:

Differing from Planck's just foregoing principle, this one is explicitly in terms of entropy change. Removal of matter from a system can also decrease its entropy.

The second law has been shown to be equivalent to the internal energy "U" being a weakly convex function, when written as a function of extensive properties (mass, volume, entropy,...).

Before the establishment of the second law, many people who were interested in inventing a perpetual motion machine had tried to circumvent the restrictions of first law of thermodynamics by extracting the massive internal energy of the environment as the power of the machine. Such a machine is called a "perpetual motion machine of the second kind". The second law declared the impossibility of such machines.

Carnot's theorem (1824) is a principle that limits the maximum efficiency for any possible engine. The efficiency solely depends on the temperature difference between the hot and cold thermal reservoirs. Carnot's theorem states:

In his ideal model, the heat of caloric converted into work could be reinstated by reversing the motion of the cycle, a concept subsequently known as thermodynamic reversibility. Carnot, however, further postulated that some caloric is lost, not being converted to mechanical work. Hence, no real heat engine could realise the Carnot cycle's reversibility and was condemned to be less efficient.

Though formulated in terms of caloric (see the obsolete caloric theory), rather than entropy, this was an early insight into the second law.

The Clausius theorem (1854) states that in a cyclic process

The equality holds in the reversible case and the strict inequality holds in the irreversible case. The reversible case is used to introduce the state function entropy. This is because in cyclic processes the variation of a state function is zero from state functionality.

For an arbitrary heat engine, the efficiency is:

where "W" is for the net work done per cycle. Thus the efficiency depends only on q/q.

Carnot's theorem states that all reversible engines operating between the same heat reservoirs are equally efficient.
Thus, any reversible heat engine operating between temperatures "T" and "T" must have the same efficiency, that is to say, the efficiency is the function of temperatures only:
formula_12

In addition, a reversible heat engine operating between temperatures "T" and "T" must have the same efficiency as one consisting of two cycles, one between "T" and another (intermediate) temperature "T", and the second between "T" and"T". This can only be the case if

Now consider the case where formula_14 is a fixed reference temperature: the temperature of the triple point of water. Then for any "T" and "T",

Therefore, if thermodynamic temperature is defined by

then the function "f", viewed as a function of thermodynamic temperature, is simply

and the reference temperature "T" will have the value 273.16. (Any reference temperature and any positive numerical value could be usedthe choice here corresponds to the Kelvin scale.)

According to the Clausius equality, for a reversible process

That means the line integral formula_19 is path independent for reversible processes.

So we can define a state function S called entropy, which for a reversible process or for pure heat transfer satisfies

With this we can only obtain the difference of entropy by integrating the above formula. To obtain the absolute value, we need the third law of thermodynamics, which states that "S" = 0 at absolute zero for perfect crystals.

For any irreversible process, since entropy is a state function, we can always connect the initial and terminal states with an imaginary reversible process and integrating on that path to calculate the difference in entropy.

Now reverse the reversible process and combine it with the said irreversible process. Applying the Clausius inequality on this loop,

Thus,

where the equality holds if the transformation is reversible.

Notice that if the process is an adiabatic process, then formula_23, so formula_24.

An important and revealing idealized special case is to consider applying the Second Law to the scenario of an isolated system (called the total system or universe), made up of two parts: a sub-system of interest, and the sub-system's surroundings. These surroundings are imagined to be so large that they can be considered as an "unlimited" heat reservoir at temperature "T" and pressure "P" so that no matter how much heat is transferred to (or from) the sub-system, the temperature of the surroundings will remain "T"; and no matter how much the volume of the sub-system expands (or contracts), the pressure of the surroundings will remain "P".

Whatever changes to "dS" and "dS" occur in the entropies of the sub-system and the surroundings individually, according to the Second Law the entropy "S" of the isolated total system must not decrease:

According to the first law of thermodynamics, the change "dU" in the internal energy of the sub-system is the sum of the heat "δq" added to the sub-system, "less" any work "δw" done "by" the sub-system, "plus" any net chemical energy entering the sub-system "d ∑μN", so that:

where μ are the chemical potentials of chemical species in the external surroundings.

Now the heat leaving the reservoir and entering the sub-system is

where we have first used the definition of entropy in classical thermodynamics (alternatively, in statistical thermodynamics, the relation between entropy change, temperature and absorbed heat can be derived); and then the Second Law inequality from above.

It therefore follows that any net work "δw" done by the sub-system must obey

It is useful to separate the work "δw" done by the subsystem into the "useful" work "δw" that can be done "by" the sub-system, over and beyond the work "p dV" done merely by the sub-system expanding against the surrounding external pressure, giving the following relation for the useful work (exergy) that can be done:

It is convenient to define the right-hand-side as the exact derivative of a thermodynamic potential, called the "availability" or "exergy" "E" of the subsystem,

The Second Law therefore implies that for any process which can be considered as divided simply into a subsystem, and an unlimited temperature and pressure reservoir with which it is in contact,

i.e. the change in the subsystem's exergy plus the useful work done "by" the subsystem (or, the change in the subsystem's exergy less any work, additional to that done by the pressure reservoir, done "on" the system) must be less than or equal to zero.

