Molecular farming
Encyclopedia
Molecular farming is the use of genetically engineered
crops to produce compounds
with therapeutic value. These crops will become biological factories used to generate drugs
and other difficult or expensive products. The term pharming
can be used to describe plant derived pharmaceuticals, but it is more commonly used for products engineered in animals. The issue of genetically modified crops has been around for a number of years and continues to be a controversial subject.
plant-derived pharmaceutical protein (PDP) was human serum albumin
, initially produced in 1990 in transgenic tobacco
and potato
plants. Fifteen years on, the first technical proteins produced in transgenic plants are on the market, and proof of concept has been established for the production of many therapeutic protein
s, including antibodies, blood products, cytokines, growth factors, hormones, recombinant enzyme
s and human and veterinary vaccine
s. Furthermore, several PDP products for the treatment of human diseases are approaching commercialization, including recombinant
gastric lipase
for the treatment of cystic fibrosis
, and antibodies for the prevention of dental caries
and the treatment of non-Hodgkin's lymphoma. There are also several veterinary vaccines in the pipeline; Dow AgroSciences
announced recently their intention to produce plant-based vaccines for the animal health industry.
and used to fight such diseases as cancer
and diabetes.
. Additionally, on the level of pharmacologically active protein
s, there are no proteins in plants that are similar to human proteins. On the other hand, plants are still sufficiently closely related to animals and humans that they are able to correctly process and configure both animal and human proteins. Their seeds and fruits also provide sterile packaging containers for the valuable therapeutics and guarantee a certain storage life.
Global demand
for pharmaceuticals is at unprecedented levels, and current production capacity will soon be overwhelmed. Expanding the existing microbial systems, although feasible for some therapeutic products, is not a satisfactory option on several grounds. First, it would be very expensive for the pharmaceutical companies. Second, other proteins of interest are too complex to be made by microbial systems. These proteins are currently being produced in animal cell culture
s, but the resulting product is often prohibitively expensive for many patients. Finally, although it is theoretically possible to synthesize protein molecules by machine, this works only for very small molecules, less than 30 amino acid
residue in length. Virtually all proteins of therapeutic value are larger than this and require live cells to produce them. For these reasons, science has been exploring other options for producing proteins of therapeutic value.
While molecular farming is one application of genetic engineering
, there are concerns that are unique to it. In the case of genetically modified (GM) foods, concerns focus on the safety of the food for human consumption
. In response, it has been argued that the genes that enhance a crop
in some way, such as drought resistance or pesticide resistance
, are not believed to affect the food itself. Other GM foods in development, such as fruits designed to ripen faster or grow larger, are believed not to affect humans any differently from non-GM varieties.
In contrast, molecular farming is not intended for crops destined for the food chain
. It produces plants that contain physiologically
active compounds that accumulate in the plant’s tissues. Considerable attention is focused, therefore, on the restraint and caution necessary to protect both consumer health and environmental biodiversity
.
There are also problems associated with the use of plants as protein bioreactors. Plant proteins have different sugar
residue
s from human or animal proteins. Freiburg
-based greenovation Biotech GmbH, in cooperation with Professor Ralf Reski
’s research group at the University of Freiburg
, has shown that this problem can be solved through the use of Physcomitrella patens
. Because the scientists cultivate the moss in moss bioreactor
s using liquid
medium, they have no worries that the genetically modified moss
es might be released into the environment.
with clean crops. Concern arose last year after GMO corn produced by StarLink
accidentally ended up in commercial food products. No products produced by plant molecular farming were available in the emerging market,until the first ones were launch around 2006. Today Molecular Farming is considered "big business". According to the Canadian Food Inspection Agency
, in a recent report, says that U.S. demand alone for biotech pharmaceuticals is expanding at 13 percent annually and to reach a market value of $28.6 billion in 2004. Molecular Farming is expected to be worth $100 billion globally by 2020.
Genetic engineering
Genetic engineering, also called genetic modification, is the direct human manipulation of an organism's genome using modern DNA technology. It involves the introduction of foreign DNA or synthetic genes into the organism of interest...
crops to produce compounds
Chemical compound
A chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...
with therapeutic value. These crops will become biological factories used to generate drugs
DRUGS
Destroy Rebuild Until God Shows are an American post-hardcore band formed in 2010. They released their debut self-titled album on February 22, 2011.- Formation :...
and other difficult or expensive products. The term pharming
Pharming (genetics)
Pharming is a portmanteau of farming and "pharmaceutical" and refers to the use of genetic engineering to insert genes that code for useful pharmaceuticals into host animals or plants that would otherwise not express those genes. As a consequence, the host animals or plants then make the...
can be used to describe plant derived pharmaceuticals, but it is more commonly used for products engineered in animals. The issue of genetically modified crops has been around for a number of years and continues to be a controversial subject.
History
The first recombinantRecombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
plant-derived pharmaceutical protein (PDP) was human serum albumin
Serum albumin
Serum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular...
