Some of the unregulated byproducts may possibly pose greater health risks than the regulated chemicals.
Due to its acidic nature, adding chloramine to the water supply may increase exposure to lead in drinking water, especially in areas with older housing; this exposure can result in increased lead levels in the bloodstream,
which may pose a significant health risk. Fortunately, water treatment
plants can add caustic chemicals at the plant which have the dual
purpose of reducing the corrosivity of the water, and stabilizing the
disinfectant.
Swimming pool disinfection
In swimming pools, chloramines are formed by the reaction of free chlorine with amine groups present in organic substances, mainly those biological in origin (e.g., urea in sweat and urine). Chloramines, compared to free chlorine, are both less effective as a sanitizer
and, if not managed correctly, more irritating to the eyes of swimmers.
Chloramines are responsible for the distinctive "chlorine" smell of
swimming pools, which is often misattributed to elemental chlorine by
the public.
Some pool test kits designed for use by homeowners do not distinguish
free chlorine and chloramines, which can be misleading and lead to
non-optimal levels of chloramines in the pool water.
There is also evidence that exposure to chloramine can contribute to respiratory problems, including asthma, among swimmers. Respiratory problems related to chloramine exposure are common and prevalent among competitive swimmers.
Though chloramine's distinctive smell has been described by some as pleasant and even nostalgic, its formation in pool water as a result of bodily fluids being exposed to chlorine can be minimised by encouraging showering and other hygiene methods prior to entering the pool, as well as refraining from swimming while suffering from digestive illnesses and taking breaks to use the bathroom.
Safety
US EPA drinking water quality standards limit chloramine concentration for public water systems to 4 parts per million
(ppm) based on a running annual average of all samples in the
distribution system. In order to meet EPA-regulated limits on
halogenated disinfection by-products, many utilities are switching from chlorination to chloramination.
While chloramination produces fewer regulated total halogenated
disinfection by-products, it can produce greater concentrations of
unregulated iodinated disinfection byproducts and N-nitrosodimethylamine. Both iodinated disinfection by-products and N-nitrosodimethylamine have been shown to be genotoxic, causing damage to the genetic information within a cell resulting in mutations which may lead to cancer.
Lead poisoning incidents
In the year 2000, Washington, DC,
switched from chlorine to monochloramine, causing lead to leach from
unreplaced pipes. The number of babies with elevated blood lead levels
rose about tenfold, and by one estimate fetal deaths rose between 32%
and 63%.
Trenton, Missouri
made the same switch, causing about one quarter of tested households to
exceed EPA drinking water lead limits in the period from 2017 to 2019.
20 children tested positive for lead poisoning in 2016 alone. In 2023, Virginia Tech
Professor Marc Edwards said lead spikes occur in several water utility
system switchovers per year, due to lack of sufficient training and lack
of removal of lead pipes.
Lack of utility awareness that lead pipes are still in use is also part
of the problem; the EPA has required all water utilities in the United
States to prepare a complete lead pipe inventory by October 16, 2024.
Synthesis and chemical reactions
Chloramine is a highly unstable compound in concentrated form. Pure chloramine decomposes violently above −40 °C (−40 °F).
Gaseous chloramine at low pressures and low concentrations of
chloramine in aqueous solution are thermally slightly more stable.
Chloramine is readily soluble in water and ether, but less soluble in chloroform and carbon tetrachloride.
This reaction is also the first step of the Olin Raschig process for hydrazine synthesis. The reaction has to be carried out in a slightly alkaline medium (pH 8.5–11). The acting chlorinating agent in this reaction is hypochlorous acid (HOCl), which has to be generated by protonation of hypochlorite, and then reacts in a nucleophilic substitution of the hydroxyl against the amino group.
The reaction occurs quickest at around pH 8. At higher pH values the
concentration of hypochlorous acid is lower, at lower pH values ammonia
is protonated to form ammonium ions (NH+ 4), which do not react further.
The chloramine solution can be concentrated by vacuum distillation and by passing the vapor through potassium carbonate which absorbs the water. Chloramine can be extracted with ether.
Gaseous chloramine can be obtained from the reaction of gaseous ammonia with chlorine gas (diluted with nitrogen gas):
The quantitative hydrolysis constant (K value) is used to express the bactericidal
power of chloramines, which depends on their generating hypochlorous
acid in water. It is expressed by the equation below, and is generally
in the range 10−4 to 10−10 (2.8×10−10 for monochloramine):
In aqueous solution, chloramine slowly decomposes to dinitrogen and ammonium chloride in a neutral or mildly alkaline (pH ≤ 11) medium:
3 NH2Cl → N2 + NH4Cl + 2 HCl
However, only a few percent of a 0.1 M
chloramine solution in water decomposes according to the formula in
several weeks. At pH values above 11, the following reaction with hydroxide ions slowly occurs:
At low pH values, nitrogen trichloride dominates and at pH 3–5
dichloramine dominates. These equilibria are disturbed by the
irreversible decomposition of both compounds:
NHCl2 + NCl3 + 2 H2O → N2 + 3 HCl + 2 HOCl
Reactions
In water, chloramine is pH-neutral. It is an oxidizing agent (acidic solution: E° = +1.48 V, in basic solution E° = +0.81 V):
Chloramine can, like hypochlorous acid, donate positively charged chlorine in reactions with nucleophiles (Nu−):
Nu− + NH3Cl+ → NuCl + NH3
Examples of chlorination reactions include transformations to
dichloramine and nitrogen trichloride in acidic medium, as described in
the decomposition section.
