Thoughts of public sector animal geneticist - all views are my own

Author: alvane (Page 2 of 5)

Poison-free, fossil-free California agriculture (1 of 3)

This is part 1 of a 1, 2, 3 part BLOG series on this January 2020 two-day event featuring Dr. Vandana Shiva at UC Santa Cruz

In late January, 2020 I attended two events at UC Santa Cruz, a sister campus to UC Davis, and also where my tuition fees go to pay for the (presumably fact-based) education of my “banana slug” son who is a senior there. It was therefore with some concern that I read that Vandana Shiva had been invited to speak on campus. Dr. Shiva has been a polarizing figure in the genetically modified (GMO) foods discussion, as detailed by Michael Specter. But I personally had never heard her speak and as a scientist and someone who is trying to understand why the GMO debate has become so polarized, I decided to sign up and listen closely to what Dr. Shiva had to say, both at her Saturday evening lecture, “Vandana Shiva In Conversation”, and the following all day event entitled “Poison-Free, Fossil-Free Food and Farming.”

The Saturday night lecture, to a very receptive and supportive crowd, conversed on a range of topics, from empowering women farmers to the importance of nutritious food, the impact of climate change on food production systems, and the importance of seed banks.  Hard to find fault with any of those topics, in fact I agreed with Dr. Shiva on a number of her points. There was a lot of disparaging of “industry” and billionaires, especially Bill Gates despite his philanthropy, and much demonization of globalization and colonization.

As an agricultural scientist I took issue with the lack of evidence to support some of the overly optimistic anecdotes that were given regarding the productivity of different organic and agroecological production systems, because if they really were so much superior it makes little sense as to why would ALL farmers, as astute business owners, would not rapidly employ such production systems. Perhaps it is more complicated than was suggested.

The contention that organic production systems outcompete conventional systems is not supported by the weight-of-evidence in the peer-reviewed literature, and is one of the reasons that less than 1% of US farmland is under organic production.  But it was when discussing anything related to GMOs, Monsanto, patents and especially glyphosate (Round-up) that things (perhaps as might be expected) went totally off the rails. I will get into a couple of the specifics of that for those who are interested in fact-checking in part 2  (Sponsoring Falsehood) and part 3  (Rounding Up Fear) of this BLOG series.

The next day a group of very like-minded people discussed collective action ways to move California agriculture to “poison free” and “fossil-free”, meaning avoiding the use of all synthetic pesticides and fertilizers. California is a large agricultural producer, the largest state in the nation. Although the speakers talked a lot about social justice and empowering farmers, there were no California farmers or farm workers, those who would presumably be most likely be impacted by the proposed changes, represented on the panel of speakers.

Crop loss to different factors in the absence of effective controls

There was discussion about the need for farm-workers to be paid a living wage, but little discussion of what removing all pesticides and fertilizers might mean for those same farm-workers in terms of their job duties, or the economic sustainability of the farms that provide their employment. In other words, there was NO discussion of what trade-offs might result from this re-envisioning of the entire agricultural production system in California.

In the course of my job I interact with California farmers and ranchers, some conventional and some organic, and others somewhere in between to meet certain value-added program requirements (e.g. “never ever”, “non-GMO”). I watch how farmers under different production systems handle the nutrient needs of their crops, and control pests; be they disease-causing microbes, hungry insects, or moisture-seeking weeds.  Chicken manure from conventional chicken houses systems is composted and used as fertilizer on organic production systems, conventional almond hulls provide a good source of nutrients for dairy cows precluded from GMO-feed, and farm-workers control weeds in production systems that do not allow to use synthetic herbicides using tillage, propane flame throwers, and manual hoeing as pictured below.

California farm workers hand weeding an organic crop in the San Joaquin Valley

India, where Dr. Shiva lives, with its population of 1.27 billion people, employs 59% of the country’s total workforce in Agriculture. Seventy percent of its rural households still depend primarily on agriculture for their livelihood, with 82 percent of farmers being small and marginal. It is also home to a quarter of the world’s hungry people and anemia affects 50 percent of women and 60 percent of children in the country. There are certainly good reasons to be concerned about improving both food security and the productivity of agriculture in that country.

However, California agriculture is not comprised of small subsistence farms. It is an agricultural powerhouse.  California’s 77,100 farms and ranches received a total of $50.13 billion for their output in 2017 with combined commodities representing 13.4 percent of the U.S. total. California’s leading crops are fruits, nuts and vegetables. Over 27 percent of California’s 77,100 farms generated sales over $100,000, greater than the national average of 19.9 percent. The average farm size in California is 328 acres, which is below the national average of 444 acres. These are large enterprises to manage and farm, and the challenges facing California farmers are likely quite different to those of a small holder, subsistence farmer. What might California agriculture look like if synthetic pesticides and fertilizers were banned?

Back in 1840, workers in the agriculture industry made up 70% of the American workforce. Today farmers and ranchers themselves make up only 1.3% of the employed US population, totaling around 2.6 million people. Part of this urban transition has been enabled by the use of synthetic herbicides in agriculture. According to the author of an article entitled The Value of Herbicides in U.S. Crop Production, “By controlling weeds effectively, herbicides do the work of 70 million laborers.” In that article it is stated that “the problem of controlling weeds without herbicides has been cited numerous times as the single biggest obstacle to crop production that organic crop growers encounter.” USDA reports on strawberry, carrot, cotton, and processing tomato concluded that national production would decline by 30%, 48%, 27%, and 20%, respectively, without the use of herbicides and with the substitution of likely alternatives.

More generally, it has been estimated that without pesticides, 70% of the world food crop would be lost; even with pesticide use, 42% is destroyed by insects and fungal damage. According to one study, “Dispensing with pesticides would require at least 90% more cropland to maintain present yields. Dispensing with fertilizer would require at least 400-600 Mha additional cropland (in addition to the ~1,400 Mha currently grown).

“The consequence of less-efficient agriculture will be the elimination of wilderness that by any measure of biodiversity far exceeds that of any kind of farming system.”

Anthony Trewavas, Fellow of the Royal Society, University of Edinburgh, Scotland

There was a real sentiment in the room that all pesticides were “poisons”, and that no amount of pesticide (or inorganic fertilizer) was acceptable. And all of this seemed to be based on the premise that agriculture today is using ever increasing amounts of more toxic (poison) pesticides. The figure below on pesticide use in U.S. Agriculture from 1960-2008 , from a 2014 report from the USDA ARS, states “Average chronic toxicity declined, as toxic products applied to cotton (such as DDT and toxaphene) and to corn (such as aldrin) were banned (particularly in the 1970s and early 1980s). Other factors affecting toxicity were the use of less toxic insecticides, such as carbaryl and chloropyrifos, the introduction of pyrethroids, the use of malathion in the boll weevil eradication program, and the use of Bt [insect-protected, genetically engineered] cotton since 1996.

Persistence fell during the 1970s after the bans of DDT and aldrin, then increased during the 1980s and early 1990s (in part with the use of high-persistence products such as metolachlor and pendimethalin); persistence has declined in recent years, reflecting the rapid increase in glyphosate use. Glyphosate has low chronic toxicity (a high chronic score) and relatively low persistence relative to the herbicides that it has replaced. As the NRC (2010) report states, glyphosate “is biodegraded by soil bacteria and it has a very low toxicity to mammals, birds, and fish.

There was none of this type of evidenced-based data presented at this all-day event. Let alone data that documented that GMO crops had actually decreased insecticide use, especially organophosphate insecticides including in India, and allowed the use of less toxic herbicides. Unfortunately, non-Bt cotton refuges were rarely planted in India, which increased selection pressure for Bt-resistant pink bollworms thereby reducing the effectiveness of Bt cotton in that country, and highlighting the importance of integrated pest management, a term I did not hear mentioned at this conference.

I was disappointed that at a public university event on agriculture there were no public sector toxicologists to present objective facts and data on pesticide use in agriculture, integrated pest management specialists, or California farmers present to discuss potential trade-offs,  and what poison-free, fossil-free California agriculture might mean for their farms, their workers, their families and their livelihoods. The discussion did not reach beyond a simplified dichotomous framing of good versus evil, and was a missed opportunity to have the more nuanced discussion that such a weighty and important topic deserves. But things got much worse at the all day event entitled “Poison-Free, Fossil-Free Food and Farming” as detailed in the final part Rounding Up Fear of this 3-part BLOG.

