The GM food and synthetic meat markets

Can the genetically modified plants market give us an idea of what the future holds for synthetic meat?

Background

Despite some slumps during the last 25 years, investors and other stakeholders have had well founded high expectations in relation to biology as a scientific and profitable discipline, and particularly biotechnology and genetics as one of its branches. This is a natural feeling as genetics is the pattern basis of living organisms, and being capable of manipulating the genome makes humans, or we should rather say scientists, some kind of gods. Just genetics may cover huge knowledge areas as diverse as medicine, energy, chemicals production, farming, or livestock to mention a few. Synthetic biology is fashionable once again and is expected to cause a new technological revolution.

Genetic engineered plants have been commercialized since the nineties and have opened a bunch of new opportunities for innovation and advantages for farmers and consumers, despite strong opposition from activists. On its side, synthetic meat (also known as cultured or lab-grown meat), which is not available on the market yet, is also expected to offer huge advantages and opportunities to innovate in the coming years.

Genetically modified (GM) food is not necessarily the same as cultured meat

Genetic engineered food, which we should rather call GM plants, and synthetic meat have certainly biological principles in common, but production processes are not necessarily the same.

Whilst GM plants are based on genes inserted or replaced to produce a predetermined type of protein that may intervene in a specific biochemical path or be of a specific interest as such, cultured meat in the beginning is produced starting from pluripotent or multipotent cells that are not necessarily genetically modified, though this move is also under development.

Genetic applications are not limited to crops in the food industry. Crowdfunding is currently helping BioCurious, a community biotech lab based in California, to research on synthetically producing Real Vegan Cheese by inserting genes into yeast that translate into the appropriate proteins, known as caseins, that can be extracted and mixed in precise quantities. Perfect Day is another company focused on animal-free dairy products making use of modified microflora that expects to commercialize its products in a short time.

Genetic engineered plants have already shown important advantages

Since 1994 when Calgene started marketing its Flavr Savr tomato, at least 31 plant species have been genetically modified and approved for commercial release in at least one country. Widespread genetically modified crops include soybean, maize, cotton, and canola among others. Distribution among countries worldwide is still uneven though and depends on local regulations, but just in the United States it is estimated that 90% of seeds used to plant soy and corn belong to GM crops. China, Argentina, Canada, Australia, and Mexico have also planted genetically modified crops in a large scale. In the European Union importation of genetically modified organisms is regulated at European institutions level but individual member states decide on cultivation regulations.

Country

GM plant species approved for cultivation

GM plant species approved for human consumption

 European Union

Carnation, maize and potato

Argentine canola, cotton, maize, potato, soybean, rice, soybean and sugar beet

 United States

alfalfa, apple, Argentine canola, chicory, cotton, creeping bent grass, flax, maize, papaya, plum, potato, rice, rose, soybean, squash, sugar beet, tobacco and tomato

alfalfa, apple, Argentine canola, chicory, cotton, creeping bentgrass, flax, maize, melon, papaya, plum, potato, rice, soybean, squash, sugar beet, sugar cane, tomato and wheat

 China

cotton, maize, papaya, petunia, poplar, rice, sweet pepper and tomato

Argentine canola, cotton, maize, rice, soybean, sugar beet, sweet pepper and tomato

 Japan

alfalfa, Argentine canola, carnation, cotton, maize, papaya, rice, rose, soybean and sugar beet

alfalfa, Argentine canola, cotton, maize, papaya, potato, soybean and sugar beet

 Argentina

alfalfa, cotton, maize, potato and soybean

alfalfa, cotton, maize, potato and soybean

 Canada

alfalfa, apple, Argentine canola, flax, maize, Polish canola, potato, soybean and sugar beet

alfalfa, apple, Argentine canola, cotton, flax, maize, papaya, potato, rice, soybean, squash, sugar beet, sugar cane and tomato

 Australia

Argentine canola, carnation, cotton, rose and safflower

alfalfa, Argentine canola, cotton, maize, potato, rice, safflower, soybean, sugar beet and wheat

 Mexico

alfalfa, cotton and soybean

alfalfa, Argentine canola, cotton, maize, potato, rice, soybean, sugar beet and tomato

Genetically modified plant species for some trait(s) that have been approved for cultivation and human consumption at some point in time in some relevant countries.

Source: ISAAA’s GM Approval Database. http://www.isaaa.org/gmapprovaldatabase/.

 

The ultimate purpose and benefits of these genetically modified seeds cover several fields. For farmers these seeds provide resistance to insects and tolerance to herbicides, heat, cold or droughts; better look to make them more appealing; and longer shelf-life. For consumers this type of products may provide specific nutrients, including calcium and protein; or even seedless fruits. For humankind a longer shelf-life may mean a better distribution of food worldwide even to very remote areas of the planet considering that there is an excess of more than 15% of food produced in rich countries. Genetically modified food has been proposed as a sustainable mean to feed the increasing human population in the future presently estimated at 7.7 billion and currently growing at a rate of about 1.07% down from 2% in the sixties. The world population is projected to reach 9.7 billion by 2050 despite declining growth rates.

World population growth rates

Legislation on genetically modified organisms (GMO) changes from country to country

Whilst in Europe genetically modified food must be labelled as such according to GMO (genetically modified organisms) legislation, in the United States this is not required, and only certified organic foods guarantee to a certain extent that no genetically modified organisms have been used in the manufacturing process. Nonetheless genetically modified organisms are subject to strict regulation, particularly in the case of human consumption.

Strictly speaking, gene-edited crops that do not carry DNA from other species are not treated as severely as GM crops from a legal point of view in several countries, for example the United States, Brazil, Canada and Australia. This is the trend in spite of using the latest genetic technologies such as CRISPR and other new breeding techniques (NBTs) because this type of genetic manipulation has been done for hundreds of years selecting the desired plants properties through the Mendelian method. Relaxing legislation in recent years for genetic manipulation that does not involve genes from different species has helped big and small companies and universities to innovate developing new seeds with outstanding properties that are already available on the market. Activists still oppose these practices and fight for regulating gene-edited crops just like GMOs as it has happened in Europe.