Nitrogen trichloride, also known as trichloramine, is the chemical compound with the formulaNCl3. This yellow, oily, and explosive liquid is most commonly encountered as a product of chemical reactions between ammonia-derivatives and chlorine (for example, in swimming pools). Alongside monochloramine and dichloramine,
trichloramine is responsible for the distinctive 'chlorine smell'
associated with swimming pools, where the compound is readily formed as a
product from hypochlorous acid reacting with ammonia and other nitrogenous substances in the water, such as urea from urine.
Intermediates in this conversion include monochloramine and dichloramine, NH2Cl and NHCl2, respectively.
Like ammonia, NCl3 is a pyramidal molecule. The N-Cl distances are 1.76 Å, and the Cl-N-Cl angles are 107°.
Reactions and uses
The chemistry of NCl3 has been well explored. It is moderately polar with a dipole moment of 0.6 D. The nitrogen center is basic but much less so than ammonia. It is hydrolyzed by hot water to release ammonia and hypochlorous acid.
Nitrogen trichloride can form in small amounts when public water supplies are disinfected with monochloramine, and in swimming pools by disinfecting chlorine reacting with urea in urine and sweat from bathers.
Nitrogen trichloride, trademarked as Agene, was at one time used to bleach flour, but this practice was banned in the United States in 1949 due to safety concerns.
Safety
Nitrogen trichloride can irritate mucous membranes—it is a lachrymatory agent, but has never been used as such.
The pure substance (rarely encountered) is a dangerous explosive, being
sensitive to light, heat, even moderate shock, and organic compounds. Pierre Louis Dulong first prepared it in 1812, and lost several fingers and an eye in two explosions. In 1813, an NCl3 explosion blinded Sir Humphry Davy temporarily, inducing him to hire Michael Faraday as a co-worker. They were both injured in another NCl3 explosion shortly thereafter.
Due to a lack of harmonization across disciplines, determinant, in its more widely accepted scientific meaning, is often used as a synonym. The main difference lies in the realm of practice: medicine (clinical practice) versus public health. As an example from clinical practice, low ingestion of dietary sources of vitamin C is a known risk factor for developing scurvy. Specific to public health policy, a determinant is a health risk that is general, abstract, related to inequalities, and difficult for an individual to control. For example, poverty is known to be a determinant of an individual's standard of health.
Risk factors or determinants are correlational and not necessarily causal, because correlation does not prove causation. For example, being young cannot be said to cause measles, but young people have a higher rate of measles because they are less likely to have developed immunity during a previous epidemic. Statistical methods are frequently used to assess the strength of an association and to provide causal evidence, for example in the study of the link between smoking and lung cancer.
Statistical analysis along with the biological sciences can establish
that risk factors are causal. Some prefer the term risk factor to mean
causal determinants of increased rates of disease, and for unproven
links to be called possible risks, associations, etc.
When done thoughtfully and based on research, identification of risk factors can be a strategy for medical screening.
Relative risk, such as "A woman is more than 100 times more likely to develop breast cancer in her 60s than in her 20s."
Fraction of incidences
occurring in the group having the property of or being exposed to the
risk factor, such as "99% of breast cancer cases are diagnosed in
women."
Increase in incidence in the exposed group, such as "each daily
alcoholic beverage increases the incidence of breast cancer by 11 cases
per 1000 women."
Hazard ratio,
such as "an increase in both total and invasive breast cancers in women
randomized to receive estrogen and progestin for an average of 5 years,
with a hazard ratio of 1.24 compared to controls."
Example
At
a wedding, 74 people ate the chicken and 22 of them were ill, while of
the 35 people who had the fish or vegetarian meal only 2 were ill. Did
the chicken make the people ill?
So the chicken eaters' risk = 22/74 = 0.297
And non-chicken eaters' risk = 2/35 = 0.057.
Those who ate the chicken had a risk over five times as high as
those who did not, that is, a relative risk of more than five. This
suggests that eating chicken was the cause of the illness, but this is not proof.
This example of a risk factor is described in terms of the relative risk it confers, which is evaluated by comparing the risk of those exposed to the potential risk factor to those not exposed.
