Investors are still waiting for next-generation biotech to deliver on its enormous promise and potential, but just one of these Holy Grails would make the wait worth it.
Biotechnology has come a long way since 1978, when Herbert Boyer successfully demonstrated that human insulin could be produced from bacteria engineered with recombinant DNA. The breakthrough technology pushed a little-known company called Genentech into the spotlight and forever changed the world. Genentech was acquired by Roche for $46.8 billion in 2009. The American bioeconomy — biotech crops, biochemicals, and biologic drugs — generated an estimated $324 billion of gross domestic product in 2012. And millions of people worldwide today rely on insulin and other biologic drugs daily.
You could argue that recombinant DNA was the first Holy Grail technology delivered by the field. Several more have followed. In fact, we’ve recently been treated to the development and ongoing commercialization of the gene-editing technology known as CRISPR — a true game-changer for the biotech ecosystem. Headache-inducing legal entanglements aside, CRISPR promises to help synthetic biology deliver on its enormous potential and could even be an integral tool needed to produce several other world-changing Holy Grails. Some are closer to reality than investors may think.
1. Clean meat
Humans raise billions of animals every year — breeding, feeding, housing, and often slaughtering them — for food products. In fact, nine American states have more cattle than people. Globally, livestock production is one of the single largest (if not the single largest) producers of greenhouse gases, consumer of antibiotics, user of land, and source of environmental waste on the planet. But livestock also provide delicious foods humans don’t want to live without. So we’ve mostly shrugged and kept the status quo of industrial farming in place.
Biotech wants to change that by providing the same (or better) foods without animals. There are various types of animal-free technologies in the works, but the one with perhaps the largest potential is clean meat. It involves growing animal cells in bioreactors to produce animal meat — whether from a turkey, chicken, cattle, or even shrimp — but with 90% or greater reductions in energy requirements, antibiotic consumption, greenhouse gas emissions, and land use.
Once clean meat production is optimized, we could potentially manufacture food products identical to those grown from animals. The only difference is that instead of needing an entire cow to serve as the vessel for growing cow cells, we could mass produce the same cells in a controlled environment. It may sound impossible or unlikely to catch on, but the technology is progressing swiftly. And capturing even 1% of a multi-trillion market is still a lot of money.
A slew of start-ups have been formed to develop the required technology, and big names are backing them up. Tyson Foods (NYSE:TSN) — the country’s largest livestock producer with market shares of 21% for poultry, 24% for beef, and 18% for pork — has a venture capital fund to expedite innovation in the relatively new space. That would also help it to stay ahead of the technology curve by adapting to new realities, instead of clinging to animal domestication technology that may soon prove to be past its prime.
2. Nitrogen-fixing plants
The $80 billion global market for synthetic nitrogen fertilizer — which accounts for 3% of global greenhouse gas emissions — only exists because most agricultural plants are incapable of acquiring naturally occurring forms of nitrogen through a process called nitrogen fixation. Instead, most plants are completely dependent on nitrogen-fixing soil microbes living on and near their root systems to transfer the essential nutrient.
That plants are lazy when it comes to acquiring nitrogen isn’t lost on agricultural companies, with a few industry leaders developing tools to help our photosynthesizing friends. Years ago Monsanto (NYSE: MON) and Novozymes committed $600 million to form the BioAg alliance. The first products are plant seeds coated with super-efficient nitrogen-fixing soil microbes, which reduce the amount of nitrogen fertilizer required while simultaneously providing a growth boost. Think of it as a probiotic, but for plants.
Early field trials achieved double-digit yield increases, although the first products available to farmers today provide mid- to high-single-digit yield advantages over traditional crops. Bayer and field-leading start-up Ginkgo Bioworks recently created a joint venture to deliver on the same promise, albeit with the goal of mostly or completely eliminating the need for nitrogen applications in agriculture. If successful, these efforts could rapidly result in a new normal for agriculture — and devastate nitrogen fertilizer companies.
3. Gas fermentation
Industrial fermentation uses a microbe (bacteria, yeast, or algae) as a catalyst to convert a carbon source (the feedstock) into a more valuable chemical or material. The feedstock is usually an agricultural sugar derived from corn or sugarcane, so it’s natural to think of fermentation as always progressing from that type of starting input. But sugars aren’t the only carbon source available. In fact, some of the first life forms on planet Earth relied on something entirely different for food: gases.