Who is selling cultured meat? What do the consultants and the data say? 4 of 4

(*****This series of 4 BLOG posts (1,2,3,4) is extracted from my paper from the Proceedings of the Range Beef Cow Symposium XXVI, November 18-20, 2019. Mitchell, NE. pages 37-49.*****)

Nobody is selling it yet, at least as far as cultured meats go, because no one has reduced the production  to a commercial scale. But the concept is being sold hard.

In October 10, 2019 a Jerusalem biotechnology company Future Meat Technologies announced it will establish the world’s first cultured meat pilot production facility, “producing GMO-free meat cultivated directly from animal cells on a commercial scale”.  According to an Israeli press article “The company plans to establish the facility south of Tel Aviv and begin operations next year. The expansion of research and development efforts come after the start-up secured $14 million in a Series A funding round. The company plans to introduce hybrid products into the market, combining plant proteins for texture with cultured fats to create the aroma and flavor of meat. While existing costs are $150 per pound of chicken and $200 per pound of beef, it aims to market its hybrid products at a “competitive cost level” from its pilot production facility by 2021.”

According to the June 2019 report by consulting firm A.T. Kearney, they predict that “In 20 years, only 40% of global meat consumption will still come from conventional meat sources”. They posit that “Cultured meat will win in the long run. However, novel vegan meat replacements will be essential in the transition phase”. In their estimation by 2040, cultured meat will make up 35 percent of meat consumed worldwide, while plant-based alternatives (e.g. Impossible, Beyond Burger) will compose 25 percent.

Projected breakdown of global meat production by 2040 according to a June 2019 A. T. Kearney Analysis.

By 2040 the FAO predicts there will be 402 million metric tons (MMT) of land-based meat consumed worldwide (169 MMT chicken, 143 MMT pork, 90 MMT beef). That does not include eggs (98 MMT), fish (200 MMT), or milk (1,051 MMT). The total of animal-based products in 2040 is therefore predicted to be 1751 MMT (compared to 1430 in 2020) as illustrated in the feature image. Doing the back of the envelope math and assuming that only the 402 MMT of land-based meat production (i.e. not the sizable milk, fish and eggs production) is replaced with “quarter pounders” of alternative sources as predicted in the image above, that would equate to [(.25 x 402 MMT) X (1,000,000,000/0.1133981)] which would be approximately 886,258,235,367 plant-based burgers, and (.35 x 402 MMT)X(1,000,000,000/0.1133981) which would be approximately:

One trillion, two hundred forty billion, seven hundred & sixty-one million, five hundred and twenty-nine thousand, five hundred & fourteen (1,240,761,529,514) cultured meat burgers annually by 2040. That is a big ask in 20 years for an industry that does not yet have a single product on the market!

As with all ‘disruptive innovations’, there is a need to consider the pros and cons of the system that is being proposed as compared to the existing system. There will always be tradeoffs, some good, some bad. There are positive externalities associated with ruminants such at the ecosystem services they provide when they graze rangeland.  Grazing ruminants are embedded in the definition of rangelands—“a natural ecosystem for the production of grazing livestock and wildlife.” Grasslands and their associated biodiversity frequently evolved with large hoofed herbivores; well-managed, herbivorous grazing by ruminants maintains rangeland health.

Ruminants also provide manure, transportation, the livelihoods and food security of an estimated 1.3 billion livestock keepers. Small ruminants – sheep and goats – produce only about 4% of global animal-source protein. However, they are a very important source of such protein in the developing world as they are able to upcycle plants that are inedible for humans into high quality animal-souce foods. THAT is the magic super-power of grazing ruminants. The rumen’s microbial population can transform inedible grasses and other cellulose-based forages into energy. Additionally ruminants produce more than just hamburgers. Milk is by far the most consumed animal-source food globally, and dairy animals also produce both milk and meat.

Mattick et al. (2015) writes of cultured meat, “These energy dynamics may be better understood through the analogy of the Industrial Revolution: Just as automobiles and tractors burning fossil fuels replaced the external work done by horses eating hay, in vitro biomass cultivation may similarly substitute industrial processes for the internal, biological work done by animal physiologies.” Meaning external energy sources will be used to replace the work of the biological processes that take place in the cow. The authors continue with this train of thought, “That is, meat production in animals is made possible by internal biological functions (temperature regulation, digestion, oxygenation, nutrient distribution, disease prevention, etc.) fueled by agricultural energy inputs (feed). Producing meat in a bioreactor could mean that these same functions will be performed at the expense of industrial energy, rather than biotic energy.” Cultured meat would replace  a biotic system with a fermentation factory powered by industrial energy. The abstract of their paper concludes:

“While uncertainty ranges are large, the findings suggest that in vitro biomass cultivation could require smaller quantities of agricultural inputs and land than livestock; however, those benefits could come at the expense of more intensive energy use as biological functions such as digestion and nutrient circulation are replaced by industrial equivalents. From this perspective, large-scale cultivation of in vitro meat and other bioengineered products could represent a new phase of industrialization with inherently complex and challenging trade-offs.”

Mattick, et al. 2015. Anticipatory Life Cycle Analysis of In Vitro Biomass Cultivation for Cultured Meat Production in the United States. Environ Sci Technol 49(19):11941-11949.

In summary, cultured meat is a term used to describe imitating a range of animal products from animal cells grown in a bioreactor. Although there is a lot of venture capital and celebrity investor buzz around this technology, there is no company that is currently selling cultured meat. There are a number of unknowns about the feasibility of culturing animal tissues at scale, and the true environmental impact of using energy to replace the biological functions carried out by the body of an animal (harvesting forage for energy and growth, waste removal, fighting off disease etc.). Growing animal cells efficiently and keeping contaminants out of the system and end product requires attentive management and innovation, whether meat is produced in a biotic system that is powered by solar energy and the physiology of a cow, or an industrial system using electricity and a bioreactor to produce cultured meat in a manufacturing plant.

Cultured meat start-ups and venture capital: What do the data say? 3 of 4

(*****This series of 4 BLOG posts (1,2,3,4) is extracted from my paper from the Proceedings of the Range Beef Cow Symposium XXVI, November 18-20, 2019. Mitchell, NE. pages 37-49.*****)

When it comes to cultured meat, venture capital funds are funding startups in California, Israel and the Netherlands. Some of the first work in this area was done by Mark Post at Maastricht University in the Netherlands to produce the proof-of-concept burger  featured at the August 2013 £250,000 (US $330,000) lab-grown burger unveiling event in London. According to an article by Mouat and Prince, “Before the hamburger event, the mystery benefactor that financed the burger was unknown. Later it was revealed that the funder was Google co-founder Sergei Brin (Net Worth: $53.8 Bn). The event was simulcast on the web and included a celebrity chef live-cooking the burger, a three-person tasting panel, and a live studio audience . At this event, Post estimated that if the process can be scaled up it would take 10–20 years to produce ‘beef,’ likely still at relatively high cost (Murray, 2018).

Memphis Meats made meatballs from cultured meat at $18,000 per pound in 2016. Somewhat ironically given the environmental footprint of airplane travel, Virgin Airlines founder Richard Branson (Net Worth: $3.8 Bn) joined Bill Gates in financing cultured meat leader Memphis Meats in part of a $17 million fundraising round in 2017.

“There is no doubt that the association of this iteration of biological technology with super-rich celebrity investors and venture capital is significant”  (Mouat and Prince, 2018).

Ground beef is not the only product that is being attempted in cell-based culture. There are a number of companies springing up making everything from ice-cream to egg whites to cowless milk. In 2014 Perfect Day (Muufri prior to August 2016) was offered USD$2 million in seed money from Horizons Ventures. According to Mouat and Prince (2018), one of the partners at Horizons Ventures, Li Ka-shing ‘loves disruptive innovations and sees it as kind of predictive lenses into the future. He loves to meet and geek with the founders and CEOs of companies within our disruptive portfolio, to understand their concepts and missions’. Horizons Ventures have also invested in Facebook, Spotify, Skype, Modern Meadow (lab-grown leather for disrupting the $90 billion per year leather industry). There has also been some state investment in these technologies (Stephens, 2015).

A list of the companies I could find is in Table 2 using data from this list maintained at Cell based tech ( among other media sources – along with their location and the product they are trying to mimic.

Table 2: Listing of companies formed to produce cellular animal-based products, and their location. Estimates of total capital raised is listed when known.

New Harvest, a 501(c)(3) research institute accelerating breakthroughs in cellular agriculture, collects and directs charitable donations and grants in the industry. Next to venture capital funds, large corporations such as Cargill, Merck, Google, UBS, and PHW Group have invested in these companies. Cargill invested in Memphis Meats. The sum of total capital raised in Table 2 is well north of USD$400 million. The Good Food Institute, a non-profit that promotes plant-based and cultured meat alternatives to meat, dairy, and eggs; estimated that in the five years leading up to 2018, USD$17.1 billion had been invested in plant-based food; with a further USD$73.3 million in cell-based meat companies.