A part of the population still disapproves genetically modified organisms

However genetic engineered food and synthetic meat come with their own shortcomings. Critics discuss about long-term health consequences in humans and unpredictable changes in nature when considering genetic manipulation. In the case of food, the concept of substantial equivalence to genetically unmodified counterparts has been introduced by regulatory agencies as one step in order to evaluate safety of any identified differences. No doubt that necessary tests for the overall safety of a GM product are costly and must be factored in prices, but still GM crops have remained competitive.

Genetically modified food is suspect, most probably unfoundedly, of an increase in the number of people suffering from food allergies due to new proteins translated from inserted genes or secondary metabolites that may result from any genetic changes. So far allergenicity in genetically modified food has not been demonstrated to be more of a problem than its non-genetically modified equals. FAO and WHO have recommended that any new protein introduced in genetically modified food should be compared to all recognized allergens establishing a procedure to test and follow up potential allergenicity in a sort of surveillance system. It is however difficult to estimate whether changes in the plant metabolism cause new secondary metabolites or significant changes in concentration of the existing ones including natural endogenous toxins.

In any case allergens could be removed with state-of-the art technology in the near future. Even more, genetically modified food can be produced totally free of known allergens contained in their non-modified counterparts thus providing an advantage for consumers. An example could be suppressing the enzyme that intervenes in the biochemical path to produce gluten in wheat for diets followed by people suffering from celiac disease.

Genetic engineered food has also been pointed as the ultimate cause of antibiotic resistance with no consistent proof, but even if that were the case more opportunities would be opened for biotech firms in R&D. Antibiotic resistance is intrinsic to nature as health scientists know for a fact that an increase in antibiotic resistance in bacteria is often the consequence of antibiotics abuse in humans to treat an infection as is true of penicillin. In nature herbicide resistance happens naturally in living organisms as is the case of different types of weeds that have become resistant to atrazine.

Despite some articles in scientific magazines, genetically modified food has not been proved to have any link with cancer to date. Once again it is important to state that the concentration of present metabolites and new secondary ones as well as endogenous toxins in certain GM plant species could be altered and thus carry health hazards, for which long-term studies are necessary. Still many processed and cured meat are currently produced making use of carcinogenic compounds such as nitrates, which basically means that we already have that problem.

Critics have also discussed the possibility of genetic engineered material transfer to intestinal bacteria as is the case of Bt corn, a type of GM corn with inserted genes that produce a pesticide naturally encoded by soil bacteria Bacillus thuringiensis. This pesticide has been traditionally sprayed over conventional corn by farmers and later washed out though in the case of Bt corn the pesticide is produced by the plant itself.

Nature conservation is also a matter of concern for activists and even some farmers. The first case of cross-pollination was reported in autumn 2000 in the United States between a genetically modified crop that was too close to an unmodified harvest, and probably more than 500 cases have been well documented. Cross-pollination and unintended transfer of genes that yield plant varieties, which could be patent protected, may bring some headaches for conventional and organic farmers in terms of food quality, labeling and legal issues. Cross-pollination may also disperse plant varieties that carry inappropriate levels of secondary metabolites that can be dangerous thus losing control in the spread of genetically manipulated organisms. This cross-pollination seems unavoidable for the moment regardless any attempts to establish measures such as buffer zones. Still, scientists are also developing genetically modified organisms that can only fertilize with manual assistance to avoid cross-pollination cases. Pollination control systems have been introduced making use of genes generally sourced from bacteria as is the case of Argentine canola, chicory and maize crops.

Probably one of the main causes for worry is companies’ intellectual property protection. Farmers and customers often state that companies benefit most from GM seed varieties that are still patent protected and thus confer market exclusivity for their use for a minimum of twenty years in most countries. As an example, pollination control systems in maize, authorized mainly in the United States, have been dominated by DuPont (Pioneer Hi-Bred International Inc.) and Bayer CropScience. However, these patents finally end up losing their protection and contribute to a wealth of knowledge that can be used by other companies and public organizations. For example, patents derived from core international patent publication number WO9626283 that describes a method to obtain male-sterile plants applied by Plant Genetic Systems NV (acquired by Bayer CropScience in 2002) in February 1996 have already lapsed in all countries assigned. Another example could be patents stemming from international patent publication number WO9617945 filed by Pioneer Hi-Bred International that describes a reversible nuclear genetic system for male sterility in transgenic plants with priority number dated in June 1995 which have also gone off patent in all countries, though the company has resorted to file other patent applications worldwide with innovative methods related to plant sterility since 2000. A more remarkable case is Monsanto’s Roundup, the trade name for the company’s broad-spectrum herbicide glyphosate, for which genetically modified resistant crops, branded as Roundup Ready Soy I, were developed and whose patents expired in 2014 thus facing competition from other manufacturers. Yet more, the University of Arkansas has released free versions of Roundup Ready Soy that can be used by any farmer at will. It is estimated that the discovery, development, and authorization of a new GMO plant may cost more than $140 million and without market exclusivity no company would ever embark on those investments.

Still the latest concern is related to bioterrorism. The introduction of certain harmful genes in insects or pollen spread over extensive cultivation areas could cause havoc in the population creating a sort of cyberattack-like dynamics with attackers and defenders but with more serious consequences. This risk is enhanced by the modern gene editors and genetic technologies. Nevertheless, opposing GM crops or research on genetic manipulation will not stop this threat but on the contrary it may even be counterproductive due to lack of knowledge to respond. It seems obvious that there should always be security measures to neutralize any accident or bioterrorist attack.

In any case disproportionate concern about genetic manipulation improvements could restrict scientific advancement, which on the other side seems unavoidable.

Competitive structure for the genetically modified plants market

The commercial seed market worldwide was estimated at more than US$50.0 billion in 2018. There are approximately 7,000 large and small seed companies operating worldwide. Approximately 50 companies have GM plants authorized in some country in the world. Many conventional seed companies are also commercializing gene-edited seeds and may be developing GM plants that could be launched into the market in the future.

