Food Safety of Cultured Meat

What is Cultured Meat?

As FAO has forecasted, 70% more food will be needed to fulfill the demand of the growing population, which is a great challenge due to resource and arable land limitations. Global demand for meat, fish, and other animal-based products is expected to rise dramatically as the world's population is increasing significantly. Thus, the human population is expected to exceed 9.5 billion by 2050, and the increase in demand for animal-based protein is projected to be doubled by the same time. Even though meat consumption is slightly decreasing in developed countries, its global consumption is exponentially increasing as consumers in developing countries such as China, India, and Russia are generally reluctant to reduce their meat consumption. On the other hand, reliance on traditional, animal-based production is a highly inefficient way of meeting the increased demand, whereas industrial animal agriculture is a significant source of environmental stress and raises concerns regarding sustainability, food safety and security, worker safety, public health, and the ethical treatment of animals.
 
Traditionally, livestock systems have been a major contributor to addressing the issue of global food and nutrition security. However, today animal husbandry must produce larger quantities of high-quality and affordable meat, milk, and eggs, through production systems that are environmentally sound, socially responsible, and economically viable, which is extremely difficult in extensive systems, despite the wide range of economic, environmental, cultural, and social services at local, regional, and global levels provided for livestock farming. Hence, a significant proportion of livestock is raised within the intensive high tech farming models in modern agriculture, which has a lower contribution to greenhouse gases and water usage than extensive agriculture, where factory farming is mainly focused on efficiencies such as the quantity of milk or meat produced rather than on other services, and impacts such as interaction with the environment, climate change, or less use of antibiotics, animal welfare, or sustainability.
 

Hence, Cell-cultured meat/seafood production has the potential to provide a significant supply of animal protein and can help enhance global food security while offering human health and environmental and animal welfare benefits. Public acceptance and successful commercialization are key factors that require addressing ethical, environmental, and human health issues, along with consumer perception and aspects such as taste and affordability. Hence, complete realization of the potential of cell-cultured meat products demands a responsible approach to food safety to warrant regulatory, investor, and public acceptance. Nonetheless, safety demonstration, in turn, requires understanding the process of cell-cultured meat manufacture to identify potential hazards and food safety requirements, where subject knowledge paves the way to identify and mitigate possible concerns while identifying opportunities to implement best practices.
 
Cell-based meat (or the lab-grown meat, cultured meat, and synthetic meat) refers to a process of in-vitro cultivation of animal cells as an alternative to sourcing meat directly from slaughtered animals, which works by taking stem cells from donor animals that are then immersed in a growth serum. These cells are used for multifaction inside a bioreactor, where they grow in optimal conditions to convert themselves into edible meat. The technology used in the process is categorized as a form of cellular agriculture. The most obvious advantage is that cellular agriculture can avoid animal cruelty in industrialized animal husbandry and slaughter. On the other hand, the huge global population pressurizes the demand for meat products, posing a problem for the supply chain across the globe.

However, animal cruelty is not completely eliminated as society expected, because manufacturers need to extract animal cells from living animals to produce cultured meat on a regular basis, which is typically done via biopsy, a painful and uncomfortable procedure that uses large needles. Nonetheless, the producer may biopsy the same animal many times for the same unique cells to make a more consistent cell-based meat product. At the initial stages of the development, researchers used fetal bovine serum (FBS) as a growth medium in small-scale lab trials. Later, various processes were introduced, where large bioreactor processes with non-FBS-based cell multiplication are gaining popularity in the current cellular agriculture industry.
 

Cellular agriculture is broadly defined as the production of meat, milk, eggs, seafood, and other products and ingredients, from cell cultures rather than from farmed animals. Hence, products of cellular agriculture can be classified with multiple criteria. One process focuses on the type of product created—either cellular (i.e., composed of living or once-living cells) or acellular (i.e., composed of proteins, lipids, or other small molecules). Cellular agriculture can also be grouped by production methods such as either tissue engineering-based or fermentation-based.
 