Mouat and Prince (2018) use the term biocapitalism to describe the investment in cultured meat. They reflect that fundraising for companies trying to produce animal-free food – depends to varying extents on “a venture capital industry with a culture that celebrates ‘disruption’; a set of biotechnical materials and relations that are being pacified into a marketable object; an existing community of concern worried about the effects of animal agriculture; and the construction of ethical agency for animal-free food to solve the problems that this community is so concerned with. It is all of these things that enable value to be leveraged off the biological material that makes up animal-free food, and so constitutes it as biocapital.

Cultured meats and LCA statistics: What do the data say? 2 of 4

(*****This series of 4 BLOG posts (1,2,3,4) is extracted from my paper from the Proceedings of the Range Beef Cow Symposium XXVI, November 18-20, 2019. Mitchell, NE. pages 37-49.*****)

The start-to-end environmental footprint – called a life cycle assessment (LCA) – of cultured meat at large scale is not available as no group has yet achieved this feat. I have tried to summarize the literature on the basis of kg of final product (Table 1), but note there are differences in a kg milk versus a kg of beef, and even a two-fold difference in the assumptions made as to the protein content of cultured meat. It is therefore close to impossible to do an apples to apples comparison. The values vary dramatically depending upon the assumptions made, and the boundaries of the LCA.

The functional unit (i.e. metric of the comparison) matters – whether kg carcass weight, kg product, kg of nutritional value (e.g., protein), and then of course the quality of that protein or food source. Changes in the functional unit (FU) alters the results quite dramatically, and therefore, the development of a FU which would reflect the complete integrative nutritional function of meat substitute is needed. It is obvious that meat substitutes have different nutritional profiles and, therefore, nutritional value. At the same time, different aspects of nutritional quality (protein and amino acid content, vitamins, fat and fatty acids, micronutrients etc.) vary in different proportion in meat substitutes. Therefore, it is necessary to develop a complex nutritional value estimate, which would reflect the qualities of meat and meat substitutes for further studies.

Table 1. Carbon Footprint CO2-eq, land use (m2), and energy use (MJ) per kg product for different products in a number of different studies. *Qantis (

In looking at Table 1, some general rules always apply: the carbon footprint per kg product increases as you go from one trophic level to the next (i.e. plants to animals that eat plants), and from single stomach (monogastric) animals (e.g.,  chickens/pigs) to ruminants (e.g., cattle and sheep). However, ruminants can eat forage that monogastrics, humans included, cannot. Ruminants consume byproducts (e.g. distiller’s grains) and crop residues (e.g. almond hulls) that would otherwise go to waste or into landfills.

Eighty-six  (86%) of the global livestock feed dry matter (DM) intake consists of feed materials that are not human edible. Producing 1 kg of boneless meat requires an average of 2.8 kg human-edible feed in ruminant systems and 3.2 kg in monogastric systems (Mottet et al., 2017).

It should also be noted that land use numbers in Table 1 do not differentiate between arable land, and land that has no other human food purpose. Many ruminants graze marginal land, or crop residues, and convert that otherwise inedible forage into milk and meat. Conversely, cellular meat will require the provision of food grade nutrients supplied directly to the cells growing in the bioreactor, and waste streams will need to be disposed of following production of the cultured product. The LCA of this aspect of cellular meat remains unknown.

It is worth noting that the very favorable cultured meat LCA (Tuomisto and Teixeira de Mattos, 2011), oft-cited by proponents of cultured meat, was funded by New Harvest, a non-profit research institute accelerating breakthroughs in cellular agriculture, and has been especially criticized for assuming cultured mammalian meat will be able to be grown using  cyanobacteria hydrolysate as the nutrient and energy source for muscle cell growth, as this medium is more commonly used for yeast cells; and for ignoring the environmental impacts of growth factors and vitamins, as the cells cannot grow without these supplements and they are both difficult to isolate and synthesize.

The functional unit (FU) of the alternative meat discussion to date has been, oddly enough, hamburger patties, ground beef.

As  mentioned previously, the FU used as the comparator can dramatically alter the sustainability metrics of any system (lb carcass weight is different to lb edible meat, and lb protein, and lb of animal source food) – especially if the comparators differ nutritionally.

An average weight steer (1,300 lb) produces an 806 lb carcass which yields 639 lb edible beef, of which 38% is ground beef (i.e.  62% is not!). Primal cuts are obviously more valuable than ground beef, and the by-products of beef (including hides, offal, blood, tallow, bones, and bone meal) which represent approximately 11.7% of the value of a carcass are not factored into many LCA analyses. There are also offal products such as beef tongue and tripe, favorites of many ethnic communities, which are unlikely to be replicated via cell culture technology.

According to the FAO, global animal agriculture is estimated to account for 14.5% of anthropogenic GHG emissions which can be broken down into beef (5.9%), cattle milk (2.9%), pork (1.3%), buffalo milk and meat (1.2%), chicken meat and(1.2%), and small ruminant milk and meat (0.9%) (FAO).

Nationally agriculture accounts for 9% emissions, slightly less than 4% is animal agriculture.

In the United States, all of agriculture is responsible for 9% of the US GHG emissions (US EPA). Fossil fuel-based energy is responsible for over 80% of total US GHG emissions, as compared to slightly less than 4% from animal agriculture. To put this in perspective, it has been estimated that eliminating ALL of US animal agriculture would decrease US GHG by 2.6%, but would also create a food supply incapable of supporting the US population’s nutritional requirements .


Lynch, J. and R. Pierrehumbert. 2019. Climate Impacts of Cultured Meat and Beef Cattle. Frontiers in Sustainable Food Systems 3(5).

Mattick, C. S. 2018. Cellular agriculture: The coming revolution in food production. Bulletin of the Atomic Scientists 74(1):32-35.

Mattick, C. S., A. E. Landis, B. R. Allenby, and N. J. Genovese. 2015. Anticipatory Life Cycle Analysis of In Vitro Biomass Cultivation for Cultured Meat Production in the United States.  Environ Sci Technol 49(19):11941-11949.

Mottet, A., C. de Haan, A. Falcucci, G. Tempio, C. Opio, and P. Gerber. 2017. Livestock: On our plates or eating at our table? A new analysis of the feed/food debate. Global Food Security 14:1-8.

Nijdam, D., T. Rood, and H. Westhoek. 2012. The price of protein: Review of land use and carbon footprints from life cycle assessments of animal food products and their substitutes. Food Policy 37(6):760-770.

Tuomisto, H. L., M. J. Ellis, and P. Haastrup. 2014. Environmental impacts of cultured meat: alternative production scenarios. Pages 8-10 in Proc. Proceedings of the 9th international conference on life cycle assessment in the agri-food sector.

Tuomisto, H. L. and M. J. Teixeira de Mattos. 2011. Environmental Impacts of Cultured Meat Production. Environmental Science & Technology 45(14):6117-6123.

Alternative meats and alternative statistics: What do the data say? 1 of 4

(*****This series of 4 BLOG posts (1,2,3,4) is extracted from my paper from the Proceedings of the Range Beef Cow Symposium XXVI, November 18-20, 2019. Mitchell, NE. pages 37-49.*****)

The alternative animal product arena is complex and quite varied. Some products are entirely plant product derived and employ only plant origin proteins or metabolites. Other endeavors are using cells of animal origin to derive a more structurally similar meat yet still with animal genomes. Most of the analysis and discussion, though, has focused on bovine alternatives because of the iconic position of cattle in many climate and sustainability discussions.

There are two ‘alternative meat’ sources that are often confused. One is so called “plant-based” or “vegan meat replacements” (e.g. Beyond Burger). These types of “veggie” burgers have been around a long time (e.g. Morningstar Farms, Boca Burgers), and now have some bells and whistles like genetically-engineered heme to make them bleed (e.g. Impossible Burger), but at the end of the day they consist of plant-sourced material being molded into a meat substitute type product. They are currently being sold at some fast food restaurants, and in supermarkets. Impossible Burger recently received safety approval for its genetically engineered heme as a color additive in ground beef analogue products, opening the way for its sale in supermarkets.