According to Yahoo Finance four agrochemical companies hold more than 60% of the global seed market in 2019 commercializing GM and non-GM seeds, which causes fears for market consolidation. These companies are Corteva Agriscience (formerly DowDuPont, United States), ChemChina (China), Bayer (Germany) and BASF (Germany). Other important seed companies not commercializing GM seeds for the moment include Groupe Limagrain (France), Land O’Lakes (United States), KWS AG (Germany), Sakata (Japan), DLF-Trifolium (Denmark), or Takii (Japan). The growth and development of this market is mainly based on the world growing population and the climate change.

Corteva, ChemChina, Bayer and BASF are the result of consecutive mergers and acquisitions during the last 20 years. Bayer acquired Monsanto, the best known GM seed company worldwide, in 2018; the state-owned ChemChina acquired the Swiss Syngenta in what was perceived as a delicate financial operation; Dow Agrosciences merged with DuPont to form Corteva; and BASF reached an agreement with Bayer AG to purchase seeds and pesticides assets in 2018 after the US Justice Department forced Bayer to sell its crop science division before purchasing Monsanto. Formerly to mention a few, Monsanto had acquired 10 organizations since 2005; ChemChina acquired 60% of Adama Agricultural Solutions, an Israeli agrochemical company with the highest generic pesticides portfolio in 2011, in a strategy to expand its own domestic market share; and Bayer CropScience acquired Argentinian Biagro Group in 2014 and SeedWorks India Pvt. Ltd in 2015. ChemChina is a good example of market development as the company’s overseas sales amount to approximately 67% of its total revenues, and also has interests in other chemical industries just like the other top three.

Corteva’s policy is to maintain a focus at a local and regional level worldwide making use of procurement teams and reinforcing relations with local suppliers emphasizing a public code of conduct. On its side, Bayer CropScience offers tailor-made solutions on a unique combination of seeds and traits, crop protection and digital tools for individual farmers in order to achieve the best harvest and a sustainable growth, and regarding suppliers the company particularly values innovation, efficiency and sustainability.

A whole industry surrounds this market apart from distributors and license agreements such as GMO testing market or other chemicals. Small biotech companies and research institutes are also involved looking for improvements in crops often in collaboration with these GM multinationals. The agricultural business includes relevant complementors that may comprise fertilizers, greenhouses, irrigation systems or growing lamps among others.

Although the seed market may look oligopolistic and dominated by a bunch of very powerful companies it does not mean there are not any opportunities for smaller seed companies and research institutions even creating collaboration agreements or looking for venture capital in a sort of co-opetition relationship. CRISPR-Cas9 and new breeding techniques (NBTs) are bringing along new prospects for shortening the development of gene-edited crops and lowering costs that may compete with more efficient solutions and innovations for farmers and customers. On the other hand, most fruits and vegetables remain unattended and offer opportunities for market development too.

For example, in respect to herbicide tolerance most products are focused on glyphosate, glufosinate and sulfonylurea, and to a lesser extent on 2,4-D and oxynil, but more research would lead to more innovative and efficient herbicides that are less hazardous to humans and animals. Pollination control systems are mainly focused on maize, Argentine canola and chicory, but these systems could also be extended to other plants. There are some other interesting potential traits worth to be researched.

Lab-grown meat could allure several groups of people

Lab-grown meat is also known as cultured meat, in vitro meat, synthetic meat or even clean meat. This type of meat is the result of growing muscle cells in a nutrient serum, generally made from animal blood, to end-up forming muscle fibers.

Lab-grown meat pursues goals that may appeal several people’s interests and ethics. The first goal is related to the environment, the second is about feeding an increasing population worldwide, the third involves animal rights, and the fourth is associated to gourmets and culinary innovations.

Environmentalists should be enthusiastic about the potential benefits of a prospective well-established synthetic meat industry. There are thousands of studies evaluating the huge environmental impact of the conventional meat industry.

Farm animals are thought to be accountable of approximately 15% of greenhouse gas emissions in the planet.

According to the United Nations Environment Program the rainforest landscape in South America is being cleared for cattle to produce meat and reckons that one average quarter pounder beef burger drains around 1,695 liters of water from valuable resources. Other studies calculate that it is necessary 100 times more water to produce 1 kg of animal protein than producing 1 kg of grain protein.

Figures vary depending on technology and location, but in respect to energy consumed to produce meat we easily come across studies suggesting that 25 kilocalories of fossil fuel energy are consumed for every 1 kilocalorie of meat protein produced whilst ratio for corn protein is 2.2:1.

However, let us not jump into conclusions yet as proteins constitute approximately 20% of a human body and vegetable proteins often lack a good balance of the 20 essential aminoacids for humans, which are the basic molecules that form them. Proteins form part of body structures and also are crucial for metabolism.

The cost of producing farm animal meat is also very high considering that it is necessary 5-7 kg of grain to produce half a kilogram of feedlot beef.

Feeding the world’s increasing population together with higher purchasing power and thus higher meat consumption in developing countries could augment environmental problems in the future. As mentioned above, some experts assure that by 2050 the population worldwide could reach 9.2 billion. The world average consumption of meat (beef and veal, pork, poultry and sheep meat) per person worldwide was estimated at 34.74 kg in 2018 according to OECD-FAO with an increasing trend in developing countries and forecast to reach 35.37 kg in 2027.

By 2050 even the most conservative estimates would predict that the average meat consumption per capita for these kinds of meat can easily reach 38 kg per annum thus making a total of 349.6 billion kg consumption worldwide. In 2018 just in the United States the average consumption per capita for these four types of meat was calculated at 101,304 kg per annum whilst EU28 corresponded to 69.49 kg per capita.

Poultry and pork are the most popular types of meat worldwide though it obviously varies depending on the country’s culture and customs. For example, EU28 consumes more pork (32.31 kg) and poultry (24.47 kg), whilst Turkey consumes more poultry (17.72 kg) and beef (10.50 kg) with very low demand for pork (0.06 kg). In respect to the environment, let us note that pig slurry causes an important impact with high cost in managing operations.

The Environmental Science and Technology magazine published a life-cycle assessment study of lab-grown meat in 2011 where it was assured that cultured meat at industrial scale would require 7-45% less energy than producing animal farm meat in Europe with the exception of poultry; 78-96% lower greenhouse gases emissions; 99% lower land use; and 96% lower water use.

