The Protection Election – How FMC and Zymergen are changing the choices

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A few weeks ago, on an otherwise empty soundstage in Wilmington, former Vice President Joe Biden accepted the Democratic Party nomination for President and said, “As president I’ll make you a promise. I’ll protect America. I’ll defend us from every attack, seen and unseen, always, without exception, every time.”

In doing so, he defined this political season as a protection election. It may be the only thing which Biden and Trump agree on this season. Just a few days later, President Trump tweeted:

GRAPHIC The only way you will stop the violence in the high crime Democrat run cities is through strength!

Two visions of protection. The Democratic vision focuses on protection against COVID-19, climate change, discrimination, loss of health care or lack of access to education. The Republican vision focuses on protection against multiculturalism, illegal immigration, violence in the streets, excessive regulation, bad trade deals and China.

It goes much deeper than any of this, or all of it.

Who and what do we protect? It’s a case of ‘protect against COVID’ vs ‘protect the economy’. It’s old-line industries that served us well vs new technology that positioned for the future. It’s GMO vs non-GMO. It’s the job I have today vs the job I want for tomorrow. It’s a health care system that is the enemy we know, vs a number of alternatives. It’s Social Security vs Control Your Own Money. It’s US-as-the-policeman-of-the-world vs Isolationism.  It’s law-and-order vs defund the police. It’s the Melting Pot vs the Multicultural Society.

Yes, Protection is an old rallying cry. But it’s not a very familiar one.

In 1896, William McKinley and William Jennings Bryan squared off over the protective tariff and the monetary standard. Since then, presidential elections have focused on themes of opportunity, values, taxes and deficits, entitlements, the role of federal government, economic advancement or foreign entanglement.

Protection Against What, Exactly?

In the world of biotechnology, it’s the same, which is to say that everyone wants protection, but no one agrees on ‘protection against what?’

Some people want to be protected against famine, disease, resource depletion — via the blessings of genetic engineering. Others want to be protected against genetic engineering gone wild. Some are craving frankenburgers, some are running away from plant-based foods as fast as their feet can carry them.

For years, there has been a pitched battle between supporters and critics of genetically modified crops. GMO started off as a descriptor of a type of innovation, and now it is a negative brand attribute. Long before young people are exposed to the science of biology and rational debate, they will see “GMO-free” on food labels.

“Protect” is a powerful word. There are 5.8 billion Google results if you search on that term, compared to 1.84 billion if you search on “promote” and 427 million for “defend”.

Not quite up there with the three magic words of direct marketing. Free, You and Now, at 15.9 billion, 25.2 billion and 12.48 billion, respectively, but impressive none the less.

Confidence has been Low

7 charts from Google relating to search term popularity, tell the tale of a nation’s rising interest in protection.

When we look at the charts for the use of terms like Assure, Care For, Defend, Ensure, Protect, Protection and Shield in Google statistics, we see rising interest levels and that they predate the outbreak of COVID. Protection is on the national consciousness.

But, protect whom, and against what? That is what the 2020 US Election is all about. The candidates are defining the enemy and selling the priority of defeating this one first, as opposed to that one.

And there are good reasons to debate American priorities. There’s little doubt that the nation feels that the United States in on the wrong track. 72 percent of the country thinks so, according to Real Clear Politics.

But it’s not as simple as “bad year, bad mood, fire the President”.  It’s not a question of Good Trump, Bad Trump. Real Clear Politics tells us that at no time in the past 11 years has a majority of the American public believed that the United States in on the right track.

True, President Trump’s job approval ratings have been anemic all along, compared to President Obama — but actually, the right track/wrong track hasn’t been much worse in the Trump era than in the Obama era, though COVID sent the ratings to low levels not seen since 2010.

American’s confidence is low, according to the Conference Board, so why isn’t the country stampeding towards a choice for change? It could be that Americans disbelieve that politicians can deliver the changes that are needed. It could be that the country is undecided about what it would like to be protected against.