These are DIFFERENT to cultured meat, which is the term I am going to use to refer to animal cells grown in cell culture. This technology has other terminology – some appealing (e.g., in vitro meat, cellular meat, fermented meat, or slaughter-free meat, clean meat), and some derogatory (e.g. artificial meat, synthetic meat, zombie meat, lab-grown meat, non-meat, or artificial muscle proteins). This is discussed in my 2018 article “Why cows are getting a bad rap in lab-grown meat debate”.

Cultured meat requires the initial collection of stem cells from living animals and then greatly expanding their numbers in a bioreactor, a device for carrying out chemical processes. These living cells must be provided with nutrients in a suitable growth medium containing food-grade components that must be effective and efficient in supporting and promoting muscle cell growth. A typical growth medium contains an energy source such as glucose, synthetic amino acids, antibiotics, fetal bovine serum, horse serum and chicken embryo extract. Some of these components are problematic for consumers wishing to avoid animal products. The status quo for culturing tissue involves the use of fetal bovine serum, a byproduct of the livestock industry collected from fetuses in pregnant cows that are being slaughtered.  Large uncertainties remain in what a viable, animal-free, growth media may look like.

The world’s first lab-grown beef burger is unveiled in London on Aug. 5, 2013. (David Parry/AFP/Press Association)

If cultured meat is to match or exceed the nutritional value of conventional meat products, nutrients found in meat not synthesized by muscle cells must be supplied as supplements in the culture medium. Conventional meat is a high-quality protein, meaning it has a full complement of essential amino acids. It also provides a source of several other desirable nutrients such as vitamins and minerals, and bioactive compounds. Therefore to be nutritionally equivalent, cultured meat medium would need to provide all of the essential amino acids, along with vitamin B12, an essential vitamin found solely in food products of animal origin. Vitamin B12 can be produced by microbes in fermentation tanks, and could be used to supplement a cultured meat product. It would also be necessary to supplement iron, an especially important nutrient for woman of reproductive age that is also high in beef.

The process for making cultured meat has technically challenging aspects. It includes manufacturing and purifying culture media and supplements in large quantities, expanding animal cells in a bioreactor, processing the resultant tissue into an edible product, removing and disposing of the spent media, and keeping the bioreactor clean. Each are themselves associated with their own set of costs, inputs and energy demands.

Cultured meat production will likely require more industrial energy than do livestock to produce equivalent quantities of meat. The reason is that all of the biological structures avoided in cellular agriculture play important roles in meat production. An animal’s skin regulates temperature; internal organs digest food, circulate nutrients, and distribute oxygen; and the immune system destroys pathogens. When meat is grown in a bioreactor, all the same functions must still be accomplished, but at the expense of industrial energy. A bioreactor regulates temperature, food is predigested and fed to cells as simple sugars and amino acids, oxygen is pumped into the bioreactor, and all equipment is sterilized to prevent the growth of pathogens. Hence, a shift from livestock production to cellular agriculture could be a transition toward greater reliance on industrial energy.

Unnatural Selection

I binge watched Unnatural Selection on NetFlix last night, because it is of dual interest to me – both from the perspective of my research, but also because of my interest in science communication. I had also spent a couple of days with the directors, Leeor Kaufman and Joe Egender, at UC Davis in late 2017 and early 2018 as they filmed some of our discussions with the public over the use of genome-editing to produce the “hornless” dairy animals we have been researching.

Ultimately the miniseries ended up not including any of the agricultural applications of genome editing, as the directors wrote to me in an Email earlier this month, “we were not able to open the discussion about food engineering within the scope of 4 episodes.” They rather focused the show on the biomedical and gene drive applications for pest control noting that “other stories – especially of the patients – became larger than we anticipated, making it very difficult to introduce such a broad subject in between.”

I can certainly understand the emotional appeal of treating genetic conditions, and that such framing lends itself to narrative storytelling. However I believe it unfortunate because the many researchers I know working in this area are addressing very real and pressing problems in food production, and we have not had much success at effective science communication on the need for these genetic innovations in agricultural production systems.

One of the more bizarre characters featured on the miniseries was a dog breeder called David Ishee located in Mississippi who was apparently trying to create a green fluorescent mastiff puppies by adding Green Fluorescent Protein (GFP)-expressing E. coli to dog sperm. I just watched dumbfounded, knowing all of the animal use authorizations and regulatory hurdles we have to go though to perform any animal research on campus. And also  because that is not how genetic engineering works, that is not how any of this works. If it was that simple, my laboratory would not have spent the last three years trying to get a CRISPR knock-in cow.


It is possible to get fluorescent animals, like the GloFish. But they are expressing a transgenic fluorescent gene under the control of a eukaryotic muscle promoter, and this recombinant DNA gene construct was integrated into the genome though genetic engineering in developing eggs. The reason you can see fluorescence clearly in Glofish is that they are somewhat translucent. Mastiff puppies are not. Even if it green fluorescent protein (GFP) did somehow find itself expressing in these puppies, it would not express or be visible in their dark hair. It is similarly lacking in the plumage of the GFP-chick in the featured image made by the Roslin Institute.

A fluorescent rabbit was made 20 years ago,  in the bizarre case of Alba the GFP-bunny. In 2000, Eduardo Kac, a professor of art and technology at the Chicago School of Art Institute produced a picture of a green fluorescent protein (GFP) transgenic bunny called “Alba”. “GFP Bunny” was realized in 2000 and first presented publicly in Avignon, France. The artist proposed that “transgenic art” is a new art form based on the use of genetic engineering to transfer natural or synthetic genes to an organism, to create unique living beings.

Alba Image

The artist came under considerable criticism for the picture which some consider to have been fabricated. According to a 2002 Wired article “The picture itself is a construction,” said Reinhard Nestelbacher, a molecular biologist at the University of Salzburg.  “The rabbit could never look like that,” he said. “The main reason is that the GFP gene is expressed, for example, in the skin and cannot be expressed in the hair.” Stuart Newman, a member of the Council for Responsible Genetics and a cell biologist at New York Medical College, said “Art misrepresents reality all the time — and he’s an artist, not a scientist, but I think people are beholden to tell the truth.”

Which raises an interesting question, are artists beholden to tell the truth about genetic engineering?

And that is I think what frustrated me most about the miniseries. This was potentially an opportunity to have a fresh look at this technology of genome editing, and how it does and does not differ from the older technology of genetic engineering. The two technologies were rapidly conflated in the miniseries, along with other issues such as the cost of medicine in the US healthcare system. And while these tensions were thoughtfully addressed, I would argue the tensions around food production are equally important and were not addressed.

There is a very real reason that the public fears the use of genetic engineering in food production, and it is not the science or decades of safe use. It is a deliberate misinformation campaign that has been waged by competing-business interests and special-interest group for decades. That topic warrants its own examination.

It was therefore somewhat ironic to see Dana Perls from “Friends of the Earth” as one of the interviewees in Unnatural Selection. She was unchallenged when allowed to repeat the same unsubstantiated talking points around genome editing and food safety risks that have been parroted for decades to demonize genetic engineering,   This to me was opening a discussion around food engineering, but in the absence of any mention of the 30 years of safe use, or the overwhelming weight-of-evidence.

Just as there is money to be made in commercializing pharmaceutics, there is money to be made in fermenting fear, uncertainty and doubt, especially against your competitors. If those same special interests again direct their well-funded coffers towards a campaign against the use of genome editing in food production, then I fear that as a society we will lose. We will forgo the benefits that could result from bringing in useful genetic variation like disease-resistance into our food species using genome editing.

One of the most powerful stories in Unnatural Selection was that of a young boy who had a genetic condition that threatened his sight. And the $850,000 treatment that might help save him from blindness. It is very moving part of the series, as we see his parents grapple with their frustration at his deteriorating sight.

There is a non-genetic condition that results in between 250,000 and 500,000 children going blind every year, Vitamin A deficiency. And yet the war that special interest groups like Greenpeace and Friends of the Earth have waged against GMOs for the past 30 years, in concert with the retarding force of government regulations on GMO crop development, has slowed the release of vitamin-A enriched crops as detailed in this recent book, Golden Rice: the imperiled birth of a GMO superfood.

The 2019 Wolf-prize for Agriculture laureate Prof. David Zilberman from University of California at Berkeley, estimated in 2014 that if Golden Rice had not be delayed in India alone it would have  “prevented 600,000 to 1.2 million cases of blindness, and about 180,000 deaths of children.” Likewise 129 nobel-laureates “have joined in a campaign to convince the Green Parties and the public that they should support the use of GMOs, especially for the sake of the developing world”,

Fortunately, after millions of dollars and years of effort, the United States, Canada, Australia, and New Zealand have all recently approved golden rice as safe for consumption. Golden rice is in now front of regulators in the Philippines and in Bangladesh, where it is expected to be approved by the end of 2019. There it will have the opportunity to benefit many poor children, each of whom have parents who I am confident are equally anxious and concerned about addressing  the preventable blindness of their children. Perhaps emerging developments in food engineering with such profound beneficial health implications are worthy of their own miniseries!