On the other hand, synthetic meat could bring along the possibility of being more innovative creating new and tastier meat for gourmets with ground-breaking characteristics such as suitable amounts of vitamins and fats to make it even healthier. Prices could be very competitive for valued scarce meats, such as red tuna, that are now too costly for the public and in danger of extinction, once scalability for producing them synthetically is resolved.

Farm animal welfare has also become a matter of major concern in developed countries. According to The American Society for the Prevention of Cruelty to Animals (ASPCA) 94% of Americans believe that animals raised for food should have a life free from abuse and cruelty, which nowadays is almost a utopia with current practices. In other developed countries the opinion trend is similar, and the topic is very sensitive especially in younger generations. According to surveys conducted in the United Kingdom and the Netherlands above 60% of respondents were in favor of promoting lab-grown meat as an alternative to farm animal meat.

Then again, there is no doubt that veganism and vegetarianism are rising and therefore new commercial businesses aiming this growing market are spurting. Synthetic meat could also appeal vegans in the future once technical difficulties are finally resolved for avoiding use of any minimal part of animals.

A veggie burger vs. a lab-grown burger

A veggie burger is generally made of vegetable proteins and often processed soy and vegetable oil. Soy protein is said to contain all essential aminoacids human beings need to take but two essential aminoacids are only present in small quantities, and on top of that this processed soy is suspect of being linked to health problems related to the endocrine system because of phytoestrogens and a solvent used that is known as hexane. Other solvents used to produce vegetable oils have also been put in question in relation to health hazards.

Plant-based meat, such as the branded Impossible Burger or the Beyond Burger, is a vegetable product that mimics meat making use of heme, a complex that includes a metalloprotein that can be produced through genetically modified soybean. The importance of heme is that it can provide the same taste and color as if it were real meat.

A lab-grown burger would be technically made of real muscle fibers together with other animal tissues that would make it tastier. Cells that end up forming these fibers grow in a nutrient serum that at the moment is generally made from animal blood, which violates vegans’ ethics. The final goal for lab-grown meat is indeed to be produced through animal-free methodologies.

In terms of environmental resources, in the foreseeable future a veggie burger will be much more efficient to produce than a lab-grown burger.

Costs of producing lab-grown meat

Mark Post, professor at Maastricht University, was the first scientist to produce a lab-grown minced meat burger in 2013 with a cost estimated at US$330,000. This first trial was certainly a big achievement despite the cost and being a burger not so delicious as expected according to the two elected tasters. Apparently, the lack of fat tissue made it less appetizing.

However, that was just a prototype and thus very costly as lowering costs is mainly a matter of refinement and scalability. There are estimates of a cost of less than US$5 per unit for some types of burger in an industrialized context making use of large bioreactors, which could happen in approximately three to four years or even earlier as reported by companies involved in this field. These large bioreactors with a minimum volume of 25,000 liters to feed 10,000 people would provide the necessary nutrients and stimulation to work out the muscle cells. Smaller bioreactors could also be possible to meet lower needs.

Growing lab-meat will eventually be more energy-efficient than conventional meat taking into account that energy will only be spent on a product that we will use entirely, where there will be no need to discard bones, fur or other organs.

Methodologies and technical difficulties to grow synthetic meat

Meat is basically formed by muscle cells and tissue. Methodologies to grow synthetic meat are based on pluripotent stem cells. In theory at least, stem cells can multiply by cell division ad infinitum. However, muscle cells lose their ability to divide once they are made with the exception of smooth muscle cells that can retain their ability to divide too.

Pluripotent stem cells, which can potentially turn into any type of tissue, may be taken from embryonic stem cells, adult stem cells or induced stem cells. Embryonic stem cells are developed from a blastocyst, which is an early-stage pre-implantation embryo. Adult stem cells, also known as pluripotent somatic stem cells, are permanently present in the body ready to replace damaged tissues and therefore can hypothetically be turned into any desired type of cell such as muscle cells. Induced stem cells are obtained through epigenetic reprogramming, that is without making any changes in the genome but inducing or repressing genes expression to obtain different phenotypic results. Stem cells are commonly used in research and regenerative medicine nowadays and it is important to notice that these cells have nothing to do with immortal cell lines such as HeLa, which are the consequence of mutations causing cancer.

Companies generally stick to their own methodologies once they got a specific strain.

Until now in order to provide the necessary nutrients to grow skeletal and smooth muscle cells researchers and companies have resorted to make use of serum in the culture, which is currently obtained from animal blood, frequently from fetuses of cows found pregnant at slaughter, making the process very expensive and presenting a dilemma for animal rights activists. In any case companies regard reducing or eliminating the amount of serum from animal sources as part of their goals, and in fact some companies already claim that they have achieved this goal. Some experts have speculated about the idea of producing serum based on photosynthetic algae or cyanobacteria. Moreover, all serum components could be compiled from different sources, at least in theory, but the key question is precisely which those main components are and in which quantity they should be used to create the magic potion that will certainly overshadow the Coca-Cola secret formula. Blood contains thousands of constituents in different quantities that together with different manufacturing processes make clear that there is no single answer for that secret formula. In the future there could be hundreds of different magic potions in many companies’ hands either as an industrial secret or in the form of complex patents to protect their investment. The right amount of ingredients processed with different techniques will probably vary providing different tastes and textures as a result. One can easily imagine the creation of several appellations of origin or brand names for different synthetic meat products in the years ahead.

Still we are talking about minced meat as steaks as we know them in three dimensions are a further complicated process where molecular scaffolding materials are engaged. One of the main technical difficulties in the production of steaks as we know them is the need of iron that is carried by myoglobin together with oxygen. Myoglobin is a cytoplasmatic protein found in the skeletal muscle tissue of vertebrates whose expression is suppressed in high-oxygen environments that are needed at the same time for skeletal muscle cells to grow in three dimensions because we cannot count on a circulatory system as it happens in living vertebrates.

Machine learning intermingled with biological expertise will probably play a crucial role in the development of this market, particularly for difficult challenges as the production of animal-free serum. On its side, 3D printers could probably play a relevant role particularly in the production of steaks.

If this market evolves as expected there is no doubt that a whole new industry could emerge operating as suppliers and complementors in a co-opetition environment.