In sum, if a proper "infinite-reservoir-like" reference state is chosen as the system surroundings in the real world, then the Second Law predicts a decrease in "E" for an irreversible process and no change for a reversible process.

This expression together with the associated reference state permits a design engineer working at the macroscopic scale (above the thermodynamic limit) to utilize the Second Law without directly measuring or considering entropy change in a total isolated system. ("Also, see process engineer"). Those changes have already been considered by the assumption that the system under consideration can reach equilibrium with the reference state without altering the reference state. An efficiency for a process or collection of processes that compares it to the reversible ideal may also be found ("See second law efficiency".)

This approach to the Second Law is widely utilized in engineering practice, environmental accounting, systems ecology, and other disciplines.

For a spontaneous chemical process in a closed system at constant temperature and pressure without non-"PV" work, the Clausius inequality Δ"S > Q/T" transforms into a condition for the change in Gibbs free energy

or d"G" < 0. For a similar process at constant temperature and volume, the change in Helmholtz free energy must be negative, formula_35. Thus, a negative value of the change in free energy (G or A) is a necessary condition for a process to be spontaneous. This is the most useful form of the second law of thermodynamics in chemistry, where free-energy changes can be calculated from tabulated enthalpies of formation and standard molar entropies of reactants and products. The chemical equilibrium condition at constant "T" and "p" without electrical work is d"G" = 0.

The first theory of the conversion of heat into mechanical work is due to Nicolas Léonard Sadi Carnot in 1824. He was the first to realize correctly that the efficiency of this conversion depends on the difference of temperature between an engine and its environment.

Recognizing the significance of James Prescott Joule's work on the conservation of energy, Rudolf Clausius was the first to formulate the second law during 1850, in this form: heat does not flow "spontaneously" from cold to hot bodies. While common knowledge now, this was contrary to the caloric theory of heat popular at the time, which considered heat as a fluid. From there he was able to infer the principle of Sadi Carnot and the definition of entropy (1865).

Established during the 19th century, the Kelvin-Planck statement of the Second Law says, "It is impossible for any device that operates on a cycle to receive heat from a single reservoir and produce a net amount of work." This was shown to be equivalent to the statement of Clausius.

The ergodic hypothesis is also important for the Boltzmann approach. It says that, over long periods of time, the time spent in some region of the phase space of microstates with the same energy is proportional to the volume of this region, i.e. that all accessible microstates are equally probable over a long period of time. Equivalently, it says that time average and average over the statistical ensemble are the same.

There is a traditional doctrine, starting with Clausius, that entropy can be understood in terms of molecular 'disorder' within a macroscopic system. This doctrine is obsolescent.

In 1856, the German physicist Rudolf Clausius stated what he called the "second fundamental theorem in the mechanical theory of heat" in the following form:

where "Q" is heat, "T" is temperature and "N" is the "equivalence-value" of all uncompensated transformations involved in a cyclical process. Later, in 1865, Clausius would come to define "equivalence-value" as entropy. On the heels of this definition, that same year, the most famous version of the second law was read in a presentation at the Philosophical Society of Zurich on April 24, in which, in the end of his presentation, Clausius concludes:

The entropy of the universe tends to a maximum.

This statement is the best-known phrasing of the second law. Because of the looseness of its language, e.g. universe, as well as lack of specific conditions, e.g. open, closed, or isolated, many people take this simple statement to mean that the second law of thermodynamics applies virtually to every subject imaginable. This is not true; this statement is only a simplified version of a more extended and precise description.

In terms of time variation, the mathematical statement of the second law for an isolated system undergoing an arbitrary transformation is:

where

The equality sign applies after equilibration. An alternative way of formulating of the second law for isolated systems is:

with formula_40 the sum of the rate of entropy production by all processes inside the system. The advantage of this formulation is that it shows the effect of the entropy production. The rate of entropy production is a very important concept since it determines (limits) the efficiency of thermal machines. Multiplied with ambient temperature formula_41 it gives the so-called dissipated energy formula_42.

The expression of the second law for closed systems (so, allowing heat exchange and moving boundaries, but not exchange of matter) is:

Here

The equality sign holds in the case that only reversible processes take place inside the system. If irreversible processes take place (which is the case in real systems in operation) the >-sign holds. If heat is supplied to the system at several places we have to take the algebraic sum of the corresponding terms.

For open systems (also allowing exchange of matter):

Here formula_49 is the flow of entropy into the system associated with the flow of matter entering the system. It should not be confused with the time derivative of the entropy. If matter is supplied at several places we have to take the algebraic sum of these contributions.