General determinants
The probability of an outcome usually depends on an interplay between multiple associated variables. When performing epidemiological studies to evaluate one or more determinants for a specific outcome, the other determinants may act as confounding factors, and need to be controlled for, e.g. by stratification.
The potentially confounding determinants varies with what outcome is
studied, but the following general confounders are common to most
epidemiological associations, and are the determinants most commonly
controlled for in epidemiological studies:
Age (0 to 1.5 years for infants, 1.5 to 6 years for young children, etc.)
Sex or gender (Male or female)
Ethnicity (Based on race)
Other less commonly adjusted for possible confounders include:
A risk marker
is a variable that is quantitatively associated with a disease or other
outcome, but direct alteration of the risk marker does not necessarily
alter the risk of the outcome. For example, driving-while-intoxicated
(DWI) history is a risk marker for pilots as epidemiologic studies
indicate that pilots with a DWI history are significantly more likely
than their counterparts without a DWI history to be involved in aviation
crashes.
In epidemiology, environmental diseases are diseases that can be directly attributed to environmental factors (as distinct from genetic factors or infection). Apart from the true monogenicgenetic disorders, which are rare, environment is a major determinant of the development of disease. Diet, exposure to toxins, pathogens, radiation, and chemicals
found in almost all personal care products and household cleaners,
stress, racism, and physical and mental abuse are causes of a large
segment of non-hereditary disease. If a disease process is concluded to
be the result of a combination of genetic and environmental factor influences, its etiological origin can be referred to as having a multifactorial pattern.
There are many different types of environmental disease including:
Disease caused by physical factors in the environment, such as skin cancer caused by excessive exposure to ultraviolet radiation in sunlight
Environmental diseases vs. pollution-related diseases
Environmental diseases are a direct result from the environment. Meanwhile, pollution-related diseases
are attributed to exposure to toxicants or toxins in the air, water,
and soil. Therefore, all pollution-related disease are environmental
diseases, but not all environmental diseases are pollution-related
diseases.
Urban-associated diseases
Urban
areas are highly dense regions that currently hold ~50% of the global
population, a number expected to grow to 70% by 2050, and produce over 80% of the global GDP.
These areas are known to have a higher incidence of certain diseases,
which is of particular concern given their rapid growth. The urban
environment includes many risk factors for a variety of different
environmental diseases. Some of these risk factors, for instance, air-pollution,
are well known, while others such as altered microbial exposure are
less familiar to the general public. For instance, asthma can be induced
and exacerbated by combustion related pollution, which is more
prevalent in urban areas.
On the other hand, urban areas, compared to their rural counterparts,
lack diverse microbial communities, which can help prevent the
development of asthma. Both of these effects lead to a higher incidence of asthma in cities. Infectious diseases
are also often more common in cities, as transfer between hosts is
facilitated by high population densities. However, recent research shows
that increased access to healthcare weakens the urban association with
these diseases, and the net effect is still unclear. Many mental health disorders have also been associated with urban areas, especially in low socioeconomic areas.
Increased levels of stress, air & light & noise pollution, and
reduced "green" space are all urban-associated environmental effects
that are adversely linked to mental health.
Though urban areas are often correlated with dirtiness and disease,
they are likely to have more access to higher quality health care which
can lead to more positive health outcomes. This benefit will continue to
grow as innovation in health technologies steadily rises. Taking this
into account, while overall trends do exist, urban risk factors are
nuanced and often city and context dependent.
There are many other diseases likely to have been caused by common anions found in natural drinking water. Fluoride
is one of the most common found in drier climates where the geology
favors release of fluoride ions to soil as the rocks decompose. In Sri
Lanka, 90% of the country is underlain by crystalline metamorphic rocks
of which most carry mica as a major mineral. Mica carries fluoride in
their structure and releases to soil when decomposes. In the dry and
arid climates, fluoride concentrates on top soil and slowly dissolves in
shallow groundwater. This has been the cause of high fluoride levels in
drinking water where the majority of the rural Sri Lankans obtain their
drinking water from backyard wells. High fluoride in drinking water has
caused a high incidence of fluorosis
among dry zone population in Sri Lanka. However, in the wet zone, high
rainfall effectively removes fluoride from soils where no fluorosis is
evident. In some parts of Sri Lanka iodine deficiency has also been
noted which has been identified as a result of iodine fixation by
hydrated iron oxide found in lateritic soils in wet coastal lowlands.
The U.S. Coast Guard has developed a Coast Guard-wide comprehensive system for surveillance of workplace diseases.
The American Medical Association's
fifth edition of the Current Medical Information and Terminology (CMIT)
was used as a reference to expand the basic list of 50 Sentinel Health
Events (Occupational) [SHE(O)] published by the National Institute for
Occupational Health and Safety (NIOSH), September, 1983.