Choosing and Adapting

So, we elect to protect, but what do we select? The choices we make, the threats we target, define us as a people, and define our times. The struggle for vaccines protection against polio and smallpox, that was one kind of striving for protection; the emergence of the Ku Klux Klan, that was quite another. One person’s threat is not always another’s, though we wish it were not so.

What gives life to the one can be the destruction of another, and we living here on Earth today are the living proof of it. In our evolutionary past, almost all life on earth was wiped out when cyanobacteria emerged, exhaling oxygen — a toxic gas to other living creatures of that time.

But we have to thank those cyanobacteria, they made a world for us to live in. Before them, there was hardly any atmospheric oxygen at all. With free oxygen arrived a faster means of ingesting energy. With that, came the megafauna — in days gone by, the dinosaurs. Later on, there was us.

Unlike bacteria, slaves to their genetic code, we have evolved as a species rooted in choice and nimble adaptation. Once we lived in trees, now on land, sea and in space. Once we lived in Africa, now everywhere. Once we used timber to make fire and release energy, today we have wood, petroleum, natural gas, solar, hydro, wind and more. We make choices — to balance our diets, our economies, our energy mix, our agriculture, our raw material supply chain. Our lives are a game of choice.

Yet we are not born to always choose wisely, we have the evolutionary right to be wrong. A thousand of us might choose the wrong path but should just a handful of breeding pairs choose an evolution-advantaged path, the human story goes forward.

A shift towards Natural

Lately, we have been re-considering our choices, and the balances by which we live our lives. We wish to do more with less, we hear about re-cycle, re-use, reduce. We often find ourselves turning to nature these days. Organisms create defenses, new forms of metabolism, new forms of converting a gas or sugar into a material or energy or into a shield against predators.

For we are an imitative species. That’s how accents form, through imitation of speech. That’s how gestures form, from imitation of signals. That’s how competition forms, from the copying of methods or goals. We copy, copy, copy — we are the Xerox of the animal kingdom.

Around the world, as seen in Google Trends, we see that interest in ‘natural ingredients’ has steadily increased over the years.

It’s interesting. A hundred years ago, nature was seen as something to be tamed, feared, dominating, done without. People didn’t love the force of nature as they experienced it then, flood, drought, famine, disease. They saw Nature as chaotic and nothing to be loved, though they may have retained nostalgia for simpler times.

Simpler, that’s an idea we had interest in all along, and never more so than now. Again, Google Trend gives us some hard data.

Yet, just as rising interest in “natural ingredients’ is paired with rising interest in ‘synthetic’, so too is rising interest in things simpler and natural with the rising fascination in ‘machine learning’.

So, — natural ingredients, protection, simpler, machine learning. Four powerful drivers in our culture.

Let us express that another way, in sentence form.

The search for protection using natural ingredients, made simpler through machine learning.

Of Zymergen and FMC

Let me tell you a story along those lines, about a company called Zymergen and one called FMC, neither of which you may have heard of. In chemical circles, FMC is well known enough, and its profile jumped in the past few years when the EU ruled that Dow and DuPont could not merge unless they sold off some crop protection assets where there was concern over monopolization.

Zymergen is much newer, and make take a little explaining, even if you have heard about them through the staggering amounts of capital they have been raising as they target new sectors to serve, such as this $300 million capital raise aimed at supporting more efforts in chemicals and materials, word of which surfaced this month.

The flood of new capital tells you that Zymergen is expected to be a disruptor, and its vase in the San Francisco Bay Area might lead you to suspect it is working in either life sciences or digital technology. Either way you guess, you’d be right, because Zymergen works at the junction where digital and life sciences converge.

Equipment, training and route: the biotech story

The basic idea is this, that there are so many potential combinations of genes, traits, metabolic pathways and the like, that any rigorous adventure in discovery is going to be based in conquering Big Data. Much as the assault on Everest had more to do with conquering the oxygen transport problem than problems of geography. Everyone knew where the South Pole was, Roald Amundsen was the first person to work out the proper sequences of equipment, training and route.

