History is pounding at agriculture’s door. One of the greatest farming enigmas to afflict growers in the last 100 years has been solved, yet the answer sits idle. At its core, the cotton riddle is simple: How to remove a naturally occurring pest deterrent from seeds, yet preserve the toxin within plants? The long-sought solution means cotton can make a massive leap from fabric to consumption—and provide 10.8 trillion grams of precious protein for the animal feed industry and human intake. Bottom line: After 7,000 years of cultivation, cotton is at the cusp of helping feed the planet.
Cotton has slipped the ball-and-chain of gossypol, a bitter-tasting toxin that ensures the vast majority of cottonseed is only suitable for cattle consumption. Gossypol has long been in the crosshairs of a cotton industry anxious for new markets, but removal exclusively from seed has proved impossible or impractical—until now. A breakthrough advance, painstakingly achieved by a stellar Texas A&M University research team, and supported by the confidence of Cotton Incorporated, has led to cottonseed devoid of gossypol, and tagged with the imprimatur of FDA and USDA. With U.S. red tape in the rearview mirror, next come the formidable hurdles of deregulation in foreign countries and the seal of a seed company, but without exaggeration, the current advance is massive, and opens an era on the near-horizon when essentially all cottonseed planted across the world could be sans gossypol. Plainly stated: When gossypol goes, it ain’t ever coming back.
In 1995, Keerti Rathore began working as a biotechnologist at Texas A&M AgriLife Research, and had never set eyes on cotton in the field. Twenty-five years later, down rows densely packed with developing bolls, he is walking in a trial field of TAM66274 cotton—his brainchild variety unique across the planet. With every step, he brushes branches and leaves packed with gossypol, a vital toxin typically present throughout the plant that serves as a wall of defense against insects and microbial disease. But gossypol within cottonseed, present at a level of ~10,000 parts per million (ppm), serves no major purpose, yet ensures the seed cannot be consumed by monograstric species, slamming the dining room door on pigs, chickens, fish and humans. The only animals fit to consume cottonseed and deal with the chemical composition of gossypol are ruminants with specialized stomachs—cows.
However, TAM66274 holds a secret: Despite the high levels of gossypol coursing through the foliage, the seed within the bolls contains a negligible level of gossypol at 300 ppm—well below the 450 ppm threshold set by FDA for human consumption. (WHO and FAO offer a bit more latitude, allowing for human consumption of gossypol below 600 ppm.) Break off a raw, green boll, dig into the layers for a seed sample, and place a rubbery specimen on the palate for a taste test: Simply, the bitter taste is gone from the seed, yet remains within the lifeblood of the plant.
Rathore’s team has achieved ultralow gossypol cottonseed (ULGCS) and the implications are seismic for producers, the feed industry and global nutrition. Why? ULGCS provides a pathway for cotton to become a dual purpose crop.
Bang for Buck
Despite the white blanket appearance of cotton fields at harvest, an individual plant produces 1.6 times more cottonseed than fiber—by weight. Currently, a major portion of the 47 million metric tons of cottonseed produced globally each year are generally funneled toward cattle, but mature cows are far from ideal consumers of cottonseed, and don’t offer much bang for buck, Rathore explains. “For example, cattle are not very efficient in protein conversion ratio (PCR). Cattle have a PCR of 20, meaning it takes about 20 lb. feed protein to get 1 lb. of beef protein. However pigs are 5.7; chickens are 4.7; and salmon are 4.7. Aquaculture and poultry, two of the fastest growing food production industries, would be high-demand categories that could be supplied by ULGCS.”
In addition, the potential for human consumption should not be underestimated, Rathore emphasizes: “We’ve currently got 47 million metric tons of cottonseed locking up 10.8 trillion grams of protein each year due to gossypol. A human needs about 50 grams of protein a day to survive, and therefore the 10.8 trillion grams of protein, accessible through ULGCS, could provide the basic protein requirement for about 590 million people.”
The numbers may be academic, but they scream out a potential marketing powerhouse for ULGCS. As things presently stand for growers, harvested cottonseed value basically pays for ginning costs. In the U.S., two-thirds of all cottonseed is funneled directly to the dairy industry, and the remaining third is sold to processing mills for crushing and oil production. Pared down, a jump in cottonseed demand, whether related to the feed industry or human consumption, would be a major boon for growers, without requiring additional inputs or acreage.
Cotton is a perennial produced as an annual; in equatorial regions, cotton plants grow into small trees. The nutritional properties of cottonseed relate to tree nuts, rather than soybeans, peanuts or sunflowers, and the taste (without gossypol) of cottonseed is often compared to a bland almond—ideal for flavor enhancement. “Think about just some of the uses,” Rathore urges. “Cotton growers could supply two of fastest growing food production industries worldwide—aquaculture and poultry—with alternative feed. For humans, the list of possibilities is endless, from roasted kernels to protein bars and shakes to flour. And all of this could be done while still making a heavy contribution toward meeting protein needs in countries across the globe. ULGCS means everyone wins. Now we need a seed company to pick this up and help it take off.”
