Hemozoin
Encyclopedia
Hemozoin is a disposal product formed from the digestion of blood
by some blood-feeding parasites. These hematophagous
organisms such as Malaria
parasites (Plasmodium
spp.), Rhodnius
and Schistosoma
digest hemoglobin
and release high quantities of free heme
, which is the non-protein component of hemoglobin
. A heme is a prosthetic group that consists of an iron
atom contained in the center of a heterocyclic porphyrin
ring. Free heme is toxic to cells, so the parasites convert it into an insoluble crystalline form called hemozoin. In malaria parasites, hemozoin is often called malaria pigment.
Since the formation of hemozoin is essential to the survival of these parasites, it is an attractive target for developing drugs
and is much-studied in Plasmodium
as a way to find drugs to treat malaria
(malaria's Achilles' heel
). Several currently-used antimalarial drug
s, such as chloroquine
and mefloquine
, are thought to kill malaria parasites by inhibiting hemozoin biocrystallization
.
realized in 1880 that "malaria pigment" is, instead, produced by the parasites, as they multiplied within the red blood cell
. The link between pigment and malaria parasites was used by Ronald Ross
to identify the stages in the Plasmodium life cycle that occur within the mosquito, since, although these forms of the parasite are different in appearance to the blood stages, they still contain traces of pigment.
Later, in 1891, T. Carbone and W.H. Brown (1911) published papers linking the degradation of hemoglobin with the production of pigment, describing the malaria pigment as a form of hematin and disproving the widely-held idea that it is related to melanin
. Brown observed that all melanins were bleaching rapidly with potassium permanganate, while with this reagent malarial pigment manifests not the slightest sign of a true bleach reaction. The name "hemozoin" was proposed by Louis Westenra Sambon. In the 1930s several authors identified hemozoin as a pure crystalline form of α-hematin and showed that the substance did not contain proteins within the crystals, but no explanation for the solubility differences between malaria pigment and α-hematin crystals was given.
. The digestion of hemoglobin releases monomeric α-hematin (ferriprotoporphyrin IX). This compound is toxic, since it is a pro-oxidant
and catalyzes the production of reactive oxygen species
. Oxidative stress
is believed to be generated during the conversion of heme (ferroprotoporphyrin) to hematin (ferriprotoporphyrin). Free hematin can also bind to and disrupt cell membrane
s, damaging cell structures and causing the lysis of the host erythrocyte. The unique reactivity of this molecule has been demonstrated in several in vitro and in vivo experimental conditions.
The malaria parasite, therefore, detoxifies the hematin, which it does by biocrystallization
—converting it into insoluble and chemically-inert β-hematin crystals (called hemozoin). In Plasmodium the food vacuole fills with hemozoin crystals, which are about 100-200 nanometre
s long and each contain about 80,000 heme molecules. Detoxification through biocrystallization is distinct from the detoxification process in mammals, where an enzyme called heme oxygenase
instead breaks excess heme into biliverdin
, iron
, and carbon monoxide
.
Several mechanisms have been proposed for the production of hemozoin in Plasmodium, and the area is highly controversial, with membrane lipid
s, histidine-rich proteins, or even a combination of the two, being proposed to catalyse the formation of hemozoin. Other authors have described a Heme Detoxification Protein, which is claimed to be more potent than either lipids or histidine-rich proteins. It is possible that many processes contribute to the formation of hemozoin.
The formation of hemozoin in other blood-feeding organisms is not as well-studied as in Plasmodium. However, studies on Schistosoma mansoni
have revealed that this parasitic worm
produces large amounts of hemozoin during its growth in the human bloodstream. Although the shapes of the crystals are different from those produced by malaria parasites, chemical analysis of the pigment showed that it is made of hemozoin. In a similar manner, the crystals formed in the gut of the kissing bug Rhodnius prolixus
during digestion of the blood meal also have a unique shape, but are composed of hemozoin. Hz formation in R. prolixus midgut occurs at physiologically relevant physico-chemical conditions and lipids play an important role in heme biocrystallization. Autocatalytic heme crystallization to Hz is revealed to be an inefficient process and this conversion is further reduced as the Hz concentration increases.
Several other mechanisms have been developed to protect a large variety of hematophagous
organisms against the toxic effects of free heme. Mosquitoes digest their blood meals
extracellularly and do not produce hemozoin. Heme is retained in the peritrophic matrix
, a layer of protein and polysaccharides that covers the midgut and separates gut cells from the blood bolus.