Harmonize US gene-edited food regulations

I have been fairly consistent about my concern that the 2017 FDA’s draft guidance to regulate “intentional genomic alterations” in food animals as new animal drugs will preclude the use of this technology in livestock breeding programs in the United States. The webinar that was held today by the FDA Center for Veterinary Medicine (CVM) did little to assuage my concern. For two hours, various speakers from the FDA CVM explained how they were going to regulate IGA (intentional genomic alterations). That is a lot of 3-letter acronyms (the scariest of all acronyms!).

There was lots of discussion of frightening sounding off-target effects, small to large-scale alterations, unintended biological consequences, unknown long term effects not apparent in early generations, deletions, insertions, inversions, lesions, translocations, mutations being deleterious regardless of whether they occur in a coding region, and challenges to addressing unintended on and off target effects. What there was not much discussion of is biology and context. And the fact that there are literally millions of “insertions, inversions, lesions, translocations, and mutations” in every plant and animal on Earth.

As we argue in this open access 2019 paper entitled “Proposed U.S. regulation of gene-edited food animals is not fit for purpose

To put this in perspective, one study of whole genome sequence data from over 2,700 individual cattle in the 1000 Bull Genomes Project revealed more than 86.5 million differences (variants) between different breeds of cattle. These variants included 2.5 million insertions and deletions of one, or more, base pairs of DNA, and 84 million single nucleotide variants, where one of the four nucleotides making up DNA (A, C, G, T) had been changed to a different one. None of these naturally-occurring variants are known to produce ill effects on the consumers of milk or beef products. In fact, every meal we have ever consumed is genetically distinct from every other meal in terms of genomic DNA sequences. Genetic variation per se does not pose a unique hazard as it relates to food safety. All non-processed foods harbor DNA as a natural component and that DNA is different in every individual of every food species (both plants and animals).

Visual representation of the magnitude of DNA sequence variation (i.e. naturally-occurring mutations) that exists between different individuals within a species. Image from Van Eenennaam et al. (2019)

A number of other countries have come out with their regulatory approaches to genome editing in food species, including the USDA opinion regarding genome edited plants, and the FDA is alone in considering a genetic alteration in a food animal to be a drug. And while under proposed U.S. law it is technically not the animal but the IGA (not the grocery store but the “intentional genomic alteration”) that is the drug, short of a centrifuge it is pretty hard to disassociate an animal from its genomic DNA! Animals carrying IGA effectively become unapproved animal drugs that are not allowed to enter commerce in the absence of a multigenerational safety and efficacy evaluation and FDA approval, analogous to the types of studies that are required for the approval of actual new animal drugs.

All of this comes about because 10 years ago the FDA announced its intent to regulate all genetically engineered animals modified by rDNA techniques, including the entire lineage of animals that contain the modification, under the new animal drug provisions of the 1938 Federal Food, Drug, and Cosmetic Act (decades before the discovery of the structure of DNA).  In that act, a new animal drug is defined as “an article (other than food) intended to affect the structure or any function of the body of … animals.”

The 2017 FDA draft guidance on gene edited animals doubles down on this approach by proposing to regulate all genomic alterations introduced into animals by gene editing as new animal drugs. This includes many of the same nucleotide insertions, substitutions, or deletions that could be obtained using conventional breeding. No longer is it the presence of a transgenic rDNA construct that triggers mandatory premarket FDA regulatory oversight prior to commercial release, but rather it is the presence of any “intentionally altered genomic DNA” in an animal that initiates oversight.

What concerns me, after listening to the webinar, is that it was really not stated what unique risks are feared to be associated with IGA, that are not also associated with UGA (unintentional genomic alterations), aka de novo mutations that are very basis of evolution. We do not regulate the millions of spontaneous genetic variations that are in our food because DNA is generally regarded as safe to consume, and it is a routine ingredient of food obtained from any species, irrespective of its sequence. Referring to a DNA sequence variant as a “drug” is likely to confuse or frighten consumers who might infer that there are biologically active substances in their food.

I am of the opinion that this proposed regulatory approach for genome editing in animals will effectively make it cost prohibitive for both U.S. researchers and livestock producers to use and potentially benefit from genome editing in food animal breeding programs. I am not alone in this concern. Over 300 scientists supported a petition calling for  the Harmonization of US gene-edited food regulations which was launched in January at the 2019 Plant and Animal Genome meeting. Signatories include over 260 US scientists from more than 40 academic institutions throughout the nation including members of the National Academy of Science, Engineering and Medicine (NASEM), and a Nobel prize laureate. When scientists are riled up enough to emerge from their laboratories and express an opinion about something as arcane as a regulatory guidance, perhaps it is worth listening.  The petition concluded with the following ask:

“We call for a harmonization of the U.S. regulatory approach to gene editing in food species so that both plant and animal breeders have access to gene editing innovations to introduce useful sustainability traits like disease resistance, climate adaptability, and food quality attributes into U.S. agricultural breeding programs.”

Proposed U.S. regulation of gene-edited food animals is not fit for purpose

It has been more than two years since the FDA released its draft “Guidance for Industry #187” “Regulation of Intentionally Altered Genomic DNA in Animals”, that proposes to regulate ANY “intentionally altered genomic DNA” in food animals as a veterinary drug, irrespective of product novelty or risk. Human intention does not equate to risk. This regulatory trigger seems to be aimed squarely at some taint associated with human intervention . Despite the fact that the public comment period for the FDA’s draft guidance for industry #187 closed on June 19, 2017, there has not yet been a formal response to the many comments by public sector scientists working in this field who see that this regulatory approach will make food animal research in this field cost prohibitive, and effectively preclude the use of gene editing in food animal breeding programs.

Dietary DNA is generally regarded as safe to consume, and is a routine ingredient of food obtained from any species. Millions of naturally-occurring DNA variations are observed when comparing the genomic sequence of any two healthy individuals of a given species. Breeders routinely select desired traits resulting from this DNA variation to develop new cultivars and varieties of food plants and animals. Regulatory agencies do not evaluate these new varieties prior to commercial release.

To put this in perspective, one study of whole genome sequence data from 2,703 individual cattle in the 1000 Bull Genomes Project revealed more than 86.5 million differences (variants) between different breeds of cattle. These variants included 2.5 million insertions and deletions of one, or more, base pairs of DNA, and 84 million single nucleotide variants, where one of the four nucleotides making up DNA  (A, C, G, T) had been changed to a different one.

A small fraction of these mutations have been selected by breeders owing to their beneficial effects on characteristics of agronomic importance. None of these naturally-occurring variants are known to produce ill effects on the consumers of milk or beef products. In fact, every meal we have ever consumed is genetically distinct from every other meal in terms of genomic DNA sequences. Genetic variation per se does not pose a unique hazard as it relates to food safety. All non-processed foods harbor DNA as a natural component and that DNA is different in every individual of every food species (both plants and animals).

Gene editing tools now allow plant and animal breeders to precisely introduce useful genetic variation into agricultural breeding programs. The U.S. Department of Agriculture (USDA) announced that it has no plans to place additional regulations on gene-edited plants that could otherwise have been developed through traditional breeding prior to commercialization. However, the U.S. Food and Drug Administration (FDA) has proposed mandatory premarket new animal drug regulatory evaluation for all food animals whose genomes have been intentionally altered using modern molecular technologies including gene editing technologies.

Mandating premarket regulatory approval for deletions, mutations, and the conversion of one wild-type allele to another wild-type allele in the same species (cisgenic) that could have been obtained using conventional breeding runs counter to the approach that was outlined by OSTP in the 1992 policy announcement (following the 1986 Coordinated Framework document).  There it is stated that, “Exercise of oversight in the scope of discretion afforded by statute should be based on the risk posed by the introduction and should not turn on the fact that an organism has been modified by a particular process or technique”. Additionally, it was clarified that “(O)versight will be exercised only where the risk posed by the introduction is unreasonable, that is, when the value of the reduction in risk obtained by additional oversight is greater than the cost thereby imposed. The extent and type of oversight measure(s) will thus be commensurate with the gravity and type of risk being addressed, the costs of alternative oversight options, and the effect of additional oversight on existing safety incentives.”