, initially produced in 1990 in transgenic tobacco
Tobacco
Tobacco is an agricultural product processed from the leaves of plants in the genus Nicotiana. It can be consumed, used as a pesticide and, in the form of nicotine tartrate, used in some medicines...
and potato
Potato
The potato is a starchy, tuberous crop from the perennial Solanum tuberosum of the Solanaceae family . The word potato may refer to the plant itself as well as the edible tuber. In the region of the Andes, there are some other closely related cultivated potato species...
plants. Fifteen years on, the first technical proteins produced in transgenic plants are on the market, and proof of concept has been established for the production of many therapeutic protein
Protein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
s, including antibodies, blood products, cytokines, growth factors, hormones, recombinant enzyme
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
s and human and veterinary vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
s. Furthermore, several PDP products for the treatment of human diseases are approaching commercialization, including recombinant
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
gastric lipase
Gastric lipase
Gastric lipase, also known as LIPF, is an enzymatic protein that, in humans, is encoded by the LIPF gene.-Function:Gastric lipase is an acidic lipase secreted by the gastric chief cells in the fundic mucosa in the stomach. It has a pH optimum of 3-6. Gastric lipase, together with lingual lipase,...
for the treatment of cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
, and antibodies for the prevention of dental caries
Dental caries
Dental caries, also known as tooth decay or a cavity, is an irreversible infection usually bacterial in origin that causes demineralization of the hard tissues and destruction of the organic matter of the tooth, usually by production of acid by hydrolysis of the food debris accumulated on the...
and the treatment of non-Hodgkin's lymphoma. There are also several veterinary vaccines in the pipeline; Dow AgroSciences
Dow AgroSciences
Dow AgroSciences LLC is a wholly owned subsidiary of the Dow Chemical Company specializing in not only agricultural chemicals such as pesticides, but also seeds and biotechnology solutions. The company is based in Indianapolis, Indiana, in the United States...
announced recently their intention to produce plant-based vaccines for the animal health industry.
Overview
Plant molecular farming uses genetic engineering to produce substances for a variety of uses. Potential products include the development of antigens for vaccines that might be mass-produced in plants such as cornMaize
Maize known in many English-speaking countries as corn or mielie/mealie, is a grain domesticated by indigenous peoples in Mesoamerica in prehistoric times. The leafy stalk produces ears which contain seeds called kernels. Though technically a grain, maize kernels are used in cooking as a vegetable...
and used to fight such diseases as cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
and diabetes.
Advantages
Plants do not carry pathogens that might be dangerous to human healthHealth
Health is the level of functional or metabolic efficiency of a living being. In humans, it is the general condition of a person's mind, body and spirit, usually meaning to be free from illness, injury or pain...
. Additionally, on the level of pharmacologically active protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s, there are no proteins in plants that are similar to human proteins. On the other hand, plants are still sufficiently closely related to animals and humans that they are able to correctly process and configure both animal and human proteins. Their seeds and fruits also provide sterile packaging containers for the valuable therapeutics and guarantee a certain storage life.
Global demand
Supply and demand
Supply and demand is an economic model of price determination in a market. It concludes that in a competitive market, the unit price for a particular good will vary until it settles at a point where the quantity demanded by consumers will equal the quantity supplied by producers , resulting in an...
for pharmaceuticals is at unprecedented levels, and current production capacity will soon be overwhelmed. Expanding the existing microbial systems, although feasible for some therapeutic products, is not a satisfactory option on several grounds. First, it would be very expensive for the pharmaceutical companies. Second, other proteins of interest are too complex to be made by microbial systems. These proteins are currently being produced in animal cell culture
Cell culture
Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...
s, but the resulting product is often prohibitively expensive for many patients. Finally, although it is theoretically possible to synthesize protein molecules by machine, this works only for very small molecules, less than 30 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
residue in length. Virtually all proteins of therapeutic value are larger than this and require live cells to produce them. For these reasons, science has been exploring other options for producing proteins of therapeutic value.
Disadvantages
Genetic engineering
Genetic engineering, also called genetic modification, is the direct human manipulation of an organism's genome using modern DNA technology. It involves the introduction of foreign DNA or synthetic genes into the organism of interest...
, there are concerns that are unique to it. In the case of genetically modified (GM) foods, concerns focus on the safety of the food for human consumption
Ingestion
Ingestion is the consumption of a substance by an organism. In animals, it normally is accomplished by taking in the substance through the mouth into the gastrointestinal tract, such as through eating or drinking...
. In response, it has been argued that the genes that enhance a crop
Crop
Crop may refer to:* Crop, a plant grown and harvested for agricultural use* Crop , part of the alimentary tract of some animals* Crop , a modified whip used in horseback riding or disciplining humans...
in some way, such as drought resistance or pesticide resistance
Pesticide resistance
Pesticide resistance is the adaptation of pest population targeted by a pesticide resulting in decreased susceptibility to that chemical. In other words, pests develop a resistance to a chemical through natural selection: the most resistant organisms are the ones to survive and pass on their...