Although β-hematin can be produced in assays
spontaneously at low pH
, the development of a simple and reliable method to measure the production of hemozoin has been difficult. This is in part due to the continued uncertainty over what molecules are involved in producing hemozoin, and partly from the difficulty in measuring the difference between aggregated or precipitated heme, and genuine hemozoin. Current assays are sensitive and accurate, but require multiple washing steps so are slow and not ideal for high-throughput screening
. However, some screens have been performed with these assays.
-oxygen
coordinate bond links the central iron of one hematin to the oxygen of the carboxylate side-chain of the adjacent hematin. These reciprocal iron–oxygen bonds are highly unusual and have not been observed in any other porphyrin dimer. β-Hematin can be either a cyclic dimer or a linear polymer
, a polymeric form has never been found in hemozoin, disproving the widely-held idea that hemozoin is produced by the enzyme
heme-polymerase.
Hemozoin crystals have a distinct triclinic structure and are weakly magnetic. The difference between diamagnetic low-spin oxyhemoglobin and paramagnetic hemozoin can be used for isolation. They also exhibit optical dichroism
, which means that they absorb light more strongly along their length than across their width, which allows the automated detection of malaria. Hemozoin is produced in a form that, under the action of an applied magnetic field
, gives rise to an induced optical dichroism
characteristic of the hemozoin concentration; and precise measurement of this induced dichroism
may be used to determine the level of malarial infection.
The best-understood examples of such hematin biocrystallization
inhibitors are quinoline
drugs such as chloroquine
and mefloquine
. These drugs bind to both free heme and hemozoin crystals, and therefore block the addition of new heme units onto the growing crystals. The small, most rapidly growing face is the face to which inhibitors are believed to bind.
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
by some blood-feeding parasites. These hematophagous
Hematophagy
Hematophagy is the practice of certain animals of feeding on blood...
organisms such as Malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
parasites (Plasmodium
Plasmodium
Plasmodium is a genus of parasitic protists. Infection by these organisms is known as malaria. The genus Plasmodium was described in 1885 by Ettore Marchiafava and Angelo Celli. Currently over 200 species of this genus are recognized and new species continue to be described.Of the over 200 known...
spp.), Rhodnius
Rhodnius
Rhodnius is a genus of bugs in the subfamily Triatominae, important vectors of Chagas disease. They were important models for Sir Vincent Wigglesworth's studies of insect physiology, specifically growth and development.-Species:...
and Schistosoma
Schistosoma
A genus of trematodes, Schistosoma, commonly known as blood-flukes and bilharzia, includes flatworms which are responsible for a highly significant parasitic infection of humans by causing the disease schistosomiasis, and are considered by the World Health Organization as the second most...
digest hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
and release high quantities of free heme
Heme
A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...
, which is the non-protein component of hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
. A heme is a prosthetic group that consists of an iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
atom contained in the center of a heterocyclic porphyrin
Porphyrin
Porphyrins are a group of organic compounds, many naturally occurring. One of the best-known porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin. Porphyrins are heterocyclic macrocycles composed of four modified pyrrole subunits interconnected at...
ring. Free heme is toxic to cells, so the parasites convert it into an insoluble crystalline form called hemozoin. In malaria parasites, hemozoin is often called malaria pigment.
Since the formation of hemozoin is essential to the survival of these parasites, it is an attractive target for developing drugs
Drug development
Drug development is a blanket term used to define the process of bringing a new drug to the market once a lead compound has been identified through the process of drug discovery...
and is much-studied in Plasmodium
Plasmodium
Plasmodium is a genus of parasitic protists. Infection by these organisms is known as malaria. The genus Plasmodium was described in 1885 by Ettore Marchiafava and Angelo Celli. Currently over 200 species of this genus are recognized and new species continue to be described.Of the over 200 known...
as a way to find drugs to treat malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
(malaria's Achilles' heel
Achilles' heel
An Achilles’ heel is a deadly weakness in spite of overall strength, that can actually or potentially lead to downfall. While the mythological origin refers to a physical vulnerability, metaphorical references to other attributes or qualities that can lead to downfall are common.- Origin :In Greek...