Equipment, training and route. That sums up the last 20 years in genetics, more or less.

The tools have been revolutionized — consider the costs and time frames for gene sequencing and for replicating DNA. If you wondered why companies like Twist Biosciences have valuations in the billions, it is because they have understood and mastered the opportunities that new equipment have brought to the world of genetics.

Training? In a hundred years, we may think of the methods of today as the Late Stone Age, but they are revolutionary now. Consider the world of CRISPR — gene editing. Rather than evolution taking the traditional, natural form of sloooow rates of gene mutation, or the sped-up methods of genetic transposition, or directed evolution — in CRISPR, we have something new and more elegant. Just a snip here, a cut there.

In conversations with the professionals in the field, they all agree we are moving into the era of biofoundries and the industrialization of Design, Build, Test, Learn.

Which Route to the Summit?

What about route? First, we need to take a short side trip into the world of genetics and how Big that Big Data can really get.

Let’s begin with the 3 billion base pairs in your DNA (it’s about 30,000 genes in all).  Overall information?  It’s 9.8 times 10 to the 903,089,986th power.

So, discovery within the world of A,C,G,T (the coding system for genetics, a series of base acids) is going to involve big numbers. It’s like having a mountain like Everest with sextillions of routes to the top.

Which brings us to the power of machines and machine learning.  Machines that are more elegantly programmed in their voyages of discovery will move faster, learn faster than others.

The Zymergen edge

That is what companies like Zymergen are about. Faster leaning within this particularly complex set of Big Data.

A good Zymergen machine is a little like the Starship Enterprise, on a continuing mission to explore strange new worlds, to seek out new life.. and boldly go where no discoverers have gone before. The Enterprise had two power systems — the conventional propulsion, and warp drive. Machine learning is the warp drive of biological discovery.

So, now we’ve learned a little about Zymergen, and we’ve defined this “search for protection using natural ingredients, made simpler through machine learning” as an inquiry completely suited to the times we live it.

The FMC gambit

But, protect against what, exactly? Let us now spend a little time on FMC, and the world of crop protection.

You see, most of us thing of discovery as an adventure in yield. Something that grows faster, grows more, more efficiently handles inputs to do same. Yet, the explosion in crop yield is based in crop protection, actually.

And it is not just the work in protecting crops from predators, pests, diseases, competitors and the like. Or creating better ways for them to tolerate poor soils, drought and other forms of weather stress.

One of the most important things we do is to teach crops to grow well in closer and closer proximity to each other. Yes, we teach them to better tolerate the world around them, and we provide them shields against external threat. It’s one thing to domesticate a plant, and another thing to civilize it. It takes a special form of tolerance to put up with ‘urban’ conditions. One plant steals the others sunlight, water, nutrients. One spreads disease to the other, or shares parasites, or pests have a twofer. Just getting corn to grow straighter so that you get more plants per square yard — that’s a big deal.

So, there are many types of protection.

And while there are many ways to protect, we have to pick our protection strategy carefully. We can’t kill the plant along with the pest, we can’t scare the nation while improving yield, we can’t poison the soil in the name of health, and we can’t clear the field of one pest only to make room for another.

Companies like FMC are good at threading the needle, more or less — lately, they’ve been eyeing the pool of natural diversity and wondering “what can we find in nature that will help us?”

After all, lots of organisms know how to fend off ants. Have a look at any garden filled with rosemary, lavender, thyme, mint or catnip.  No ants.  Point of it is, nature has perfectly good defenses for noxious things.

Gimme Some Action

In the world of crop protection, people call them “actions’” and “activities”. The finding of modes of action is the holy grail of crop protection and everyone is after them. These days, the more natural, the better.

That’s what FMC was on the hunt for, as the search for new modes of action became a search for a partner like Zymergen.