If humans could harness the power of gas fermentation through economically viable technologies, then it would be a true game-changer. Why? Gas fermentation — or using microbes to efficiently gobble up carbon dioxide, carbon monoxide, and methane and churn out chemicals that could be sold as an additional revenue stream — could be one of the most cost effective ways to reduce emissions from industrial processes.
Several companies are up to the challenge. LanzaTech has partnered with several steel mills in Asia to capture emissions from steelmaking, bubble the gases through fermentation tanks as food for engineered microbes, and create low-cost ethanol and other chemicals. If the technology becomes viable, then it could be a key differentiator for investors in industrial stocks, especially if carbon emissions begin to be regulated worldwide.
Meanwhile, Calysta and Cargill are working on using methane from natural gas, rather than industrial emissions, to grow protein for fish feed. Intrexon (NYSE:XON) is doing the same to produce commodity chemicals and fuel blendstocks, although these can be made through traditional, low-cost petrochemical routes.
There are incredible challenges to overcome to commercialize gas fermentation, which hints that utilizing (free) waste gases from emissions may be the only viable route. But if the industry finds a way to make it work, then our world could look quite a bit different.
4. Genetic vaccinations
The development of the first vaccine (all the way back in 1796) led to incredible advances in public health that we’re still reaping today. Thanks to vaccines, we’ve functionally eradicated over one dozen diseases that previously killed millions of people each year. By the end of 21st century, we’ll likely take that power to the next level.
Although they’re still in the earliest stages of development today, gene-editing technologies such as CRISPR should allow us to literally cut out and replace genetic mutations that cause a host of hereditary diseases. The first proposed treatments — some of which are nearing clinical trials — will target rare diseases with “simple” genetic variations that are caused by a single mutation, such as Friedreich’s ataxia and sickle cell anemia.
These therapies should pave the way for genetic vaccinations of more complex diseases. On paper, it will be possible to correct genetic mutations in human embryos that cause or make resulting individuals susceptible to various cancers, type 2 diabetes, heart disease, and other ailments. These genetic vaccines may sound controversial today, but ethical discussions evolve with time and technology. By the end of this century, I would expect genetic vaccinations to be as commonplace as traditional vaccinations are today.
5. Self-replicating cell-free systems
Synthetic biologists often refer to cells as micro-factories. Metabolic processes are assembly lines, and enzymes are robotic hands that keep production humming along. We feed sugar into the micro-factory and it churns out a specialized chemical product. It’s a suitable metaphor, but micro-factories have limitations.
For instance, a lot of energy is spent in processes not directly related to producing the chemical we want. Cells need to divide, defend against predators, and run other processes necessary for life. We accept these limitations because cells provide one incredible advantage over traditional chemical processes: They self-replicate. If you have one micro-factory, then you can coax it to make billions and billions of copies of itself.
But some scientists want to go even further. What if we could isolate only the assembly line and robotic hands directly related to the task at hand to increase efficiency and yield with a smaller footprint? The technology is called cell-free. While making waves today as a research and development tool, these systems are difficult to create and maintain and don’t self-replicate. Therefore, they aren’t close to ready for prime time, although several labs are attempting to address those drawbacks.
If they succeed, then our world will look quite a bit different. On paper, a self-replicating cell-free system designed for manufacturing would allow us to produce renewable chemicals at unimaginable yields, costs, and volumes. It may be the only way to produce renewable fuels at costs that compete or beat petroleum, which explains the recent interest from the U.S. Department of Energy. It may also be pretty valuable for producing foods and materials on, say, Mars.
The technology is over 10 years away, but it could become an important tool — or the tool — for industrial biotech companies that must today rely on microbial cells. Several companies are toying around with the technology, although there are many advances that need to be made before it becomes a reality.
What does it all mean for investors?
Using biology as technology has provided human civilization with everything from food to beer to T-shirts to cutting-edge pharmaceuticals. But the pace of advancement continues to accelerate. After all, CRISPR went from non-existent 10 years ago to having already been used in several products on the market today, while the technology ecosystem continues to gain strength. That will serve as a positive feedback loop that enables more start-ups to achieve more accomplishments, faster.
It also hints that the rate of breakthroughs, and perhaps the delivery of several Holy Grails, could increase in the near future. That could have major implications for several multi-billion and even multi-trillion dollar markets, ranging from meat production to synthetic fertilizer production to chemical production. The companies that usher in these breakthroughs could deliver Genentech-like returns to investors that stomach the risk and see the vision. Some aren’t publicly traded yet, but if and when they hold an IPO, then you can at least be ready.