Bio-engineering: unlocking nature’s treasures

By Catherine Jewell, Publications Division, WIPO

For Oded Shoseyov, a pioneering materials engineer, serial inventor and entrepreneur, nature is a source of inspiration. For the past 30 years, he has been unlocking nature’s secrets to come up with exciting new plant-based materials that offer significant advantages over petroleum-based synthetic materials, particularly in terms of their sustainability. Professor Shoseyov discusses some of his most significant inventions and highlights the importance of intellectual property (IP) rights in ensuring that their benefits are widely accessible to society.

How did you get into plant nanotech?

I was born into farming and have always been interested in agriculture. My family has been managing vineyards for more than 130 years. I started out studying chemistry and then moved into agriculture and the bio-engineering of proteins. In 1990, I joined the Faculty of Agriculture at Hebrew University as Professor of Plant Molecular Biology, where I now run a relatively big laboratory with many students working on protein engineering and nano-biotechnology.

Plants have always been my focus, but my research also extends to industrial and medical areas. For example, for many years now, I have been developing ways to use genes sourced from humans to produce human collagen in plants. I don’t confine my work to plants but always find myself going back to them to produce proteins, or make composites with plant-derived materials. Plants are very efficient; they produce everything for us including oxygen and are very resourceful.

As a serial inventor, with 62 patents to your name, how did you first encounter patents?

It’s a long story and it didn’t come naturally. As a young scientist, when I started out my primary focus was to publish scientific papers and secure my tenure. But shortly after joining the Hebrew University of Jerusalem, over a serendipitous lunch with the co-founder of a company I was consulting for, I found myself deferring publication of my scientific paper until a patent application covering my research findings had been filed. I was also offered a handsome research grant to find an application for my research and a promise from the co-founder that if I found a useful application, he would establish a company and give me 4 percent equity in it and a fair share of licensing royalties. Needless to say, I did find a useful application for the research, which led to us setting up Futuragene, which was later acquired by Suzano, one of Brazil’s largest paper companies, for USD 100 million. It was a great success, but it made me realize that I could do more with my research; it didn’t need to end in a scientific paper. That was my first exposure to patents and their importance in driving economies.

What was the application you found?

This particular application made it possible to accelerate the growth of eucalyptus plants for the pulp and paper industry. These were the first commercially available transgenic forestry plants to gain regulatory approval in Brazil. Since then, I have established a number of companies, including, Melodea, and Collplant (see box). While I am not involved in their day-to-day management, I still play a role in them, either as a consultant, a board member or chief scientist.

Is there a common thread to your inventions?

Nature has had billions of years of evolution to develop functional materials that are sustainable,

says Professor Shoseyov.

Yes. They all relate to materials science and biomaterials in particular. Biomaterials are far superior to synthetic materials. As the former minister of oil of Saudi Arabia once said, the Stone Age did not end for lack of stone; similarly, the Oil Age is going to end long before we run out of oil. And I would add that there is a good reason for this, namely that biomaterials are much better. We simply need to look and learn how natural systems function and we have to innovate!

Nature has had billions of years of evolution to develop functional materials that are sustainable. In 200 years of modern chemistry, scientists have not been able to do so. That’s why we are seeing new islands of plastic in the oceans. So, we need to do something different, but we don’t need to reinvent the wheel. I always say, if you want to have a new idea, open an old book! That book was written over 3 billion years of evolution, and the text is the DNA of all living organisms. All we need is to read that DNA code and start our progress from there.

If you want to have a new idea, open an old book! That book was written over 3 billion years of evolution, and the text is the DNA of all living organisms. All we need is to read that DNA code and start our progress from there.

What is so appealing about working with bio-materials?

The strength and functionality of biomaterials comes from the fact that they are self-assembled; they are built from the bottom up. The synthetic implants that orthopedic surgeons screw into our bodies often fail because their mechanical properties don’t fit with the surrounding tissues. Why? Because they are not self-assembled. Nobody takes my head and screws it onto my neck or takes my skin and glues it to my body. In nature, every living organism is made from cells that self-assemble to create tissues and organs. That’s life. And that’s the right way to build things.

Tell us more about CNC (cellulose nano crystals) and its applications.

CNC is great. It derives from cellulose fibers, nature’s most abundant material. It’s renewable and it’s made of sugar, but on a weight basis, CNC is nearly 10 times stronger than steel, which makes for many exciting applications. When you mix CNC with water at a 3 percent concentration, it transforms into liquid crystals, and when you apply that solution to any surface – paper, plastic, concrete – as the water evaporates, the crystals self-assemble to form a very strong and transparent film. It also creates a barrier to oil and oxygen. That makes it a great packaging solution. In the past, standard juice cartons were made of a laminate of a polymer (e.g. polyethylene or PET), aluminum and cardboard. While it’s a very good packaging solution, it’s non-recyclable.