Legislation on lab-grown meat

When talking about lab-grown meat it is expected that new regulations will soon come into effect particularly in aspects related to manufacturing and labelling. Even terminology has been put in question with requests to limit the use of “beef” or “meat” exclusively for products obtained from farm animals.

In the United States there is also controversy about which agency should have jurisdiction about lab-grown meat. The FDA has jurisdiction over genetically engineered animals whilst the Food Safety and Inspection Service, which depends on the United States Department of Agriculture (USDA) is in charge of regulating the commercial supply of meat, poultry and egg products.

In Europe, where lab-grown meat is not authorized for commercialization yet but seems to enjoy favorable reception, the term often used to refer to this type of product is “meat analogue”, “alternative meat products”, or “novel foods”, where plant-based products mimicking meat are often included. The term “clean meat” seems to have wide acceptance.

Market structure for lab-grown meat

There are approximately 23 companies working on synthetic meat worldwide. Most of them are working on beef and to a lesser extent pork and chicken while there are 3 companies focused on seafood. In the United States 2 companies produce synthetic meat destined to the pet food market.

Country

Companies involved in synthetic meat

 United States

Balletic Foods, Blue Nalu, Bond Pet Food (pet food), Finless Foods, Just, Kiran Meats, Memphis Meats, Mission Barns, New Age Meats, Wild Earth (pet food), Wild Type

 Israel

Aleph Farms, Biofood Systems, Future Meat Technologies, SuperMeat

 The Netherlands

Meatable, Mosa Meats

 Canada

Appleton Farms, SeaFuture

 Japan

Shiok Meats

 Spain

Cubiq Foods (Omega-3)

 China

Avant Meats

 United Kingdom

Higher Steaks

 Turkey

Biftek

We have chosen 8 relevant companies to get an idea of what is the current state of this promising market.

Just, Inc., formerly Hampton Creek, Inc. that was founded in 2011 in the United States, produces plant-based food that is sold worldwide, and started working on cultured meat in 2016. The company claims that they already have the necessary technology to produce clean meat and that only government regulations are preventing the launch of their products into the market. Just has already been able to make foie gras and is currently working on cultured chorizo and cultured nuggets. The company also alleges that it has found a formula to compile a cell culture without the need to make use of serum and thus animal blood.

Finless Foods, Inc. was founded in 2017 specializing in seafood. The company works on progenitor cells, in the early phases of stem cells development, to produce different types of lineage cells adding specific nutrients to the broth. The company has started working on bluefin tuna. Finless Foods promotes its products as sustainable environmentally friendly good quality food at affordable prices and plans to launch its first product at the end of 2019.

Memphis Meats, Inc. was founded at 2015 as a food technology company by three scientists to produce cultured meat. The company is fully supported by strong investors such as Tyson Foods, the American meat giant. The company is working on cultured beef, chicken and duck making use of stem cells to turn them into muscle tissue. Memphis Meats expects to launch its products by 2021. This company filed a very strong international patent publication number WO2017124100 in January 2017 related to methods for extending the replicative capacity of somatic cells during an ex vivo cultivation process where CRISPR-Cas9 technology is involved. Other interesting patents held by the company include methods for scalable skeletal muscle lineage making use of a myogenic transcription factor (WO2015066377); increasing the culture density in the absence of serum (WO2018208628); and increasing the efficiency of cultivation modifying the cells with a myogenic transcription factor and introducing into the cells polynucleotide sequences encoding a telomerase reverse transcriptase, glutamine synthetase, insulin-like growth factor, and albumin (WO2019014652).

SuperMeat The Essence of Meat Ltd. is an Israeli startup founded in 2015 to develop chicken cultured meat through crowdfunding. The company emphasizes that its products are eco-friendly, more humane, fight world hunger and will be non-GMO. The company filed international patent publication number WO2018189738 in April 2018 where it is described a method for producing cultured meat-containing hybrid food making use of numerous types of cells from different species (hepatocytes, myoblasts, osteoblasts, fibroblasts, lipoblasts, odontoblasts, etc.) which also includes a plant-originated substance to enhance organoleptic and nutritional properties in specific quantities.

Future Meat Technologies Ltd. is an Israeli biotech company founded in 2017 by one of the co-founders of SuperMeat that aims to manufacture non-GMO fat and muscle cells in a serum-free medium increasing food safety and reducing ecological impact worldwide focusing on local and individual needs. Plans include to make use of small proprietary bioreactors that can be sold to individual clients using capsules comprising the proprietary starter tissue and necessary nutrients manufactured by the company. The company claims that its cellular agriculture technology has been developed by biologists, bioengineers and reputed chefs. Future Meat Technologies has received funds from a collaborative grant between Israel and China and Israel’s Modern Agriculture Foundation as well as companies such as Tyson Foods. International patent publication number WO2018011805A9 filed by Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. in July 2017 describes a system for growing cells in a small bioreactor with a delivery system for a perfusion solution.

Impossible Foods Inc. is an American company founded in 2011 that produces plant-based substitutes for meat and dairy products. The company claims that just eating its star product Impossible Burger 2.0 we humans save the equivalent of 96% less land, 87% less water and 89% fewer emissions according to an environmental life cycle analysis. Impossible Foods has filed approximately 7 international PCT patents since 2012 related to affinity reagents for protein purification, pH switchable reagents, soy-based cheese, ground meat replicas, etc. International patent publication number WO2015038796 filed by the company in September 2014 discloses methods and compositions for the expression and secretion of heme-containing polypeptides.

Wild Type Inc. with a team of five and backed up by Spark Capital is working on salmon meat. The company filed international patent publication number WO2018227016 in June 2018 that describes systems and methods to produce ex vivo meat with all claims affected by two patents and two scientific disclosures.

Cubiq Foods works on cultivated fat from animal cells like Omega-3 for industrial clients.

This developing market is the result of an adequate surrounding environment. For example, Counter Culture Labs is an American community of scientists and biotech professionals based in California that works as a hub helping synthetic biology projects to spin off. In relation to funding we have New Harvest, a public charity that was established in 2004 to operate as a research institute working in the field of cellular agriculture funding and conducting open, public, collaborative research to produce animal products without animals.