Statistical mechanics gives an explanation for the second law by postulating that a material is composed of atoms and molecules which are in constant motion. A particular set of positions and velocities for each particle in the system is called a microstate of the system and because of the constant motion, the system is constantly changing its microstate. Statistical mechanics postulates that, in equilibrium, each microstate that the system might be in is equally likely to occur, and when this assumption is made, it leads directly to the conclusion that the second law must hold in a statistical sense. That is, the second law will hold on average, with a statistical variation on the order of 1/ where "N" is the number of particles in the system. For everyday (macroscopic) situations, the probability that the second law will be violated is practically zero. However, for systems with a small number of particles, thermodynamic parameters, including the entropy, may show significant statistical deviations from that predicted by the second law. Classical thermodynamic theory does not deal with these statistical variations.

The first mechanical argument of the Kinetic theory of gases that molecular collisions entail an equalization of temperatures and hence a tendency towards equilibrium was due to James Clerk Maxwell in 1860; Ludwig Boltzmann with his H-theorem of 1872 also argued that due to collisions gases should over time tend toward the Maxwell-Boltzmann distribution.

Due to Loschmidt's paradox, derivations of the Second Law have to make an assumption regarding the past, namely that the system is uncorrelated at some time in the past; this allows for simple probabilistic treatment. This assumption is usually thought as a boundary condition, and thus the second Law is ultimately a consequence of the initial conditions somewhere in the past, probably at the beginning of the universe (the Big Bang), though other scenarios have also been suggested.

Given these assumptions, in statistical mechanics, the Second Law is not a postulate, rather it is a consequence of the fundamental postulate, also known as the equal prior probability postulate, so long as one is clear that simple probability arguments are applied only to the future, while for the past there are auxiliary sources of information which tell us that it was low entropy. The first part of the second law, which states that the entropy of a thermally isolated system can only increase, is a trivial consequence of the equal prior probability postulate, if we restrict the notion of the entropy to systems in thermal equilibrium. The entropy of an isolated system in thermal equilibrium containing an amount of energy of formula_50 is:

where formula_52 is the number of quantum states in a small interval between formula_50 and formula_54. Here formula_55 is a macroscopically small energy interval that is kept fixed. Strictly speaking this means that the entropy depends on the choice of formula_55. However, in the thermodynamic limit (i.e. in the limit of infinitely large system size), the specific entropy (entropy per unit volume or per unit mass) does not depend on formula_55.

Suppose we have an isolated system whose macroscopic state is specified by a number of variables. These macroscopic variables can, e.g., refer to the total volume, the positions of pistons in the system, etc. Then formula_58 will depend on the values of these variables. If a variable is not fixed, (e.g. we do not clamp a piston in a certain position), then because all the accessible states are equally likely in equilibrium, the free variable in equilibrium will be such that formula_58 is maximized as that is the most probable situation in equilibrium.

If the variable was initially fixed to some value then upon release and when the new equilibrium has been reached, the fact the variable will adjust itself so that formula_58 is maximized, implies that the entropy will have increased or it will have stayed the same (if the value at which the variable was fixed happened to be the equilibrium value).
Suppose we start from an equilibrium situation and we suddenly remove a constraint on a variable. Then right after we do this, there are a number formula_58 of accessible microstates, but equilibrium has not yet been reached, so the actual probabilities of the system being in some accessible state are not yet equal to the prior probability of formula_62. We have already seen that in the final equilibrium state, the entropy will have increased or have stayed the same relative to the previous equilibrium state. Boltzmann's H-theorem, however, proves that the quantity increases monotonically as a function of time during the intermediate out of equilibrium state.

The second part of the Second Law states that the entropy change of a system undergoing a reversible process is given by:

where the temperature is defined as:

See here for the justification for this definition. Suppose that the system has some external parameter, x, that can be changed. In general, the energy eigenstates of the system will depend on x. According to the adiabatic theorem of quantum mechanics, in the limit of an infinitely slow change of the system's Hamiltonian, the system will stay in the same energy eigenstate and thus change its energy according to the change in energy of the energy eigenstate it is in.

The generalized force, X, corresponding to the external variable x is defined such that formula_65 is the work performed by the system if x is increased by an amount dx. E.g., if x is the volume, then X is the pressure. The generalized force for a system known to be in energy eigenstate formula_66 is given by:

Since the system can be in any energy eigenstate within an interval of formula_55, we define the generalized force for the system as the expectation value of the above expression:

To evaluate the average, we partition the formula_52 energy eigenstates by counting how many of them have a value for formula_71 within a range between formula_72 and formula_73. Calling this number formula_74, we have:

The average defining the generalized force can now be written:

We can relate this to the derivative of the entropy with respect to x at constant energy E as follows. Suppose we change x to x + dx. Then formula_52 will change because the energy eigenstates depend on x, causing energy eigenstates to move into or out of the range between formula_50 and formula_79. Let's focus again on the energy eigenstates for which formula_71 lies within the range between formula_72 and formula_73. Since these energy eigenstates increase in energy by Y dx, all such energy eigenstates that are in the interval ranging from E – Y dx to E move from below E to above E. There are

such energy eigenstates. If formula_84, all these energy eigenstates will move into the range between formula_50 and formula_79 and contribute to an increase in formula_58. The number of energy eigenstates that move from below formula_79 to above formula_79 is given by formula_90. The difference

is thus the net contribution to the increase in formula_58. Note that if Y dx is larger than formula_55 there will be the energy eigenstates that move from below E to above formula_79. They are counted in both formula_95 and formula_90, therefore the above expression is also valid in that case.