A protocell (or protobiont) is a self-organized, endogenously ordered, spherical collection of lipids proposed as a rudimentary precursor to cells during the origin of life.A central question in evolution
is how simple protocells first arose and how their progeny could
diversify, thus enabling the accumulation of novel biological emergences
over time (i.e. biological evolution).
Although a functional protocell has not yet been achieved in a
laboratory setting, the goal to understand the process appears well
within reach.
A protocell is a pre-cell in abiogenesis, and was a contained system consisting of simple biologically relevant molecules like ribozymes,
and encapsulated in a simple membrane structure – isolating the entity
from the environment and other individuals – thought to consist of
simple fatty acids, mineral structures, or rock-pore structures.
Overview
Compartmentalization was important in the origin of life.
Membranes form enclosed compartments that are separate from the
external environment, thus providing the cell with functionally
specialized aqueous spaces. As the lipid bilayer of membranes is
impermeable to most hydrophilic
molecules (dissolved by water), modern cells have membrane
transport-systems that achieve nutrient uptake as well as the export of
waste.
Prior to the development of these molecular assemblies, protocells
likely employed vesicle dynamics that are relevant to cellular
functions, such as membrane trafficking and self-reproduction, using amphiphilic molecules. On the primitive Earth, numerous chemical reactions of organic compounds produced the ingredients of life. Of these substances, amphiphilic molecules might be the first player in the evolution from molecular assembly to cellular life. Vesicle dynamics could progress towards protocells with the development of self-replication coupled with early metabolism. It is possible that protocells might have had a primitive metabolic system (Wood-Ljungdahl pathway) at alkaline hydrothermal vents or other geological environments like impact crater lakes from meteorites, which are known to be composed of elements found in the Wood-Ljungdahl pathway.
Another conceptual model of a protocell relates to the term "chemoton" (short for 'chemical automaton') which refers to the fundamental unit of life introduced by Hungariantheoretical biologistTibor Gánti.
It is the oldest known computational abstract of a protocell. Gánti
conceived the basic idea in 1952 and formulated the concept in 1971 in
his book The Principles of Life (originally written in Hungarian,
and translated to English only in 2003). He surmised the chemoton as
the original ancestor of all organisms, or the last universal common ancestor.
The basic assumption of the chemoton model is that life should fundamentally and essentially have three properties: metabolism, self-replication, and a bilipid membrane. The metabolic and replication functions together form an autocatalytic
subsystem necessary for the basic functions of life, and a membrane
encloses this subsystem to separate it from the surrounding environment.
Therefore, any system having such properties may be regarded as alive,
and will contain self sustaining cellular information that is subject to
natural selection. Some consider this model a significant contribution to origin of life as it provides a philosophy of evolutionary units.
Selectivity for compartmentalization
The three main structures phospholipids form in solution: the liposome (a closed bilayer), the micelle and the bilayer.
Self-assembled vesicles are essential components of primitive cells. The second law of thermodynamics requires that the universe becomes increasingly disordered (entropy), yet life is distinguished by its great degree of organization. Therefore, a boundary is needed to separate life processes from non-living matter. This fundamental necessity is underpinned by the universality of the cell membrane which is the only cellular structure found in all organisms on Earth.
In the aqueous environment in which all known cells function, a
non-aqueous barrier is required to surround a cell and separate it from
its surroundings.
This non-aqueous membrane establishes a barrier to free diffusion,
allowing for regulation of the internal environment within the barrier.
The necessity of thermodynamically isolating a subsystem is an
irreducible condition of life. In modern biology, such isolation is ordinarily accomplished by amphiphilic bilayers of a thickness of around 10−8 meters.
Researchers including Irene A. Chen and Jack W. Szostak
have demonstrated that simple physicochemical properties of elementary
protocells can give rise to simpler conceptual analogues of essential
cellular behaviors, including primitive forms of Darwinian competition
and energy storage. Such cooperative interactions between the membrane
and encapsulated contents could greatly simplify the transition from
replicating molecules to true cells.
Competition for membrane molecules would favor stabilized membranes,
suggesting a selective advantage for the evolution of cross-linked fatty
acids and even the phospholipids of today. This micro-encapsulation allowed for metabolism within the membrane, exchange of small molecules and prevention of passage of large substances across it. The main advantages of encapsulation include increased solubility of the cargo and creating energy in the form of chemical gradients. Energy is thus often said to be stored by cells in molecular structures such as carbohydrates (including sugars), lipids, and proteins, which release energy when chemically combined with oxygen during cellular respiration.
