The development of revolutionary technology for producing growth elements in tobacco plants and the production of food colorings from yeast fermentation processes – these are the ways in which two Israeli companies are harnessing biotechnology methods enabling humans to consume more healthy, natural, and environment-friendly food. While doing so, they are also helping to strengthen the northern Israel region as a food-tech stronghold
The warning sign issued by scientists and professionals is clear – the growth of the world’s population and its dwindling resources mean that, in the future, it will no longer be possible to produce enough meat to feed everyone. No-one engaged in this field has any doubt of the urgent need to find an immediate solution for this problem.
This is the background to the meteoric development of meat substitutes and cultivated meat industries. The two are not the same – meat substitutes are based on plant protein or protein resulting from fermentation, while cultivated meat, in contrast, is real meat. Cells are taken from a live cow and grown in a bioreactor with plant material while providing them with an environment that simulates growing in a real cow. The result is a genuine piece of meat.
The advantages are tremendous: first, the end-product is not a substitute for meat but rather, identical in taste and composition to the real thing. The difference is that this meat is produced without harming animals, while using significantly less energy, and with a fraction of the water needed to grow a cow.
So, what’s the problem? Dr. Dana Yarden and Dr. Amit Yaari, from the Israeli startup BioBetter, explain that growing cattle, fish, or poultry cells in a bioreactor requires what are known as ‘growth factors’ – proteins with which it is possible to control the division or differentiation of the cells. Unlike bacteria that don’t need more than water and sugar to thrive, cells of complex beings need signals, and these are the growth factors. Without growth factors, it is simply impossible to grow cells.
The problem is that growth factors are extremely expensive, and this, in turn, raises the cost of producing cultivated meat to more than 300 dollars per kilo. In practice, 55%-65% of the cost of producing cultivated meat is derived from the cost of the growth factors. The cost is so high that it raises a question mark over the feasibility of the entire cultivated meat technology. Without a solution to this problem, cultivated meat cannot be produced at reasonable and affordable prices.
A further problem is production capacity. For example, the total production capacity of the global insulin industry in a year is around 17 thousand tons and is used primarily for pharmaceutical applications. This capacity will allow to address only 10% of the cultivated meat industry requirement, not to mention the entire predicted scope of cellular agriculture.
From Smoking Products to Meat Production
This is where BioBetter enters the picture. The company was established by Prof. Oded Shoseyov from the Hebrew University, Dr. Dana Yarden, and Avi Tzur – an industrialist who lives in Brazil where he worked in the field of tobacco and was the company’s first investor. They were joined a short time later by the company’s CEO Dr. Amit Yaari who completed his doctorate on collagen produced from tobacco plants in Prof. Shoseyov’s laboratory. BioBetter, that started out in the Innovation Authority’s Katzrin incubator, and which focused on manufacturing pharmaceuticals, made the transition to the field of food-tech following the Covid pandemic.
The company operates from Kiryat Shmona and contributes to the city’s standing as a food-tech stronghold. “Kiryat Shmona became the food-tech capital of Israel as the result of efforts by Erel Margalit’s JVP Fund (that recently invested 10 million dollars – the largest ever investment in a startup based in Kiryat Shmona) and the opening of the Fresh Start food-tech incubator, and we understood that we had the capability of producing a critical component of the cultivated meat industry. Everything came together nicely with agriculture in the northern region of Israel. This is very significant in the field’s development and that of other startups in the region.
“We enjoyed the support of the Innovation Authority the whole way – during the initial years of operation in the Katzrin incubator, and also over the past two years with the transition to activity in the field of cultivated meat. The Authority makes great effort to advance food-tech R&D and has also recently supported the cultivated meat consortium program that provides impetus to both new and existing companies to enter this important and interesting field. The Authority is clearly investing extensive thought and effort to develop the field of biotechnology in Israel”.
BioBetter’s solution is based on an understanding of the need for ‘disruptive technology’ – technology that completely alters the industry’s existing technology and offers a solution: in our case, the use of plants as bioreactors.