“How you can solve the problem? You can tell people that you do things differently, but you have to pivot, broaden.” FMC’s chief scientific officer is Kathy Shelton, she came to FMC with the DuPont acquisition and works out of the amazing lab that DuPont built not long ago, the Stine Research Center, in Newark, Delaware, just west of Wilmington. They might as well have called it the Ezra Pound Research Center, because Pound was the one who said, when asked how to make something special, said “make it new”.

FMC bought the lab in the acquisition, and acquired the team, and has continued to expand it. Shelton summed it up succinctly, “We want to create new actions, specific to the pests, efficacious and safe.”

New, specific, effective, safe, natural.

We might as well add speed at this point — not just because of the competitive pressures among crop protection companies, but because pests, predators and competitors evolve, and can do so quickly. Today’s solution won’t work forever.

So, a daunting and ambitious list that Shelton’s group at FMC were taking on. “We wanted to think hard about who could help us,” she told The Digest. “We wanted a very different perspective, in defining the problem we wanted to solve. That process of defining the problem was an exciting part of the process.”

As Zach Serber told The Digest, “The problems are local and intimate, it’s crop by crop, and ecosystem by ecosystem, we need custom solutions, we need specificity.”

But not just specificity for its own sake.

Listenting to Nature

As Zymergen co-founder Zach Serber talked me through some of the problems not long ago, like a guy describing how to make a bad pizza that specifically tastes exactly like every other bad pizza ever made on earth, customized down to the last molecule of blah and blandness.

“Specificity doesn’t add much [on its own], it’s just specificity. Novelty is what’s going to matter.”

He perks up like a college football coach with a new formation and a hot play. “New modes of action they haven’t seen before, unique enough to make a difference.”

Novelty takes speed and intelligence to run the scenarios, to add up the probabilities, to simulate the conditions, to isolate the options.

“The need is not novel. It’s the pace we can achieve, now,” Serber noted. “And we can partner with nature, use existing solutions that the natural world has already proved. We are using our computational tools to listen to nature, and then mass produce.”

Wonders to be found

It takes time to recognize an enemy, not only to design a defeat. Al-Queda was organized in the late 1980s, but Osama bin Laden took ten years to make it to the Top 10 Wanted List. Reaction to COVID-19 was slowed by skepticism over the extent of the threat.

And the numbers are daunting in disease because of the complexity of life. There are sextillions, googolplexes of options. And we might as well note how unhelpful Nature acts, in making its pathways unobvious. Leaving us to uncover in the universe of unseen things, in the undiscovered country, what nature already knows.

Zach Serber explains, “there are so many compounds, all incredibly diverse, all natural, never been characterized. In the old days, you had to date them all, and one by one, using instincts and judgments to try and prioritize. Retrospectively, it was sort of like a set of matchmakers.”

“Now, we focus on how to improve the algorithm, and use the variables and knobs we can tune, and the downselect criteria. At first, the downselects might be in the hundreds of thousands, but then you get thousands, to hundreds, to ten.”

Protection That Went Wrong: the Story of the Boll Weevil

We mentioned speed, and that is the co-factor of Protection, along with specificity. It is a matter of swiftly recognizing a threat, and swiftly countering it. As we found with COVID, slow to recognize and slow to act is a recipe for disaster.

We didn’t invent slow to see, slow to act in our own time. It’s the old story. It Happened With The Boll Weevil, Too — you could just about write it like the title of a book, as a cautionary tale.

It was America’s first national scourge. Then, as with COVID, we saw the initial confusion about the level of threat, where it would strike, what it was, how much damage it might do, the weird alternative solutions, the simplicity of the idea of quarantine and the inability to make it happen.

You see, the boll weevil plagued US cotton production for almost a century, caused billions in crop damage and devastated the Southern economy.

As Wikipedia notes, “By the mid-1920s, it had entered all cotton-growing regions in the U.S., traveling 40 to 160 miles per year. It remains the most destructive cotton pest in North America. The boll weevil contributed to the economic woes of Southern farmers during the 1920s, a situation exacerbated by the Great Depression in the 1930s.”