The first ones to punch will punch twice but successive initiatives and startups will also enjoy excellent opportunities provided further scientific studies assure quality and safety and public acceptance is widely met. As the market develops further suppliers and complementors will probably appear and new business models may emerge.

JM Cejudo, MSc in Biological Sciences

 

Antidepressants could be expanded in the treatment of migraine

Antidepressants are often used for migraine prophylaxis, but their use is limited to off-license. A high percentage of patients not fully satisfied with their current treatments could justify more research to develop licensed antidepressants to deal with this medical condition.

Main use of antidepressants

The purpose of prescribing antidepressants is to help relieve symptoms of depression, anxiety disorders and other medical conditions that include migraine prophylaxis, at least used off-label. It is important to note that these medicines do not cure the disease but just treat symptoms.

The mechanism of action of these drugs is mainly based on targeting imbalances of neurotransmitters in the brain that could be part or a consequence of the origin of these medical conditions.

Antidepressants in the treatment of migraine

Migraine and depression may share modulatory factors

Chronic stress and depression are frequent in migraineurs and thus seem to share, at least in part, modulatory factors. Just in the United States 8% – 12% of people aged over 12 years old are using antidepressants, with females representing approximately three quarters of patients. It is estimated that around 22% of migraineurs may be suffering from depression, and it seems common that patients are diagnosed with depression or anxiety just after being diagnosed with migraine – this may be influenced by the fact that antidepressants are not always covered by health insurance to treat migraine as a first-line therapy, particularly in the United States.

Migraineur

According to many studies, it seems obvious that serotonin plays a relevant role in migraine and depression.

Serotonin, released from brainstem serotonergic nuclei, is thought to be mediated by its direct action upon the cranial vasculature. Vessel vasodilation seems one of the main causes that result in migraine headaches. Other scientists have suggested that serotonin could intervene in central pain control pathways or could be the consequence of cerebral cortical projections of brainstem serotonergic nuclei. Low levels of serotonin could make easier the activation of the trigeminovascular nociceptive pathways in conjunction with cortical spreading depression.

In any case, serotonin receptors (5-HT receptors) have been one of the main targets in the development of antimigraine drugs. There are at least 7 classes and 14 subtypes of 5-HT receptors, all with varied biological effects. 5-HT1B serotonin agonists in blood vessels known as triptans are the most relevant antimigraine abortive drugs now. Still, triptans are also agonists at the 5-HT1D receptor, which contributes to their antimigraine effect caused by vasoconstriction of blood vessels in the brain.

On the other hand, scientists believe that an imbalance in serotonin levels, particularly diminished activity of serotonin pathways, may influence mood in a way that leads to depression. It is important to notice that this theory has not been fully substantiated though. Some authors suggest that an imbalance in serotonin levels may not be the only cause to suffer from depression and that other factors may also influence, or even be the main cause on their own for certain patients.

SAMe (S-adenosyl-l-methionine), an amino acid-based substance produced naturally throughout the human body, has been postulated as a potent antidepressant that could also be useful to treat migraines due to its modulating effect on serotonin. SAMe has been available as a dietary supplement in the US since 1999, but it has been used as a prescription drug in Germany since 1989.

Studies and experts’ opinions may lead us to think that serotonin levels and imbalances may affect certain individuals under certain circumstances that may prompt migraine and depression or anxiety disorders at the same time. However, it is clear that serotonin is not the only cause for migraine and depression because not all people suffering from migraine have depression and vice versa.

TCAs and SSRIs are the main antidepressant categories used in migraine prophylaxis

Focusing on the prevention of migraine, tricyclic antidepressants (TCAs) and selective-serotonin re-uptake inhibitors (SSRIs) are the most often used categories of antidepressants because these types of product seem to block serotonin reuptake. However, more selective serotonin reuptake inhibitors are not very effective in migraine prevention. Within the TCA category amitriptyline and nortriptyline dominate this segment whilst duloxetine hydrochloride is the leading SSRI drug for migraine treatment.

From a patients’ profiling point of view, as an example, a study showed that migraine attacks after use of tricyclic antidepressants (TCAs) was reduced in all NOS3 genotypes (nitric oxide synthase 3) patients, though there was no significant effect in intensity of headache. Researchers detected an inhibitory role in migraine generation, predominantly in patients with homozygous genotype, due to the decreased frequency of migraine attacks.

Nonetheless, a major concern in the use of antidepressants is their side effects. The use of amitriptyline conveys major worries about suicidality that may not be worth running the risk of their prescription. Patients also report suicidal thoughts with other antidepressants including SAMe.

Serotonin syndrome may also happen in patients that take triptans, TCAs or SSRIs abusively. Symptoms for serotonin syndrome include high body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils, and diarrhea. Under extreme circumstances it may also include seizures and extensive muscle breakdown.

Anyhow, antidepressants should be avoided in elderly migraineurs and patients with comorbid overweight, epilepsy, or concentration and mental psychic performance.

The antidepressants market in the treatment of migraine

In the United States no antidepressant is officially approved to treat migraine, but just in the US market amitriptyline may be generating more than $10.0 million annually specifically targeting this indication at manufacturers’ level. Both nortriptyline and duloxetine hydrochloride combined may be around another $10.0 million. In Germany and the United Kingdom amitriptyline is estimated to have sales of approximately $1.60 million and $2.99 million respectively per annum for the prevention of migraine alone.

Some products containing amitriptyline are approved for the treatment of migraine in Germany. In the United Kingdom this active ingredient is used unlicensed for migraine prophylaxis according to the British National Formulary (BNF). In the United States it is used off-label.

Amitriptyline oral tablets and combinations with chlordiazepoxide, a sedative drug, or perphenazine, an antipsychotic drug, are off patent.

Nortriptyline oral capsules and solution and duloxetine hydrochloride delayed release pellets capsules have also lost their patent protection.

Medical devices may treat migraine and depression too

The connection between depression and migraine is also perceived strongly in the interest shown by some companies in the development and use of medical devices.

Patent publication number WO9400189 filed in 1992 by Cyberonics describes alleviation of migraine attacks by selectively applying by electrodes a predetermined electrical signal to the patient’s vagus nerve with an implanted neurostimulator device. Cyberonics markets the Vagus Nerve Stimulation (VNS) Therapy System, which was FDA-approved in 1997 and received CE Mark in 1994 for the treatment of refractory epilepsy and treatment-resistant depression. However, this is just an example as there are a large number of patents related to medical devices describing treatment of depression and migraine that have been filed by many companies.