). Several currently-used antimalarial drug
Antimalarial drug
Antimalarial medications, also known as antimalarials, are designed to prevent or cure malaria. Such drugs may be used for some or all of the following:* Treatment of malaria in individuals with suspected or confirmed infection...
s, such as chloroquine
Chloroquine
Chloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-History:Chloroquine , N'--N,N-diethyl-pentane-1,4-diamine, was discovered in 1934 by Hans Andersag and co-workers at the Bayer laboratories who named it "Resochin". It was ignored for a decade because it was...
and mefloquine
Mefloquine
Mefloquine hydrochloride is an orally administered medication used in the prevention and treatment of malaria. Mefloquine was developed in the 1970s at the United States Department of Defense's Walter Reed Army Institute of Research as a synthetic analogue of quinine...
, are thought to kill malaria parasites by inhibiting hemozoin biocrystallization
Biocrystallization
Biocrystallization is the formation of crystals from organic macromolecules by living organisms. This may be a stress response, a normal part of metabolism such as processes that dispose of waste compounds, or a pathology. Template mediated crystallization is qualitatively different from in vitro...
.
Discovery
Black-brown pigment was observed by Johann Heinrich Meckel in 1847, in the blood and spleen of a person suffering from insanity. However, it was not until 1849 that the presence of this pigment was connected to infection with malaria. Initially, it was thought that this pigment was produced by the body in response to infection, but Charles Louis Alphonse LaveranCharles Louis Alphonse Laveran
Charles Louis Alphonse Laveran was a French physician.In 1880, while working in the military hospital in Constantine, Algeria, he discovered that the cause of malaria is a protozoan, after observing the parasites in a blood smear taken from a patient who had just died of malaria.He also helped...
realized in 1880 that "malaria pigment" is, instead, produced by the parasites, as they multiplied within the red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
. The link between pigment and malaria parasites was used by Ronald Ross
Ronald Ross
Sir Ronald Ross KCB FRS was a British doctor who received the Nobel Prize for Physiology or Medicine in 1902 for his work on malaria. He was the first Indian-born person to win a Nobel Prize...
to identify the stages in the Plasmodium life cycle that occur within the mosquito, since, although these forms of the parasite are different in appearance to the blood stages, they still contain traces of pigment.
Later, in 1891, T. Carbone and W.H. Brown (1911) published papers linking the degradation of hemoglobin with the production of pigment, describing the malaria pigment as a form of hematin and disproving the widely-held idea that it is related to melanin
Melanin
Melanin is a pigment that is ubiquitous in nature, being found in most organisms . In animals melanin pigments are derivatives of the amino acid tyrosine. The most common form of biological melanin is eumelanin, a brown-black polymer of dihydroxyindole carboxylic acids, and their reduced forms...
. Brown observed that all melanins were bleaching rapidly with potassium permanganate, while with this reagent malarial pigment manifests not the slightest sign of a true bleach reaction. The name "hemozoin" was proposed by Louis Westenra Sambon. In the 1930s several authors identified hemozoin as a pure crystalline form of α-hematin and showed that the substance did not contain proteins within the crystals, but no explanation for the solubility differences between malaria pigment and α-hematin crystals was given.
Formation
During its intraerythrocytic asexual reproduction cycle Plasmodium falciparum consumes up to 80% of the host cell hemoglobinHemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
. The digestion of hemoglobin releases monomeric α-hematin (ferriprotoporphyrin IX). This compound is toxic, since it is a pro-oxidant
Pro-oxidant
Pro-oxidants are chemicals that induce oxidative stress, through either creating reactive oxygen species or inhibiting antioxidant systems. The oxidative stress produced by these chemicals can damage cells and tissues...
and catalyzes the production of reactive oxygen species
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
. Oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
is believed to be generated during the conversion of heme (ferroprotoporphyrin) to hematin (ferriprotoporphyrin). Free hematin can also bind to and disrupt cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
s, damaging cell structures and causing the lysis of the host erythrocyte. The unique reactivity of this molecule has been demonstrated in several in vitro and in vivo experimental conditions.
Biocrystallization
Biocrystallization is the formation of crystals from organic macromolecules by living organisms. This may be a stress response, a normal part of metabolism such as processes that dispose of waste compounds, or a pathology. Template mediated crystallization is qualitatively different from in vitro...