At the end of the day, food animals with intentional genomic alterations produce food, and if the food they produce is not biologically active via an oral route of administration it does not make sense to regulate these intentional genomic alterations as drugs. Referring to a DNA sequence variant as a “drug” is likely to confuse or frighten consumers who might infer that there are biologically active substances in their food.

A DNA alteration is not a drug, but rather part of the genetic code uniquely associated with any organism. Through its natural function within a cell, DNA controls how an organism grows and its unique form and function. The phenotype will ultimately be determined by the interaction of an organism’s genomic DNA sequence and the environment in which it lives. We do not regulate the millions of spontaneous genetic alterations that are in our food because DNA is generally regarded as safe to consume, and it is a routine ingredient of food obtained from any species, irrespective of its sequence.

The FDA’s draft “Guidance for Industry #187” entitled “Regulation of Intentionally Altered Genomic DNA in Animals” is not fit for purpose as it relates to food animals that could otherwise have been developed through traditional breeding techniques.   Myself and fellow academic researchers reject the idea that intentional genomic DNA alterations should be regulated as a veterinary drug in food animals, and consider that the proposed approach will thwart the development of genetic approaches by public sector researchers and small companies to use gene editing to solve zoonotic disease and animal welfare problems in the United States.

Please support the petition above calling for harmonization of the U.S. biotechnology regulatory system so that both plants and food animals that could otherwise have been developed through traditional breeding techniques are not subject to additional premarket regulatory requirements based solely on the fact that intentional genomic alterations were introduced using modern biotechnologies or rDNA techniques in the breeding process.

Harmonizing the regulations associated with gene editing in food species is imperative to allow both plant and animal breeders access to gene editing tools to introduce useful sustainability traits like disease resistance, climate adaptability, and food quality attributes into U.S. agricultural breeding programs.

Proposition 12 – Humane vs. Humane

Back in January I wrote a blog entitled Proposition 2 déjà vu about a proposed  California ballot initiative entitled “The Prevention of Cruelty to Farm Animals Act”. Sure enough that initiative qualified for the 2018 ballot, despite the clear data on the impacts as detailed in my three blog posts on this issue (Six hens a laying, Evidence-based animal welfare recommendations, Proposition 2 déjà vu).

I am quaintly of the opinion that objective evidence should drive public policy, and not emotions, despite having lived in California for over 30 years. And as a public scientist I remain convinced that objective facts and data are the best way to inform policy.

However, ballot initiatives in California are basically a pay-to-play scorecard. If you have the money to get the requisite number of signatures (365,880 valid signatures), then your initiative will be on the ballot, facts be damned. And so it was with Proposition 12, a Humane Society of the United States (HSUS)‐backed initiative addressing animal confinement, which has raised $5.37 million to date… And so now let’s cue the opposition funding which will no doubt be “big ag” or “corporate farming” or “evil egg” or “big chicken”, or a tearful segment of a mother on Dr. Oz, or a shockumentary on NetFlix…..but no – crickets (actually cage-free, mute crickets to be precise). As in no organized-opposition from those who grow your food, or research the best way to produce food sustainably (Hint: people who might know some things).

Wait – what? Agriculture and scientists have had enough. We know science and facts are useless (see my previous 3 blogs re this initiative and almost all of the outreach work I have ever done in agricultural science), and there just is no point in fighting initiatives funded by wealthy animal activist industry groups who use persuasive arguments based entirely on emotion while conveniently failing to mention the multiple trade-offs and unintended consequences associated with their proposed course of action. And so the usual adversaries of demonstrably bad agricultural policy i.e. “big ag”, known as farmers by the general public, and “tobacco scientists”,  known as public university faculty and researchers to most, have thrown in the towel.

And I understand that response. It is exhausting trying to fight these large, well-funded activist groups who will stop at nothing to get their way – facts and scientific consensus be damned, and it can be a lucrative pastime. Ask those trying to fight the anti-vaxxers, or the anti-GMO industry. Slowly I see my animal scientist colleagues quietly retreating into the “spiral of silence” – a tranquil place where no one fabricates facts, and where pure science can be carried out peacefully sans messy public confrontations – sometimes referred to as “the ivory tower.”

Last time UC Davis got involved in this discussion by providing objective facts regarding Proposition 2 “Treatment of Farm Animals” over a decade ago in 2008, it cost the taxpayers more than a million dollars in a lawsuit with HSUS – money that did not go to educating our students or carrying out research, and the lawsuit about wore out one of my faculty colleagues. Likely UC administration is happy we are playing dead this time around on Proposition 12 too.

And who can blame the University? It is not fun to be in the middle of a politicized, scientific controversy. However, if professionals in the field are unwilling to stand up for objective data and evidence-based decisions, who will? And that is where this discussion gets interesting.

Who is opposing Proposition 12 – if not industry or subject-matter experts? The Humane Farming Association (HFA), an animal cruelty organization that opposes the proposition on the grounds that it legalizes for several more years some practices HFA opposes. So Proposition 12 does not move fast enough for the Humane Farming Association.

Say again? With a modest $550,000, a committee backed entirely by the Humane Farming Association, is the sole funder of opposition to Proposition 12, the “The Prevention of Cruelty to Farm Animals”. And here is where it gets good. Who doesn’t like a little Humane vs Humane mud wrestling?

Bradley Miller, spokesperson for HFA’s Californian’s Against Cruelty, Cages, and Fraud “Stop the Rotten Egg Initiative” stated of rival HSUS

The Humane Society of the United States [HSUS] is once again deceiving voters, flip-flopping on the issue of cages, and perpetuating the suffering of egg-laying hens”                                            HFA

There is a video made by HFA (below and can be accessed here) summarizing their version of the June 19, 2018 California State Legislature hearing regarding Proposition 12 which contains some interesting conflict-of-interest footage, including some questioning as to how much money HSUS was making from Proposition 12 (Spoiler alert: HSUS does not have those numbers).

According to HFA, HSUS ended up collecting 664,000 signatures for the ballot, but less than a quarter (164,000) of those were collected by volunteers, the remaining signatures were collected by HSUS paid-“bounty-hunter” signature gatherers, like the one I met at the CA Davis market in January, telling me that Proposition 12 would remove non-existent “veal-crates”, and sow “gestation crates” from California production systems. This video is worth a listen, as Miller suggests the major opposition to Proposition 12 will be the humane farming associations.

Miller further stated on the HFA “Stop the Rotten Egg” page:

Prop 12 is now just a publicity stunt in search of a lawsuit. Not only does this come at taxpayer expense, HSUS’s reckless exploitation of California’s ballot measure system is putting in grave danger a wide array of existing consumer, animal, and environmental protection laws. Of the initiatives appearing on the November ballot, Proposition 12 is the dirtiest of the dozenWe’re confident that California voters won’t get fooled again and that this fraudulent initiative will be decisively rejected.”                                                                                                                                 HFA

And then there is a quote from Friends of Animals (FoA) on the HFA “Stop the Rotten Egg” page,

“This initiative should be fiercely opposed by everyone who cares about farm animal suffering. HSUS’s collusion with the egg industry is disturbing. From legalizing battery cages to allowing as little as one square foot of space per hen — this initiative would be a disaster for millions of egg-laying hens who would still be left suffering in battery cages throughout California.”                     FoA

And yet another quote from People for the Ethical Treatment of Animals (PETA) on the HFA “Stop the Rotten Egg” page

Beware! This initiative is being painted in rosy terms, but don’t be fooled… What it would actually do is allow farms to keep egg-laying hens in cages until 2022, at which time factory farms would still be able to confine uncaged hens to massive, crowded sheds with only 1 square foot of space per bird.”                                                                                                                                                        PETA

And finally this from Animals 24/7 on the HFA “Stop the Rotten Egg” page

“Time and again HFA has accurately identified fatal flaws in legislation advanced by HSUS.”    Animals 24/7

So what is a voter to do? Be guided by The Humane Society of the United States (HSUS), the Humane Farming Association (HFA), People for the Ethical Treatment of Animals (PETA), Friends of Animals (FoA), or Animals 24/7? Some of the above, none of the above, one of the above? Who is representing animal welfare, and how can you tell? You could try asking the scientific community who have spent their careers researching these questions, or farmers who happen to know a thing or two about farming – but that does not seem to be a popular route.

In the absence of objective, evidence-based measurements – there is just a “blob” of emotions, competing world-views, and fund-raising agendas. And that is not a great foundation upon which to base decisions around animal agriculture or public policy. Case in point: Proposition 2 from 2008 (see what that did to California farmers: Six hens a laying).