In Europe, electroCore’s nVNS technology has a CE mark for primary headache (migraine and cluster headache), bronchoconstriction, epilepsy, gastric motility disorders, and anxiety and depression with medical prescription. gammaCore-S® is currently under study for the acute treatment of migraine.

The Fisher Wallace Stimulator received FDA clearance in 1991 for the treatment of insomnia, anxiety, depression and pain, and it is occasionally used off-label for the treatment of migraine.

Antidepressants in personalized migraine prevention may be profitable

In a more personalized medicine in the near future there may be opportunities to develop antidepressants to treat specific subtypes of migraines with ameliorated adverse effects. Understanding serotonin pathways better and improving patients’ genetic profiling will help to find better targets.

The development of a more personalized medicine will force existing products to find their market niches. Improving formulations of existing antidepressants that fit better specific genetic or biochemical patients’ profiles may be profitable for companies and advantageous for these patients. Covering these improved formulations with patents in order to trade them may also be interesting for small companies that do not have the economic muscle to market the product. Prices will be necessarily higher, but a number of patients will increase their quality of life. If these improved formulations are similar enough to the original approved active ingredient the approval process may be shortened and thus costs will also be reduced.

For more information about the antimigraine market in the United States, Germany and the United Kingdom please follow this link

Gene therapy could cure some migraine subtypes

What is gene therapy?

Gene therapy is a disruptive technology that could change the paradigm to treat a disease if it is proven effective.

Up to now, when scientists discovered a new gene potentially involved in the advent of a disease subsequent research mainly evolved around potential development of new products that targeted this new gene as well as associated interacting proteins and biochemical pathways. Nonetheless the future may bring along new approaches as science and technology advance.

Gene therapy in the treatment of migraine

Gene therapy is a technique to transfer genetic material targeting specific cells to repair, replace or inactivate malfunctioning genes that produce either defective proteins or no proteins at all in order to prevent or treat a disease. To transfer a gene, it is necessary to make use of a vector that is generally a genetically engineered virus prepared to cause no harm to the patient. The vector is injected or given intravenously, though in variant techniques a sample from the patient’s tissue can be extracted and exposed to the vector to be returned to the patient afterwards. The viruses infect targeted cells transferring the modified genetic material that will ultimately cause the desired therapeutic effect.

However not everything is as easy as it looks. Gene therapy conveys high health risks and at the moment it is only considered for those diseases that have no cure and whose genes are properly identified. The main barrier to manipulate genes is based on the fact that genes may control many biochemical pathways directly and indirectly, what is known as pleiotropic proteins. These genes often influence in the advent of other potential diseases and / or side effects in the same individual at the same time.

Since 1999 some attempts to use gene therapy have been tried with partial success. In one study conducted by a team of French researchers, eleven children suffering from serious immunodeficiency were treated with limited success, but two of them developed leukemia due to the vector used to transfer the genetic material. Other cases together with opinionated experts have also questioned gene therapy viability.

More recently CRISPR technology, an innovative genetic editing system, has raised great expectations once more. Nevertheless, according to Stanford University, patients receiving this treatment often develop antibodies against Cas9, an enzyme used in this new technology that cuts DNA fragments precisely. According to experts in this field, it is possible, however, to find workarounds such as different nucleases that do not prompt the autoimmune reaction so strongly and / or administration of immunosuppressants. Yet, the autoimmune system is not the only problem to be overcome when dealing with gene therapy and this technique. Further studies seem to show that there is also a risk of developing tumors due to a defective P53 gene. This gene codes for a protein that protects DNA from damaging changes, thus preventing potential tumors and other unwelcome effects. So, when P53 gene does not work properly DNA modification and desired therapeutic effect are easier, but they are also riskier. Some researchers believe that cell culture in a lab could be a solution to this problem, testing those genetically modified cells that have kept a functional P53 gene in a sort of quality control before reimplantation. In conclusion the use of this technique is still far from being implemented soon, and experts believe that it will probably be carried out in a very different way. Targeting RNA instead of DNA could also be another way to overcome DNA-related technical problems.

Migraine genetics

Gene therapy products are considered “biological products”. In the United States, this type of product is regulated by the FDA’s Center for Biologics Evaluation and Research (CBER). Clinical studies in humans require the submission of an investigational new drug application (IND) before clinical trials are conducted in the United States. Marketing a gene therapy product requires submission and approval of a “biologics license application” (BLA).

European Union regulations define “biological medicinal products” as “a protein or nucleic acid–based pharmaceutical substance used for therapeutic or in vivo diagnostic purposes, which is produced by means other than direct extraction from a native (nonengineered) biological source“. The terms “biotechnology medicines” and “biological medicinal products” are also commonly used.

 A quick look at migraine genetics

It is generally accepted that migraine is a multifactorial disorder with multiple genes playing a low penetrance role that is also influenced by environmental non-genetic factors. Thus, migraine is categorized in different subtypes, though it is mainly classified as a neurovascular condition activated from the trigeminovascular system where neurotransmitter pathways apparently play a relevant part, on their turn also controlled by other genes.

Genes that take part in migraine are often categorized as neurotransmitter genes, vascular genes and hormone genes. To get an idea of the complexity of migraine etiology we can give some examples of genes and proteins that take part in this medical condition, but it is far from being an exhaustive explanation for migraine origin, which is still unknown. There is some evidence that trigeminal nociceptive terminals are activated prompting the release of CGRP (calcitonin gene-related peptide), a pleiotropic neurological intermediary. CGRP is a 37 aminoacid peptide which seems to increase the sensitivity of perivascular nociceptors and dilate cranial vessels for some individuals who seem to be more susceptible, eventually known as migraineurs. RAMP1 gene (receptor activity modifying protein 1) codes for a key receptor subunit of CGRP, therefore also playing a relevant role. Still not all migraines are linked to CGRP and therefore not all patients may benefit from treatments targeting this peptide. Other genes may be the essential cause of a migraine, for example pituitary adenylate cyclase-activating polypeptide (PACAP), which is a neuronal messenger molecule thought to influence migraine, or female sex hormones involved in migraine susceptibility. There are many more genes and biochemical pathways suspected of influencing this medical condition.