—converting it into insoluble and chemically-inert β-hematin crystals (called hemozoin). In Plasmodium the food vacuole fills with hemozoin crystals, which are about 100-200 nanometre
Nanometre
A nanometre is a unit of length in the metric system, equal to one billionth of a metre. The name combines the SI prefix nano- with the parent unit name metre .The nanometre is often used to express dimensions on the atomic scale: the diameter...
s long and each contain about 80,000 heme molecules. Detoxification through biocrystallization is distinct from the detoxification process in mammals, where an enzyme called heme oxygenase
Heme oxygenase
This reaction can occur in virtually every cell; the classic example is the formation of a bruise, which goes through different colors as it gradually heals: red heme to green biliverdin to yellow bilirubin...
instead breaks excess heme into biliverdin
Biliverdin
Biliverdin is a green tetrapyrrolic bile pigment, and is a product of heme catabolism. It is the pigment responsible for a greenish color sometimes seen in bruises.- Metabolism :...
, iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
, and carbon monoxide
Carbon monoxide
Carbon monoxide , also called carbonous oxide, is a colorless, odorless, and tasteless gas that is slightly lighter than air. It is highly toxic to humans and animals in higher quantities, although it is also produced in normal animal metabolism in low quantities, and is thought to have some normal...
.
Several mechanisms have been proposed for the production of hemozoin in Plasmodium, and the area is highly controversial, with membrane lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
s, histidine-rich proteins, or even a combination of the two, being proposed to catalyse the formation of hemozoin. Other authors have described a Heme Detoxification Protein, which is claimed to be more potent than either lipids or histidine-rich proteins. It is possible that many processes contribute to the formation of hemozoin.
The formation of hemozoin in other blood-feeding organisms is not as well-studied as in Plasmodium. However, studies on Schistosoma mansoni
Schistosoma mansoni
Schistosoma mansoni is a significant parasite of humans, a trematode that is one of the major agents of the disease schistosomiasis. The schistosomiasis caused by Schistosoma mansoni is intestinal schistosomiasis....
have revealed that this parasitic worm
Trematoda
Trematoda is a class within the phylum Platyhelminthes that contains two groups of parasitic flatworms, commonly referred to as "flukes".-Taxonomy and biodiversity:...
produces large amounts of hemozoin during its growth in the human bloodstream. Although the shapes of the crystals are different from those produced by malaria parasites, chemical analysis of the pigment showed that it is made of hemozoin. In a similar manner, the crystals formed in the gut of the kissing bug Rhodnius prolixus
Rhodnius prolixus
Rhodnius prolixus is the second most important triatomine vector of the Chagas parasite due to its efficient adaptation to the human domicile in northern South America, where sylvatic populations also exist, and in Central America where it is exclusively domestic...
during digestion of the blood meal also have a unique shape, but are composed of hemozoin. Hz formation in R. prolixus midgut occurs at physiologically relevant physico-chemical conditions and lipids play an important role in heme biocrystallization. Autocatalytic heme crystallization to Hz is revealed to be an inefficient process and this conversion is further reduced as the Hz concentration increases.
Several other mechanisms have been developed to protect a large variety of hematophagous
Hematophagy
Hematophagy is the practice of certain animals of feeding on blood...
organisms against the toxic effects of free heme. Mosquitoes digest their blood meals
extracellularly and do not produce hemozoin. Heme is retained in the peritrophic matrix
Peritrophic matrix
The peritrophic matrix or peritrophic membrane is a semi-permeable, non-cellular structure which surrounds the food bolus in an organism’s midgut. Although they are often found in insects, peritrophic matrixes are found in seven different phyla...
, a layer of protein and polysaccharides that covers the midgut and separates gut cells from the blood bolus.
Although β-hematin can be produced in assays
Enzyme assay
Enzyme assays are laboratory methods for measuring enzymatic activity. They are vital for the study of enzyme kinetics and enzyme inhibition.-Enzyme units:...
spontaneously at low pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
, the development of a simple and reliable method to measure the production of hemozoin has been difficult. This is in part due to the continued uncertainty over what molecules are involved in producing hemozoin, and partly from the difficulty in measuring the difference between aggregated or precipitated heme, and genuine hemozoin. Current assays are sensitive and accurate, but require multiple washing steps so are slow and not ideal for high-throughput screening
High-throughput screening
High-throughput screening is a method for scientific experimentation especially used in drug discovery and relevant to the fields of biology and chemistry. Using robotics, data processing and control software, liquid handling devices, and sensitive detectors, High-Throughput Screening allows a...
. However, some screens have been performed with these assays.