One of the reasons for the growth factors’ high cost is their complex structure which not all cell types can produce. Bacteria or yeast cannot efficiently produce growth factors and need numerous and inefficient stages of production which raise the cost. BioBetter uses tobacco plants that can also correctly and efficiently produce complex human proteins such as collagen, antibodies and other proteins. The company inserts the genetic sequence that causes the production of growth factors into the plant’s genome, thereby enabling to plant a seed in a field that grew naturally, creates the protein, and preserves sterility and suitable conditions within the cell – until the harvest.
As BioBetter’s CEO, Dr. Yaari explains: “one extremely significant advantage of molecular farming (the production of proteins in plants that grow in open fields) is that everything exists already. Tobacco farmers have equipment, fields, and experience and there is no need for significant capital investment (Capex). Furthermore, when adopting a longer-term view, many tobacco farmers have become unemployed due to the decline in tobacco consumption. Yet another advantage is that the operational costs are dramatically lower compared to other solutions because there is no need for amino-acids, sugars, heating, expensive human labor etc.”.
BioBetter has developed a unique and patent-protected purification technology that cleans the growth factors of the plant proteins and disposes of the nicotine and proteins in a quick, efficient, and cheap manner that is suitable for very large-scale operations. At the end of the cleaning process, the quantities of remnant tobacco impurities in the cultivated meat are negligible.
“Our solution is extremely environment-friendly”, explains co-founder Dr. Yarden. “We make use of plants that only consume air, water and light and can therefore achieve very large-scale results, with the only limitation being the area of land at our disposal.
BioBetter initially produced the growth factors and cleaned them and were the first in Israel to develop a long line of cell tests. “We started to give samples for testing to local and international meat companies and, according to them, our development works well compared to the existing commercial material on the market. We are now striving to finalize commercial contracts with these companies”, says Dr. Yaari. BioBetter’s solution currently integrates with the market because there are still no companies producing and selling cultivated meat on a large scale. The entire industry is concentrated in the northern region, in a small biotechnology company in Kiryat Shmona. Over the next two years, they plan to increase growing capacity to several dunams and to produce hundreds of grams of growth factors a year.
One of the company’s other goals is to receive regulatory approval – a lengthy and complex process. Dr. Yarden, a physician by training, says: “I come from the world of pharmaceutical development and was happy to discover how much of a leader Israel is in regulatory activity for approving new food and the extent to which the Ministry of Health is maintaining a dialogue with the evolving industry. Israel is very advanced in the area of new food regulation and the Ministry of Health assists companies out of an understanding of the processes required to receive approvals. Naturally, with a production plant in Israel, we will apply for the relevant approvals here, and there are many other cultivated meat companies already active in Israel. A significant market is developing at the same time in the US and so we will also apply for FDA approval. I view this as a positive challenge”.
BioBetter’s goals at present are primarily to achieve ‘scale up’ and to begin marketing the products for use as food. They also hope to expand activity to further factors because while many companies use factors of cattle, none of them produce factors of poultry and fish.
“These are areas that we want to explore first”, says Dr. Yaari. “Our vision is to develop our production capability and to be a world leader in supplying growth factors – and all from the Upper Galilee, even if in the short-term, we also have to produce in the US”.
Making Life Colorful
Another new Israeli technology is causing a revolution in a different culinary field – the food colors industry. Phytolon has developed a technology that allows production of natural food colors using yeast fermentation processes. The new food colors offer industry and consumers significant health, economic, and environmental advantages.
Phytolon was established by three partners: Dr. Tal Zeltzer, Dr. Guy Polturak, and Dr. Halim Jubran, who today serves as the company’s CEO. The company’s name, as appropriate for one active in the field of food colors, consists of the words “Phyto” (“plant” in Latin) and “lon” (“color” in Arabic). The company, that relies on scientific inventions of the Weizmann Institute, grew in the Trendlines Incubator established by the Innovation Authority, and presently operates out of Yokneam Illit.