Expressing the above expression as a derivative with respect to E and summing over Y yields the expression:

The logarithmic derivative of formula_58 with respect to x is thus given by:

The first term is intensive, i.e. it does not scale with system size. In contrast, the last term scales as the inverse system size and will thus vanishes in the thermodynamic limit. We have thus found that:

Combining this with

Gives:

If a system is in thermal contact with a heat bath at some temperature T then, in equilibrium, the probability distribution over the energy eigenvalues are given by the canonical ensemble:

Here Z is a factor that normalizes the sum of all the probabilities to 1, this function is known as the partition function. We now consider an infinitesimal reversible change in the temperature and in the external parameters on which the energy levels depend. It follows from the general formula for the entropy:

that

Inserting the formula for formula_106 for the canonical ensemble in here gives:

There are two principal ways of formulating thermodynamics, (a) through passages from one state of thermodynamic equilibrium to another, and (b) through cyclic processes, by which the system is left unchanged, while the total entropy of the surroundings is increased. These two ways help to understand the processes of life. This topic is mostly beyond the scope of this present article, but has been considered by several authors, such as Erwin Schrödinger, Léon Brillouin and Isaac Asimov. It is also the topic of current research.

To a fair approximation, living organisms may be considered as examples of (b). Approximately, an animal's physical state cycles by the day, leaving the animal nearly unchanged. Animals take in food, water, and oxygen, and, as a result of metabolism, give out breakdown products and heat. Plants take in radiative energy from the sun, which may be regarded as heat, and carbon dioxide and water. They give out oxygen. In this way they grow. Eventually they die, and their remains rot away, turning mostly back into carbon dioxide and water. This can be regarded as a cyclic process. Overall, the sunlight is from a high temperature source, the sun, and its energy is passed to a lower temperature sink, i.e. radiated into space. This is an increase of entropy of the surroundings of the plant. Thus animals and plants obey the second law of thermodynamics, considered in terms of cyclic processes. Simple concepts of efficiency of heat engines are hardly applicable to this problem because they assume closed systems.

From the thermodynamic viewpoint that considers (a), passages from one equilibrium state to another, only a roughly approximate picture appears, because living organisms are never in states of thermodynamic equilibrium. Living organisms must often be considered as open systems, because they take in nutrients and give out waste products. Thermodynamics of open systems is currently often considered in terms of passages from one state of thermodynamic equilibrium to another, or in terms of flows in the approximation of local thermodynamic equilibrium. The problem for living organisms may be further simplified by the approximation of assuming a steady state with unchanging flows. General principles of entropy production for such approximations are subject to unsettled current debate or research. Nevertheless, ideas derived from this viewpoint on the second law of thermodynamics are enlightening about living creatures.

In systems that do not require for their descriptions the general theory of relativity, bodies always have positive heat capacity, meaning that the temperature rises with energy. Therefore, when energy flows from a high-temperature object to a low-temperature object, the source temperature is decreased while the sink temperature is increased; hence temperature differences tend to diminish over time. This is not always the case for systems in which the gravitational force is important and the general theory of relativity is required. Such systems can spontaneously change towards uneven spread of mass and energy. This applies to the universe in large scale, and consequently it may be difficult or impossible to apply the second law to it. Beyond this, the thermodynamics of systems described by the general theory of relativity is beyond the scope of the present article.

The theory of classical or equilibrium thermodynamics is idealized. A main postulate or assumption, often not even explicitly stated, is the existence of systems in their own internal states of thermodynamic equilibrium. In general, a region of space containing a physical system at a given time, that may be found in nature, is not in thermodynamic equilibrium, read in the most stringent terms. In looser terms, nothing in the entire universe is or has ever been truly in exact thermodynamic equilibrium.

For purposes of physical analysis, it is often enough convenient to make an assumption of thermodynamic equilibrium. Such an assumption may rely on trial and error for its justification. If the assumption is justified, it can often be very valuable and useful because it makes available the theory of thermodynamics. Elements of the equilibrium assumption are that a system is observed to be unchanging over an indefinitely long time, and that there are so many particles in a system, that its particulate nature can be entirely ignored. Under such an equilibrium assumption, in general, there are no macroscopically detectable fluctuations. There is an exception, the case of critical states, which exhibit to the naked eye the phenomenon of critical opalescence. For laboratory studies of critical states, exceptionally long observation times are needed.

In all cases, the assumption of thermodynamic equilibrium, once made, implies as a consequence that no putative candidate "fluctuation" alters the entropy of the system.