When phospholipids
or simple lipids like fatty acids are placed in water, the molecules
spontaneously arrange such that the hydrophobic tails are shielded from
the water, resulting in the formation of membrane structures such as bilayers, vesicles, and micelles. In modern cells, vesicles are involved in metabolism, transport, buoyancy control, and enzyme storage. They can also act as natural chemical reaction chambers. A typical vesicle or micelle in aqueous solution forms an aggregate with the hydrophilic "head" regions in contact with surrounding solvent, sequestering the hydrophobic single-tail regions in the micelle center. This phase is caused by the packing behavior of single-tail lipids in a bilayer. Although the spontaneous self-assembly process that form lipid monolayer
vesicles and micelles in nature resemble the kinds of primordial
vesicles or protocells that might have existed at the beginning of
evolution, they are not as sophisticated as the bilayer membranes of today's living organisms.
However, in a prebiotic context, electrostatic interactions induced by
short, positively charged, hydrophobic peptides containing seven amino
acids in length or fewer, can attach RNA to a vesicle membrane, the
basic cell membrane.
Rather than being made up of phospholipids, early membranes may have formed from monolayers or bilayers of simple fatty acids, which may have formed more readily in a prebiotic environment.
Fatty acids have been synthesized in laboratories under a variety of
prebiotic conditions and have been found on meteorites, suggesting their
natural synthesis in nature. Oleic acid vesicles represent good models of membrane protocells
Cohen et al. (2022) suggest that plausible prebiotic production
of fatty acids — leading to the development of early protocell membranes
— is enriched on metal-rich mineral surfaces, possibly from impact
craters, increasing the prebiotic environmental mass of lipids by 102 times.
They evaluate three different possible synthesis pathways of fatty
acids in the Hadean, and found that these metal surfaces could produce
1011 - 1015 kg of 6-18 carbon fatty acids. Of
these products, the 8-18C fatty acids are compatible with membrane
formation. They also propose that alternative amphiphiles like alcohols
are co-synthesized with fatty acid, and can help improve membrane
stability. However, despite this production, the authors state that net
fatty acid synthesis would not yield sufficient concentrations for
spontaneous membrane formation without significant evaporation of
Earth's aqueous environments.
Membrane transport
Schematic
showing two possible conformations of the lipids at the edge of a pore.
In the top image the lipids have not rearranged, so the pore wall is
hydrophobic. In the bottom image some of the lipid heads have bent over,
so the pore wall is hydrophilic.
For cellular organisms, the transport of specific molecules across
compartmentalizing membrane barriers is essential in order to exchange
content with their environment and with other individuals. For example,
content exchange between individuals enables the exchange of genes
between individuals (horizontal gene transfer), an important factor in the evolution of cellular life.
While modern cells can rely on complicated protein machineries to
catalyze these crucial processes, protocells must have accomplished this
using more simple mechanisms.
Protocells composed of fatty acids would have been able to easily exchange small molecules and ions with their environment.
Modern phospholipid bilayer cell membranes exhibit low permeability,
but contain complex molecular assemblies which both actively and
passively transport relevant molecules across the membrane in a highly
specific manner. In the absence of these complex assemblies, simple
fatty acid based protocell membranes would be more permeable and allow
for greater non-specific transport across membranes. Molecules that would be highly permeable across protocell membranes include nucleoside monophosphate (NMP), nucleoside diphosphate (NDP), and nucleoside triphosphate (NTP), and may withstand millimolar concentrations of Mg2+. Osmotic pressure can also play a significant role regarding this passive membrane transport.
Environmental effects have been suggested to trigger conditions under which a transport of larger molecules, such as DNA and RNA, across the membranes of protocells is possible. For example, it has been proposed that electroporation resulting from lightning strikes could enable such transport.
Electroporation is the rapid increase in bilayer permeability induced
by the application of a large artificial electric field across the
membrane. During electroporation, the lipid molecules in the membrane
shift position, opening up a pore (hole) that acts as a conductive
pathway through which hydrophobic molecules like nucleic acids can pass the lipid bilayer.
A similar transfer of content across protocells and with the
surrounding solution can be caused by freezing and subsequent thawing.
This could, for instance, occur in an environment in which day and night
cycles cause recurrent freezing. Laboratory experiments have shown that
such conditions allow an exchange of genetic information between
populations of protocells.
This can be explained by the fact that membranes are highly permeable
at temperatures slightly below their phase transition temperature. If
this point is reached during the freeze-thaw cycle, even large and
highly charged molecules can temporarily pass the protocell membrane.
Some molecules or particles are too large or too hydrophilic to
pass through a lipid bilayer even under these conditions, but can be
moved across the membrane through fusion or budding of vesicles, events which have also been observed for freeze-thaw cycles. This may eventually have led to mechanisms that facilitate movement of molecules to the inside of the protocell (endocytosis) or to release its contents into the extracellular space (exocytosis).
It has been proposed that life began in hydrothermal vents in the deep sea, but a 2012 study suggests that hot springs have the ideal characteristics for the origin of life.