Dr. Jubran explains that one of the 21st century’s global food world trends is the search for natural and healthy solutions at the expense of synthetic solutions. The value in this approach is not only in the production of healthier food but also food which enables us to preserve the environment.
The food colors industry is also undergoing a change as part of the general trend. This is because the synthetic colors that exist today raise concerns about consumer health. It is important to understand that the entire colors market is estimated at 11 billion dollars, targeting sectors such as cosmetics and textile in addition to food.
The problem with abandoning synthetic colors is that natural colors developed until today are simply not of a good enough quality to compete with synthetic colors. Furthermore, because they are based on plant extracts (carrot, beetroot, paprika etc.), their production relies entirely on agriculture. The result is that their economic and functional value is lower than synthetic colorings, as well as having a low environmental value because they use land and water and cause greenhouse gas emissions during the growing process.
Biotechnology Will Solve the World’s Problems
“We have introduced the production of natural colors without using plants and agriculture”, Dr. Jubran explains. Phytolon uses micro-organisms – baker’s yeast – that, via a biotechnological process, become a tool for producing food ingredients for industrial use. The technology it has developed creates the plants’ colors via a process of yeast fermentation.
Phytolon’s solution has economic value – saving the use of high-cost agriculture and is cheaper than the other natural colors on the market; environmental value – no land is needed; and functional value because their food colors are higher-quality and more stable than the existing natural food colors. It is important to note that yeast is not part of the product and is disposed of after production. Colors produced using this method have no taste or odor and are therefore easily adopted by industry.
The company currently operates two production lines: the purple color of beetroot and the yellow color of the sabra cactus. After production, the colors can be mixed at various quantities to attain a very broad spectrum including yellow, orange, pink, red, and purple. These comprise 75% of the existing and most in-demand colors in the food industry. This is a solution that is suitable for almost all products on the market. In the future, the company also intends to enter the cosmetics and textile sectors.
Phytolon recently completed a large fundraising round. The company is engaged in a process of ‘scale up’ and expects the product to be ready for sale in 2023, after completing the regulatory stage. This is not expected to be complex as the products are based on two components already familiar to the regulator – plant-based pigments and baker’s yeast – and the product will therefore probably receive approval next year.
As for the target audience, the company is in contact with the world’s largest and leading food and food ingredient corporations. Other target audiences are the manufacturers and distributers of food companies with several of whom Phytolon is already engaged in work and active pilot tests.
Dr. Jubran explains that Phytolon is just one part of a very large revolution in the world of biotechnology and food that is based on the transition to use of fermentation, not only for food components, but also for pharmaceuticals. “Insulin and different vitamins and enzymes are also produced with yeast. The fermentation is aimed at replacing agriculture or unhealthy synthetic chemistry. Biotechnology enables us to achieve wonders.
“We are on the borderline between biotechnology and food-tech and benefitting from both worlds: our method is biotechnological, and our approach is to advance the food world. We knew about the economic, health, and environmental value we could provide, and our growth as a company reflects the success and growth of this field that has become relevant worldwide. We believe in biotechnology’s ability to solve the world’s problems – both environmental and health. We have amazing tools and endless possibilities to apply them”.
And if we’re discussing making the world a better place, it is worthwhile getting to know the social aspects of Phytolon: “We are natives of northern Israel”, says Dr. Jubran, “and we insisted on establishing the company in the periphery. We believe that if there are entrepreneurs who can strengthen the periphery, it’s us. More than 50% of our company’s employees are women, including at executive level, and we have workers from all sectors of the population: Jews and Arabs, secular and religious. We are all one family.
“One of our activities, conducted with the support and funding of the Innovation Authority and in conjunction with the ORT-Braude College in the north, is a training program for students from the periphery. We employ interns in their final year of engineering studies who receive training here. Some of them continue with us at the company as food and technology engineers”.