The “antibiotic era” is awesome, but it might not last forever.
The discovery of antibiotic and antimicrobial compounds and their use in medicine is one of the great achievements of modern science. While these compounds had been used in some capacity throughout human history, the modern “antibiotic era” meant once unmanageable diseases such as tuberculosis could be easily cured using antibiotics. Antimicrobials have since saved countless lives and prevented a great deal of human suffering.
However, the routine use of antibiotics and antimicrobials—including in conventional meat production—has led to an increase in the frequency of antimicrobial-resistant strains. This rise in antimicrobial resistance (AMR) threatens to set us back decades to a time when a simple infection could be deadly.
In a recently published commentary piece in Nature Food, we discuss the potential of cultivated meat to help address the threat of antimicrobial resistance. Below we break down our thinking on this emerging topic.
Doesn’t cell culture use antibiotics too?
With 70% of medically-important antibiotics used for animal agriculture, conventional meat is a major contributor to the risk of antimicrobial resistance. By removing the animal from the equation, alternative proteins—including plant-based, cultivated, fermentation-derived, and hybrid products—are a global health solution.
But even if conventional meat is a major driver of AMR, can we be confident that cultivated meat will help solve this problem? Could it potentially be worse than conventional meat? These are fair questions. Anyone who has worked in an animal cell or tissue culture lab knows that microbial contamination is a common challenge, and that this challenge is often addressed by adding antibiotics to the cell culture media.
The people asking these questions raise perfectly reasonable concerns based on their knowledge of standard laboratory techniques! The science of alternative proteins advances by engaging earnestly with the hard questions and adjusting the approach accordingly. We must approach these questions with open-mindedness and humility. Fortunately, the available evidence provides a high degree of confidence that antibiotic-free production is not only possible but much more likely than the cultivated meat industry depending on routine antibiotic use to prevent contamination.
Whether the future cultivated meat industry is likely to use antibiotics comes down to two questions: 1) Is it feasible to produce mammalian cells and tissues at scale without using antibiotics? 2) If so, what are the pros and cons of antibiotic use in this context?
Is antibiotic-free cultivated meat production feasible?
This is pretty easy to answer! The cultivated meat industry’s goal is to cultivate animal cells at scale without losing batches due to contamination, or worse, producing unsafe products. We know this can be done because the biopharmaceutical industry is already doing it routinely. Whereas cell cultures in academic research are subject to frequent handling, reagents are shared between multiple researchers, and there are many opportunities for contamination to be introduced, the same is not true in commercial-scale biopharma manufacturing. The contamination-related batch failure rate in biopharma has been estimated at roughly 2%, suggesting that contamination is successfully controlled without antibiotics in the large majority of cases.
Of course, the cost of production for biopharma products is much higher than what is tolerated by the food industry, and the cultivated meat industry may face additional challenges due to the use of larger vessels or differences in facility design. Even so, the current state of biopharma provides a clear demonstration that commercial-scale, antibiotic-free production of animal cell cultures is possible while also giving us a rough starting point to understand what it might look like. Further advances to extend this capability at larger scales or under less stringent manufacturing controls is a matter of optimization, not requiring entirely novel technology development. Furthermore, we know that antibiotic free meat cultivation is possible because the one product currently on the market as of October 2022 is produced without antibiotics.
The one area of the meat cultivation process where we anticipate that antibiotics might be used is in the initial cell isolation and cell line development stages, rather than in the manufacturing of the final product. However, because this happens on a dramatically smaller scale, we would not expect cell line development to pose major AMR risks even if antibiotics are used. Therefore, it’s important to distinguish between pre-production and production steps. For cultivated meat to be a useful part of the solution to the AMR crisis, antibiotic-free production is essential, but pre-production antibiotic use is likely to be acceptable.
What are the pros and cons of antibiotic use for cultivating meat at scale?