“American cotton farmers want this, and they see the need and value,” Rathore continues. “Cotton is grown for fiber, and cottonseed is a secondary product that offers very little for farmers, all because of gossypol. If a feed industry like aquaculture gets involved, the demand for cottonseed will go up, and although I’m no economist, that makes financial sense and directly benefits farmers.”
Red Ryder to Elephant Gun
When Rathore carried his background biotech and genetic engineering to A&M’s cotton country in 1995, the longstanding riddle of gossypol removal jumped at him, particularly the fascinating historical details and promise of Hopi cotton. Across centuries, the Hopi tribe of northeast Arizona developed a variety of glandless cotton entirely devoid of gossypol. In 1954, plant geneticist Scott McMichael placed Hopi cotton on USDA’s radar, and ushered in several decades of investigation, culminating in the availability of glandless seed. According to Rathore’s research, “By 1980, there were several glandless commercial cotton varieties offered by the Gregg, Lambright, Lockett, Rogers, and Paymaster cottonseed companies.”
However, the glandless varieties lasted on the market about as long as snowflakes in summer. By definition, glandless cotton lacks gossypol, and therefore Hopi cotton, at least in terms of nationwide production, threw out the baby with the bathwater. Seed with no gossypol meant plants with no gossypol, and therefore the foliage was relatively defenseless and exposed to insects and microbial infection.
However, glandless cotton was subject to more problems than lack of protection, Rathore details: “While the loss of host plant resistance certainly played a substantial role in the commercial viability of glandless cottonseed, other factors also contributed to the trait’s demise. Because the seed had to be tightly isolated to prevent outcrossing with glanded cotton, breeding and seed production costs were higher than conventional programs. Most farmers were reluctant to absorb this extra cost from seed companies because they did not receive adequate compensation for their glandless crop. In fact, most growers in the production regions at the time routinely saved their own seed for replanting which meant they did not reinvest into the research and development of private seed companies. Therefore, a systemic failure along the supply chain to compensate adequately for additional risks and costs of producing glandless cotton also led to the commercial failure of the trait.”
The last echoes of glandless cotton died in the early 1990s, replaced by the whispers of a biotech future. Shutting down the gossypol factory exclusively in cottonseed was akin to a needle-in-a-haystack operation, but Rathore was keen for the hunt, and relied on a chain of tech developments (antisense and cotton gene discovery) in order to silence the seed-specific gossypol production gene. Much to Rathore’s chagrin, his first few attempts were unsuccessful—the cottonseed was in open rebellion. The drop in gossypol levels of Rathore’s initial cottonseed creations wasn’t precipitous, and adding insult to injury, the drop didn’t carry over to the next generation. “Sometimes people don’t realize how much time was spent in the research process,” he notes. “For example, putting a gene into a cotton cell and getting a whole plant back took 12-14 months, plus another 6 month to grow the plant and get seeds back to make checks and confirmations.”
In 2004, Rathore gained use of a new gene-silencing weapon akin to switching from a Red Ryder to an elephant gun—game-changing RNA interference (RNAi). By 2005, Rathore was confident RNAi was working, evidenced in several lines with extremely low levels of gossypol within the seed, as well as several successive generations that followed suit.
At the edge of a breakthrough and certain of the gossypol removal technology, Rathore assembled his lab team and presented a clear message: “I told them we weren’t seeking wealth. I told them this is a technology for humanity, and not our gain. My whole team, and 99% of the ag scientists I know, all feel the same way. Please don’t tell me university ag scientists seek wealth. No, our motivation is to try and help feed the world.”
Rathore published his findings in 2006, bolstered by Cotton Incorporated’s indispensable financial support. “Cotton Incorporated was a major push for us and they had been interested and involved with gossypol research for decades. Tom Wedegaertner was the go-to guy and made sure we had tremendous help.”
After 11 years of additional work that entailed generations of hundreds of additional lines, molecular and biochemical analyses, several in-house field trials of selected lines, and independent contractor trials in Texas, Mississippi and North Carolina, all the agronomic performance data, fiber yield, seed yield, fiber and seed quality, and seed composition information was handed to USDA-APHIS in the fall of 2017. APHIS’ green light came in October 2018, followed by FDA’s affirmative nod in October 2019. (FDA already had human consumption trial data from the past Hopi cotton studies.)
Wedegaertner, director of Cottonseed Research at Cotton Incorporated, says U.S. deregulation initially was estimated at $10-$15 million, but tallied a significantly less $1 million: “As a whole, the cotton industry has wanted to get rid of seed gossypol for at least the last 75 years. Over about 25 years, Cotton Incorporated has invested $5 million in this project. It’s been a culmination of an incredible amount of research going back a long way. Whatever happens next, we’ve got proof because of this huge step provided by A&M.”