, are not believed to affect the food itself. Other GM foods in development, such as fruits designed to ripen faster or grow larger, are believed not to affect humans any differently from non-GM varieties.
In contrast, molecular farming is not intended for crops destined for the food chain
Food chain
A food web depicts feeding connections in an ecological community. Ecologists can broadly lump all life forms into one of two categories called trophic levels: 1) the autotrophs, and 2) the heterotrophs...
. It produces plants that contain physiologically
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...
active compounds that accumulate in the plant’s tissues. Considerable attention is focused, therefore, on the restraint and caution necessary to protect both consumer health and environmental biodiversity
Biodiversity
Biodiversity is the degree of variation of life forms within a given ecosystem, biome, or an entire planet. Biodiversity is a measure of the health of ecosystems. Biodiversity is in part a function of climate. In terrestrial habitats, tropical regions are typically rich whereas polar regions...
.
There are also problems associated with the use of plants as protein bioreactors. Plant proteins have different sugar
Sugar
Sugar is a class of edible crystalline carbohydrates, mainly sucrose, lactose, and fructose, characterized by a sweet flavor.Sucrose in its refined form primarily comes from sugar cane and sugar beet...
residue
Residue (chemistry)
In chemistry, residue is the material remaining after a distillation or an evaporation, or to a portion of a larger molecule, such as a methyl group. It may also refer to the undesired byproducts of a reaction....
s from human or animal proteins. Freiburg
Freiburg
Freiburg im Breisgau is a city in Baden-Württemberg, Germany. In the extreme south-west of the country, it straddles the Dreisam river, at the foot of the Schlossberg. Historically, the city has acted as the hub of the Breisgau region on the western edge of the Black Forest in the Upper Rhine Plain...
-based greenovation Biotech GmbH, in cooperation with Professor Ralf Reski
Ralf Reski
Ralf Reski is a German Professor of Plant Biotechnology and former Dean of the Faculty of Biology of the University of Freiburg...
’s research group at the University of Freiburg
University of Freiburg
The University of Freiburg , sometimes referred to in English as the Albert Ludwig University of Freiburg, is a public research university located in Freiburg im Breisgau, Baden-Württemberg, Germany.The university was founded in 1457 by the Habsburg dynasty as the...
, has shown that this problem can be solved through the use of Physcomitrella patens
Physcomitrella patens
Physcomitrella patens is a moss used as a model organism for studies on plant evolution, development and physiology.-Model organism:...
. Because the scientists cultivate the moss in moss bioreactor
Moss bioreactor
thumb|350px|Moss bioreactor with [[Physcomitrella patens]]A moss bioreactor is a photobioreactor used for the cultivation and propagation of mosses...
s using liquid
Liquid
Liquid is one of the three classical states of matter . Like a gas, a liquid is able to flow and take the shape of a container. Some liquids resist compression, while others can be compressed. Unlike a gas, a liquid does not disperse to fill every space of a container, and maintains a fairly...
medium, they have no worries that the genetically modified moss
Moss
Mosses are small, soft plants that are typically 1–10 cm tall, though some species are much larger. They commonly grow close together in clumps or mats in damp or shady locations. They do not have flowers or seeds, and their simple leaves cover the thin wiry stems...
es might be released into the environment.
Controversy
The fact that the plants are used to produce drugs is alarming activists. They worry that once production begins, the altered plants might find their way into the food supply or cross-pollinatePollination
Pollination is the process by which pollen is transferred in plants, thereby enabling fertilisation and sexual reproduction. Pollen grains transport the male gametes to where the female gamete are contained within the carpel; in gymnosperms the pollen is directly applied to the ovule itself...
with clean crops. Concern arose last year after GMO corn produced by StarLink
Transgenic maize
Genetically modified maize has been deliberately genetically modified to have agronomically desirable traits. Traits that have been engineered into corn include resistance to herbicides and resistance to insect pests, the latter being achieved by incorporation of a gene that codes for the...
accidentally ended up in commercial food products. No products produced by plant molecular farming were available in the emerging market,until the first ones were launch around 2006. Today Molecular Farming is considered "big business". According to the Canadian Food Inspection Agency
Canadian Food Inspection Agency
The Canadian Food Inspection Agency is a science based regulatory agency that is dedicated to the safeguarding of food, animals, and plants, which enhance the health and well-being of Canada's people, environment and economy...
, in a recent report, says that U.S. demand alone for biotech pharmaceuticals is expanding at 13 percent annually and to reach a market value of $28.6 billion in 2004. Molecular Farming is expected to be worth $100 billion globally by 2020.
External links
- molecularfarming.com Official site
- Molecular Farming – Plant Bioreactors
- http://www.bio-pro.de/magazin/umfeld/archiv_2005/index.html?lang=en&artikelid=%2Fartikel%2F03016%2Findex.htmlMoss bioreactors do not smell (Interview with Ralf ReskiRalf ReskiRalf Reski is a German Professor of Plant Biotechnology and former Dean of the Faculty of Biology of the University of Freiburg...
)] - Molecular Pharming - pharmaceuticals with the help of GM plants