It can easily happen that a physical system exhibits internal macroscopic changes that are fast enough to invalidate the assumption of the constancy of the entropy. Or that a physical system has so few particles that the particulate nature is manifest in observable fluctuations. Then the assumption of thermodynamic equilibrium is to be abandoned. There is no unqualified general definition of entropy for non-equilibrium states.

There are intermediate cases, in which the assumption of local thermodynamic equilibrium is a very good approximation, but strictly speaking it is still an approximation, not theoretically ideal. For non-equilibrium situations in general, it may be useful to consider statistical mechanical definitions of other quantities that may be conveniently called 'entropy', but they should not be confused or conflated with thermodynamic entropy properly defined for the second law. These other quantities indeed belong to statistical mechanics, not to thermodynamics, the primary realm of the second law.

Even though the applicability of the second law of thermodynamics is limited for non-equilibrium systems, the laws governing such systems are still being discussed. One of the guiding principles for systems which are far from equilibrium is the maximum entropy production principle. It states that a system away from equilibrium evolves in such a way as to maximize entropy production, given present constraints.

The physics of macroscopically observable fluctuations is beyond the scope of this article.

Thermodynamic Asymmetry in Time

The second law of thermodynamics is a physical law that is not symmetric to reversal of the time direction. This does not conflict with notions that have been observed of the fundamental laws of physics, namely CPT symmetry, since the second law applies statistically, it is hypothesized, on time-asymmetric "boundary conditions".

The second law has been proposed to supply a partial explanation of the difference between moving forward and backwards in time, such as why the cause precedes the effect (the causal arrow of time).

Irreversibility in thermodynamic processes is a consequence of the asymmetric character of thermodynamic operations, and not of any internally irreversible microscopic properties of the bodies. Thermodynamic operations are macroscopic external interventions imposed on the participating bodies, not derived from their internal properties. There are reputed "paradoxes" that arise from failure to recognize this.

Loschmidt's paradox, also known as the reversibility paradox, is the objection that it should not be possible to deduce an irreversible process from the time-symmetric dynamics that describe the microscopic evolution of a macroscopic system.

In the opinion of Schrödinger, "It is now quite obvious in what manner you have to reformulate the law of entropyor for that matter, all other irreversible statementsso that they be capable of being derived from reversible models. You must not speak of one isolated system but at least of two, which you may for the moment consider isolated from the rest of the world, but not always from each other." The two systems are isolated from each other by the wall, until it is removed by the thermodynamic operation, as envisaged by the law. The thermodynamic operation is externally imposed, not subject to the reversible microscopic dynamical laws that govern the constituents of the systems. It is the cause of the irreversibility. The statement of the law in this present article complies with Schrödinger's advice. The cause–effect relation is logically prior to the second law, not derived from it.

The Poincaré recurrence theorem considers a theoretical microscopic description of an isolated physical system. This may be considered as a model of a thermodynamic system after a thermodynamic operation has removed an internal wall. The system will, after a sufficiently long time, return to a microscopically defined state very close to the initial one. The Poincaré recurrence time is the length of time elapsed until the return. It is exceedingly long, likely longer than the life of the universe, and depends sensitively on the geometry of the wall that was removed by the thermodynamic operation. The recurrence theorem may be perceived as apparently contradicting the second law of thermodynamics. More obviously, however, it is simply a microscopic model of thermodynamic equilibrium in an isolated system formed by removal of a wall between two systems. For a typical thermodynamical system, the recurrence time is so large (many many times longer than the lifetime of the universe) that, for all practical purposes, one cannot observe the recurrence. One might wish, nevertheless, to imagine that one could wait for the Poincaré recurrence, and then re-insert the wall that was removed by the thermodynamic operation. It is then evident that the appearance of irreversibility is due to the utter unpredictability of the Poincaré recurrence given only that the initial state was one of thermodynamic equilibrium, as is the case in macroscopic thermodynamics. Even if one could wait for it, one has no practical possibility of picking the right instant at which to re-insert the wall. The Poincaré recurrence theorem provides a solution to Loschmidt's paradox. If an isolated thermodynamic system could be monitored over increasingly many multiples of the average Poincaré recurrence time, the thermodynamic behavior of the system would become invariant under time reversal.

James Clerk Maxwell imagined one container divided into two parts, "A" and "B". Both parts are filled with the same gas at equal temperatures and placed next to each other, separated by a wall. Observing the molecules on both sides, an imaginary demon guards a microscopic trapdoor in the wall. When a faster-than-average molecule from "A" flies towards the trapdoor, the demon opens it, and the molecule will fly from "A" to "B". The average speed of the molecules in "B" will have increased while in "A" they will have slowed down on average. Since average molecular speed corresponds to temperature, the temperature decreases in "A" and increases in "B", contrary to the second law of thermodynamics.

One response to this question was suggested in 1929 by Leó Szilárd and later by Léon Brillouin. Szilárd pointed out that a real-life Maxwell's demon would need to have some means of measuring molecular speed, and that the act of acquiring information would require an expenditure of energy.