Wedegaertner hopes growers might pocket a $50-$100 premium per ton of ULGCS cottonseed, contingent on supply and demand. “Starting off, gins will have to keep ULGCS separate or have a dedicated oil mill, and this may open the door for vertically integrated systems. A given mill would need to be fed by 50,000 to 100,000 acres of cotton. Existing oil mills are set up to make cow feed, but they’ll be able to process high protein meal, flour and concentrates, and ultimately we could see an entirely new industry if new human uses are found.”
Kick the Tires
Following the ball, what happens now? What else needs to occur prior to ULGCS availability? “All segments of the cotton industry have worked together for so long to get this gossypol bugger out of our protein,” Wedegaertner explains. “We can produce plenty of carbohydrates in this country. Rice, corn, potatoes and more, but high quality protein is going to become increasingly scarce and more valuable. We’ve got protein right here as a byproduct of our cotton fiber crop, and there’s no reason we shouldn’t be utilizing it for a higher use than just feeding to cows.”
At present, major seed companies have kicked the ULGCS tires, but are hesitant to make the production move and confront international ROI. Bluntly stated, ULGCS doesn’t come with a licensed biotech trait and a means for seed companies to capture value, although the benefits would rain down on growers, ginners and oil mills. “Everybody knows we need a seed company to really get involved,” Wedegaertner says, “and maybe we’ll end up with a small startup to get the ball rolling, and things will take off. It’s fair to say that right now the train is stalled and needs to go to the next station.”
“We’re in kind of a holding mode,” Rathore echoes. “Certainly, we don’t have the deep pockets to chase deregulation everywhere. Five years? Frankly, I don’t know how long it will take.”
Despite Rathore’s frustration, he emphasizes the humanitarian importance of ULGCS, and the need for individual countries to carry out deregulation. “U.S. farmers have funded the development of this technology, but they are willing to give it freely in a humanitarian fashion to other countries. The human consumption trials with Hopi cottonseed all show success and the nutritional studies all have proven true.”
Raised in India, Rathore is acutely aware of nutritional deficiencies, and the lengths to which poverty-stricken masses will go to obtain protein. Case in point—beware the grass pea. A hardy plant capable of growth with minimal moisture, grass pea is a legume that strikes a devil’s bargain in Asia and Africa. “If regular crops fail, people will grow grass pea even though it is filled with a powerful neurotoxin. People in these poor places are so desperate for protein they’re willing to eat grass pea, even knowing it causes paralysis in the lower extremities following consumption for a month or so. That shows the desperation of people for protein and the potential reach of edible cottonseed.”
Twenty years in the ULGCS trenches beside Rathore, A&M research associate and laboratory manager LeAnne Campbell was raised in the Third World, and was a frequent witness to the effects of malnutrition. “Just a little protein makes a huge difference and we are sitting on an underutilized resource in cottonseed. Meanwhile, most U.S. cotton farmers have supported this for years, knowing they could get two crops from the same amount of land and effort. We’ve been over so many hurdles, but we’ve kept going and now we’re looking for a seed company to partner with. ULGCS can be incorporated with all other traits and provide a benefit like no other. Why would you not use something that is useful for everyone?”
A Shame to Waste
Where does ULGCS rank in the pantheon of agricultural breakthroughs? Wedegaertner places it on a high pedestal, above the module builder and round bale picker. “Most advances, particularly mechanical ones, eventually become obsolete,” he says. “That won’t happen with gossypol technology. Once we get gossypol out of seed, nobody will ever put it back in. Once gone, it’s forever.”
Rathore, Campbell and Wedegaertner have carried ULGCS to the goal line and are of one accord: All cottonseed will eventually be gossypol free. “It’ll be a different world for cotton growers,” Wedegaertner describes. “The aquaculture industry is starved for protein and that’s one of the fastest growing industries on the planet. The timing is great for the impact of cottonseed protein. There is going to be a day when all cottonseed planted will be ULGCS. It may not be the exact thing we’ve got now, but ultimately, this is where the cottonseed industry is going.”
Gossypol-free cotton will become the industry standard, Campbell concurs: “It’s going to happen. It has to happen. What a shame it would be to waste.”
Rathore is ever faithful, confident that cottonseed, loosed from the shackles of gossypol, will provide a permanent boost to grower income, a source of protein for feed industries, and an accepted part of the human diet: “I am certainly hopeful for utilization after 25 years in research, and I’m hopeful someone will refine what I’ve done. Maybe it will and maybe it won’t be in my lifetime, but ULGCS is coming soon to all cottonseed. This must happen for the world and for agriculture.”
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