So it seems some cracks are appearing in the humpty dumpty coalition of “animal-themed corporations” also known as the “humane community”.  And perhaps nowhere is this rift more bizarrely illustrated than in this “Stop the Rotten Egg” page  animated video, “Proposition 12: California’s Caged Chickens Say NO!”.

For anyone that has ever met the former President and CEO of HSUS, Wayne Pecelle, who resigned February 2018 in a #MeToo moment  after a number of women accused him of sexual harassment,  the big-toothed male lead featured in this animated video is a thinly disguised provocation from one humane society (HFA) whose operations are based on the West Coast in California to another (HSUS) based on the East Coast in Maryland. Ironically the largest egg producing state in the US by far is Iowa.

On an unrelated note, buried in the fine print of Proposition 12, are the following strikeouts (and additions) that remove the scientific and agricultural research exemptions that were previously written into SECTION 5. SECTION 25992 OF THE CALIFORNIA HEALTH AND SAFETY CODE (line A below).

The proposed Proposition 12 language includes the following exemptions:

“This Chapter will not apply:

(a) During scientific or agricultural medical research.”

In other words, scientific and agricultural research animals at universities and other research facilities are subject to the provisions of the initiative – just like all of the farm animls. The implications of this change to the research exemption on things such as teaching, scientific or agricultural research, especially for genetic and nutrition research (we need individual cages to collect observations or phenotypes on each animal, and to record which egg comes from which hen), may well not be discovered until after the ballot votes are cast when agriculturalists and scientists go to perform specialized research on calves, pigs, or poultry.

It may be that those university researchers retreating to the “spiral of silence” to avoid the discomfort of a heated public discussion of Proposition 12, will eventually find their research projects thwarted by the inevitable passage of the initiative (I may have quaint opinions on how objective evidence should drive public policy, but I am a realist living in California). Yet another casualty of public policy based on emotion and propaganda, rather than informed by objective evidence and science-based recommendations.

As Mr. Miller, spokesperson for HFA’s Californian’s Against Cruelty, Cages, and Fraud, ironically lamented during his testimony before the California State Legislature, including the words “farm animal” and “protection” in a ballot initiative in California is enough to get it passed, irrespective of how the text reads, and what the ultimate impacts of its passage will be on the welfare of animals, and the people of California.

Antibiotic Use and Food Animals

Because I did not think biotechnology and hen housing were controversial enough topics, I thought I would wade into antibiotic use in food animals. Actually, the only reason I am doing this blog is because of a Twitter exchange with Marc Brazeau from Food and Farm Discussion Lab late last year. He posed several questions to me and I postponed responding unitl I had a little time to delve into the science. The answers are necessarily a bit sciency – if you want to cut to the chase, scroll directly down to Question 7.

1. How much are antibiotics used in food animal agriculture?

We have sales records from 2009-2016 from the FDA for food animal sales, but I couldn’t find any on the human side of things since April of 2012 (2011 data). The quality of the data is not great – in that it is sales data – and because some food animal products are labelled for multiple species it is a bit hard to interpret use – was that drug sold to treat a horse or a cow or a dog? The data are broken down into “medically-important” versus “not medically-important” as determined by the FDA (Appendix A).

In 2016, there were 8.36 million kg of “medically-important” and 5.62 million kg of “not medically-important” antimicrobial drugs (e.g. ionophores) sold. The good news is that these numbers represent 14% and 4% decreases, respectively, over 2015 sales data. These can be contrasted to the last data available for humans which is 3.29 million kg sold in the U.S. market in 2011. Hard to detemine the trend in human prescriptions in the absence of data.

The FDA warns that there are a number of differences in the circumstances in which antimicrobial drugs are used in human and veterinary medicine that must be carefully considered before making comparisons between human and animal use, including:

  • The number of humans in the U.S. population (approx. 320 million) compared to the much, much larger number of animals in each of the many animal species (e.g., approx. 9 billion chickens slaughtered annually)
  • The differences in physical characteristics of humans compared to various animal species (e.g., physiology and weight– average adult human, 182 lb vs adult cattle live weight, 1,363 lb).
  • Veterinarians commonly utilize human antimicrobial drugs in their companion animal patients; therefore, amounts presented for certain human antimicrobial drugs may represent some unknown portion sold for use in companion animals. More on this point later!

According to the FDA it is, therefore “difficult to draw conclusions from any direct comparisons between the quantity of antimicrobial drugs sold for use in humans and the animal drug sales and distribution data (and species specific estimates) for use in animals.”

2. What types of antibiotics are used in animal agriculture?

It should be noted that there were some fairly sweeping changes that went into effect in 2017  as part of an effort to promote the judicious use of “medically-important” antimicrobial drugs in food animals.

The FDA has approved antibiotics for only these 3 uses in food animals:

  • Disease treatment for animals that are sick;
  • Disease control for a group of animals when some of the animals are sick;
  • Disease prevention for animals that are at risk of becoming sick.

Animal health companies, farmers and veterinarians cooperated with the FDA to develop a guidance which ended the use of antibiotics important to human medicine to promote growth in animals or to improve feed efficiency (i.e., production purposes). The remaining therapeutic uses in feed and water are required to be under the supervision of licensed veterinarians through the Veterinary Feed Directive (VFD) (feed uses) or prescriptions (water uses) which went into effect on 1/1/2017. These changes were enacted to ensure these drugs are used judiciously and only when appropriate for specific animal health purposes.

As can be seen from the graph above, by far the biggest class of antibiotics used in food-producing animals in 2016 was tetracyclines, a class of antibiotics which represented only ~ 3.5% of human antibiotic sales in 2011. This number will likely fall in 2017 as a result of the cessation of the use of “medically-important” antibiotics  for production purposes.

3. What is the current state of knowledge about the transfer of resistant bacteria from livestock farms and manure use to human populations? Farm workers first and foremost.

Based on the available literature, direct transfer to humans seems to occur at a pretty minor level. One paper estimated that direct infection with resistant bacteria from an animal source, or through ingestion of bacteria from contaminated meat or water, was a relatively small risk in comparison with the overall burden of resistant disease. There was one example in the US in the past year where a Salmonella outbreak of S. heidelberg infected 54 people of whom 34 (63%) reported contact with ill calves (0 deaths). To put this in perspective, there are 1.2 million food-borne Salmonella infections per year (450 deaths). Interestingly, dogs and cats can also carry and transmit Salmonella and Campylobacter organisms, along with other pathogens traditionally associated with “foodborne diseases”.  One older paper raises the question of whether dogs or other companion animals are involved in transmitting such pathogens to food-producing animals or humans, an issue which is often overlooked.

We share our homes and our microbiota with our companion animals

According to one paper examining the prevalence of within-household sharing of fecal Escherichia coli between dogs and their owners, both direct contact and environmental reservoirs were seen to be routes of cross-species sharing of bacteria and genes for resistance. The authors warned that cross-species bacterial sharing is a potential public health concern, and good hygiene is recommended (i.e. wash your hands after cleaning up after your pets!!).

It is known than human exposure to zoonotic nematodes and cestodes and other parasites associated with feces of companion animals in the United States is an ongoing public health problem. And statistically it is more likely most people will come into contact with one of the 140,000,000 dogs and cats in the US, than directly with livestock.  The transmission of antimicrobial-resistant organisms between humans and pets warrants further investigation, especially as pets can be treated with  “medically-important” antimicrobial drugs.

4. Is there evidence showing resistance originates in the animal population and then moves to humans?

A recent 2017 systematic review and meta-analysis to summarise the effect that interventions to reduce antibiotic use in food-producing animals have on the presence of antibiotic-resistant bacteria in animals and humans, and funded by the WHO, concluded:

Interventions that restrict antibiotic use in food-producing animals are associated with a reduction in the presence of antibiotic-resistant bacteria in these animals. A smaller body of evidence suggests a similar association in the studied human populations, particularly those with direct exposure to food-producing animals. The implications for the general human population are less clear, given the low number of studies. 

The Centers for Disease Control (CDC) issued a 2013 study on the most concerning antibiotic resistance threats and none of the most urgent threats have any relation to farm animals. On the broader CDC list, which includes less urgent threats, only two of 18 involve bacteria associated with farm animals.

A comprehensive 2016 review of 50 studies published in Critical Reviews in Food Science and Nutrition concluded that there is an established connection between animal antibiotic use and antibiotic resistance in animals, but no established causal relationship between animal antibiotic use and human resistance related to campylobacter.