One of my companies, Melodea, has found a better and cheaper alternative using 100 percent recyclable cellulose. Melodea was established around a patented technology developed in my research lab. It develops and manufactures CNC and works with customers to develop various applications. This is important because they (the customers) have a better understanding of the need and have channels to the market. For example, it is working with Sweden’s Holmen AB, and Brazil’s Klabin SA, to produce CNC-based bio-packaging on an industrial scale.

In fact, Melodea and its partners are also addressing a major environmental headache, namely the millions of tonnes of sludge produced every year by the paper industry. Europe alone produces 11 million tonnes of it annually. For Melodea and partners, however, it’s a valuable raw material, which is transformed into eco-friendly packaging for non-consumable products. When it comes to food packaging, however, for safety reasons, we use virgin pulp.

CNC can also be used to strengthen textiles. If you take cotton yarn, and coat it with a thin layer of CNC, just 1 percent is added to its weight, but its toughness increases 500 percent. Similarly, coating glass with CNC makes it tougher, providing a useful option for glass construction and aviation where there is a need for lightweight but durable windshields, etc.

What other secrets has nature revealed to you?

We have also been working on resilin, the protein that allows cat fleas to jump 200 times their height! It’s the best rubber on earth! You find it in arthropods; insects, like dragon flies that fly short distances. We’re working with different partners to develop a sports shoe with a resilin mid-sole and flexible electronics, like touchscreens. For these purposes, we can produce it cost-effectively by embedding the resilin gene into bacteria (E.coli) and fermenting it. In future, we want to use it to make eco-friendly tires, but for such large-scale production, we will need to produce it in plants and at high yields to bring costs down. We’re working on it, and in time it will happen.

How did your work on plant-based collagen come about?

Products to rejuvenate skin (using dermal fillers, for example) have become increasingly popular. Personal care companies were looking for a safer, cheaper and more effective alternative to mammalian collagen and to hyaluronic acid, so I started looking into whether collagen could be made in plants. It was a complex challenge because it involved taking five human genes to make a single functional protein. I wrote a short paper on how to do it and eventually, with the backing of a technology incubator, I did a proof of concept and set up a company. That’s how Collplant started.

So how do you produce plant-based collagen?

We genetically engineered tobacco plants (because they’re not in the food chain), which now contain the five human genes needed to produce collagen. We propagate the plants from seed in the 25,000 square meters of greenhouses we have across Israel – and distribute the plantlets to farmers to grow. When harvested, the leaves are transported in cooling trucks to Collplant’s factory, where they are crushed to extract the juice and concentrate the collagen, which we then purify in clean rooms and make different medical implants. We recently completed clinical trials and secured regulatory approval in the European Union and Israel for an injectable product to treat diabetic foot ulcers and tendonitis.

We have also developed a plant-based collagen bio-ink for 3D printing of tissues and organs. It’s still at the pre-clinical stage but we have an exciting project underway with two companies in the United States, namely, United Therapeutics and 3D Systems, to 3D-print human lungs. You will see that around 2024.

How are IP rights important to your companies?

As a business asset, IP rights are as important as your staff. With IP rights, it is possible to work with partners like United Therapeutics and 3D Systems and achieve remarkable things. Without IP rights and the protection they offer, my companies would be vulnerable and it would be practically impossible to attract investors. Like regulations, IP rights are essential tools. Without them, we risk losing our ability to maintain healthy societies on this planet.

Why was it important for you to commercialize your research?

I believe universities have a responsibility that goes beyond teaching and educating engineers and scientists. With our scientific discoveries we have an opportunity to affect the lives of so many people. Commercialization and IP protection are the only way to assure these discoveries are realized.

As a business asset, IP rights are as important as your staff. With IP rights, it is possible to work with partners … and achieve remarkable things. Without IP rights and the protection they offer […] it would be practically impossible to attract investors.

What is your next project?

I have several projects brewing in my lab at Hebrew University focused mainly on improving plant systems to produce animal proteins for the food and the pharma industries. We are also developing novel bio-based composite materials with superior mechanical properties as well as novel 3D printing technologies.

Who is your greatest inspiration and why?

Leonardo de Vinci by far. He was the ultimate multidisciplinary scientist and inventor.

What advice do you have for young aspiring researchers/entrepreneurs?

Stay away from people who say no. Always look for the highest targets and collaborate with smart people.