The conclusion is based mainly on the chemistry of modern cells, where
the cytoplasm is rich in potassium, zinc, manganese, and phosphate ions,
not widespread in marine environments. Such conditions, the researchers
argue, are found only where hot hydrothermal fluid brings the ions to
the surface—places such as geysers, mud pots, fumaroles and other geothermal
features. Within these fuming and bubbling basins, water laden with
zinc and manganese ions could have collected, cooled and condensed in
shallow pools. However, a recent discovery of alkaline hydrothermal vents
with an ionic concentration of sodium lower than in seawater suggests
that high concentrations of potassium can be found at marine
environments.
A study in the 1990s showed that montmorillonite clay can help create RNA chains of as many as 50 nucleotides joined together spontaneously into a single RNA molecule. Later, in 2002, it was discovered that by adding montmorillonite to a solution of fatty acid micelles (lipid spheres), the clay sped up the rate of vesicle formation 100-fold.
Some minerals can catalyze the stepwise formation of hydrocarbon tails of fatty acids from hydrogen and carbon monoxide gases—gases that may have been released from hydrothermal vents or geysers. Fatty acids of various lengths are eventually released into the surrounding water,
but vesicle formation requires a higher concentration of fatty acids,
so it is suggested that protocell formation started at land-bound
hydrothermal freshwater environments such as geysers, mud pots, fumaroles and other geothermal features where water evaporates and concentrates the solute.
In 2019, Nick Lane
and colleagues show that vesicles form readily in seawater conditions
at pH between 6.5 and >12 and temperatures 70 °C, meant to mimic the
conditions of alkaline hydrothermal vents, with the presence of lipid
mixtures,
however a prebiotic source to such mixtures is unclear in those
environments. Simple amphiphilic compounds in seawater do not assemble
into vesicles because of the high concentration of ionic solutes.
Research has shown that vesicles can be bound and stabilized by
prebiotic amino acids even while in the presence of salt ions and
magnesium ions.
In hot spring conditions, self-assembly of vesicles occurs, which have a lower concentration of ionic solutes. Scientists oligomerized
RNA in alkaline hydrothermal vent conditions in the laboratory.
Although they were estimated to be 4 units in length, it implies RNA
polymers possibly were synthesized at such environments.
Experimental research at hot springs gave higher yields of RNA-like
polymers than in the laboratory. The polymers were encapsulated in fatty
acid vesicles when rehydrated, further supporting the hot spring
hypothesis of abiogenesis. These wet-dry cycles also improved vesicle stability and binding. UV exposure has also been shown to promote the synthesis of stable biomolecules like nucleotides.
In the origin of chemiosmosis,
if early cells originated at alkaline hydrothermal vents, proton
gradients can be maintained by the acidic ocean and alkaline water from
white smokers while an inorganic membranous structure is in a rock
cavity. If early cells originated in terrestrial pools such as hot springs, quinones present in meteorites like the Murchison meteorite
would promote the development of proton gradients by coupled redox
reactions if the ferricyanide, the electron acceptor, was within the
vesicle and an electron donor like a sulfur compound was outside of the
lipid membrane.
Because of the "water problem", a primitive ATP synthase and other
biomolecules would go through hydrolysis due to the absence of wet-dry
cycles at hydrothermal vents, unlike at terrestrial pools.
Other researchers propose hydrothermal pore systems coated in mineral
gels at deep sea hydrothermal vents to an alternative compartment of
membranous structures, promote biochemical reactions of biopolymers, and
could solve the "water problem".
David Deamer and Bruce Damer argue that biomolecules would become
trapped within these pore systems upon polymerization and would not
undergo combinatorial selection. Catalytic FeS and NiS walls at alkaline hydrothermal vents has also been suggested to have promoted polymerization.
However, Jackson (2016) evaluates how the pH gradient between
alkaline hydrothermal vents and acidic Hadean seawater might influence
prebiotic synthesis.
Three main criticisms emerge from this evaluation. Firstly, the
maintenance and stability of membranes positioned suitably between
turbulent pH gradients seemed implausible. They claim that the
proposition of CaCO3 and Mg(OH)2 precipitates
interacting with fluid mixing in subsurface pores do not produce
satisfactory environments. Secondly, they suggest that the molecular
assemblies required to utilize key energetic gradients available at
hydrothermal systems were too complex to have been relevant at the
origin of life. Lastly, they argue that even if a molecular assembly
could have harvested available hydrothermal energy, those assemblies
would have been too large to operate within the proposed membrane
thicknesses accepted by proponents of the hydrothermal vent hypothesis.
In 2017, Jackson takes a further stance, suggesting that even if an
organism successfully originated in alkaline hydrothermal pores,
exploiting natural pH gradients for energy, it would not be able to
withstand the drastic change of environment after emergence from the
vent environment in which it had solely evolved.