At first, they didn’t know what it was. They called it the Texas Sharpshooter, when reports first surfaced in newspapers in 1892 and 1893, and noted that it had “made its appearance in a number of the localities of Southwest Texas and is causing great injury to the cotton plant.”

They didn’t stop at Brownsville, yet the threat was not well recognized. Infestation reached Coahuila by June 1893, Corpus Christi by August.

Little was done. One grower caught a boll weevil and sent a specimen to the USDA in Washington DC which passed it to the entomology department and characterized the pest.

USDA officials wrote back, phlegmatically noting that they had received specimens of the pest ten years earlier, had not known whether the pest was in the United States or not, said it was “not surprising that the pest has crossed the Rio Grande,” added that “it is safe to say that other Mexican insects affecting cotton will make their appearance in Southwestern Texas,, and admitted that “it is difficult to suggest any remedial measures”

It wasn’t until December 1894 that Tyler Townsend at USDA wrote “Report on the Mexican Cotton-Boll Weevil in Texas”, and it was March 1895 before the report appeared in Insect Life. He recommended burning all the affected fields, then two weeks of flooding those that had irrigation. As an alternative, he suggested that growers simply not plant any cotton in affected areas for two years — the weevil was known to only attack cotton. None of that happened.

By late 1895 it was too late, a report that year from Louisiana noted it came from Texas with “no opinion on how it got to Louisiana”. Newspaper reports referred to “this great evil” and called for ”a cheap and efficient agent for the destruction of an insect commonly called the boll worm”. By then, it was almost impossible to stop. It reached Alabama by 1909, and by 1930 the pest was so established that conservative Southern Democrats who were irritating President Franklin D. Roosevelt were being referred to as “Boll Weevils”. The pest had established itself in the very fabric of American politics and language.

Goodbye, 8-year slog to approval

If you’ve been not been reading up on viruses that affect humans, lately, you’re not alive, yet not all viruses are transmitted solely by human contact, there are some very dangerous ones carried by ticks, fleas and mosquitoes — these are called vector-borne diseases, and the Center for Disease Control has a unit working to protect us from them.

There’s been good news this past month with Zika virus and Lyme disease, and it’s a biotechnology triumph in pest protection. In August, Evolva was finally able to register NootkaShield (branded nootkatone) as an active ingredient with the US Environmental Protection Agency, for use in insecticides and insect repellents,

Nootkatone is an ingredient found in minute quantities in the bark of Nootka cypress and in the skin of grapefruit. Nootkatone has been tested against a variety of biting pests, to repel ticks spreading Lyme disease, or mosquitoes spreading Zika, dengue or West Nile viruses.

Nootkatone can now be used to develop new insect repellents and insecticides for protecting people, yet products will not be commercially available until at least 2022. Part of that is time for formulation, part of that timeline is manufacturing, part for a new round of EPA review.

It’s been a long road. It was back in 2014 that Evolva started to work with the support of the US Centers for Disease Control and Prevention. In 2017, Evolva received a contract from the Department of Health and Human Services Biomedical Advanced Research and Development Authority to develop a next-generation active ingredient.

If products come by 2022, that’ll be eight years. And, to put this in context, the World Health Organization declared Zika virus a global public health emergency some years ago.

Marking the Ballot in a Protection Election

They say that speed kills but it is delay that kills in developing tools like repellents.

So, artificial intelligence, machine learning — it’s found a mission. Regulatory regimes could use a lot of help, but industry can make discoveries faster, more specific, and lean more into the natural world.

“Can’ is one thing, ‘do’ is another. It’s an ambitious set of tasks which FMC and Zymergen have set themselves, as they take up their work.

It may be a Protection Election, in November, the American public will make decisions about what to protect, and how, that will have far-ranging consequences. In the world of crop protection — and the food, feed, fiver and fuels that comes from that world — FMC has marked its ballot. It’s voted for natural, specific, effective, fast — and Zymergen.

“I wish it had been sooner,” Kathy Shelton mused. “As soon as we met and started, we knew that this was the place.”



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