Maxwell's 'demon' repeatedly alters the permeability of the wall between "A" and "B". It is therefore performing thermodynamic operations on a microscopic scale, not just observing ordinary spontaneous or natural macroscopic thermodynamic processes.


Can DNA be created?

DNA synthesis is the natural or artificial creation of deoxyribonucleic acid (DNA) molecules. The term DNA synthesis can refer to DNA replication - DNA biosynthesis ("in vivo" DNA amplification), polymerase chain reaction - enzymatic DNA synthesis ("in vitro" DNA amplification) or gene synthesis - physically creating artificial gene sequences.
In nature, DNA molecules are created by all living cells through the process of DNA replication, with replication initiator proteins splitting the cell's DNA and copying each split strand, with the copied strands then joining together with their template strand into a new DNA molecule. Various means exist to artificially stimulate the replication of naturally occurring DNA, or to create artificial gene sequences. The process of DNA replication occurs typically as part of cell division, during interphase.

DNA synthesis

A polymerase chain reaction is a form of enzymatic DNA synthesis in the laboratory, using cycles of repeated heating and cooling of the reaction for DNA melting and enzymatic replication of the DNA.

Artificial gene synthesis is the process of synthesizing a gene "in vitro" without the need for initial template DNA samples. In 2010 J. Craig Venter and his team were the first to use entirely synthesized DNA to create a self-replicating microbe, dubbed Mycoplasma laboratorium.

Twist Bioscience developed a silicon-based manufacturing process to industrialize the production of synthetic DNA. By synthesizing DNA on silicon instead of on traditional plastic plates, cost-effective, high-quality synthesis of genes, gene fragments, oligo pools and variant libraries (groups of gene sequences) for antibody and protein engineering, as well as consumable products for next-generation sequencing is enabled.
Oligonucleotide synthesis is the chemical synthesis of sequences of nucleic acids. The process has been automated since the late 1970s and can be used to form desired genetic sequences as well as for other uses in medicine and molecular biology.

New nucleobase pairs can also be synthesized, A-T (adenine - thymine) and G-C (guanine - cytosine). A third base pair would expand the number of amino acids that can be encoded by DNA from the existing 20 amino acids to a possible 172.

Artificial gene synthesis, sometimes known as DNA printing is a method in synthetic biology that is used to create artificial genes in the laboratory. Based on solid-phase DNA synthesis, it differs from molecular cloning and polymerase chain reaction (PCR) in that it does not have to begin with preexisting DNA sequences. Therefore, it is possible to make a completely synthetic double-stranded DNA molecule with no apparent limits on either nucleotide sequence or size

Artificial gene synthesis

The method has been used to generate functional bacterial or yeast chromosomes containing approximately one million base pairs. Creating novel nucleobase pairs in addition to the two base pairs in nature could greatly expand the genetic code.

Synthesis of the first complete gene, a yeast tRNA, was demonstrated by Har Gobind Khorana and coworkers in 1972. Synthesis of the first peptide- and protein-coding genes was performed in the laboratories of Herbert Boyer and Alexander Markham, respectively.

Commercial gene synthesis services are now available. Approaches are most often based on a combination of organic chemistry and molecular biology techniques and entire genes may be synthesized "de novo", without the need for template DNA. Gene synthesis is an important tool in many fields of recombinant DNA technology including heterologous gene expression, vaccine development, gene therapy and molecular engineering. The synthesis of nucleic acid sequences can be more economical than classical cloning and mutagenesis procedures. It is also a powerful and flexible engineering tool for creating and designing new DNA sequences and protein functions.

While the ability to make increasingly long stretches of DNA efficiently and at lower prices is a technological driver of this field, increasingly attention is being focused on improving the design of genes for specific purposes. Early in the genome sequencing era, gene synthesis was used as an (expensive) source of cDNAs that were predicted by genomic or partial cDNA information but were difficult to clone. As higher quality sources of sequence verified cloned cDNA have become available, this practice has become less urgent.

Producing large amounts of protein from gene sequences (or at least the protein coding regions of genes, the open reading frame) found in nature can sometimes prove difficult and is a problem of sufficient impact that scientific conferences have been devoted to the topic. Many of the most interesting proteins sought by molecular biologists are normally regulated to be expressed in very low amounts in wild type cells. Redesigning these genes offers a means to improve gene expression in many cases. Rewriting the open reading frame is possible because of the degeneracy of the genetic code. Thus it is possible to change up to about a third of the nucleotides in an open reading frame and still produce the same protein. The available number of alternate designs possible for a given protein is astronomical. For a typical protein sequence of 300 amino acids there are over 10 codon combinations that will encode an identical protein. Using optimization methods such as replacing rarely used codons with more common codons sometimes have dramatic effects. Further optimizations such as removing RNA secondary structures can also be included. At least in the case of "E. coli", protein expression is maximized by predominantly using codons corresponding to tRNA that retain amino acid charging during starvation. Computer programs written to perform these, and other simultaneous optimizations are used to handle the enormous complexity of the task. A well optimized gene can improve protein expression 2 to 10 fold, and in some cases more than 100 fold improvements have been reported. Because of the large numbers of nucleotide changes made to the original DNA sequence, the only practical way to create the newly designed genes is to use gene synthesis.