At the moment, only some hemiplegic migraine subtypes have been accurately identified with causative genes. CACNA1A on chromosome 19p13 (FHM1), ATP1A2 at 1q23 (FHM2), and SCN1A at 2q24 (FHM3). It seems that FHM1, FHM2 and FHM3 mutations increase levels of glutamate and potassium in the synaptic cleft. PRRT2 (proline rich transmembrane protein 2) mutations have also been associated with hemiplegic migraine.

 Are there any clinical trials being conducted to treat migraine with gene therapy?

There are currently a significant number of studies making use of gene therapy to treat hereditary conditions. Examples include several types of cancer, immunodeficiency, sickle cell disease, diabetes concurrent with hepatocellular carcinoma, hemophilia, Alzheimer Disease and others mainly in early stages of development, though some studies have reached phase III trials as it is the case of peripheral arterial disease or spinal muscular atrophy.

We are not aware of any studies being conducted to treat migraine with gene therapy at the moment.

Are there any patents filed related to the treatment of migraine through gene therapy?

Some universities, research institutions and several pharmaceutical companies have filed patent applications related to diagnostic markers or genes involved in migraine such as those concerned with or affecting CGRP among others.

More directly related to gene therapy, there are already thousands of patent applications disclosing vector systems, antibodies, delivery techniques, enhancers, and different methods and techniques targeting specific genes or just genes in general. In particular, there are hundreds of patent applications filed in relation with CRISPR (clustered regularly interspaced short palindromic repeats) technology.

Regarding p53 gene activity concerns, as an example among many others we can mention MultiVir Inc., an American company, that filed international patent publication number WO2009094647 in January 2009 describing p53 biomarker profiles to be used in anti-hyperproliferative disease gene therapy.

In any case we have not found any patents specifically describing treatment of any migraine subtype through gene therapy yet.

 Is it possible to cure migraine with gene therapy?

For the moment advances in migraine genetics may help identify how genes influence biological pathways to develop more targeted drugs for migraine therapy.

Meanwhile the future treatment of migraine seems better approached with personalized medicine or precision medicine improving the definition of disease subtypes and more precise biomarkers that allow better tailor-made treatments for specific patients. Data mining and analysis in genetics, biochemistry and lifestyle will help to develop this type of personalized medicine.

Certainly, there is hope that gene therapy could cure at least some migraine subtypes in the near future, but gene therapy techniques need a significant improvement together with more advances and better understanding of migraine genetics. Maybe the best migraine subtype candidate to be approached through gene therapy is hemiplegic migraine variants – that is certain types of familial hemiplegic migraine and sporadic hemiplegic migraine.

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Medical devices will lose share in terms of revenues in the total US anti-migraine market by 2022

Anti-migraine medical devices

Anti-migraine medical devices will grab 5% market share in the United Kingdom and 3% in Germany in revenues in 2022

Whilst medical devices will gain two percentage points versus therapeutic drugs from 2018 to 2022 in terms of market share revenues for the total UK and German anti-migraine markets, CR Life Sc predicts that medical devices will lose two percentage points to grab only 7% of the total market to treat migraine in the United States.

During 2017 the medical devices market for the treatment of migraine in Germany has been able to seize approximately 1% share. Meanwhile the UK market for this type of devices has generated twice as much revenues to get 3% share. These devices are mainly available through specialist clinics and neurologists.

Anti-migraine medical devices face significant challenges and many opportunities

93% of revenues are expected to be generated by therapeutic drugs in 2022 in the United States. Abortive drugs (analgesics and antiemetics, specific antimigraine drugs, and more innovative medicines) will still lead the market. Anti-CGRP monoclonal antibodies and gepants together with new preventive drugs will help to drive the anti-migraine therapeutic drugs market. Expected high prices for these innovative products has become a major concern for government payors and insurance companies.

CR Life Sc estimates that neurostimulators and intraoral devices will have growth rates above 16% in revenues by 2022, but still according to the market neurostimulators may be underperforming.

Currently approved anti-migraine medical devices mainly target non-invasive Vagus Nerve Stimulation (VNS), Trigeminal Nerve Stimulation (TNS) and Transcranial Magnetic Stimulation (TMS), but Cranial Electrotherapy Stimulation (CES) devices and Vestibular Neurostimulators could also enter this market. Other invasive devices aiming at occipital nerves, trigeminal nerves, sphenopalatine ganglion, vagus nerve and spinal cord are also under study.

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CR Life Sc Insights has launched the most complete Antimigraine Market Report unravelling many opportunities and some threats

CR Life Sc Insights has produced the most complete market report for the Antimigraine Market. The report conveys a strategic analysis to 2022 for therapeutic drugs, diagnostics and medical devices in the United States, United Kingdom and Germany.

 

An overview of the anti-migraine market as accurate as possible in three relevant countries

 

In order to assess the market properly it is necessary to have an overview as complete and accurate as possible. Most of the reports available on the market just give partial views with a lack of adequate understanding for the whole picture.

 

The treatment of migraine offers many opportunities and some threats for healthcare companies. This report will make the reader an expert in this field.

 

This report is independent and economically unbiased and it is not sponsored by any stakeholder with an interest in the antimigraine market.

 

What you can find in this report

 

CR Life Sc Insights has conducted primary and secondary research involving more than 500 companies and institutions, more than 80 active ingredients and compounds as well as medical devices, and about 200 patents, to produce a report that contains 634 pages, 70 figures and 65 tables.

 

The structure and segmentation of this report makes an interesting and easy reading to reach conclusions and prompt adequate analysis and planning.

 

Who should buy this report

Investors, consultancy firms, professionals and any stakeholders in the pharma, diagnostics and medical devices fields will benefit from reading and having at hand this comprehensive report.

The Antimigraine Market.
The Antimigraine Market.
Therapetic drugs, diagnostics and medical devices. Strategic analysis to 2022. United States, United Kingdom and Germany.

Price: US $6,500

Contact us to receive more information and an Executive Summary.