Further, non-genetically engineered animal muscle cells only proliferate or increase up to a certain degree, thus the process needs additional improvements the within bioreactor process to mitigate such limitations. A bioreactor is a very large vessel that contains biological reactions and processes to implement a scaffold-based system to grow meat cells, which uses a specific structure for cells to grow on and around. The scaffolding helps the cells differentiate into a specific meat-like formation, where materials used can be cornstarch fibers, plant skeletons, fungi, and gelatin as common scaffold materials. Instead of animal muscle cell precursors (otherwise known as myosatellites), researchers have been using cultured stem cells, which is important because extracted muscle cells will only proliferate to a certain extent.
 
In addition, researchers are trying cultured stem cells as an alternative type of cell(s) that could proliferate exponentially so that they could scale up production, and later differentiate the cells into the various cell types that make up animal meat (muscle, fat, and blood cells) in a bioreactor. In this process, the stem cells still come from animals or animal embryos, but what differentiates the two methods is that in the scaffold-based system, the cells can be genetically engineered to proliferate indefinitely. These cells are otherwise known as pluripotent (which make many kinds of cells, like stem cells) or totipotent (which make every kind of cell, as do embryos). This would greatly expand a manufacturer’s capacity to make lab-cultured "meat," but the methods by which companies make these cells proliferate come with human health and food safety ramifications. The first-ever approval of a cell-cultured meat was recently granted by the Singapore Food Agency (SFA) for cell-cultured chicken used as an ingredient in a hybrid product made with plant protein.
 

Once a biopsy is taken from a live animal, the piece of muscle will be cut to liberate the stem cells, which have the ability to proliferate but can also transform themselves into different types of cells, such as muscle cells and fat cells. The cells will start to divide after they are cultured in an appropriate culture medium, which will provide nutrients, hormones, and growth factors. The best medium is known to contain fetal bovine serum (FBS), which is going to be rate-limiting, and not acceptable for vegetarians, or vegans. These cells can grow more than one trillion cells and naturally merge to form myotubes that are no longer than 0.3 mm, where these myotubes are then placed in a ring growing into a small piece of muscle tissue. This piece of muscle can multiply up to more than a trillion strands and these fibers are attached to a sponge-like scaffold that floods the fibers with nutrients and mechanically stretches them, exercising the muscle cells to increase their size and protein content. The process uses fewer animals to produce huge amounts of meat due to cell proliferation, thereby avoiding killing too many animals but potentially lots of calves if FBS is still used. Throughout this process, the cells are kept in a monitored environment that replicates the temperature inside the body of a cow.
 
A major initial problem with the FBS culture is that in vitro meat aims to be slaughter-free. In addition, FBS is expensive and affects to a large extent the production cost of the meat. In addition to FBS, antibiotics and fungicides have been commonly used to avoid contamination of cell cultures. Nevertheless, cell culture needs hormones, growth factors, etc., in the culture medium to sustain cell proliferation and differentiation such as in all mammals, which is an important issue since hormone growth promoters are prohibited in farming systems for conventional meat production in some regions like European Union.

In fact, the industry is still far away from the real muscle, which is made up of organized fibers, blood vessels, nerves, connective tissue, and fat cells. Stem cells or muscle cells reproduce unorganized muscle fibers, which is the simplest approach, while some researchers are trying to reproduce thin slices of muscles such as muscle fibers and other cell types quite well imbricated together. Hence, the production of a real steak-like thick piece of meat is still a dream, due to the necessity of perfusing oxygen inside the meat to mimic the diffusion of oxygen as it occurs in real tissue.
 
Conventional meat is part of an animal in contact with the external environment, although each tissue (including muscles) is protected by the skin and/or by mucosa, whereas in vitro meat claims to be safer than conventional meat, based on the fact that lab-grown meat is produced in an environment fully controlled, without interaction of any other organism. Actually, without any digestive organs nearby and without any potential contamination at slaughter, cultured muscle cells do not have the same opportunity to encounter intestinal pathogens such as E. coli, Salmonella, or Campylobacter, the three pathogens that are responsible for millions of episodes of illness annually.
 