Oligonucleotides are chemically synthesized using building blocks called nucleoside phosphoramidites. These can be normal or modified nucleosides which have protecting groups to prevent their amines, hydroxyl groups and phosphate groups from interacting incorrectly. One phosphoramidite is added at a time, the 5' hydroxyl group is deprotected and a new base is added and so on. The chain grows in the 3' to 5' direction, which is backwards relative to biosynthesis. At the end, all the protecting groups are removed. Nevertheless, being a chemical process, several incorrect interactions occur leading to some defective products. The longer the oligonucleotide sequence that is being synthesized, the more defects there are, thus this process is only practical for producing short sequences of nucleotides. The current practical limit is about 200 bp (base pairs) for an oligonucleotide with sufficient quality to be used directly for a biological application. HPLC can be used to isolate products with the proper sequence. Meanwhile, a large number of oligos can be synthesized in parallel on gene chips. For optimal performance in subsequent gene synthesis procedures they should be prepared individually and in larger scales.

Usually, a set of individually designed oligonucleotides is made on automated solid-phase synthesizers, purified and then connected by specific annealing and standard ligation or polymerase reactions. To improve specificity of oligonucleotide annealing, the synthesis step relies on a set of thermostable DNA ligase and polymerase enzymes. To date, several methods for gene synthesis have been described, such as the ligation of phosphorylated overlapping oligonucleotides, the Fok I method and a modified form of ligase chain reaction for gene synthesis. Additionally, several PCR assembly approaches have been described. They usually employ oligonucleotides of 40-50 nucleotides long that overlap each other. These oligonucleotides are designed to cover most of the sequence of both strands, and the full-length molecule is generated progressively by overlap extension (OE) PCR, thermodynamically balanced inside-out (TBIO) PCR or combined approaches. The most commonly synthesized genes range in size from 600 to 1,200 bp although much longer genes have been made by connecting previously assembled fragments of under 1,000 bp. In this size range it is necessary to test several candidate clones confirming the sequence of the cloned synthetic gene by automated sequencing methods.

Moreover, because the assembly of the full-length gene product relies on the efficient and specific alignment of long single stranded oligonucleotides, critical parameters for synthesis success include extended sequence regions comprising secondary structures caused by inverted repeats, extraordinary high or low GC-content, or repetitive structures. Usually these segments of a particular gene can only be synthesized by splitting the procedure into several consecutive steps and a final assembly of shorter sub-sequences, which in turn leads to a significant increase in time and labor needed for its production.
The result of a gene synthesis experiment depends strongly on the quality of the oligonucleotides used. For these annealing based gene synthesis protocols, the quality of the product is directly and exponentially dependent on the correctness of the employed oligonucleotides. Alternatively, after performing gene synthesis with oligos of lower quality, more effort must be made in downstream quality assurance during clone analysis, which is usually done by time-consuming standard cloning and sequencing procedures.
Another problem associated with all current gene synthesis methods is the high frequency of sequence errors because of the usage of chemically synthesized oligonucleotides. The error frequency increases with longer oligonucleotides, and as a consequence the percentage of correct product decreases dramatically as more oligonucleotides are used.
The mutation problem could be solved by shorter oligonucleotides used to assemble the gene. However, all annealing based assembly methods require the primers to be mixed together in one tube. In this case, shorter overlaps do not always allow precise and specific annealing of complementary primers, resulting in the inhibition of full length product formation.
Manual design of oligonucleotides is a laborious procedure and does not guarantee the successful synthesis of the desired gene. For optimal performance of almost all annealing based methods, the melting temperatures of the overlapping regions are supposed to be similar for all oligonucleotides. The necessary primer optimization should be performed using specialized oligonucleotide design programs. Several solutions for automated primer design for gene synthesis have been presented so far.

To overcome problems associated with oligonucleotide quality several elaborate strategies have been developed, employing either separately prepared fishing oligonucleotides, mismatch binding enzymes of the mutS family or specific endonucleases from bacteria or phages. Nevertheless, all these strategies increase time and costs for gene synthesis based on the annealing of chemically synthesized oligonucleotides.

Massively parallel sequencing has also been used as a tool to screen complex oligonucleotide libraries and enable the retrieval of accurate molecules. In one approach, oligonucleotides are sequenced on the 454 pyrosequencing platform and a robotic system images and picks individual beads corresponding to accurate sequence. In another approach, a complex oligonucleotide library is modified with unique flanking tags before massively parallel sequencing. Tag-directed primers then enable the retrieval of molecules with desired sequences by dial-out PCR.