Structure
β-Hematin crystals are made of dimers of hematin molecules that are, in turn, joined together by hydrogen bonds to form larger structures. In these dimers, an ironIron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
-oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
coordinate bond links the central iron of one hematin to the oxygen of the carboxylate side-chain of the adjacent hematin. These reciprocal iron–oxygen bonds are highly unusual and have not been observed in any other porphyrin dimer. β-Hematin can be either a cyclic dimer or a linear polymer
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
, a polymeric form has never been found in hemozoin, disproving the widely-held idea that hemozoin is produced by the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
heme-polymerase.
Hemozoin crystals have a distinct triclinic structure and are weakly magnetic. The difference between diamagnetic low-spin oxyhemoglobin and paramagnetic hemozoin can be used for isolation. They also exhibit optical dichroism
Dichroism
Dichroism has two related but distinct meanings in optics. A dichroic material is either one which causes visible light to be split up into distinct beams of different wavelengths , or one in which light rays having different polarizations are absorbed by different amounts.The original meaning of...
, which means that they absorb light more strongly along their length than across their width, which allows the automated detection of malaria. Hemozoin is produced in a form that, under the action of an applied magnetic field
Magnetic field
A magnetic field is a mathematical description of the magnetic influence of electric currents and magnetic materials. The magnetic field at any given point is specified by both a direction and a magnitude ; as such it is a vector field.Technically, a magnetic field is a pseudo vector;...
, gives rise to an induced optical dichroism
Dichroism
Dichroism has two related but distinct meanings in optics. A dichroic material is either one which causes visible light to be split up into distinct beams of different wavelengths , or one in which light rays having different polarizations are absorbed by different amounts.The original meaning of...
characteristic of the hemozoin concentration; and precise measurement of this induced dichroism
Dichroism
Dichroism has two related but distinct meanings in optics. A dichroic material is either one which causes visible light to be split up into distinct beams of different wavelengths , or one in which light rays having different polarizations are absorbed by different amounts.The original meaning of...
may be used to determine the level of malarial infection.
Inhibitors
Hemozoin formation is an excellent drug target, since it is a process that is essential to the survival of the malaria parasite and absent from the human host. The drug target hematin is host-derived and largely outside the genetic control of the parasite, which makes the development of drug resistance more difficult. Many clinically-used drugs are thought to act by inhibiting the formation of hemozoin in the food vacuole. This prevents the detoxification of the heme released in this compartment, and kills the parasite.The best-understood examples of such hematin biocrystallization
Biocrystallization
Biocrystallization is the formation of crystals from organic macromolecules by living organisms. This may be a stress response, a normal part of metabolism such as processes that dispose of waste compounds, or a pathology. Template mediated crystallization is qualitatively different from in vitro...
inhibitors are quinoline
Quinoline
Quinoline is a heterocyclic aromatic organic compound. It has the formula C9H7N and is a colourless hygroscopic liquid with a strong odour. Aged samples, if exposed to light, become yellow and later brown...
drugs such as chloroquine
Chloroquine
Chloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-History:Chloroquine , N'--N,N-diethyl-pentane-1,4-diamine, was discovered in 1934 by Hans Andersag and co-workers at the Bayer laboratories who named it "Resochin". It was ignored for a decade because it was...
and mefloquine
Mefloquine
Mefloquine hydrochloride is an orally administered medication used in the prevention and treatment of malaria. Mefloquine was developed in the 1970s at the United States Department of Defense's Walter Reed Army Institute of Research as a synthetic analogue of quinine...
. These drugs bind to both free heme and hemozoin crystals, and therefore block the addition of new heme units onto the growing crystals. The small, most rapidly growing face is the face to which inhibitors are believed to bind.
See also
- BiocrystallizationBiocrystallizationBiocrystallization is the formation of crystals from organic macromolecules by living organisms. This may be a stress response, a normal part of metabolism such as processes that dispose of waste compounds, or a pathology. Template mediated crystallization is qualitatively different from in vitro...
- Drug discoveryDrug discoveryIn the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are discovered or designed.In the past most drugs have been discovered either by identifying the active ingredient from traditional remedies or by serendipitous discovery...
- History of malariaHistory of malariaThe history of malaria predates humanity, as this ancient disease evolved before humans did. Malaria, a widespread and potentially lethal infectious disease, has afflicted people for much of human history, and has affected settlement patterns...
- Parasitic diseaseParasitic diseaseA parasitic disease is an infectious disease caused or transmitted by a parasite. Many parasites do not cause diseases. Parasitic diseases can affect practically all living organisms, including plants and mammals...
s