There is an interesting example of an antibiotic drug called avoparcin that was used in EU agriculture for livestock growth promotion. The human equivalent is vancomycin which is used to treat E. faecium, and there was concern around vancomycin-resistant E. faecium (VRE). Avoparcin was banned in Denmark in 1997 as part of their elimination of production uses of antibiotics, and as a result VRE declined in farm animals but increased in hospitals where human vancomycin use & VRE are highly correlated. The US never approved avoparcin in livestock yet VRE started here in the 1990s due most likely to human vancomycin usage or quite possibly use in companion animals as VRE precursors have been isolated in dogs.

Likewise, this paper states that in 2005 the emergence of fluoroquinolone-resistant Campylobacter jejuni in the clinical setting in conjunction with fluoroquinolone administration in animals prompted the FDA to ban fluoroquinolone use in poultry, although it remains unclear if the dramatic increase of fluoroquinolone-resistant strains was due to fluoroquinolone use in livestock. In the USA, no decline in the levels of ciprofloxacin resistance was observed following the ban of fluoroquinolones in chickens. While it is possible that insufficient time has elapsed for trends to be detectable, it is also possible that fluoroquinolone-resistant strains may remain in the environment in the absence of antibiotic selective pressure.

On a broader scale, the EU and especially Sweden and Denmark have removed all growth promoting uses of antibiotics, and I am not familiar with any data showing this has moved the needle on resistance in human populations.

5. How reasonable is it to be concerned that bacteria resistant to an Ag-centric ABx becomes just a mutation or two away from resistance to medically important ABx with a similar mode of action.

According to the WHO-funded 2017 systematic review and meta-analysis,

There is currently no consensus regarding the effect that antibiotic use in food-producing animals has on antibiotic resistance in the human population. Furthermore, the effect of interventions that restrict antibiotics in food-producing animals on antibiotic resistance in both animals and humans is somewhat unclear.”

In the discussion section, this 2015 paper states that,

The topic of agricultural antibiotic use is complex. As we noted at the start, many believe that agricultural antibiotics have become a critical threat to human health. While the concern is not unwarranted, the extent of the problem may be exaggerated. There is no evidence that agriculture is ‘largely to blame’ for the increase in resistant strains and we should not be distracted from finding adequate ways to ensure appropriate antibiotic use in all settings, the most important of which being clinical medicine.”

You can be worried about it, but I think the objective data is much stronger on resistance coming for the most part by way of human medicine use. Anytime antibiotics are used they will lead to resistance – whether used to treat livestock, dogs or people.

6 . What are the recommendations of the World Health Organization Guidelines on use of medically important antimicrobials in food-producing animals ?

The first three recommendations of the WHO guidelines are based on “low quality evidence

  1. We recommend an overall reduction in use of all classes of medically important antimicrobials in food-producing animals.
  2. We recommend complete restriction of use of all classes of medically important antimicrobials in food-producing animals for growth promotion.
  3. We recommend complete restriction of use of all classes of medically important antimicrobials in food-producing animals for prevention of infectious diseases that have not yet been clinically diagnosed.

And the last two are conditional recommendations based on “very low quality evidence

Recommendation: Control and treatment use (in the presence of disease)

4a. Recommendation: We suggest that antimicrobials classified as critically important for human medicine should not be used for control of the dissemination of a clinically diagnosed infectious disease identified within a group of food-producing animals.

4b. Recommendation: We suggest that antimicrobials classified as highest priority critically important for human medicine should not be used for treatment of food-producing animals with a clinically diagnosed infectious disease.

The fact that the WHO acknowledges there is low or very low quality evidence to support these apparently logical recommendations, does suggest that there is little data on the transfer of resistant bacteria from livestock farms. Irrespective, the first recommendation for an overall reduction in use of all classes of medically important antimicrobials in food-producing animals to me lacks the required nuance when dealing with disease. A blanket reduction (as in just decreasing the physical mass or amount) of antibiotics used in food animals does not necessarily mean improvement.

For example, replacing an effective antimicrobial with an ineffective antimicrobial that is used at a lower dose would result in an overall reduction in the use of antibiotics, but not with the desired effect as the animal would still be sick. And some “medically-important” antibiotics are more important/critical than others. It is analogous to the comparison that is sometimes made that the weight of glyphosate herbicide use has gone up in recent years, but that has to be looked at in terms of the effectiveness and weight and toxicity of alternative herbicides that were used to control the weed problem. Same thing here – what are alternatives for treatment and how effective are they (i.e. weigh up pros and cons and determine the most judicious choice of treatment)?

Recommendations 4a and 4b are based on very low evidence. The report states that when a veterinarian is faced with treating a clinically diagnosed infectious disease in food animal(s), “The GDG [Guideline Development Group] concluded that although evidence from the systematic reviews and additional studies indicates it will achieve the human health benefit of lowered antimicrobial resistance in bacteria, this recommendation should be conditional due to the very low quality of available evidence. ….Furthermore, the undesirable consequences associated with such a restriction of use of antimicrobials appear to be relatively small or non-existent. Finally, several countries have successfully accomplished such a restriction of antimicrobials in food-producing animals, demonstrating its feasibility.

The second to last sentence seems rather callous in its regard for the sick animal and is particularly worrying from an animal welfare perspective. There is a remark in the guidance that states,

To prevent harm to animal health and welfare, exceptions to recommendations 4a and 4b can be made when, in the judgment of veterinary professionals, bacterial culture and sensitivity results demonstrate that the selected drug is the only treatment option.”

To my knowledge there is no country that does not allow treatment of animals with a clinically diagnosed infectious disease. And so one wonders where that leaves veterinarians when their only option is a drug that is critically important to human medicine – do they use avoid using “antimicrobials classified as highest priority critically important for human medicine” based on very low quality evidence or do they use them to prevent harm to animal health and welfare?

Some of the replacements of antibiotics that have been used in Europe are themselves associated with their own set of problems, for example the application of zinc oxide has been a key alternative to the reduction of antibiotics usage in Sweden and Denmark. The European Commission, however, has pointed to zinc oxide as having a serious impact on the environment as much of the substance gets excreted and ends up in fields when the manure is applied on the lands. In some studies, the use of zinc oxide has been associated with the occurrence of methicillin-resistant Staphylococcus aureus (MRSA) as the resistant bacteria might carry zinc-resistance genes.  That is, as always, tradeoffs associated with different choices and the antibiotic replacements are not without their own set of risks and tradeoffs.

7. I don’t care – I just want food animals never to get treated with antibiotics irrespective

We still don’t have strong evidence linking animal use with antibiotic resistance in the human population. Antibiotics along with other management and health factors go into animal welfare – if we can’t use them animals will get sicker and this can affect One Health (the unity of multiple practices that work together locally, nationally, and globally to help achieve optimal health for people, animals, and the environment) goals.

For example, the “no antibiotics ever” (never ever) marketing campaign may actually put the food supply at risk. If there is more untreated infectious disease, then pathogen prevalence could increase and this would increase the pathogen load of the  raw product coming into plant which could affect food safety from the perspective of food-borne pathogens.

And more generally is the question of what should be done with sick animals then? At the moment there are three choices:

  • treat the animal(s) and dump the animals into someone else’s supply chain
  • leave untreated and sell the ones that survive which seems rather callous and Darwinian
  • euthanize sick animals (including entire flocks) which comes with its own set of sustainability issues

Dairy Heifer with a bad case of pinkeye and blindness in that eye in a production system that prohibits the use of antibiotics for treatment of the bacteria which cause that disease

There is an understanding that this is an important issue and the industry is working to address it but I personally think there is both a One Health and welfare need to keep access to strategic uses. The dairy heifer in the picture above has a raging pink eye in her right eye as you can see and was on a “never ever” antibiotic farm in Northern California – so she never ever got antibiotics and her eye just blew up and developed a perforated ulcer. At the time the picture was taken, she was 14 months away from producing milk. Personally I will take the conventional milk that allowed her to get treatment in the same way I treated my own kid’s pink eye with antibiotics.

If the entire food supply chain mandated never ever treatment regimen,  there would be a real welfare dilemma in terms of what to do with sick animals. At the current time the conventional supply chain takes in the “rejects” (i.e. sick animals that needed to be treated with antibiotics) of the never ever supply chain. To me there is something just not right about a system that depends, in fact relies, upon the fact that someone else’s customers will consume their rejects so that their value-added (i.e. more expensive) product can carry an absence label for what is an essential tool in their own production system. It is a bit like the EU rejecting the cultivation of GMO crops and then importing GMO soybean and corn grown in other countries to feed their livestock populations – exporting the problem to someone else’s backyard does not solve the problem. And pretending that sick animals don’t  exist does not address this problem either. Our food animals deserve a more honest and transparent discussion of this topic.







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