This emergence, however, is essential to the niche differentiation of
life, allowing for the diversification of habitats and energetic
strategies. Counters to these arguments suggest that the close
resemblance between biochemical pathways and geochemical systems at
alkaline hydrothermal vents gives merit to the hypothesis, and that
selection on these protocells would improve resilience to environmental
change, allowing for emergence and distribution.
It has been considered by other researchers that life originating
in hydrothermal volcanic ponds exposed to UV radiation, zinc sulfide
photocatalysis, and occurrence of continuous wet-dry cycling would not
resemble modern biochemistry.
Maximal ATP synthesis is shown to occur at high water activity and low
ion concentrations. Despite this, hydrothermal vents are still
considered to be a feasible environment as some shallow hydrothermal
vents emit freshwater and the concentration of divalent cations in
Hadean oceans were likely lower than in modern oceans. Nick Lane and
coauthors state that "alkaline hydrothermal systems tend to precipitate
Ca2+ and Mg2+ ions as aragonite and brucite, so
their concentrations are typically much lower than mean ocean values.
Modelling work in relation to Hadean systems indicates that hydrothermal
concentrations of Ca2+ and Mg2+ would likely have
been <1 mM, which is in the range that enhanced phosphorylation
here. Other conditions considered here, including salinity and high
pressure, would have only limited effects on ATP synthesis in submarine
hydrothermal systems (which typically have pressures in the range of 100
to 300 Bars). Alkaline hydrothermal systems might also have generated
Fe3+ in situ for ADP phosphorylation. Thermodynamic modelling
shows that the mixing of alkaline hydrothermal fluids with seawater in
submarine systems can promote continuous cycling between ferrous and
ferric iron, potentially forming soluble hydrous ferric chlorides, which
our experiments show have the same effect as ferric sulphate".
Montmorillonite bubbles
Another
group suggests that primitive cells might have formed inside inorganic
clay microcompartments, which can provide an ideal container for the
synthesis and compartmentalization of complex organic molecules. Clay-armored bubbles form naturally when particles of montmorillonite
clay collect on the outer surface of air bubbles under water. This
creates a semi permeable vesicle from materials that are readily
available in the environment. The authors remark that montmorillonite is
known to serve as a chemical catalyst, encouraging lipids to form
membranes and single nucleotides to join into strands of RNA. Primitive
reproduction can be envisioned when the clay bubbles burst, releasing
the lipid membrane-bound product into the surrounding medium.
Membraneless droplets
Another
way to form primitive compartments that may lead to the formation of a
protocell is polyesters membraneless structures that have the ability to
host biochemicals (proteins and RNA) and/or scaffold the assemblies of
lipids around them. While these droplets are leaky towards genetic materials, this leakiness could have facilitated the progenote hypothesis.
Coacervates
Researchers have also proposed early encapsulation in aqueous phase-separated droplets called coacervates.
These droplets are driven by the accumulation of macromolecules,
producing a distinct dense phase liquid droplet within a more dilute
liquid medium.
These droplets can propagate, retaining their internal composition,
through shear forces and turbulence in the medium, and could have acted
as a means of replicating encapsulation for an early protocell. However,
replication was highly disordered and droplet fusion is common, calling
into question coacervates true potential for distinct
compartmentalization leading to competition and early
Darwinian-selection.
Sexual reproduction
Eigenet al. and Woese proposed that the genomes of early protocells were composed of single-stranded RNA, and that individual genes corresponded to separate RNA segments, rather than being linked end-to-end as in present-day DNA genomes. A protocell that was haploid
(one copy of each RNA gene) would be vulnerable to damage, since a
single lesion in any RNA segment would be potentially lethal to the
protocell (e.g. by blocking replication or inhibiting the function of an
essential gene).
Vulnerability to damage could be reduced by maintaining two or
more copies of each RNA segment in each protocell, i.e. by maintaining
diploidy or polyploidy. Genome redundancy would allow a damaged RNA
segment to be replaced by an additional replication of its homolog.
For such a simple organism, the proportion of available resources tied
up in the genetic material would be a large fraction of the total
resource budget. Under limited resource conditions, the protocell
reproductive rate would likely be inversely related to ploidy number,
and the protocell's fitness would be reduced by the costs of redundancy.
Consequently, coping with damaged RNA genes while minimizing the costs
of redundancy would likely have been a fundamental problem for early
protocells.
A cost-benefit analysis was carried out in which the costs of
maintaining redundancy were balanced against the costs of genome damage.