Just because antibiotic-free meat cultivation is possible doesn’t mean it will happen by default. While many cultivated meat companies are motivated to exclude antibiotics from their production practices, it is fair to consider the economic factors that may ultimately sway that decision one way or the other. As a thought experiment, we can consider the hypothetical “pros and cons” list that a purely profit-motivated cultivated meat company might develop when deciding whether their production process should include routine antibiotic use.
- The major advantage of antibiotic use in cultivated meat production is obvious—it prevents the growth of unwanted microorganisms. Cell culture media is ideal for growing not only animal cells but also many types of microbes. If microbes are not prevented from entering or growing, they can easily take over a culture, meaning that the whole batch will need to be scrapped. By using antibiotics in their production process, companies might be able to slightly improve the rate at which batches succeed.
- They might also be able to skip some other costly strategies for preventing contamination, for example by purchasing less expensive equipment or facilities. The magnitude of this second effect is harder to estimate, but it will become less important the more we develop other low-cost strategies that don’t involve antibiotics, such as media filtration as a part of media recycling or even co-culture with immune cells.
- Perhaps most importantly, antibiotics can negatively impact the behavior of cultured cells, sometimes substantially. This includes reductions in growth rate of up to 62% and undesirable effects on differentiation.
- Antibiotics can also degrade scaffold materials, which could affect the texture of the final product and the cell culture environment.
- The use of antibiotics and antimicrobials may expose companies to additional regulatory burdens. For example, the Singapore Food Agency requires cultivated meat companies to provide data on whether their use of antimicrobials would contribute to AMR. While regulatory pathways in other countries are still being ironed out as of October 2022, guidelines for other related industries already exist and may influence those used in cultivated meat. For example, Good Cell Culture Practice guidelines indicate that antibiotic use should be avoided wherever possible. In advance of clear regulatory guidance, it may behoove companies to be conservative by avoiding unnecessary antibiotic use.
- Then there is the monetary cost of antibiotic use. While antibiotics are not terribly expensive compared to other high-cost media components such as growth factors, using them at scale would introduce an additional cost that a profit-motivated actor would like to avoid if possible.
- Finally, companies able to claim antibiotic-free production might have a strategic advantage when it comes to consumer acceptance and food safety.
Where do we go from here?
GFI feels confident that the future cultivated meat industry will not rely on routine antibiotic use for production based on the information currently available. Public statements from over a dozen cultivated meat startups—including GOOD Meat, Aleph Farms, Wildtype, Mission Barns, Meatable, Supermeat, Biotech Foods, Peace of Meat, Biftek, Higher Steaks, Finless Foods, New Age Meats, and UPSIDE Foods—support this conclusion. The possible exceptions are in R&D and pre-production cell line development, but the volume of antibiotics used here are minuscule compared to other uses of antibiotics. Because of this difference in scale, responsible use of antibiotics in pre-production stages is highly unlikely to contribute to AMR risk.
From a performance standpoint, the methods used to prevent and detect contamination in the biopharmaceutical industry are transferable to cultivated meat. After all, the batch failure rate due to contamination is low in biopharma, and this is an industry that has to meet an exceptionally high bar when it comes to safety. For cultivated meat to succeed on an industrial scale, we need innovations that will maintain this high level of safety at much larger volumes while also reducing costs. In other words, we need to do the same thing biopharma is already doing, but much cheaper!
Though perhaps conceptually simple, achieving this will require substantial innovation and time. To the extent that there is a risk of companies turning to antibiotic use to reduce costs—which already seems unlikely given the cons discussed previously—the development of low-cost, reliable methods for preventing contamination will also help ensure that cultivated meat production remains consistently antibiotic-free.
The science is clear: the way the world currently produces meat threatens public health. With demand for meat projected to double by 2050 as the global population approaches 10 billion, we need new ways of making meat that satisfy growing demand without the risks to AMR. Cultivated meat does just that and gives us a shot at keeping our medically-important antibiotics working for decades to come.
Header image courtesy of Mosa Meat
Cultivated meat as a tool for fighting antimicrobial resistance
GFI’s Claire Bomkamp on how antibiotic use in livestock and aquaculture production is driving resistance to medically important antibiotics.