Increasingly, genes are ordered in sets including functionally related genes or multiple sequence variants on a single gene. Virtually all of the therapeutic proteins in development, such as monoclonal antibodies, are optimized by testing many gene variants for improved function or expression.

Major applications of synthetic genes include synthesis of DNA sequences identified by high throughput sequencing but never cloned into plasmids and the ability to safely obtain genes for vaccine research without the need to grow the full pathogens. Digital manipulation of digital genetic code before synthesis into DNA can be used to optimize protein expression in a particular host, or remove non-functional segments in order to facilitate further replication of the DNA.

Synthesis of DNA allows DNA digital data storage.

The significant drop in cost of gene synthesis in recent years due to increasing competition of companies providing this service has led to the ability to produce entire bacterial plasmids that have never existed in nature. The field of synthetic biology utilizes the technology to produce synthetic biological circuits, which are stretches of DNA manipulated to change gene expression within cells and cause the cell to produce a desired product.

On June 28, 2007, a team at the J. Craig Venter Institute published an article in "Science Express", saying that they had successfully transplanted the natural DNA from a "Mycoplasma mycoides" bacterium into a "Mycoplasma capricolum" cell, creating a bacterium which behaved like a "M. mycoides".

On Oct 6, 2007, Craig Venter announced in an interview with UK's "The Guardian" newspaper that the same team had synthesized a modified version of the single chromosome of "Mycoplasma genitalium" using chemicals. The chromosome was modified to eliminate all genes which tests in live bacteria had shown to be unnecessary. The next planned step in this "minimal genome project" is to transplant the synthesized minimal genome into a bacterial cell with its old DNA removed; the resulting bacterium will be called "Mycoplasma laboratorium". The next day the Canadian bioethics group, ETC Group issued a statement through their representative, Pat Mooney, saying Venter's "creation" was "a chassis on which you could build almost anything". The synthesized genome had not yet been transplanted into a working cell.

On May 21, 2010, "Science" reported that the Venter group had successfully synthesized the genome of the bacterium "Mycoplasma mycoides" from a computer record, and transplanted the synthesized genome into the existing cell of a "Mycoplasma capricolum" bacterium that had its DNA removed. The "synthetic" bacterium was viable, i.e. capable of replicating billions of times. The team had originally planned to use the "M. genitalium" bacterium they had previously been working with, but switched to "M. mycoides" because the latter bacterium grows much faster, which translated into quicker experiments. Venter describes it as "the first species... to have its parents be a computer". The transformed bacterium is dubbed "Synthia" by ETC. A Venter spokesperson has declined to confirm any breakthrough at the time of this writing.

In March 2014, Jef Boeke of the Langone Medical Centre at New York University, published that his team has synthesized one of the "S. cerevisiae" 16 yeast chromosomes, the chromosome III, that he named synIII. The procedure involved replacing the genes in the original chromosome with synthetic versions and the finished human made chromosome was then integrated into a yeast cell. It required designing and creating 273,871 base pairs of DNA – fewer than the 316,667 pairs in the original chromosome. In March 2017 6 yeast chromosomes were reported to have been synthesized.

DNA sequences have been described which use newly created nucleobases to form a third base pair, in addition to the two base pairs found in nature, A-T (adenine – thymine) and G-C (guanine – cytosine). Multiple research groups have been searching for a third base pair for DNA, including teams led by Steven A. Benner, Philippe Marliere, and Ichiro Hirao. Some new base pairs have been reported.

In 2012, a group of American scientists led by Floyd Romesberg, a chemical biologist at the Scripps Research Institute in San Diego, California, published that his team designed an unnatural base pair (UBP). The two new artificial nucleotides or "Unnatural Base Pair" (UBP) were named d5SICS and dNaM. More technically, these artificial nucleotides bearing hydrophobic nucleobases, feature two fused aromatic rings that form a (d5SICS–dNaM) complex or base pair in DNA. In 2014 the same team from the Scripps Research Institute reported that they synthesized a stretch of circular DNA known as a plasmid containing natural T-A and C-G base pairs along with the best-performing UBP Romesberg's laboratory had designed, and inserted it into cells of the common bacterium "E. coli" that successfully replicated the unnatural base pairs through multiple generations. This is the first known example of a living organism passing along an expanded genetic code to subsequent generations. This was in part achieved by the addition of a supportive algal gene that expresses a nucleotide triphosphate transporter which efficiently imports the triphosphates of both d5SICSTP and dNaMTP into "E. coli" bacteria. Then, the natural bacterial replication pathways use them to accurately replicate the plasmid containing d5SICS–dNaM.

The successful incorporation of a third base pair is a significant breakthrough toward the goal of greatly expanding the number of amino acids which can be encoded by DNA, from the existing 20 amino acids to a theoretically possible 172, thereby expanding the potential for living organisms to produce novel proteins. The artificial strings of DNA do not encode for anything yet, but scientists speculate they could be designed to manufacture new proteins which could have industrial or pharmaceutical uses.

Artificial gene synthesis