This analysis led to the conclusion that, under a wide range of
circumstances, the selected strategy would be for each protocell to be
haploid, but to periodically fuse with another haploid protocell to form
a transient diploid. The retention of the haploid state maximizes the
growth rate. The periodic fusions permit mutual reactivation of
otherwise lethally damaged protocells. If at least one damage-free copy
of each RNA gene is present in the transient diploid, viable progeny can
be formed. For two, rather than one, viable daughter cells to be
produced would require an extra replication of the intact RNA gene
homologous to any RNA gene that had been damaged prior to the division
of the fused protocell. The cycle of haploid reproduction, with
occasional fusion to a transient diploid state, followed by splitting to
the haploid state, can be considered to be the sexual cycle in its most
primitive form. In the absence of this sexual cycle, haploid protocells with damage in an essential RNA gene would simply die.
This model for the early sexual cycle is hypothetical, but it is
very similar to the known sexual behavior of the segmented RNA viruses,
which are among the simplest organisms known. Influenza virus, whose genome consists of 8 physically separated single-stranded RNA segments,
is an example of this type of virus. In segmented RNA viruses, "mating"
can occur when a host cell is infected by at least two virus particles.
If these viruses each contain an RNA segment with a lethal damage,
multiple infection can lead to reactivation providing that at least one
undamaged copy of each virus gene is present in the infected cell. This
phenomenon is known as "multiplicity reactivation". Multiplicity
reactivation has been reported to occur in influenza virus infections
after induction of RNA damage by UV-irradiation, and ionizing radiation.
Starting with a technique commonly used to deposit molecules on a
solid surface, Langmuir–Blodgett deposition, scientists are able to
assemble phospholipid membranes of arbitrary complexity layer by layer. These artificial phospholipid membranes support functional insertion both of purified and of in situ expressed membrane proteins. The technique could help astrobiologists understand how the first living cells originated.
Surfactant molecules arranged on an air–water interface
Jeewanu protocells are synthetic chemical particles that possess cell-like structure and seem to have some functional living properties. First synthesized in 1963 from simple minerals and basic organics while exposed to sunlight, it is still reported to have some metabolic capabilities, the presence of semipermeable membrane, amino acids, phospholipids, carbohydrates and RNA-like molecules. The nature and properties of the Jeewanu remains to be clarified.
In a similar synthesis experiment a frozen mixture of water, methanol, ammonia and carbon monoxide
was exposed to ultraviolet (UV) radiation. This combination yielded
large amounts of organic material that self-organised to form globules
or vesicles when immersed in water.
The investigating scientist considered these globules to resemble cell
membranes that enclose and concentrate the chemistry of life, separating
their interior from the outside world. The globules were between 10 and
40 micrometres (0.00039 and 0.00157 in), or about the size of red blood
cells. Remarkably, the globules fluoresced,
or glowed, when exposed to UV light. Absorbing UV and converting it
into visible light in this way was considered one possible way of
providing energy to a primitive cell. If such globules played a role in
the origin of life, the fluorescence could have been a precursor to
primitive photosynthesis.
Such fluorescence also provides the benefit of acting as a sunscreen,
diffusing any damage that otherwise would be inflicted by UV radiation.
Such a protective function would have been vital for life on the early
Earth, since the ozone layer, which blocks out the sun's most destructive UV rays, did not form until after photosynthetic life began to produce oxygen.
The synthesis of three kinds of "jeewanu" have been reported; two of
them were organic, and the other was inorganic. Other similar inorganic
structures have also been produced. The investigating scientist (V. O.
Kalinenko) referred to them as "bio-like structures" and "artificial
cells". Formed in distilled water (as well as on agar gel) under the
influence of an electric field, they lack protein, amino acids, purine
or pyrimidine bases, and certain enzyme activities. According to NASA
researchers, "presently known scientific principles of biology and
biochemistry cannot account for living inorganic units" and "the
postulated existence of these living units has not been proved".
Analogous Research: Fuel Cells
In March 2014, NASA's Jet Propulsion Laboratory demonstrated a unique way to study the origins of life: fuel cells.
Fuel cells are similar to biological cells in that electrons are also
transferred to and from molecules. In both cases, this results in
electricity and power. The study of fuel cells suggest that an important
factor in protocell development was that the Earth provides electrical
energy at the seafloor. "This energy could have kick-started life and
could have sustained life after it arose. Now, we have a way of testing
different materials and environments that could have helped life arise
not just on Earth, but possibly on Mars, Europa and other places in the Solar System."
Ethics, controversy, and research considerations
Protocell research has created controversy and opposing opinions, including criticism of vague definitions of "artificial life".
The creation of a basic unit of life is the most pressing ethical
concern, although the most widespread worry about protocells is their
potential threat to human health and the environment through
uncontrolled replication.
Additionally, postulation into the conditions for protocellular
origins of life on Earth remain debated. Scientists in the field
emphasize the importance of further hypothesis based experimentation
over theoretical conjecture to more concretely constrain the prebiotic
plausibility of different protocell morphologies, geologic conditions,
and synthetic schemes.
