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Increasing Longevity by Decreasing Oxidization

Somewhere in a coffee shop in America, some green-haired millennial is typing away feverishly on their brand new Macbook Air, broadcasting to their Twitter followers about how evil capitalism is. As they pour a dab of pasture-grazed New Zealand cow’s milk into their freshly roasted cup of Guatemalan organic free-trade coffee, they lament their woes to the world. Why can’t society give me more? Why can’t I enjoy success without hard work? On the other side of the globe, some hard workers in New Zealand are pulling off some pretty major feats to put that delicious milk on the table.

It all starts at LIC, a New Zealand cooperative whose core business is dairy genetics. (They’re responsible for inseminating 80% of New Zealand’s national dairy herd.) Next to LIC’s headquarters in Hamilton sit the prized bulls who’ve sired tens of thousands of calves. When the time comes, the bull is loaded into a custom tractor-trailer and taken to a building that’s been there for decades. (The bull is transported this way so it doesn’t stub its toe while walking over and consequently produce less sperm.) The bull is led up to an attractive cow who stands waiting while a human handler watches and waits. Once the bull convinces the cow that he’s not just another player interested in a one-night stand, he mounts her, and this is where all the fun begins.

Collecting a "jump"
Collecting a “jump” – Source: Livestock Improvement Corporation (LIC)

The human handler then needs to “manipulate” the bull with a device that collects the prized semen – or a “jump” as it’s called in dairy lexicon. Once collected, some of the semen is frozen and shipped to various parts of the world. It’s where life starts, and it’s a fitting place for a longevity company to start as well.

An Accidental Discovery

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Founded in 2015, Hamilton, New Zealand startup Synthase Biotech has taken in $3.36 million in funding and contributions to develop a platform technology that seems to have limitless promise. The technology behind the company came about as somewhat of an accident while researchers were looking for an alternative to latex when the Japanese were constraining supply. In an Arizona desert exists a shrub that contains latex that also contains an enzyme that prevents the latex from oxidizing. (Oxidization is how a substance reacts to oxygen, and in some instances it’s not good – like rust.) It’s this plant enzyme that may, eventually, be used to increase longevity in humans.

Turns out that humans don’t react well to prolonged exposure to oxygen over time. While oxygen is what you need to live, it’s also what can ultimately take you out in the end.  You’ve probably all heard of “antioxidants” which can prevent oxidative damage to cells and tissues by scavenging unconstrained radicals. It’s damage that arises from unconstrained “free” radicals that can eventually be fatal. Synthase Biotech has an enzyme that it calls Aloxsyn® which has “extraordinary specificity and rates of reaction against toxic lipid peroxides.” In other words, this enzyme can be used to halt and even repair much of the damage that aspects of oxidization can do to mammalian cells, and the company has developed a way to produce the enzyme using a fermentation process.

We sat down to talk with Dr. Andrew West of Synthase Biotech, which has IP protection around the use of this enzyme, Aloxsyn®, in their first product applications for frozen bull semen and cattle embryos.

Improving Cow Fertility

Given how much work happens in Hamilton around frozen bull semen, it was a likely place to start. If a cow isn’t fertile, it’s not producing milk. Consequently, you want to maximize cow fertility in order to maximize milk production. Keeping a cow that doesn’t produce milk is uneconomic and produces unnecessary greenhouse emissions from its belching, or whatever it is they’re supposed to be doing that’s wrecking the planet.

Ideally, fresh semen works best for artificial insemination, but there are many use cases where frozen semen is needed. You may need to transport the semen long distances, or you may want to preserve some semen from a prized bull to be used next year. When using frozen semen instead of fresh semen, fertility rates can drop as you might expect. However, when adding some Aloxsyn® to the mix, you can get a better outcome. That’s based on a major trial that Synthase Biotech recently conducted.

If you’re talking cattle, the final customer is always the farmer. That’s who Aloxsyn® is helping. But it’s just one of many potential applications for this technology.

Additional Applications

Synthase’s proprietary bioactive, Aloxsyn®, may have a positive impact anywhere inflammation can be found. Dr. West believes that the number of potential applications for the company’s enzyme are very large. One application Synthase is looking at is storage of blood platelets, which will require some trial testing, but which represents a huge potential market. Then, there are more sperm applications.

Once a bull has a jump, that sperm dies almost immediately if it doesn’t end up inside the cow where it belongs. Whilst working on frozen sperm, it looks like Aloxsyn® also extends the life of fresh cattle sperm by five days. (LIC scientists showed us a proprietary solution they’re using that increases the life of cattle sperm by three days.) Why stop at cattle sperm? Fertility of pigs and horses could also be of interest as well, not to mention human fertility.

Applications for Aloxsyn
Source: Synthase Biotech

All of these fertility applications are higher margin, but there are also lower margin applications that can be considered such as increasing the shelf life of food. With around 30% of food waste in developed markets attributed to food spoilage, it’s another way that we may be able to help feed all the billions of mouths coming online. (Seems like a fitting application considering that they’re about increasing human fertility.) In order to address high-volume applications like this, production would need to be scaled and costs would need to be driven down. It all requires investment and partnerships with interested parties who want to collaborate.

No longevity company is without some grand visions of what the future might hold. In some preliminary experiments, a rat’s heart was stopped from beating for 30 minutes and then blood applied with the enzyme. The rat heart recovered 100% of its function. A rat with a severe stroke could fully recover if Aloxsyn® was applied within 45 minutes of that stroke. The implication here is an interesting one. Perhaps lipid peroxides in all that backed up blood behind the clot serve to damage the brain when the clot is overcome, and Aloxsyn® cleans up those toxins? It’s a promising example of what the future might hold, and if you have about $100,000 to pony up, Dr. West says Synthase Biotech will work to create a mouse that produces its own Aloxsyn®, a mouse that just might live longer. It’s a drop in the bucket for the many billionaires out there seeking the fountain of youth. For New Zealand investors, however, that sort of work is pretty risky.

The New Zealand Biotech Scene

The New Zealand Herald published a pretty comprehensive article on Synthase Biotech last year which contains some relevant information about the state of biotech in New Zealand. It’s dismal. Investors don’t look favorably on life sciences companies and that could be because the New Zealand stock exchange isn’t of a size that would support them. (The entire New Zealand stock exchange has a market cap of just $142 billion. To put that number in perspective, Johnson & Johnson is over twice that size with a market cap of $363 billion.)

On the other hand, Australia is much more accepting towards biotechs with about 200 listings on the ASX. Synthase is not pursuing an ASX listing, but if the company moves into development of a human drug based on Aloxsyn®, it will need millions of dollars for clinical trials. Significant investments over time will allow Synthase to add a range of human applications to complement its livestock ones. After a few years of selling animal products, their manufacturing operation will have all the kinks sorted out, and that’s half the battle before embarking on some human trials.

Conclusion

The more we know about the world, the more we realize how little we know. That’s obvious when you consider how some of the world’s greatest inventions – penicillin, X-rays, the microwave, LSD – were all discovered by accident. The Peter Thiel types out there who are willing to sink large sums into the burgeoning longevity industry might find the capital requirements for companies like Synthase Biotech to be more economical. According to a talk by Finistere Ventures a few years back, agtech valuations in the United States are half of fintech valuations, while New Zealand agtech valuations are half of that. If the fountain of youth exists in The Land of the Long White Cloud, it’s likely to be selling at bargain-basement prices.

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