The cultured meat is not produced from animals raised in a confined space, where the risk of an outbreak is eliminated and there is no need for costly vaccinations against diseases like influenza to safeguard animals. There may have unknown potential effects on the muscle structure and possibly on human metabolism and health when in vitro meat is consumed. Antibiotic resistance is known as one of the major problems facing livestock, but, cultured meat is kept in a controlled environment and close monitoring can easily stop any sign of infection. Besides, it has been projected that the nutritional content of cultured meat can be controlled by adjusting fat composites used in the medium of production. Because the ratio between saturated fatty acids and polyunsaturated fatty acids can be easily controlled, where saturated fats can be replaced by other types of fats, such as omega-3, but the risk of higher rancidity has to be controlled. As a major drawback, no strategy has been created or tested to endow cultured meat with different micronutrients specific to animal products. As of now, it is not certain that the other biological compounds and the way they are organized in cultured cells could potentiate the positive effects of micronutrients on human health. However, cultured meat cannot exclude a reduction in the health benefits of micronutrients due to the culture medium, depending on its composition, but enrichment of excess chemicals to the medium makes cultured meat more chemically adulterated food with less of a clean label.
 

Safety assessment for cell-cultured products is possibly going to be on general principles of risk assessment, which may be derived from evaluation of conventional meat and seafood products, as well as from evaluation of products in related fields, such as fermented foods, novel foods, foods produced with or from genetically engineered (GE) organisms, cloned animals, as well as drugs and medical devices. Thus, many existing safety testing methods may be adaptable to cell-cultured products. Effective risk assessment for the field is likely to require an approach that directly adopts some of these methods and modifies others while supplementing with novel strategies.
 
Cell-cultured meat and seafood production may rely on manufacturing methods not currently used for food, which means the inputs, by-products, and outputs from each manufacturing step require an assessment to identify potential safety concerns. Microbiological contamination with bacteria (including mycoplasma), fungi, and viruses can occur throughout the entire manufacturing process, where Mycoplasma contamination may be of particular concern. Mycoplasma is a small bacteria that can infect a wide range of hosts and be pathogenic, which are common cell culture contaminants, estimated to infect 5%–35% of the world's cell lines. Mycoplasma is resistant to antibiotics, can pass through filters, and grow slowly so may not be detected for months or even years in continuous cell cultures. The host can be animals, personnel, other cell cultures, cell media components, equipment and supplies, and equipment, etc. can all be sources of mycoplasma contamination and spread.
 

Thus, some regulatory agencies have already started to develop broad guidance for safety assessments even though such guidance to date is not yet very detailed as the technology continues to develop. Further, regulatory agencies have relied on insight and data directly from industry to date, rather than from academic or third-party experts or peer-reviewed publications, partly due to the imbalance in public versus private funding in cellular agriculture today. Hence, continued successful commercialization requires public and private investment, efficient regulatory approval processes, and public acceptance. These milestones require assurance that products can be produced, marketed, and consumed without harm to workers, consumers, or the environment. A proactive approach employs the development of adequate evidence to assess risk and demonstrate safety in advance of commercialization. Safety testing, in particular, plays a critical role in the development of safe products, regulatory authorization, and guaranteeing that statements made to investors and the public are based on sound evidence.
 
References:
https://ift.onlinelibrary.wiley.com/doi/full/10.1111/1541-4337.12853
https://www.foodincanada.com/features/the-food-safety-advantages-of-lab-grown-meat/
https://www.frontiersin.org/articles/10.3389/fnut.2020.00007/full
https://www.centerforfoodsafety.org/blog/6458/is-lab-grown-meat-healthy-and-safe-to-consume